AVAHO

Computer-aided detection (CADe) during colonoscopy may not lead to major improvements in key measures, particularly in community-based settings, according to a new study.

In a randomized clinical trial using EndoVigilant, there wasn’t a significant difference in adenomas per colonoscopy (APC) in procedures with the CADe tool versus those without it. In addition, the adenoma detection rate (ADR) and serrated polyp detection rate were similar in the CADe and non-CADe groups.

“Although we were disappointed that AI [artificial intelligence] did not improve detection of adenomas or serrated polyps in our study, we are still optimistic that this exciting technology will eventually impact endoscopy in a very positive way,” senior author Shai Friedland, MD, a professor of medicine at Stanford (Calif.) University and gastroenterologist with the Veterans Affairs Palo Alto Health Care System, said in an interview.

“The ultimate goal should be to improve the ability of colonoscopy to prevent morbidity and mortality from colon cancer, especially for endoscopists who may not be performing as well as they could be,” he said. “AI can potentially help prevent missed lesions due to fatigue or distraction, much like a warning system that averts car accidents. It can also potentially help endoscopists recognize dangerous – but rare – subtle lesions such as small, flat, and depressed cancers.”

The study was published online in the American Journal of Gastroenterology.
 

Analyzing detection rates

Several studies have evaluated the use of different CADe devices to reduce adenoma miss rates during colonoscopy, and some have found that the technology contributed to significantly higher ADR and APC, the study authors write. However, most of these studies have been performed in academic settings.

Dr. Friedland and colleagues conducted a randomized controlled trial, called AI-SEE, to evaluate the use of CADe during colonoscopy in four community-based endoscopy centers located in California, Connecticut, Maryland, and New Jersey between September 2020 and September 2021. The trial included seven board-certified clinicians, who had ADR of 25%-37% before the study. The participants were randomly assigned to colonoscopies with or without CADe in blocks of 16 patients to ensure masking. Both groups had similar patient demographics.

The research team enrolled patients aged 45 years or older who presented for screening or low-risk surveillance colonoscopy, which was defined as a patient qualifying for a surveillance interval of 3 years or greater based on the U.S. Multi-Society Task Force 2020 Guidelines. Patients were excluded if they had a history of inflammatory bowel disease, known or suspected polyposis or hereditary colon cancer syndrome, history of colon resection, or a referral for a diagnostic colonoscopy.

Among 769 enrolled patients, 387 were randomly assigned to undergo colonoscopy with EndoVigilant, an AI-enabled CADe software for colonoscopy. It augments existing white-light colonoscopy in real time by highlighting colon polyps and displaying a graphic box around the lesion on the monitor. It can be deployed as a single- or dual-monitor device. Although the study was originally designed to use two monitors, three investigators expressed strong preference for the single-monitor mode, so the protocol allowed endoscopists to choose.

Primary outcomes included APC and adenoma per extraction (APE), which is the percentage of polyps removed that are adenomas. Secondary endpoints included procedural time, ADR, serrated polyp detection rate, serrated polyps per colonoscopy, and nonadenomatous, nonserrated polyps per colonoscopy.

Overall, the use of CADe didn’t show a significant difference in APC, at 0.73, compared with 0.67 for non-CADe.

Although the use of CADe didn’t lead to increased identification of serrated polyps per colonoscopy – both at 0.08 – CADe led to increased identification of nonadenomatous, nonserrated polyps per colonoscopy, at 0.90 versus 0.51.

There also wasn’t a significant difference in distribution regarding adenomatous polyp location, size, or morphology. However, there was a trend toward greater identification of 6-9 mm APC using CADe, at 0.13 versus 0.08.

Mean withdrawal time was longer in the CADe group, at 11.7 minutes versus 10.7 minutes. However, when no polyps were identified, the withdrawal times were similar, at 9.1 minutes versus 8.8 minutes.

In addition, there was no difference in ADR for screening colonoscopies between the non-CADe and CADe groups, at 34.6% versus 34.3%, or for surveillance procedures, at 43.9% versus 40%. CADe also didn’t improve serrated polyp detection rates for screening or surveillance.

CADe was also associated with decreased APE in all colonoscopies (44.8 vs. 56.8) as well as in screening colonoscopies (43 vs. 57.8).

A comparison of single-monitor CADe with dual-monitor CADe found no significant difference in the average number of adenomas or serrated polyps identified per colonoscopy. However, dual-monitor CADe identified significantly more non-adenomatous, nonserrated polyps per colonoscopy (1.18 vs. 0.42), more adenomas sized at least 10 mm (0.19 vs. 0.05), and more flat polyps (0.18 vs. 0).

The study was terminated early after the interim analysis point, marked by 769 valid subjects. At this point, the comparison of APC between the two groups resulted in a new sample size estimate required for final analysis of 6,557 per group. This revised large study size estimate made it impractical to continue, the study authors wrote. No adverse events were observed during the study.

“What our study shows is that current systems – and the one we used in this study performs very well when tested on a database of images or videos – don’t make a major impact on very crude outcome measures, such as the total number of adenomas detected by a group of endoscopists at typical private endoscopy centers,” Dr. Friedland said. “I’m not convinced that we have a good answer yet for where to go from here, but we need to keep working with our AI colleagues to figure out how to use this exciting technology to improve outcomes in colon cancer.”
 

Additional considerations

In a separate evaluation of EndoVigilant, the frame level sensitivity was 0.9 and the frame level specificity was 0.97. These calculations were conducted on a dataset not used in training or validation of this model, the authors noted.

In this study, it’s possible that experienced community-based endoscopists are proficient at detecting the adenomas highlighted by the CADe system, so the technology may not detect a significant number of additional adenomas, the authors wrote. It’s also possible that some endoscopists ignore lesions highlighted by CADe, including small lesions that might be difficult to identify as adenomas or are seen as clinically unimportant, which could reduce the potential benefit of CADe.

“It’s important to remember that these tools are meant to be endoscopist assistance devices, not endoscopist replacements. They provide added benefit by pointing out polyps while we do the best exam we can,” Aasma Shaukat, MD, a professor of medicine and gastroenterologist at NYU Langone Health, New York, said in an interview.

Dr. Shaukat, who wasn’t involved with this study, has researched CADe for screening and surveillance colonoscopies. She and colleagues found that CADe use improved APC without an increase in resection of nonneoplastic lesions.

“Different trials have reported different results, and at the end of the day, it’s an endoscopist assistance tool, like spellcheck in a document,” she said. “It’s nice if spellcheck points to an incorrect spelling, but you don’t have to use it. Similarly, we often don’t know in these studies what an endoscopist felt or believed about the tool when using it.”

The benefits of CADe could vary based on its software, setting, number of patients, patient characteristics, number of clinicians, provider experience and training, dual- versus single-monitor setup, and even time of day, she noted. Future studies could clarify these factors, as well as improve the technology.

“This is just the beginning of AI in this field, and while bounding boxes to indicate potential polyps is a good start, it’s not the be-all, end-all,” Dr. Shaukat said.

“We want AI software to be able to tell us more about the size of the polyp, histology, prep quality, landmarks in the colon, adequacy of resection, and more. There’s some work being geared toward developing the algorithms to do these additional aspects,” she added.

The study was sponsored by EndoVigilant. Some of the authors reported consultant roles with Neptune Medical, AgilTx, Intuitive Surgical, Capsovision, and EndoVigilant. Dr. Shaukat reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Computer-aided detection (CADe) during colonoscopy may not lead to major improvements in key measures, particularly in community-based settings, according to a new study.

In a randomized clinical trial using EndoVigilant, there wasn’t a significant difference in adenomas per colonoscopy (APC) in procedures with the CADe tool versus those without it. In addition, the adenoma detection rate (ADR) and serrated polyp detection rate were similar in the CADe and non-CADe groups.

“Although we were disappointed that AI [artificial intelligence] did not improve detection of adenomas or serrated polyps in our study, we are still optimistic that this exciting technology will eventually impact endoscopy in a very positive way,” senior author Shai Friedland, MD, a professor of medicine at Stanford (Calif.) University and gastroenterologist with the Veterans Affairs Palo Alto Health Care System, said in an interview.

“The ultimate goal should be to improve the ability of colonoscopy to prevent morbidity and mortality from colon cancer, especially for endoscopists who may not be performing as well as they could be,” he said. “AI can potentially help prevent missed lesions due to fatigue or distraction, much like a warning system that averts car accidents. It can also potentially help endoscopists recognize dangerous – but rare – subtle lesions such as small, flat, and depressed cancers.”

The study was published online in the American Journal of Gastroenterology.
 

Analyzing detection rates

Several studies have evaluated the use of different CADe devices to reduce adenoma miss rates during colonoscopy, and some have found that the technology contributed to significantly higher ADR and APC, the study authors write. However, most of these studies have been performed in academic settings.

Dr. Friedland and colleagues conducted a randomized controlled trial, called AI-SEE, to evaluate the use of CADe during colonoscopy in four community-based endoscopy centers located in California, Connecticut, Maryland, and New Jersey between September 2020 and September 2021. The trial included seven board-certified clinicians, who had ADR of 25%-37% before the study. The participants were randomly assigned to colonoscopies with or without CADe in blocks of 16 patients to ensure masking. Both groups had similar patient demographics.

The research team enrolled patients aged 45 years or older who presented for screening or low-risk surveillance colonoscopy, which was defined as a patient qualifying for a surveillance interval of 3 years or greater based on the U.S. Multi-Society Task Force 2020 Guidelines. Patients were excluded if they had a history of inflammatory bowel disease, known or suspected polyposis or hereditary colon cancer syndrome, history of colon resection, or a referral for a diagnostic colonoscopy.

Among 769 enrolled patients, 387 were randomly assigned to undergo colonoscopy with EndoVigilant, an AI-enabled CADe software for colonoscopy. It augments existing white-light colonoscopy in real time by highlighting colon polyps and displaying a graphic box around the lesion on the monitor. It can be deployed as a single- or dual-monitor device. Although the study was originally designed to use two monitors, three investigators expressed strong preference for the single-monitor mode, so the protocol allowed endoscopists to choose.

Primary outcomes included APC and adenoma per extraction (APE), which is the percentage of polyps removed that are adenomas. Secondary endpoints included procedural time, ADR, serrated polyp detection rate, serrated polyps per colonoscopy, and nonadenomatous, nonserrated polyps per colonoscopy.

Overall, the use of CADe didn’t show a significant difference in APC, at 0.73, compared with 0.67 for non-CADe.

Although the use of CADe didn’t lead to increased identification of serrated polyps per colonoscopy – both at 0.08 – CADe led to increased identification of nonadenomatous, nonserrated polyps per colonoscopy, at 0.90 versus 0.51.

There also wasn’t a significant difference in distribution regarding adenomatous polyp location, size, or morphology. However, there was a trend toward greater identification of 6-9 mm APC using CADe, at 0.13 versus 0.08.

Mean withdrawal time was longer in the CADe group, at 11.7 minutes versus 10.7 minutes. However, when no polyps were identified, the withdrawal times were similar, at 9.1 minutes versus 8.8 minutes.

In addition, there was no difference in ADR for screening colonoscopies between the non-CADe and CADe groups, at 34.6% versus 34.3%, or for surveillance procedures, at 43.9% versus 40%. CADe also didn’t improve serrated polyp detection rates for screening or surveillance.

CADe was also associated with decreased APE in all colonoscopies (44.8 vs. 56.8) as well as in screening colonoscopies (43 vs. 57.8).

A comparison of single-monitor CADe with dual-monitor CADe found no significant difference in the average number of adenomas or serrated polyps identified per colonoscopy. However, dual-monitor CADe identified significantly more non-adenomatous, nonserrated polyps per colonoscopy (1.18 vs. 0.42), more adenomas sized at least 10 mm (0.19 vs. 0.05), and more flat polyps (0.18 vs. 0).

The study was terminated early after the interim analysis point, marked by 769 valid subjects. At this point, the comparison of APC between the two groups resulted in a new sample size estimate required for final analysis of 6,557 per group. This revised large study size estimate made it impractical to continue, the study authors wrote. No adverse events were observed during the study.

“What our study shows is that current systems – and the one we used in this study performs very well when tested on a database of images or videos – don’t make a major impact on very crude outcome measures, such as the total number of adenomas detected by a group of endoscopists at typical private endoscopy centers,” Dr. Friedland said. “I’m not convinced that we have a good answer yet for where to go from here, but we need to keep working with our AI colleagues to figure out how to use this exciting technology to improve outcomes in colon cancer.”
 

Additional considerations

In a separate evaluation of EndoVigilant, the frame level sensitivity was 0.9 and the frame level specificity was 0.97. These calculations were conducted on a dataset not used in training or validation of this model, the authors noted.

In this study, it’s possible that experienced community-based endoscopists are proficient at detecting the adenomas highlighted by the CADe system, so the technology may not detect a significant number of additional adenomas, the authors wrote. It’s also possible that some endoscopists ignore lesions highlighted by CADe, including small lesions that might be difficult to identify as adenomas or are seen as clinically unimportant, which could reduce the potential benefit of CADe.

“It’s important to remember that these tools are meant to be endoscopist assistance devices, not endoscopist replacements. They provide added benefit by pointing out polyps while we do the best exam we can,” Aasma Shaukat, MD, a professor of medicine and gastroenterologist at NYU Langone Health, New York, said in an interview.

Dr. Shaukat, who wasn’t involved with this study, has researched CADe for screening and surveillance colonoscopies. She and colleagues found that CADe use improved APC without an increase in resection of nonneoplastic lesions.

“Different trials have reported different results, and at the end of the day, it’s an endoscopist assistance tool, like spellcheck in a document,” she said. “It’s nice if spellcheck points to an incorrect spelling, but you don’t have to use it. Similarly, we often don’t know in these studies what an endoscopist felt or believed about the tool when using it.”

The benefits of CADe could vary based on its software, setting, number of patients, patient characteristics, number of clinicians, provider experience and training, dual- versus single-monitor setup, and even time of day, she noted. Future studies could clarify these factors, as well as improve the technology.

“This is just the beginning of AI in this field, and while bounding boxes to indicate potential polyps is a good start, it’s not the be-all, end-all,” Dr. Shaukat said.

“We want AI software to be able to tell us more about the size of the polyp, histology, prep quality, landmarks in the colon, adequacy of resection, and more. There’s some work being geared toward developing the algorithms to do these additional aspects,” she added.

The study was sponsored by EndoVigilant. Some of the authors reported consultant roles with Neptune Medical, AgilTx, Intuitive Surgical, Capsovision, and EndoVigilant. Dr. Shaukat reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Computer-aided detection (CADe) during colonoscopy may not lead to major improvements in key measures, particularly in community-based settings, according to a new study.

In a randomized clinical trial using EndoVigilant, there wasn’t a significant difference in adenomas per colonoscopy (APC) in procedures with the CADe tool versus those without it. In addition, the adenoma detection rate (ADR) and serrated polyp detection rate were similar in the CADe and non-CADe groups.

“Although we were disappointed that AI [artificial intelligence] did not improve detection of adenomas or serrated polyps in our study, we are still optimistic that this exciting technology will eventually impact endoscopy in a very positive way,” senior author Shai Friedland, MD, a professor of medicine at Stanford (Calif.) University and gastroenterologist with the Veterans Affairs Palo Alto Health Care System, said in an interview.

“The ultimate goal should be to improve the ability of colonoscopy to prevent morbidity and mortality from colon cancer, especially for endoscopists who may not be performing as well as they could be,” he said. “AI can potentially help prevent missed lesions due to fatigue or distraction, much like a warning system that averts car accidents. It can also potentially help endoscopists recognize dangerous – but rare – subtle lesions such as small, flat, and depressed cancers.”

The study was published online in the American Journal of Gastroenterology.
 

Analyzing detection rates

Several studies have evaluated the use of different CADe devices to reduce adenoma miss rates during colonoscopy, and some have found that the technology contributed to significantly higher ADR and APC, the study authors write. However, most of these studies have been performed in academic settings.

Dr. Friedland and colleagues conducted a randomized controlled trial, called AI-SEE, to evaluate the use of CADe during colonoscopy in four community-based endoscopy centers located in California, Connecticut, Maryland, and New Jersey between September 2020 and September 2021. The trial included seven board-certified clinicians, who had ADR of 25%-37% before the study. The participants were randomly assigned to colonoscopies with or without CADe in blocks of 16 patients to ensure masking. Both groups had similar patient demographics.

The research team enrolled patients aged 45 years or older who presented for screening or low-risk surveillance colonoscopy, which was defined as a patient qualifying for a surveillance interval of 3 years or greater based on the U.S. Multi-Society Task Force 2020 Guidelines. Patients were excluded if they had a history of inflammatory bowel disease, known or suspected polyposis or hereditary colon cancer syndrome, history of colon resection, or a referral for a diagnostic colonoscopy.

Among 769 enrolled patients, 387 were randomly assigned to undergo colonoscopy with EndoVigilant, an AI-enabled CADe software for colonoscopy. It augments existing white-light colonoscopy in real time by highlighting colon polyps and displaying a graphic box around the lesion on the monitor. It can be deployed as a single- or dual-monitor device. Although the study was originally designed to use two monitors, three investigators expressed strong preference for the single-monitor mode, so the protocol allowed endoscopists to choose.

Primary outcomes included APC and adenoma per extraction (APE), which is the percentage of polyps removed that are adenomas. Secondary endpoints included procedural time, ADR, serrated polyp detection rate, serrated polyps per colonoscopy, and nonadenomatous, nonserrated polyps per colonoscopy.

Overall, the use of CADe didn’t show a significant difference in APC, at 0.73, compared with 0.67 for non-CADe.

Although the use of CADe didn’t lead to increased identification of serrated polyps per colonoscopy – both at 0.08 – CADe led to increased identification of nonadenomatous, nonserrated polyps per colonoscopy, at 0.90 versus 0.51.

There also wasn’t a significant difference in distribution regarding adenomatous polyp location, size, or morphology. However, there was a trend toward greater identification of 6-9 mm APC using CADe, at 0.13 versus 0.08.

Mean withdrawal time was longer in the CADe group, at 11.7 minutes versus 10.7 minutes. However, when no polyps were identified, the withdrawal times were similar, at 9.1 minutes versus 8.8 minutes.

In addition, there was no difference in ADR for screening colonoscopies between the non-CADe and CADe groups, at 34.6% versus 34.3%, or for surveillance procedures, at 43.9% versus 40%. CADe also didn’t improve serrated polyp detection rates for screening or surveillance.

CADe was also associated with decreased APE in all colonoscopies (44.8 vs. 56.8) as well as in screening colonoscopies (43 vs. 57.8).

A comparison of single-monitor CADe with dual-monitor CADe found no significant difference in the average number of adenomas or serrated polyps identified per colonoscopy. However, dual-monitor CADe identified significantly more non-adenomatous, nonserrated polyps per colonoscopy (1.18 vs. 0.42), more adenomas sized at least 10 mm (0.19 vs. 0.05), and more flat polyps (0.18 vs. 0).

The study was terminated early after the interim analysis point, marked by 769 valid subjects. At this point, the comparison of APC between the two groups resulted in a new sample size estimate required for final analysis of 6,557 per group. This revised large study size estimate made it impractical to continue, the study authors wrote. No adverse events were observed during the study.

“What our study shows is that current systems – and the one we used in this study performs very well when tested on a database of images or videos – don’t make a major impact on very crude outcome measures, such as the total number of adenomas detected by a group of endoscopists at typical private endoscopy centers,” Dr. Friedland said. “I’m not convinced that we have a good answer yet for where to go from here, but we need to keep working with our AI colleagues to figure out how to use this exciting technology to improve outcomes in colon cancer.”
 

Additional considerations

In a separate evaluation of EndoVigilant, the frame level sensitivity was 0.9 and the frame level specificity was 0.97. These calculations were conducted on a dataset not used in training or validation of this model, the authors noted.

In this study, it’s possible that experienced community-based endoscopists are proficient at detecting the adenomas highlighted by the CADe system, so the technology may not detect a significant number of additional adenomas, the authors wrote. It’s also possible that some endoscopists ignore lesions highlighted by CADe, including small lesions that might be difficult to identify as adenomas or are seen as clinically unimportant, which could reduce the potential benefit of CADe.

“It’s important to remember that these tools are meant to be endoscopist assistance devices, not endoscopist replacements. They provide added benefit by pointing out polyps while we do the best exam we can,” Aasma Shaukat, MD, a professor of medicine and gastroenterologist at NYU Langone Health, New York, said in an interview.

Dr. Shaukat, who wasn’t involved with this study, has researched CADe for screening and surveillance colonoscopies. She and colleagues found that CADe use improved APC without an increase in resection of nonneoplastic lesions.

“Different trials have reported different results, and at the end of the day, it’s an endoscopist assistance tool, like spellcheck in a document,” she said. “It’s nice if spellcheck points to an incorrect spelling, but you don’t have to use it. Similarly, we often don’t know in these studies what an endoscopist felt or believed about the tool when using it.”

The benefits of CADe could vary based on its software, setting, number of patients, patient characteristics, number of clinicians, provider experience and training, dual- versus single-monitor setup, and even time of day, she noted. Future studies could clarify these factors, as well as improve the technology.

“This is just the beginning of AI in this field, and while bounding boxes to indicate potential polyps is a good start, it’s not the be-all, end-all,” Dr. Shaukat said.

“We want AI software to be able to tell us more about the size of the polyp, histology, prep quality, landmarks in the colon, adequacy of resection, and more. There’s some work being geared toward developing the algorithms to do these additional aspects,” she added.

The study was sponsored by EndoVigilant. Some of the authors reported consultant roles with Neptune Medical, AgilTx, Intuitive Surgical, Capsovision, and EndoVigilant. Dr. Shaukat reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

As various surgical procedures become more feasible for patients with chronic lymphocytic leukemia (CLL), a team of hematologist-oncologists and cardiologists published a new report advising colleagues to carefully consider the risks and benefits of such operations.

In the past decade, as targeted therapies have permitted better management of CLL, a new realm of possibilities has opened up for patients with this blood cancer.

“Previously, patients may not have been candidates for elective surgeries, such as hip replacements,” said hematologist-oncologist Helen Ma, MD, of the University of Irvine (Calif.) and VA Long Beach Healthcare System. She is the lead author of the report, which appeared in the British Journal of Hematology.

“Now that targeted therapies are controlling CLL well, patients may elect to have procedures that they may not have considered if their blood counts were very low or they felt too unwell to go through such invasive surgeries,” said Dr. Ma in an interview. In fact, the study authors noted that, “with currently available treatments, many patients with CLL are living considerably longer than the 1-year life expectancy threshold that proceduralists require.”

But extra surgical risks persist. “Both CLL and its treatment can increase the risk of complications during and after procedures, though available data are not consistently stratified by stage and whether patients are undergoing treatment,” the report authors noted.

Research has linked CLL to higher rates of blood transfusions in cardiac surgeries: One study, conducted partially in the era of targeted therapy, found that 87% of these surgery patients with CLL needed blood products vs. 65% of those who didn’t have CLL (P = .01). Studies didn’t find any extra risk of infections in patients with CLL, however, and there are conflicting findings about whether hospital mortality is higher.

Another study, also conducted partially in the era of targeted therapy, found that patients with CLL who had percutaneous coronary intervention procedures “developed higher rates of in-hospital mortality, any complication, bleeding and postoperative stroke compared to those seen in patients without leukemia.”

The authors of the new report noted that “patients with more advanced stage are at increased risk of bleeding and thromboembolic events relevant to their disease and invasive procedures.” Patients at more than minimal risk should undergo electrocardiograms prior to cardiac procedures, they wrote. Stress tests, coronary angiography, and percutaneous coronary intervention may also be warranted.

“To optimize evaluation and perioperative management, we strongly recommend the prospective collaborative inclusion of a multidisciplinary team including hematologists/oncologists, cardiologists (ideally cardio-oncologists), surgeons and anesthetists, as well as their ongoing involvement during the postoperative period,” the authors wrote.

As for medications, the researchers said that “generally, antibody therapy has no impact on surgery.” They added, “There is no evidence to hold treatment with anti-CD20 monoclonal antibodies prior to procedures unless the patient has cytopenias that may be a contra-indication. If that is the case, we recommend holding until counts recover to the parameters required for the procedure.”

In regard to Bruton’s tyrosine kinase inhibitors such as ibrutinib, “patients undergoing major surgeries with high risk of bleeding should hold Bruton’s tyrosine kinase inhibitors for a week prior to surgery to ensure adequate platelet function recovery given the disruption between collagen and platelet aggregation. Medications can be resumed 3-7 days after achieving postoperative hemostasis, depending on the type of surgery and risk of bleeding.”

As for venetoclax, “prior to surgery, patients should receive granulocyte colony-stimulating factor for neutropenia, blood transfusions for anemia, and platelet transfusions for thrombocytopenia to maintain procedural parameters.”

In the big picture, study lead author Dr. Ma said, “patients with CLL are doing well on continuous targeted treatments, and if there are otherwise no contraindications, they should be considered for procedures to improve their quality of life.”

In an interview, Stanford (Calif.) University surgeon Joe Forrester MD, MSc, who’s familiar with the report findings, said its conclusions are valid. “The nice thing is that a lot of the [CLL] therapies don’t have a lot of surgical side effects. Most should not preclude a patient from going to surgery.”

He advised colleagues to make sure to be open with patients about the heightened surgical risks due to CLL, such when they need emergency procedures. And it’s important to be realistic about whether patients will live long enough to benefit from the rare surgeries – such as weight-loss procedures – that won’t show major benefits for 5-10 years, he said.

The Lymphoma Research Foundation supported the study. Dr. Ma, several coauthors, and Dr. Forrester report no disclosures. One coauthor reports multiple relationships with industry.

As various surgical procedures become more feasible for patients with chronic lymphocytic leukemia (CLL), a team of hematologist-oncologists and cardiologists published a new report advising colleagues to carefully consider the risks and benefits of such operations.

In the past decade, as targeted therapies have permitted better management of CLL, a new realm of possibilities has opened up for patients with this blood cancer.

“Previously, patients may not have been candidates for elective surgeries, such as hip replacements,” said hematologist-oncologist Helen Ma, MD, of the University of Irvine (Calif.) and VA Long Beach Healthcare System. She is the lead author of the report, which appeared in the British Journal of Hematology.

“Now that targeted therapies are controlling CLL well, patients may elect to have procedures that they may not have considered if their blood counts were very low or they felt too unwell to go through such invasive surgeries,” said Dr. Ma in an interview. In fact, the study authors noted that, “with currently available treatments, many patients with CLL are living considerably longer than the 1-year life expectancy threshold that proceduralists require.”

But extra surgical risks persist. “Both CLL and its treatment can increase the risk of complications during and after procedures, though available data are not consistently stratified by stage and whether patients are undergoing treatment,” the report authors noted.

Research has linked CLL to higher rates of blood transfusions in cardiac surgeries: One study, conducted partially in the era of targeted therapy, found that 87% of these surgery patients with CLL needed blood products vs. 65% of those who didn’t have CLL (P = .01). Studies didn’t find any extra risk of infections in patients with CLL, however, and there are conflicting findings about whether hospital mortality is higher.

Another study, also conducted partially in the era of targeted therapy, found that patients with CLL who had percutaneous coronary intervention procedures “developed higher rates of in-hospital mortality, any complication, bleeding and postoperative stroke compared to those seen in patients without leukemia.”

The authors of the new report noted that “patients with more advanced stage are at increased risk of bleeding and thromboembolic events relevant to their disease and invasive procedures.” Patients at more than minimal risk should undergo electrocardiograms prior to cardiac procedures, they wrote. Stress tests, coronary angiography, and percutaneous coronary intervention may also be warranted.

“To optimize evaluation and perioperative management, we strongly recommend the prospective collaborative inclusion of a multidisciplinary team including hematologists/oncologists, cardiologists (ideally cardio-oncologists), surgeons and anesthetists, as well as their ongoing involvement during the postoperative period,” the authors wrote.

As for medications, the researchers said that “generally, antibody therapy has no impact on surgery.” They added, “There is no evidence to hold treatment with anti-CD20 monoclonal antibodies prior to procedures unless the patient has cytopenias that may be a contra-indication. If that is the case, we recommend holding until counts recover to the parameters required for the procedure.”

In regard to Bruton’s tyrosine kinase inhibitors such as ibrutinib, “patients undergoing major surgeries with high risk of bleeding should hold Bruton’s tyrosine kinase inhibitors for a week prior to surgery to ensure adequate platelet function recovery given the disruption between collagen and platelet aggregation. Medications can be resumed 3-7 days after achieving postoperative hemostasis, depending on the type of surgery and risk of bleeding.”

As for venetoclax, “prior to surgery, patients should receive granulocyte colony-stimulating factor for neutropenia, blood transfusions for anemia, and platelet transfusions for thrombocytopenia to maintain procedural parameters.”

In the big picture, study lead author Dr. Ma said, “patients with CLL are doing well on continuous targeted treatments, and if there are otherwise no contraindications, they should be considered for procedures to improve their quality of life.”

In an interview, Stanford (Calif.) University surgeon Joe Forrester MD, MSc, who’s familiar with the report findings, said its conclusions are valid. “The nice thing is that a lot of the [CLL] therapies don’t have a lot of surgical side effects. Most should not preclude a patient from going to surgery.”

He advised colleagues to make sure to be open with patients about the heightened surgical risks due to CLL, such when they need emergency procedures. And it’s important to be realistic about whether patients will live long enough to benefit from the rare surgeries – such as weight-loss procedures – that won’t show major benefits for 5-10 years, he said.

The Lymphoma Research Foundation supported the study. Dr. Ma, several coauthors, and Dr. Forrester report no disclosures. One coauthor reports multiple relationships with industry.

As various surgical procedures become more feasible for patients with chronic lymphocytic leukemia (CLL), a team of hematologist-oncologists and cardiologists published a new report advising colleagues to carefully consider the risks and benefits of such operations.

In the past decade, as targeted therapies have permitted better management of CLL, a new realm of possibilities has opened up for patients with this blood cancer.

“Previously, patients may not have been candidates for elective surgeries, such as hip replacements,” said hematologist-oncologist Helen Ma, MD, of the University of Irvine (Calif.) and VA Long Beach Healthcare System. She is the lead author of the report, which appeared in the British Journal of Hematology.

“Now that targeted therapies are controlling CLL well, patients may elect to have procedures that they may not have considered if their blood counts were very low or they felt too unwell to go through such invasive surgeries,” said Dr. Ma in an interview. In fact, the study authors noted that, “with currently available treatments, many patients with CLL are living considerably longer than the 1-year life expectancy threshold that proceduralists require.”

But extra surgical risks persist. “Both CLL and its treatment can increase the risk of complications during and after procedures, though available data are not consistently stratified by stage and whether patients are undergoing treatment,” the report authors noted.

Research has linked CLL to higher rates of blood transfusions in cardiac surgeries: One study, conducted partially in the era of targeted therapy, found that 87% of these surgery patients with CLL needed blood products vs. 65% of those who didn’t have CLL (P = .01). Studies didn’t find any extra risk of infections in patients with CLL, however, and there are conflicting findings about whether hospital mortality is higher.

Another study, also conducted partially in the era of targeted therapy, found that patients with CLL who had percutaneous coronary intervention procedures “developed higher rates of in-hospital mortality, any complication, bleeding and postoperative stroke compared to those seen in patients without leukemia.”

The authors of the new report noted that “patients with more advanced stage are at increased risk of bleeding and thromboembolic events relevant to their disease and invasive procedures.” Patients at more than minimal risk should undergo electrocardiograms prior to cardiac procedures, they wrote. Stress tests, coronary angiography, and percutaneous coronary intervention may also be warranted.

“To optimize evaluation and perioperative management, we strongly recommend the prospective collaborative inclusion of a multidisciplinary team including hematologists/oncologists, cardiologists (ideally cardio-oncologists), surgeons and anesthetists, as well as their ongoing involvement during the postoperative period,” the authors wrote.

As for medications, the researchers said that “generally, antibody therapy has no impact on surgery.” They added, “There is no evidence to hold treatment with anti-CD20 monoclonal antibodies prior to procedures unless the patient has cytopenias that may be a contra-indication. If that is the case, we recommend holding until counts recover to the parameters required for the procedure.”

In regard to Bruton’s tyrosine kinase inhibitors such as ibrutinib, “patients undergoing major surgeries with high risk of bleeding should hold Bruton’s tyrosine kinase inhibitors for a week prior to surgery to ensure adequate platelet function recovery given the disruption between collagen and platelet aggregation. Medications can be resumed 3-7 days after achieving postoperative hemostasis, depending on the type of surgery and risk of bleeding.”

As for venetoclax, “prior to surgery, patients should receive granulocyte colony-stimulating factor for neutropenia, blood transfusions for anemia, and platelet transfusions for thrombocytopenia to maintain procedural parameters.”

In the big picture, study lead author Dr. Ma said, “patients with CLL are doing well on continuous targeted treatments, and if there are otherwise no contraindications, they should be considered for procedures to improve their quality of life.”

In an interview, Stanford (Calif.) University surgeon Joe Forrester MD, MSc, who’s familiar with the report findings, said its conclusions are valid. “The nice thing is that a lot of the [CLL] therapies don’t have a lot of surgical side effects. Most should not preclude a patient from going to surgery.”

He advised colleagues to make sure to be open with patients about the heightened surgical risks due to CLL, such when they need emergency procedures. And it’s important to be realistic about whether patients will live long enough to benefit from the rare surgeries – such as weight-loss procedures – that won’t show major benefits for 5-10 years, he said.

The Lymphoma Research Foundation supported the study. Dr. Ma, several coauthors, and Dr. Forrester report no disclosures. One coauthor reports multiple relationships with industry.

New data released by the U.S. Department of Defense show that the incidence of many types of cancer is higher among military pilots and aviation support personnel in comparison with the general population.

“Military aircrew and ground crew were overall more likely to be diagnosed with cancer, but less likely to die from cancer compared to the U.S. population,” the report concludes.

The study involved 156,050 aircrew and 737,891 ground crew. Participants were followed between 1992 and 2017. Both groups were predominantly male and non-Hispanic.

Data on cancer incidence and mortality for these two groups were compared with data from groups of similar age in the general population through use of the Surveillance, Epidemiology, and End Results (SEER) Database of the National Cancer Institute.

For aircrew, the study found an 87% higher rate of melanoma, a 39% higher rate of thyroid cancer, a 16% higher rate of prostate cancer, and a 24% higher rate of cancer for all sites combined.

A higher rate of melanoma and prostate cancer among aircrew has been reported previously, but the increased rate of thyroid cancer is a new finding, the authors note.

The uptick in melanoma has also been reported in studies of civilian pilots and cabin crew. It has been attributed to exposure to hazardous ultraviolet and cosmic radiation.

For ground crew members, the analysis found a 19% higher rate of cancers of the brain and nervous system, a 15% higher rate of thyroid cancer, a 9% higher rate of melanoma and of kidney and renal pelvis cancers, and a 3% higher rate of cancer for all sites combined.

There is little to compare these findings with: This is the first time that cancer risk has been evaluated in such a large population of military ground crew.
 

Lower rates of cancer mortality

In contrast to the increase in cancer incidence, the report found a decrease in cancer mortality.

When compared with a demographically similar U.S. population, the mortality rate among aircrew was 56% lower for all cancer sites; for ground crew, the mortality rate was 35% lower.

However, the report authors emphasize that “it is important to note that the military study population was relatively young.”

The median age at the end of follow-up for the cancer incidence analysis was 41 years for aircrew and 26 years for ground crew. The median age at the end of follow-up for the cancer mortality analysis was 48 years for aircrew and 41 years for ground crew.

“Results may have differed if additional older former Service members had been included in the study, since cancer risk and mortality rates increase with age,” the authors comment.

Other studies have found an increase in deaths from melanoma as well as an increase in the incidence of melanoma. A meta-analysis published in 2019 in the British Journal of Dermatology found that airline pilots and cabin crew have about twice the risk of melanoma and other skin cancers than the general population. Pilots are also more likely to die from melanoma.
 

Further study underway

The findings on military air and ground crew come from phase 1 of a study that was required by Congress in the 2021 defense bill. Because the investigators found an increase in the incidence of cancer, phase 2 of the study is now necessary.

The report authors explain that phase 2 will consist of identifying the carcinogenic toxicants or hazardous materials associated with military flight operations; identifying operating environments that could be associated with increased amounts of ionizing and nonionizing radiation; identifying specific duties, dates of service, and types of aircraft flown that could have increased the risk for cancer; identifying duty locations associated with a higher incidence of cancers; identifying potential exposures through military service that are not related to aviation; and determining the appropriate age to begin screening military aircrew and ground crew for cancers.

A version of this article first appeared on Medscape.com.

New data released by the U.S. Department of Defense show that the incidence of many types of cancer is higher among military pilots and aviation support personnel in comparison with the general population.

“Military aircrew and ground crew were overall more likely to be diagnosed with cancer, but less likely to die from cancer compared to the U.S. population,” the report concludes.

The study involved 156,050 aircrew and 737,891 ground crew. Participants were followed between 1992 and 2017. Both groups were predominantly male and non-Hispanic.

Data on cancer incidence and mortality for these two groups were compared with data from groups of similar age in the general population through use of the Surveillance, Epidemiology, and End Results (SEER) Database of the National Cancer Institute.

For aircrew, the study found an 87% higher rate of melanoma, a 39% higher rate of thyroid cancer, a 16% higher rate of prostate cancer, and a 24% higher rate of cancer for all sites combined.

A higher rate of melanoma and prostate cancer among aircrew has been reported previously, but the increased rate of thyroid cancer is a new finding, the authors note.

The uptick in melanoma has also been reported in studies of civilian pilots and cabin crew. It has been attributed to exposure to hazardous ultraviolet and cosmic radiation.

For ground crew members, the analysis found a 19% higher rate of cancers of the brain and nervous system, a 15% higher rate of thyroid cancer, a 9% higher rate of melanoma and of kidney and renal pelvis cancers, and a 3% higher rate of cancer for all sites combined.

There is little to compare these findings with: This is the first time that cancer risk has been evaluated in such a large population of military ground crew.
 

Lower rates of cancer mortality

In contrast to the increase in cancer incidence, the report found a decrease in cancer mortality.

When compared with a demographically similar U.S. population, the mortality rate among aircrew was 56% lower for all cancer sites; for ground crew, the mortality rate was 35% lower.

However, the report authors emphasize that “it is important to note that the military study population was relatively young.”

The median age at the end of follow-up for the cancer incidence analysis was 41 years for aircrew and 26 years for ground crew. The median age at the end of follow-up for the cancer mortality analysis was 48 years for aircrew and 41 years for ground crew.

“Results may have differed if additional older former Service members had been included in the study, since cancer risk and mortality rates increase with age,” the authors comment.

Other studies have found an increase in deaths from melanoma as well as an increase in the incidence of melanoma. A meta-analysis published in 2019 in the British Journal of Dermatology found that airline pilots and cabin crew have about twice the risk of melanoma and other skin cancers than the general population. Pilots are also more likely to die from melanoma.
 

Further study underway

The findings on military air and ground crew come from phase 1 of a study that was required by Congress in the 2021 defense bill. Because the investigators found an increase in the incidence of cancer, phase 2 of the study is now necessary.

The report authors explain that phase 2 will consist of identifying the carcinogenic toxicants or hazardous materials associated with military flight operations; identifying operating environments that could be associated with increased amounts of ionizing and nonionizing radiation; identifying specific duties, dates of service, and types of aircraft flown that could have increased the risk for cancer; identifying duty locations associated with a higher incidence of cancers; identifying potential exposures through military service that are not related to aviation; and determining the appropriate age to begin screening military aircrew and ground crew for cancers.

A version of this article first appeared on Medscape.com.

New data released by the U.S. Department of Defense show that the incidence of many types of cancer is higher among military pilots and aviation support personnel in comparison with the general population.

“Military aircrew and ground crew were overall more likely to be diagnosed with cancer, but less likely to die from cancer compared to the U.S. population,” the report concludes.

The study involved 156,050 aircrew and 737,891 ground crew. Participants were followed between 1992 and 2017. Both groups were predominantly male and non-Hispanic.

Data on cancer incidence and mortality for these two groups were compared with data from groups of similar age in the general population through use of the Surveillance, Epidemiology, and End Results (SEER) Database of the National Cancer Institute.

For aircrew, the study found an 87% higher rate of melanoma, a 39% higher rate of thyroid cancer, a 16% higher rate of prostate cancer, and a 24% higher rate of cancer for all sites combined.

A higher rate of melanoma and prostate cancer among aircrew has been reported previously, but the increased rate of thyroid cancer is a new finding, the authors note.

The uptick in melanoma has also been reported in studies of civilian pilots and cabin crew. It has been attributed to exposure to hazardous ultraviolet and cosmic radiation.

For ground crew members, the analysis found a 19% higher rate of cancers of the brain and nervous system, a 15% higher rate of thyroid cancer, a 9% higher rate of melanoma and of kidney and renal pelvis cancers, and a 3% higher rate of cancer for all sites combined.

There is little to compare these findings with: This is the first time that cancer risk has been evaluated in such a large population of military ground crew.
 

Lower rates of cancer mortality

In contrast to the increase in cancer incidence, the report found a decrease in cancer mortality.

When compared with a demographically similar U.S. population, the mortality rate among aircrew was 56% lower for all cancer sites; for ground crew, the mortality rate was 35% lower.

However, the report authors emphasize that “it is important to note that the military study population was relatively young.”

The median age at the end of follow-up for the cancer incidence analysis was 41 years for aircrew and 26 years for ground crew. The median age at the end of follow-up for the cancer mortality analysis was 48 years for aircrew and 41 years for ground crew.

“Results may have differed if additional older former Service members had been included in the study, since cancer risk and mortality rates increase with age,” the authors comment.

Other studies have found an increase in deaths from melanoma as well as an increase in the incidence of melanoma. A meta-analysis published in 2019 in the British Journal of Dermatology found that airline pilots and cabin crew have about twice the risk of melanoma and other skin cancers than the general population. Pilots are also more likely to die from melanoma.
 

Further study underway

The findings on military air and ground crew come from phase 1 of a study that was required by Congress in the 2021 defense bill. Because the investigators found an increase in the incidence of cancer, phase 2 of the study is now necessary.

The report authors explain that phase 2 will consist of identifying the carcinogenic toxicants or hazardous materials associated with military flight operations; identifying operating environments that could be associated with increased amounts of ionizing and nonionizing radiation; identifying specific duties, dates of service, and types of aircraft flown that could have increased the risk for cancer; identifying duty locations associated with a higher incidence of cancers; identifying potential exposures through military service that are not related to aviation; and determining the appropriate age to begin screening military aircrew and ground crew for cancers.

A version of this article first appeared on Medscape.com.

Detecting melanoma early, when it is easier to treat, remains a “paramount goal,” but guidelines surrounding optimal melanoma screening practices and diagnostic evaluations need greater clarity, according to the authors of a new consensus statement.

That is why a group of expert panelists evaluated the existing evidence and a range of clinical scenarios to help clarify the optimal strategies for early detection and assessment of cutaneous melanoma.

Overall, the panelists agreed that a risk-stratified approach is likely the most appropriate strategy for melanoma screening and follow-up and supported the use of visual and dermoscopic examination. However, the panelists did not reach consensus on the role for gene expression profile (GEP) testing in clinical decision-making, citing the need for these assays to be validated in large randomized clinical trials.

In an accompanying editorial, two experts highlighted the importance of carefully evaluating the role of diagnostic tests.

“Diagnostic tests such as GEP must face critical scrutiny; if not, there are immediate concerns for patient care, such as the patient being erroneously informed that they do not have cancer or told that they do have cancer when they do not,” write Alan C. Geller, MPH, RN, from the Harvard T.H. Chan School of Public Health, Boston, and Marvin A. Weinstock, MD, PhD, from Brown University, Providence, R.I.

The consensus statement was published online in JAMA Dermatology.
 

The need for guidance

Although focusing melanoma screening on higher-risk populations may be cost effective, compared with population-based screening, the major guidelines lack consistent guidance to support a risk-stratified approach to skin cancer screening and best practices on diagnosing cutaneous melanoma.

In the prebiopsy setting, the appropriate use of diagnostic tools for evaluating the need for biopsy remain poorly defined, and, in the post-biopsy setting, questions remain concerning the diagnostic accuracy of molecular techniques, diagnostic GEP testing, next-generation sequencing, and immunohistochemical assessment for various markers of melanoma.

To provide consensus recommendations on optimal screening practices, prebiopsy and postbiopsy diagnostics, and prognostic assessment of cutaneous melanoma, a group of 42 panelists voted on hypothetical scenarios via an emailed survey. The panel then came together for a consensus conference, which included 51 experts who discussed their approach to the various clinical case scenarios. Most attendees (45 of the 51) answered a follow-up survey for their final recommendations.

The panelists reached a consensus, with 70% agreement, to support a risk-stratified approach to melanoma screening in clinical settings and public screening events. The experts agreed that higher-risk individuals (those with a relative risk of 5 or greater) could be appropriately screened by a general dermatologist or pigmented lesion evaluation. Higher-risk individuals included those with severe skin damage from the sun, systemic immunosuppression, or a personal history of nonmelanoma or melanoma skin cancer.

Panelists agreed that those at general or lower risk (RR < 2) could be screened by a primary care provider or through regular self- or partner examinations, whereas those at moderate risk could be screened by their primary care clinician or general dermatologist. The experts observed “a shift in acceptance” of primary care physicians screening the general population, and an acknowledgement of the importance of self- and partner examinations as screening adjuncts for all populations.

In the prebiopsy setting, panelists reached consensus that visual and dermoscopic examination was appropriate for evaluating patients with “no new, changing, or unusual skin lesions or with a new lesion that is not visually concerning.”

The panelists also reached consensus that lesions deemed clinically suspicious for cancer or showing features of cancer on reflectance confocal microscopy should be biopsied. Although most respondents (86%) did not currently use epidermal tape stripping routinely, they agreed that, in a hypothetical situation where epidermal tape stripping was used, that lesions positive for PRAME or LINC should be biopsied.

In the postbiopsy setting, views on the use of GEP scores varied. Although panelists agreed that a low-risk prognostic GEP score should not outweigh concerning histologic features when patients are selected to undergo sentinel lymph node biopsy (SLNB), they did not reach consensus for imaging recommendations in the setting of a high-risk prognostic GEP score and low-risk histology and/or negative nodal status.

“The panelists await future, well-designed prospective studies to determine if use of these and newer technologies improves the care of patients with melanoma,” the panelists write.

In the editorial, Mr. Geller and Dr. Weinstock highlighted concerns about the cost and potential access issues associated with these newer technologies, given that the current cost of GEP testing exceeds $7,000.

The editorialists also emphasize that “going forward, the field should be advanced by tackling one of the more pressing, common, potentially morbid, and costly procedures – the prognostic use of sentinel lymph node biopsy.”

Of critical importance is “whether GEP can reduce morbidity and cost by safely reducing the number of SLNBs performed,” Mr. Geller and Dr. Weinstock write.

The funding for the administration and facilitation of the consensus development conference and the development of the manuscript was provided by Dermtech, in an unrestricted award overseen by the Melanoma Research Foundation and managed and executed at UPMC by the principal investigator. Several of the coauthors disclosed relationships with industry. Mr. Geller is a contributor to UptoDate for which he receives royalties. Dr. Weinstock receives consulting fees from AbbVie.

A version of this article first appeared on Medscape.com.

Detecting melanoma early, when it is easier to treat, remains a “paramount goal,” but guidelines surrounding optimal melanoma screening practices and diagnostic evaluations need greater clarity, according to the authors of a new consensus statement.

That is why a group of expert panelists evaluated the existing evidence and a range of clinical scenarios to help clarify the optimal strategies for early detection and assessment of cutaneous melanoma.

Overall, the panelists agreed that a risk-stratified approach is likely the most appropriate strategy for melanoma screening and follow-up and supported the use of visual and dermoscopic examination. However, the panelists did not reach consensus on the role for gene expression profile (GEP) testing in clinical decision-making, citing the need for these assays to be validated in large randomized clinical trials.

In an accompanying editorial, two experts highlighted the importance of carefully evaluating the role of diagnostic tests.

“Diagnostic tests such as GEP must face critical scrutiny; if not, there are immediate concerns for patient care, such as the patient being erroneously informed that they do not have cancer or told that they do have cancer when they do not,” write Alan C. Geller, MPH, RN, from the Harvard T.H. Chan School of Public Health, Boston, and Marvin A. Weinstock, MD, PhD, from Brown University, Providence, R.I.

The consensus statement was published online in JAMA Dermatology.
 

The need for guidance

Although focusing melanoma screening on higher-risk populations may be cost effective, compared with population-based screening, the major guidelines lack consistent guidance to support a risk-stratified approach to skin cancer screening and best practices on diagnosing cutaneous melanoma.

In the prebiopsy setting, the appropriate use of diagnostic tools for evaluating the need for biopsy remain poorly defined, and, in the post-biopsy setting, questions remain concerning the diagnostic accuracy of molecular techniques, diagnostic GEP testing, next-generation sequencing, and immunohistochemical assessment for various markers of melanoma.

To provide consensus recommendations on optimal screening practices, prebiopsy and postbiopsy diagnostics, and prognostic assessment of cutaneous melanoma, a group of 42 panelists voted on hypothetical scenarios via an emailed survey. The panel then came together for a consensus conference, which included 51 experts who discussed their approach to the various clinical case scenarios. Most attendees (45 of the 51) answered a follow-up survey for their final recommendations.

The panelists reached a consensus, with 70% agreement, to support a risk-stratified approach to melanoma screening in clinical settings and public screening events. The experts agreed that higher-risk individuals (those with a relative risk of 5 or greater) could be appropriately screened by a general dermatologist or pigmented lesion evaluation. Higher-risk individuals included those with severe skin damage from the sun, systemic immunosuppression, or a personal history of nonmelanoma or melanoma skin cancer.

Panelists agreed that those at general or lower risk (RR < 2) could be screened by a primary care provider or through regular self- or partner examinations, whereas those at moderate risk could be screened by their primary care clinician or general dermatologist. The experts observed “a shift in acceptance” of primary care physicians screening the general population, and an acknowledgement of the importance of self- and partner examinations as screening adjuncts for all populations.

In the prebiopsy setting, panelists reached consensus that visual and dermoscopic examination was appropriate for evaluating patients with “no new, changing, or unusual skin lesions or with a new lesion that is not visually concerning.”

The panelists also reached consensus that lesions deemed clinically suspicious for cancer or showing features of cancer on reflectance confocal microscopy should be biopsied. Although most respondents (86%) did not currently use epidermal tape stripping routinely, they agreed that, in a hypothetical situation where epidermal tape stripping was used, that lesions positive for PRAME or LINC should be biopsied.

In the postbiopsy setting, views on the use of GEP scores varied. Although panelists agreed that a low-risk prognostic GEP score should not outweigh concerning histologic features when patients are selected to undergo sentinel lymph node biopsy (SLNB), they did not reach consensus for imaging recommendations in the setting of a high-risk prognostic GEP score and low-risk histology and/or negative nodal status.

“The panelists await future, well-designed prospective studies to determine if use of these and newer technologies improves the care of patients with melanoma,” the panelists write.

In the editorial, Mr. Geller and Dr. Weinstock highlighted concerns about the cost and potential access issues associated with these newer technologies, given that the current cost of GEP testing exceeds $7,000.

The editorialists also emphasize that “going forward, the field should be advanced by tackling one of the more pressing, common, potentially morbid, and costly procedures – the prognostic use of sentinel lymph node biopsy.”

Of critical importance is “whether GEP can reduce morbidity and cost by safely reducing the number of SLNBs performed,” Mr. Geller and Dr. Weinstock write.

The funding for the administration and facilitation of the consensus development conference and the development of the manuscript was provided by Dermtech, in an unrestricted award overseen by the Melanoma Research Foundation and managed and executed at UPMC by the principal investigator. Several of the coauthors disclosed relationships with industry. Mr. Geller is a contributor to UptoDate for which he receives royalties. Dr. Weinstock receives consulting fees from AbbVie.

A version of this article first appeared on Medscape.com.

Detecting melanoma early, when it is easier to treat, remains a “paramount goal,” but guidelines surrounding optimal melanoma screening practices and diagnostic evaluations need greater clarity, according to the authors of a new consensus statement.

That is why a group of expert panelists evaluated the existing evidence and a range of clinical scenarios to help clarify the optimal strategies for early detection and assessment of cutaneous melanoma.

Overall, the panelists agreed that a risk-stratified approach is likely the most appropriate strategy for melanoma screening and follow-up and supported the use of visual and dermoscopic examination. However, the panelists did not reach consensus on the role for gene expression profile (GEP) testing in clinical decision-making, citing the need for these assays to be validated in large randomized clinical trials.

In an accompanying editorial, two experts highlighted the importance of carefully evaluating the role of diagnostic tests.

“Diagnostic tests such as GEP must face critical scrutiny; if not, there are immediate concerns for patient care, such as the patient being erroneously informed that they do not have cancer or told that they do have cancer when they do not,” write Alan C. Geller, MPH, RN, from the Harvard T.H. Chan School of Public Health, Boston, and Marvin A. Weinstock, MD, PhD, from Brown University, Providence, R.I.

The consensus statement was published online in JAMA Dermatology.
 

The need for guidance

Although focusing melanoma screening on higher-risk populations may be cost effective, compared with population-based screening, the major guidelines lack consistent guidance to support a risk-stratified approach to skin cancer screening and best practices on diagnosing cutaneous melanoma.

In the prebiopsy setting, the appropriate use of diagnostic tools for evaluating the need for biopsy remain poorly defined, and, in the post-biopsy setting, questions remain concerning the diagnostic accuracy of molecular techniques, diagnostic GEP testing, next-generation sequencing, and immunohistochemical assessment for various markers of melanoma.

To provide consensus recommendations on optimal screening practices, prebiopsy and postbiopsy diagnostics, and prognostic assessment of cutaneous melanoma, a group of 42 panelists voted on hypothetical scenarios via an emailed survey. The panel then came together for a consensus conference, which included 51 experts who discussed their approach to the various clinical case scenarios. Most attendees (45 of the 51) answered a follow-up survey for their final recommendations.

The panelists reached a consensus, with 70% agreement, to support a risk-stratified approach to melanoma screening in clinical settings and public screening events. The experts agreed that higher-risk individuals (those with a relative risk of 5 or greater) could be appropriately screened by a general dermatologist or pigmented lesion evaluation. Higher-risk individuals included those with severe skin damage from the sun, systemic immunosuppression, or a personal history of nonmelanoma or melanoma skin cancer.

Panelists agreed that those at general or lower risk (RR < 2) could be screened by a primary care provider or through regular self- or partner examinations, whereas those at moderate risk could be screened by their primary care clinician or general dermatologist. The experts observed “a shift in acceptance” of primary care physicians screening the general population, and an acknowledgement of the importance of self- and partner examinations as screening adjuncts for all populations.

In the prebiopsy setting, panelists reached consensus that visual and dermoscopic examination was appropriate for evaluating patients with “no new, changing, or unusual skin lesions or with a new lesion that is not visually concerning.”

The panelists also reached consensus that lesions deemed clinically suspicious for cancer or showing features of cancer on reflectance confocal microscopy should be biopsied. Although most respondents (86%) did not currently use epidermal tape stripping routinely, they agreed that, in a hypothetical situation where epidermal tape stripping was used, that lesions positive for PRAME or LINC should be biopsied.

In the postbiopsy setting, views on the use of GEP scores varied. Although panelists agreed that a low-risk prognostic GEP score should not outweigh concerning histologic features when patients are selected to undergo sentinel lymph node biopsy (SLNB), they did not reach consensus for imaging recommendations in the setting of a high-risk prognostic GEP score and low-risk histology and/or negative nodal status.

“The panelists await future, well-designed prospective studies to determine if use of these and newer technologies improves the care of patients with melanoma,” the panelists write.

In the editorial, Mr. Geller and Dr. Weinstock highlighted concerns about the cost and potential access issues associated with these newer technologies, given that the current cost of GEP testing exceeds $7,000.

The editorialists also emphasize that “going forward, the field should be advanced by tackling one of the more pressing, common, potentially morbid, and costly procedures – the prognostic use of sentinel lymph node biopsy.”

Of critical importance is “whether GEP can reduce morbidity and cost by safely reducing the number of SLNBs performed,” Mr. Geller and Dr. Weinstock write.

The funding for the administration and facilitation of the consensus development conference and the development of the manuscript was provided by Dermtech, in an unrestricted award overseen by the Melanoma Research Foundation and managed and executed at UPMC by the principal investigator. Several of the coauthors disclosed relationships with industry. Mr. Geller is a contributor to UptoDate for which he receives royalties. Dr. Weinstock receives consulting fees from AbbVie.

A version of this article first appeared on Medscape.com.

Febrile neutropenia (FN) is a life-threatening oncologic emergency requiring timely evaluation and treatment. Chemotherapy-induced neutropenia is a major risk for life-threatening infection, and fever may be the only sign.^1,2 Unrecognized fever can progress to sepsis and may result in increased morbidity and mortality. FN is defined as the presence of fever with a single temperature of  ≥ 38.3 °C or a sustained temperature > 38 °C sustained over 1 hour with an absolute neutrophil count (ANC) of < 500 cells/mm³ or < 1000 cells/mm³ and expected to decrease to < 500 within 48 hours.^2,3 It is critical to quickly identify these patients on presentation to the emergency department (ED) and take appropriate steps to initiate treatment as soon as possible. To streamline care, the American Society of Clinical Oncology (ASCO) recommends that laboratory assessments be initiated within 15 minutes of triage and empiric antibiotic therapy be administered within 1 hour.²

In alignment with the Infectious Disease Society of America (IDSA) guidelines, the National Comprehensive Cancer Network (NCCN) highlights the importance of the initial assessment of fever and neutropenia and presents available treatment options for both inpatient and outpatient management of FN.¹ Once patients are identified, the appropriate laboratory tests and physical assessments should be initiated immediately. These tests include a complete blood count with differential, complete metabolic panel (CMP), and blood cultures from 2 separate IV sites.^1-3 The guidelines offer additional suggestions for cultures and radiographic assessments that may be completed based on clinical presentation.

Several available studies provide insight into methods of protocol creation and possible barriers to timely management. Previous research showed that an FN protocol for pediatric oncology patients aimed at antibiotic administration within 1 hour showed significant improvement from 35.0% to 55.4% of patients being treated on time.^3,4 Prescribers became more comfortable in using the protocol, and timing improved as the study progressed. Barriers noted were inconsistent ED triage, rotating ED staff, and limited understanding of the protocol.³ Yoshida and colleagues worked with the same population. Over the course of 1 year, 60% of patients were receiving antibiotics within 1 hour. The mean time decreased from 83 to 65 minutes, which the study investigators noted would continue to decrease with increased protocol comfort and use.⁵ Mattison and colleagues used nursing staff to identify patients with FN and begin antibiotic treatment. On triage, nurses took note of a temperature of > 38 °C or a sepsislike clinical picture that initiated their antibiotic proforma.^4,6 This resulted in 48.1% of patients receiving antibiotics within 15 minutes and 63.3% overall within 30 minutes of arrival.⁵ Other barriers to consider are ED crowding and the admission of higher acuity patients, which may delay the treatment of patients with FN.

The US Department of Veterans Affairs (VA) Richard L. Roudebush VA Medical Center (RLRVAMC) in Indianapolis, Indiana is a level 1A facility serving about 62,000 veterans annually and more than 13,000 unique veterans visiting the ED. RLRVAMC ED staff rotate often so the creation of a process will facilitate appropriate treatment as quickly as possible. The purpose of this protocol was to improve the mean time from triage to administration of antibiotics for patients with FN presenting to the ED.

Implementation

To quantify the perceived delay in antibiotic prescribing, a pre- and postprotocol retrospective chart review of patients who presented with FN to the RLRVAMC ED was conducted. Patients were identified through the electronic health record (EHR) based on 3 criteria: recorded/reported fever as defined above, ANC < 1000 cells/mm³, and administration of cancer treatment (IV and oral) within 4 weeks. The data collected in the postimplementation phase were identical to the pre-implementation phase. This included timing of blood cultures, choice/appropriateness of antibiotics based on guidelines, and length of admission. The pre-implementation period started on August 1, 2018, and ended on August 1, 2019, to allow for an adequate pre-implementation sample size. The protocol was then implemented on October 1, 2019, and data collection for the postimplementation phase began on October 1, 2019, and ended on October 1, 2020.

The protocol was accompanied by EHR order sets initiated by both nurses and health care practitioners (HCPs), including physicians, nurse practitioners, and physician assistants. The nursing order set consisted of vitals and appropriate laboratory monitoring, and the practitioner order set housed medication orders and additional clinical monitoring for more patient-specific scenarios. On identification of at-risk patients, the nursing staff could initiate the neutropenic fever protocol without consulting an HCP. The patient was then assigned a higher acuity rank, and the HCP was tasked with seeing the patient immediately. In conjunction with a complete physical assessment, the HCP ordered appropriate antibiotics through the designated order set to streamline antibiotic selection. Antibiotic options included cefepime or piperacillin-tazobactam, and vancomycin when clinically indicated. Alternatives for patients allergic to penicillin also were available. The protocol intended to streamline workup and antibiotic selection but was not designed as a substitute for solid clinical decision making and complete assessment on behalf of the HCP; therefore, additional workup may have been necessary and documented in the EHR.

Findings

This patient population comprised 17 patients pre-implementation and 12 patients postimplementation, most of whom had solid tumor malignancies (88.2% and 83.3%, respectively) receiving platinum, taxane, or antimetabolite-based chemotherapy. In the pre-implementation group, most patients (70.5%) coming through the ED were treated with palliative intent. Only 25% of these received any prophylactic granulocyte-colony stimulating factor (G-CSF) based on risk for FN. The mean time from triage to the first dose of antibiotics decreased from 3.3 hours before protocol implementation to 2.3 hours after. Only 6% in the pre-implementation group compared with 17% in the postimplementation group received the first dose of antibiotics within the recommended 1-hour interval from triage. The most common antibiotics administered were cefepime and vancomycin. Eleven patients in each group (65% and 92%, respectively) were admitted to the inpatient service for further care, with 10 and 8 patients, respectively, experiencing a hospitalization > 72 hours. Of note, 41% of patients died pre-implementation vs 17% postimplementation.

Interpretation

The goal of this protocol was to optimize ED care of patients presenting with FN to better align with guideline-recommended time lines and antibiotics. The mean time from triage to administration of antibiotics decreased by 1.0 hour from the pre- to postimplementation phase, similar to the study by Mattison and colleagues.³ When removing an outlier from the postimplementation group, the mean time from triage to first dose further decreased to 1.8 hours. The percentage of patients receiving antibiotics within 1 hour of triage nearly tripled from 6% to 17%. Additionally, the percentage of patients empirically treated with appropriate antibiotics consistent with NCCN/ASCO/IDSA guidelines increased from 65% to 83%. Although goals for the optimization of care have not yet been reached, this protocol is the first step in the right direction.

Limitations

Several limitations and concerns arise when implementing a new protocol or workflow process. Overall, these limitations may contribute to delays, such as the willingness of team members to use an unfamiliar protocol or issues locating a new protocol. The nursing staff is challenged to triage patients quickly, which may add to an already busy environment. Frequent physician turnover may require more frequent education sessions. Also, a lag time between implementation and using the protocol may result in decreased protocol use during the designated postimplementation data collection phase.

On review, ED staff were excited to find a protocol that streamlined decision making and increased awareness for patients at risk. The COVID-19 pandemic may have been a confounder for the postimplementation phase. Data may have been skewed as some patients might have elected to stay at home to avoid potential COVID-19 exposure in the ED. Additionally, increased ED use by patients with COVID-19 may have resulted in longer wait times for an available bed, thereby minimizing the impact of the protocol on time from triage to administration of antibiotics. COVID-19 may also have contributed to postimplementation mortality. Of note, barcode medication administration (BCMA) was implemented in the ED in May 2019, which may account for undocumented delays in antibiotic administration as staff may have been unfamiliar with BCMA workflow.

Due to the retrospective nature of a chart review, the data rely on the timely input and accuracy of documented information. Data after the patient’s ED encounter (except inpatient hospitalization and deaths during the implementation period) were not collected due to the scope of the program being limited to the ED only. Last, this protocol was implemented at a single site, and the generalizability to implement the same protocol at other VA medical centers may be limited. After reaching out to other VA sites and several non-VA facilities, we were unable to find a site with a similar protocol or program emphasizing the importance of timely care, although there may have been established laboratory test and medication order sets within the EHR.

Future Direction

The newly established FN order sets will continue to streamline clinical decision making and antibiotic selection in this population. In our study, we learned that most patients coming through the ED were being treated with palliative intent. As a result, these patients also may have a higher risk for complications like FN. We hope to further analyze the impact on this group and consider the role of empiric dose reduction or increased G-CSF support to minimize FN.

More than half of the patients who were admitted to the inpatient service, remained in extended care for > 72 hours. Inpatient recovery time may cause delays in future cancer treatment cycles, dose reductions, and contribute to an overall decline in performance status. Six patients in the pre-implementation phase and 1 in the postimplementation phase were eligible for outpatient management per independent Multinational Association of Supportive Care in Cancer assessment. To increase comfort, a future goal would be to create an outpatient treatment order set on discharge from the ED to help identify and outline treatment options for low-risk patients. In addition to the ED, training staff in clinics with a similar protocol may enhance the identification of patients with FN. This may require a tailored protocol for this location using health technicians in taking vital signs before the HCP visit.

This protocol helped establish “code sepsis.” Code sepsis alerts are broadcast to alert pertinent members of the health care team to provide immediate medical attention to the veteran. Pharmacy can expedite the compounding of antibiotics and record review while radiology prioritizes the portable X-ray for quick and efficient imaging. The nursing team comes ready to administer antibiotics once cultures are drawn. The HCP's attention is focused on the physical examination to determine any additional steps/care that need to be accomplished. At our site, we plan to continue HCP, nursing, and other team member education on this oncologic emergency and the availability of a streamlined protocol. We would like to re-assess the data with a long team study now that the protocol has been in place for 3 years. We hope to continue to provide strong patient care with enhanced adherence to guidelines for patients with FN presenting to RLRVAMC.

Conclusions

Early identification and timely empiric antibiotic therapy are critical to improving outcomes for patients presenting to the ED with FN. The neutropenic fever protocol reduced time to antibiotics by about 1 hour with a higher percentage of patients receiving them in < 1 hour. Additional optimization of the order sets along with increased protocol comfort and staff education will help further reduce the time to antibiotic administration in alignment with guideline recommendations.

Febrile neutropenia (FN) is a life-threatening oncologic emergency requiring timely evaluation and treatment. Chemotherapy-induced neutropenia is a major risk for life-threatening infection, and fever may be the only sign.^1,2 Unrecognized fever can progress to sepsis and may result in increased morbidity and mortality. FN is defined as the presence of fever with a single temperature of  ≥ 38.3 °C or a sustained temperature > 38 °C sustained over 1 hour with an absolute neutrophil count (ANC) of < 500 cells/mm³ or < 1000 cells/mm³ and expected to decrease to < 500 within 48 hours.^2,3 It is critical to quickly identify these patients on presentation to the emergency department (ED) and take appropriate steps to initiate treatment as soon as possible. To streamline care, the American Society of Clinical Oncology (ASCO) recommends that laboratory assessments be initiated within 15 minutes of triage and empiric antibiotic therapy be administered within 1 hour.²

In alignment with the Infectious Disease Society of America (IDSA) guidelines, the National Comprehensive Cancer Network (NCCN) highlights the importance of the initial assessment of fever and neutropenia and presents available treatment options for both inpatient and outpatient management of FN.¹ Once patients are identified, the appropriate laboratory tests and physical assessments should be initiated immediately. These tests include a complete blood count with differential, complete metabolic panel (CMP), and blood cultures from 2 separate IV sites.^1-3 The guidelines offer additional suggestions for cultures and radiographic assessments that may be completed based on clinical presentation.

Several available studies provide insight into methods of protocol creation and possible barriers to timely management. Previous research showed that an FN protocol for pediatric oncology patients aimed at antibiotic administration within 1 hour showed significant improvement from 35.0% to 55.4% of patients being treated on time.^3,4 Prescribers became more comfortable in using the protocol, and timing improved as the study progressed. Barriers noted were inconsistent ED triage, rotating ED staff, and limited understanding of the protocol.³ Yoshida and colleagues worked with the same population. Over the course of 1 year, 60% of patients were receiving antibiotics within 1 hour. The mean time decreased from 83 to 65 minutes, which the study investigators noted would continue to decrease with increased protocol comfort and use.⁵ Mattison and colleagues used nursing staff to identify patients with FN and begin antibiotic treatment. On triage, nurses took note of a temperature of > 38 °C or a sepsislike clinical picture that initiated their antibiotic proforma.^4,6 This resulted in 48.1% of patients receiving antibiotics within 15 minutes and 63.3% overall within 30 minutes of arrival.⁵ Other barriers to consider are ED crowding and the admission of higher acuity patients, which may delay the treatment of patients with FN.

The US Department of Veterans Affairs (VA) Richard L. Roudebush VA Medical Center (RLRVAMC) in Indianapolis, Indiana is a level 1A facility serving about 62,000 veterans annually and more than 13,000 unique veterans visiting the ED. RLRVAMC ED staff rotate often so the creation of a process will facilitate appropriate treatment as quickly as possible. The purpose of this protocol was to improve the mean time from triage to administration of antibiotics for patients with FN presenting to the ED.

Implementation

To quantify the perceived delay in antibiotic prescribing, a pre- and postprotocol retrospective chart review of patients who presented with FN to the RLRVAMC ED was conducted. Patients were identified through the electronic health record (EHR) based on 3 criteria: recorded/reported fever as defined above, ANC < 1000 cells/mm³, and administration of cancer treatment (IV and oral) within 4 weeks. The data collected in the postimplementation phase were identical to the pre-implementation phase. This included timing of blood cultures, choice/appropriateness of antibiotics based on guidelines, and length of admission. The pre-implementation period started on August 1, 2018, and ended on August 1, 2019, to allow for an adequate pre-implementation sample size. The protocol was then implemented on October 1, 2019, and data collection for the postimplementation phase began on October 1, 2019, and ended on October 1, 2020.

The protocol was accompanied by EHR order sets initiated by both nurses and health care practitioners (HCPs), including physicians, nurse practitioners, and physician assistants. The nursing order set consisted of vitals and appropriate laboratory monitoring, and the practitioner order set housed medication orders and additional clinical monitoring for more patient-specific scenarios. On identification of at-risk patients, the nursing staff could initiate the neutropenic fever protocol without consulting an HCP. The patient was then assigned a higher acuity rank, and the HCP was tasked with seeing the patient immediately. In conjunction with a complete physical assessment, the HCP ordered appropriate antibiotics through the designated order set to streamline antibiotic selection. Antibiotic options included cefepime or piperacillin-tazobactam, and vancomycin when clinically indicated. Alternatives for patients allergic to penicillin also were available. The protocol intended to streamline workup and antibiotic selection but was not designed as a substitute for solid clinical decision making and complete assessment on behalf of the HCP; therefore, additional workup may have been necessary and documented in the EHR.

Findings

This patient population comprised 17 patients pre-implementation and 12 patients postimplementation, most of whom had solid tumor malignancies (88.2% and 83.3%, respectively) receiving platinum, taxane, or antimetabolite-based chemotherapy. In the pre-implementation group, most patients (70.5%) coming through the ED were treated with palliative intent. Only 25% of these received any prophylactic granulocyte-colony stimulating factor (G-CSF) based on risk for FN. The mean time from triage to the first dose of antibiotics decreased from 3.3 hours before protocol implementation to 2.3 hours after. Only 6% in the pre-implementation group compared with 17% in the postimplementation group received the first dose of antibiotics within the recommended 1-hour interval from triage. The most common antibiotics administered were cefepime and vancomycin. Eleven patients in each group (65% and 92%, respectively) were admitted to the inpatient service for further care, with 10 and 8 patients, respectively, experiencing a hospitalization > 72 hours. Of note, 41% of patients died pre-implementation vs 17% postimplementation.

Interpretation

The goal of this protocol was to optimize ED care of patients presenting with FN to better align with guideline-recommended time lines and antibiotics. The mean time from triage to administration of antibiotics decreased by 1.0 hour from the pre- to postimplementation phase, similar to the study by Mattison and colleagues.³ When removing an outlier from the postimplementation group, the mean time from triage to first dose further decreased to 1.8 hours. The percentage of patients receiving antibiotics within 1 hour of triage nearly tripled from 6% to 17%. Additionally, the percentage of patients empirically treated with appropriate antibiotics consistent with NCCN/ASCO/IDSA guidelines increased from 65% to 83%. Although goals for the optimization of care have not yet been reached, this protocol is the first step in the right direction.

Limitations

Several limitations and concerns arise when implementing a new protocol or workflow process. Overall, these limitations may contribute to delays, such as the willingness of team members to use an unfamiliar protocol or issues locating a new protocol. The nursing staff is challenged to triage patients quickly, which may add to an already busy environment. Frequent physician turnover may require more frequent education sessions. Also, a lag time between implementation and using the protocol may result in decreased protocol use during the designated postimplementation data collection phase.

On review, ED staff were excited to find a protocol that streamlined decision making and increased awareness for patients at risk. The COVID-19 pandemic may have been a confounder for the postimplementation phase. Data may have been skewed as some patients might have elected to stay at home to avoid potential COVID-19 exposure in the ED. Additionally, increased ED use by patients with COVID-19 may have resulted in longer wait times for an available bed, thereby minimizing the impact of the protocol on time from triage to administration of antibiotics. COVID-19 may also have contributed to postimplementation mortality. Of note, barcode medication administration (BCMA) was implemented in the ED in May 2019, which may account for undocumented delays in antibiotic administration as staff may have been unfamiliar with BCMA workflow.

Due to the retrospective nature of a chart review, the data rely on the timely input and accuracy of documented information. Data after the patient’s ED encounter (except inpatient hospitalization and deaths during the implementation period) were not collected due to the scope of the program being limited to the ED only. Last, this protocol was implemented at a single site, and the generalizability to implement the same protocol at other VA medical centers may be limited. After reaching out to other VA sites and several non-VA facilities, we were unable to find a site with a similar protocol or program emphasizing the importance of timely care, although there may have been established laboratory test and medication order sets within the EHR.

Future Direction

The newly established FN order sets will continue to streamline clinical decision making and antibiotic selection in this population. In our study, we learned that most patients coming through the ED were being treated with palliative intent. As a result, these patients also may have a higher risk for complications like FN. We hope to further analyze the impact on this group and consider the role of empiric dose reduction or increased G-CSF support to minimize FN.

More than half of the patients who were admitted to the inpatient service, remained in extended care for > 72 hours. Inpatient recovery time may cause delays in future cancer treatment cycles, dose reductions, and contribute to an overall decline in performance status. Six patients in the pre-implementation phase and 1 in the postimplementation phase were eligible for outpatient management per independent Multinational Association of Supportive Care in Cancer assessment. To increase comfort, a future goal would be to create an outpatient treatment order set on discharge from the ED to help identify and outline treatment options for low-risk patients. In addition to the ED, training staff in clinics with a similar protocol may enhance the identification of patients with FN. This may require a tailored protocol for this location using health technicians in taking vital signs before the HCP visit.

This protocol helped establish “code sepsis.” Code sepsis alerts are broadcast to alert pertinent members of the health care team to provide immediate medical attention to the veteran. Pharmacy can expedite the compounding of antibiotics and record review while radiology prioritizes the portable X-ray for quick and efficient imaging. The nursing team comes ready to administer antibiotics once cultures are drawn. The HCP's attention is focused on the physical examination to determine any additional steps/care that need to be accomplished. At our site, we plan to continue HCP, nursing, and other team member education on this oncologic emergency and the availability of a streamlined protocol. We would like to re-assess the data with a long team study now that the protocol has been in place for 3 years. We hope to continue to provide strong patient care with enhanced adherence to guidelines for patients with FN presenting to RLRVAMC.

Conclusions

Early identification and timely empiric antibiotic therapy are critical to improving outcomes for patients presenting to the ED with FN. The neutropenic fever protocol reduced time to antibiotics by about 1 hour with a higher percentage of patients receiving them in < 1 hour. Additional optimization of the order sets along with increased protocol comfort and staff education will help further reduce the time to antibiotic administration in alignment with guideline recommendations.

Febrile neutropenia (FN) is a life-threatening oncologic emergency requiring timely evaluation and treatment. Chemotherapy-induced neutropenia is a major risk for life-threatening infection, and fever may be the only sign.^1,2 Unrecognized fever can progress to sepsis and may result in increased morbidity and mortality. FN is defined as the presence of fever with a single temperature of  ≥ 38.3 °C or a sustained temperature > 38 °C sustained over 1 hour with an absolute neutrophil count (ANC) of < 500 cells/mm³ or < 1000 cells/mm³ and expected to decrease to < 500 within 48 hours.^2,3 It is critical to quickly identify these patients on presentation to the emergency department (ED) and take appropriate steps to initiate treatment as soon as possible. To streamline care, the American Society of Clinical Oncology (ASCO) recommends that laboratory assessments be initiated within 15 minutes of triage and empiric antibiotic therapy be administered within 1 hour.²

In alignment with the Infectious Disease Society of America (IDSA) guidelines, the National Comprehensive Cancer Network (NCCN) highlights the importance of the initial assessment of fever and neutropenia and presents available treatment options for both inpatient and outpatient management of FN.¹ Once patients are identified, the appropriate laboratory tests and physical assessments should be initiated immediately. These tests include a complete blood count with differential, complete metabolic panel (CMP), and blood cultures from 2 separate IV sites.^1-3 The guidelines offer additional suggestions for cultures and radiographic assessments that may be completed based on clinical presentation.

Several available studies provide insight into methods of protocol creation and possible barriers to timely management. Previous research showed that an FN protocol for pediatric oncology patients aimed at antibiotic administration within 1 hour showed significant improvement from 35.0% to 55.4% of patients being treated on time.^3,4 Prescribers became more comfortable in using the protocol, and timing improved as the study progressed. Barriers noted were inconsistent ED triage, rotating ED staff, and limited understanding of the protocol.³ Yoshida and colleagues worked with the same population. Over the course of 1 year, 60% of patients were receiving antibiotics within 1 hour. The mean time decreased from 83 to 65 minutes, which the study investigators noted would continue to decrease with increased protocol comfort and use.⁵ Mattison and colleagues used nursing staff to identify patients with FN and begin antibiotic treatment. On triage, nurses took note of a temperature of > 38 °C or a sepsislike clinical picture that initiated their antibiotic proforma.^4,6 This resulted in 48.1% of patients receiving antibiotics within 15 minutes and 63.3% overall within 30 minutes of arrival.⁵ Other barriers to consider are ED crowding and the admission of higher acuity patients, which may delay the treatment of patients with FN.

The US Department of Veterans Affairs (VA) Richard L. Roudebush VA Medical Center (RLRVAMC) in Indianapolis, Indiana is a level 1A facility serving about 62,000 veterans annually and more than 13,000 unique veterans visiting the ED. RLRVAMC ED staff rotate often so the creation of a process will facilitate appropriate treatment as quickly as possible. The purpose of this protocol was to improve the mean time from triage to administration of antibiotics for patients with FN presenting to the ED.

Implementation

To quantify the perceived delay in antibiotic prescribing, a pre- and postprotocol retrospective chart review of patients who presented with FN to the RLRVAMC ED was conducted. Patients were identified through the electronic health record (EHR) based on 3 criteria: recorded/reported fever as defined above, ANC < 1000 cells/mm³, and administration of cancer treatment (IV and oral) within 4 weeks. The data collected in the postimplementation phase were identical to the pre-implementation phase. This included timing of blood cultures, choice/appropriateness of antibiotics based on guidelines, and length of admission. The pre-implementation period started on August 1, 2018, and ended on August 1, 2019, to allow for an adequate pre-implementation sample size. The protocol was then implemented on October 1, 2019, and data collection for the postimplementation phase began on October 1, 2019, and ended on October 1, 2020.

The protocol was accompanied by EHR order sets initiated by both nurses and health care practitioners (HCPs), including physicians, nurse practitioners, and physician assistants. The nursing order set consisted of vitals and appropriate laboratory monitoring, and the practitioner order set housed medication orders and additional clinical monitoring for more patient-specific scenarios. On identification of at-risk patients, the nursing staff could initiate the neutropenic fever protocol without consulting an HCP. The patient was then assigned a higher acuity rank, and the HCP was tasked with seeing the patient immediately. In conjunction with a complete physical assessment, the HCP ordered appropriate antibiotics through the designated order set to streamline antibiotic selection. Antibiotic options included cefepime or piperacillin-tazobactam, and vancomycin when clinically indicated. Alternatives for patients allergic to penicillin also were available. The protocol intended to streamline workup and antibiotic selection but was not designed as a substitute for solid clinical decision making and complete assessment on behalf of the HCP; therefore, additional workup may have been necessary and documented in the EHR.

Findings

This patient population comprised 17 patients pre-implementation and 12 patients postimplementation, most of whom had solid tumor malignancies (88.2% and 83.3%, respectively) receiving platinum, taxane, or antimetabolite-based chemotherapy. In the pre-implementation group, most patients (70.5%) coming through the ED were treated with palliative intent. Only 25% of these received any prophylactic granulocyte-colony stimulating factor (G-CSF) based on risk for FN. The mean time from triage to the first dose of antibiotics decreased from 3.3 hours before protocol implementation to 2.3 hours after. Only 6% in the pre-implementation group compared with 17% in the postimplementation group received the first dose of antibiotics within the recommended 1-hour interval from triage. The most common antibiotics administered were cefepime and vancomycin. Eleven patients in each group (65% and 92%, respectively) were admitted to the inpatient service for further care, with 10 and 8 patients, respectively, experiencing a hospitalization > 72 hours. Of note, 41% of patients died pre-implementation vs 17% postimplementation.

Interpretation

The goal of this protocol was to optimize ED care of patients presenting with FN to better align with guideline-recommended time lines and antibiotics. The mean time from triage to administration of antibiotics decreased by 1.0 hour from the pre- to postimplementation phase, similar to the study by Mattison and colleagues.³ When removing an outlier from the postimplementation group, the mean time from triage to first dose further decreased to 1.8 hours. The percentage of patients receiving antibiotics within 1 hour of triage nearly tripled from 6% to 17%. Additionally, the percentage of patients empirically treated with appropriate antibiotics consistent with NCCN/ASCO/IDSA guidelines increased from 65% to 83%. Although goals for the optimization of care have not yet been reached, this protocol is the first step in the right direction.

Limitations

Several limitations and concerns arise when implementing a new protocol or workflow process. Overall, these limitations may contribute to delays, such as the willingness of team members to use an unfamiliar protocol or issues locating a new protocol. The nursing staff is challenged to triage patients quickly, which may add to an already busy environment. Frequent physician turnover may require more frequent education sessions. Also, a lag time between implementation and using the protocol may result in decreased protocol use during the designated postimplementation data collection phase.

On review, ED staff were excited to find a protocol that streamlined decision making and increased awareness for patients at risk. The COVID-19 pandemic may have been a confounder for the postimplementation phase. Data may have been skewed as some patients might have elected to stay at home to avoid potential COVID-19 exposure in the ED. Additionally, increased ED use by patients with COVID-19 may have resulted in longer wait times for an available bed, thereby minimizing the impact of the protocol on time from triage to administration of antibiotics. COVID-19 may also have contributed to postimplementation mortality. Of note, barcode medication administration (BCMA) was implemented in the ED in May 2019, which may account for undocumented delays in antibiotic administration as staff may have been unfamiliar with BCMA workflow.

Due to the retrospective nature of a chart review, the data rely on the timely input and accuracy of documented information. Data after the patient’s ED encounter (except inpatient hospitalization and deaths during the implementation period) were not collected due to the scope of the program being limited to the ED only. Last, this protocol was implemented at a single site, and the generalizability to implement the same protocol at other VA medical centers may be limited. After reaching out to other VA sites and several non-VA facilities, we were unable to find a site with a similar protocol or program emphasizing the importance of timely care, although there may have been established laboratory test and medication order sets within the EHR.

Future Direction

The newly established FN order sets will continue to streamline clinical decision making and antibiotic selection in this population. In our study, we learned that most patients coming through the ED were being treated with palliative intent. As a result, these patients also may have a higher risk for complications like FN. We hope to further analyze the impact on this group and consider the role of empiric dose reduction or increased G-CSF support to minimize FN.

More than half of the patients who were admitted to the inpatient service, remained in extended care for > 72 hours. Inpatient recovery time may cause delays in future cancer treatment cycles, dose reductions, and contribute to an overall decline in performance status. Six patients in the pre-implementation phase and 1 in the postimplementation phase were eligible for outpatient management per independent Multinational Association of Supportive Care in Cancer assessment. To increase comfort, a future goal would be to create an outpatient treatment order set on discharge from the ED to help identify and outline treatment options for low-risk patients. In addition to the ED, training staff in clinics with a similar protocol may enhance the identification of patients with FN. This may require a tailored protocol for this location using health technicians in taking vital signs before the HCP visit.

This protocol helped establish “code sepsis.” Code sepsis alerts are broadcast to alert pertinent members of the health care team to provide immediate medical attention to the veteran. Pharmacy can expedite the compounding of antibiotics and record review while radiology prioritizes the portable X-ray for quick and efficient imaging. The nursing team comes ready to administer antibiotics once cultures are drawn. The HCP's attention is focused on the physical examination to determine any additional steps/care that need to be accomplished. At our site, we plan to continue HCP, nursing, and other team member education on this oncologic emergency and the availability of a streamlined protocol. We would like to re-assess the data with a long team study now that the protocol has been in place for 3 years. We hope to continue to provide strong patient care with enhanced adherence to guidelines for patients with FN presenting to RLRVAMC.

Conclusions

Early identification and timely empiric antibiotic therapy are critical to improving outcomes for patients presenting to the ED with FN. The neutropenic fever protocol reduced time to antibiotics by about 1 hour with a higher percentage of patients receiving them in < 1 hour. Additional optimization of the order sets along with increased protocol comfort and staff education will help further reduce the time to antibiotic administration in alignment with guideline recommendations.

A new study confirms that a plant-based diet with exercise can lower the risk of prostate cancer progressing or recurring.

The findings, which were reported at the 2023 ASCO Genitourinary Cancers Symposium in February, are based on a study of 2,038 men (median age, 64 years) with prostate cancer at stage T1, T2, or T3a.

“Consuming a whole foods plant-based diet may be an option to decrease risk for recurrence and improve overall survivorship,” said Vivian N. Liu, a clinical research coordinator at the University of California, San Francisco, who presented the findings.

The patients were interviewed about their diets at about 31.5 months after diagnosis. The study group was broken down into four groups based on how much of their diet consisted of a plant-based diet. Men in the highest quintile group who consumed at least 2.4 servings daily of fruit, 4.2 servings of vegetables, 2.6 servings of dairy, and 1.2 servings of meat (not seafood), had a 52% lower risk of progression (hazard ratio, 0.48; 95% confidence interval, 0.36-0.65; P-trend < 0.001) and a 53% lower risk of recurrence (HR, 0.47; 95% CI, 0.32-0.68; P-trend < 0.001), which was statistically significant. This compares with men in the lowest quintile who consumed 0.8 servings a day of fruit, 2.1 servings of vegetables, 3.1 servings of dairy, and 1.4 servings of meat. The findings were adjusted for total caloric intake, race, and smoking status.

For men over 65 years old, researchers found that a plant-based diet was associated with lower risk of recurrence (HR, 0.41; 95% CI, 0.24-0.7; P-trend = 0.03). And for those who exercised daily – in this case walking at a fast pace more than 3 times a week – a plant-based diet had a 56% (HR, 0.33; 95% CI, 0.26-0.73) lower risk of progression in the highest quintile group and a 59% decrease in recurrence (HR, 0.41; 95% CI, 0.25-0.68).

A new analysis like this, Ms. Liu said, “could guide people to make better, more healthful choices across their whole diet rather than adding or removing select foods.”

The primary endpoint was progression including recurrence, secondary treatment, bone metastases, and death due to prostate cancer, and the secondary endpoint was recurrence (PSA > 0.2ng/mL at 2 consecutive follow-up visits or during secondary treatment). At 7.4 years follow-up, there were 204 cases of progression.

“Fruits and vegetables contain antioxidants and anti-inflammatory components as well as dietary fiber that improve glucose control and reduce inflammation,” Ms. Liu said. In contrast, she said, animal-based foods may increase insulin resistance and insulin levels and boost levels of insulin-like growth factor 1, which is associated with prostate cancer risk. More studies, especially randomized controlled trials, are needed to provide evidence whether healthful plant-based foods and prostate cancer progression are connected.

NYU Langone Health urologist Natasha Gupta, MD, published a systematic review in 2022 on the impact of a plant-based diet on prostate cancer.* The review, which included 5 interventional studies and 11 observational studies, found that consuming a plant-based diet was associated with improvements in general health for men with prostate cancer. The observational studies found either a lower risk of prostate cancer or no significant difference.

“Patients often ask if there is anything that they can do to reduce the risk of recurrence, and it is great to be able to tell patients that a healthy lifestyle including plant-based foods and physical activity is helpful,” Dr. Gupta said.

The review’s coauthor, Stacy Loeb, MD, also of NYU Langone Health, said the new study was “a well-done observational study by experts in nutritional epidemiology from UCSF. It adds to a large body of evidence showing that plant-based diets improve health outcomes.”

“In the short-term, purchasing plant-based protein sources, such as beans and lentils, is less expensive than buying meat. Plant-based diets also reduce the risk of obesity, diabetes, and cardiovascular disease, which are associated with hundreds of thousands of dollars over a lifetime,” she said.

Limitations of the new study included the small number of non-White participants and self-reporting of diet. The study doesn’t examine the cost of various diets or the availability of plant-based foods like fresh produce, which can be limited in some neighborhoods.

Ms. Liu and colleagues plan to conduct a study that examines postdiagnostic plant-based diets in relation to prostate cancer–specific mortality. She and her team will also examine the plant-based dietary indices in relation to prostate cancer–specific quality of life at 2, 5, and 10 years from baseline.

The study authors, Dr. Loeb, and Dr. Gupta report no disclosures.

Correction, 3/17/23: An earlier version of this article misstated the name of NYU Langone Health.

A new study confirms that a plant-based diet with exercise can lower the risk of prostate cancer progressing or recurring.

The findings, which were reported at the 2023 ASCO Genitourinary Cancers Symposium in February, are based on a study of 2,038 men (median age, 64 years) with prostate cancer at stage T1, T2, or T3a.

“Consuming a whole foods plant-based diet may be an option to decrease risk for recurrence and improve overall survivorship,” said Vivian N. Liu, a clinical research coordinator at the University of California, San Francisco, who presented the findings.

The patients were interviewed about their diets at about 31.5 months after diagnosis. The study group was broken down into four groups based on how much of their diet consisted of a plant-based diet. Men in the highest quintile group who consumed at least 2.4 servings daily of fruit, 4.2 servings of vegetables, 2.6 servings of dairy, and 1.2 servings of meat (not seafood), had a 52% lower risk of progression (hazard ratio, 0.48; 95% confidence interval, 0.36-0.65; P-trend < 0.001) and a 53% lower risk of recurrence (HR, 0.47; 95% CI, 0.32-0.68; P-trend < 0.001), which was statistically significant. This compares with men in the lowest quintile who consumed 0.8 servings a day of fruit, 2.1 servings of vegetables, 3.1 servings of dairy, and 1.4 servings of meat. The findings were adjusted for total caloric intake, race, and smoking status.

For men over 65 years old, researchers found that a plant-based diet was associated with lower risk of recurrence (HR, 0.41; 95% CI, 0.24-0.7; P-trend = 0.03). And for those who exercised daily – in this case walking at a fast pace more than 3 times a week – a plant-based diet had a 56% (HR, 0.33; 95% CI, 0.26-0.73) lower risk of progression in the highest quintile group and a 59% decrease in recurrence (HR, 0.41; 95% CI, 0.25-0.68).

A new analysis like this, Ms. Liu said, “could guide people to make better, more healthful choices across their whole diet rather than adding or removing select foods.”

The primary endpoint was progression including recurrence, secondary treatment, bone metastases, and death due to prostate cancer, and the secondary endpoint was recurrence (PSA > 0.2ng/mL at 2 consecutive follow-up visits or during secondary treatment). At 7.4 years follow-up, there were 204 cases of progression.

“Fruits and vegetables contain antioxidants and anti-inflammatory components as well as dietary fiber that improve glucose control and reduce inflammation,” Ms. Liu said. In contrast, she said, animal-based foods may increase insulin resistance and insulin levels and boost levels of insulin-like growth factor 1, which is associated with prostate cancer risk. More studies, especially randomized controlled trials, are needed to provide evidence whether healthful plant-based foods and prostate cancer progression are connected.

NYU Langone Health urologist Natasha Gupta, MD, published a systematic review in 2022 on the impact of a plant-based diet on prostate cancer.* The review, which included 5 interventional studies and 11 observational studies, found that consuming a plant-based diet was associated with improvements in general health for men with prostate cancer. The observational studies found either a lower risk of prostate cancer or no significant difference.

“Patients often ask if there is anything that they can do to reduce the risk of recurrence, and it is great to be able to tell patients that a healthy lifestyle including plant-based foods and physical activity is helpful,” Dr. Gupta said.

The review’s coauthor, Stacy Loeb, MD, also of NYU Langone Health, said the new study was “a well-done observational study by experts in nutritional epidemiology from UCSF. It adds to a large body of evidence showing that plant-based diets improve health outcomes.”

“In the short-term, purchasing plant-based protein sources, such as beans and lentils, is less expensive than buying meat. Plant-based diets also reduce the risk of obesity, diabetes, and cardiovascular disease, which are associated with hundreds of thousands of dollars over a lifetime,” she said.

Limitations of the new study included the small number of non-White participants and self-reporting of diet. The study doesn’t examine the cost of various diets or the availability of plant-based foods like fresh produce, which can be limited in some neighborhoods.

Ms. Liu and colleagues plan to conduct a study that examines postdiagnostic plant-based diets in relation to prostate cancer–specific mortality. She and her team will also examine the plant-based dietary indices in relation to prostate cancer–specific quality of life at 2, 5, and 10 years from baseline.

The study authors, Dr. Loeb, and Dr. Gupta report no disclosures.

Correction, 3/17/23: An earlier version of this article misstated the name of NYU Langone Health.

A new study confirms that a plant-based diet with exercise can lower the risk of prostate cancer progressing or recurring.

The findings, which were reported at the 2023 ASCO Genitourinary Cancers Symposium in February, are based on a study of 2,038 men (median age, 64 years) with prostate cancer at stage T1, T2, or T3a.

“Consuming a whole foods plant-based diet may be an option to decrease risk for recurrence and improve overall survivorship,” said Vivian N. Liu, a clinical research coordinator at the University of California, San Francisco, who presented the findings.

The patients were interviewed about their diets at about 31.5 months after diagnosis. The study group was broken down into four groups based on how much of their diet consisted of a plant-based diet. Men in the highest quintile group who consumed at least 2.4 servings daily of fruit, 4.2 servings of vegetables, 2.6 servings of dairy, and 1.2 servings of meat (not seafood), had a 52% lower risk of progression (hazard ratio, 0.48; 95% confidence interval, 0.36-0.65; P-trend < 0.001) and a 53% lower risk of recurrence (HR, 0.47; 95% CI, 0.32-0.68; P-trend < 0.001), which was statistically significant. This compares with men in the lowest quintile who consumed 0.8 servings a day of fruit, 2.1 servings of vegetables, 3.1 servings of dairy, and 1.4 servings of meat. The findings were adjusted for total caloric intake, race, and smoking status.

For men over 65 years old, researchers found that a plant-based diet was associated with lower risk of recurrence (HR, 0.41; 95% CI, 0.24-0.7; P-trend = 0.03). And for those who exercised daily – in this case walking at a fast pace more than 3 times a week – a plant-based diet had a 56% (HR, 0.33; 95% CI, 0.26-0.73) lower risk of progression in the highest quintile group and a 59% decrease in recurrence (HR, 0.41; 95% CI, 0.25-0.68).

A new analysis like this, Ms. Liu said, “could guide people to make better, more healthful choices across their whole diet rather than adding or removing select foods.”

The primary endpoint was progression including recurrence, secondary treatment, bone metastases, and death due to prostate cancer, and the secondary endpoint was recurrence (PSA > 0.2ng/mL at 2 consecutive follow-up visits or during secondary treatment). At 7.4 years follow-up, there were 204 cases of progression.

“Fruits and vegetables contain antioxidants and anti-inflammatory components as well as dietary fiber that improve glucose control and reduce inflammation,” Ms. Liu said. In contrast, she said, animal-based foods may increase insulin resistance and insulin levels and boost levels of insulin-like growth factor 1, which is associated with prostate cancer risk. More studies, especially randomized controlled trials, are needed to provide evidence whether healthful plant-based foods and prostate cancer progression are connected.

NYU Langone Health urologist Natasha Gupta, MD, published a systematic review in 2022 on the impact of a plant-based diet on prostate cancer.* The review, which included 5 interventional studies and 11 observational studies, found that consuming a plant-based diet was associated with improvements in general health for men with prostate cancer. The observational studies found either a lower risk of prostate cancer or no significant difference.

“Patients often ask if there is anything that they can do to reduce the risk of recurrence, and it is great to be able to tell patients that a healthy lifestyle including plant-based foods and physical activity is helpful,” Dr. Gupta said.

The review’s coauthor, Stacy Loeb, MD, also of NYU Langone Health, said the new study was “a well-done observational study by experts in nutritional epidemiology from UCSF. It adds to a large body of evidence showing that plant-based diets improve health outcomes.”

“In the short-term, purchasing plant-based protein sources, such as beans and lentils, is less expensive than buying meat. Plant-based diets also reduce the risk of obesity, diabetes, and cardiovascular disease, which are associated with hundreds of thousands of dollars over a lifetime,” she said.

Limitations of the new study included the small number of non-White participants and self-reporting of diet. The study doesn’t examine the cost of various diets or the availability of plant-based foods like fresh produce, which can be limited in some neighborhoods.

Ms. Liu and colleagues plan to conduct a study that examines postdiagnostic plant-based diets in relation to prostate cancer–specific mortality. She and her team will also examine the plant-based dietary indices in relation to prostate cancer–specific quality of life at 2, 5, and 10 years from baseline.

The study authors, Dr. Loeb, and Dr. Gupta report no disclosures.

Correction, 3/17/23: An earlier version of this article misstated the name of NYU Langone Health.

With #Ozempic and #ozempicweightloss continuing to trend on social media, along with the mainstream media focusing on celebrities who rely on Ozempic (semaglutide) for weight loss, the daily requests for this new medication have been increasing.

Accompanying these requests are concerns and questions about potential risks, including this most recent message from one of my patients: “Dr. P – I saw the warnings. Is this medication going to make me get thyroid cancer? Please let me know!”

Let’s look at what we know to date, including recent studies, and how to advise our patients on this very hot topic.
 

Using GLP-1 receptor agonists for obesity

We have extensive prior experience with glucagon-like peptide 1 (GLP-1) receptor agonists, such as semaglutide, for treating type 2 diabetes and now recently as agents for weight loss.

Large clinical trials have documented the benefits of this medication class not only for weight reduction but also for cardiovascular and renal benefits in patients with diabetes. The subcutaneously injectable medications work by promoting insulin secretion, slowing gastric emptying, and suppressing glucagon secretion, with a low risk for hypoglycemia.

The Food and Drug Administration approved daily-injection GLP-1 agonist liraglutide for weight loss in 2014, and weekly-injection semaglutide for chronic weight management in 2021, in patients with a body mass index ≥ 27 with at least one weight-related condition or a BMI ≥ 30.

The brand name for semaglutide approved for weight loss is Wegovy, and the dose is slightly higher (maximum 2.4 mg/wk) than that of Ozempic (maximum 2.0 mg/wk), which is semaglutide approved for type 2 diabetes.

In trials for weight loss, data showed a mean change in body weight of almost 15% in the semaglutide group at week 68 compared with placebo, which is very impressive, particularly compared with other FDA-approved oral long-term weight loss medications.

The newest synthetic dual-acting agent is tirzepatide, which targets GLP-1 but is also a glucose-dependent insulinotropic polypeptide (GIP) agonist. The weekly subcutaneous injection was approved in May 2022 as Mounjaro for treating type 2 diabetes and produced even greater weight loss than semaglutide in clinical trials. Tirzepatide is now in trials for obesity and is under expedited review by the FDA for weight loss.
 

Why the concern about thyroid cancer?

Early on with the FDA approvals of GLP-1 agonists, a warning accompanied the products’ labels to not use this class of medications in patients with medullary thyroid cancer, a family history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome type 2. This warning was based on data from animal studies.

Human pancreatic cells aren’t the only cells that express GLP-1 receptors. These receptors are also expressed by parafollicular cells (C cells) of the thyroid, which secrete calcitonin and are the cells involved in medullary thyroid cancer. A dose-related and duration-dependent increase in thyroid C-cell tumor incidence was noted in rodents. The same relationship was not demonstrated in monkeys. Humans have far fewer C cells than rats, and human C cells have very low expression of the GLP-1 receptor.

Over a decade ago, a study examining the FDA’s database of reported adverse events found an increased risk for thyroid cancer in patients treated with exenatide, another GLP-1 agonist. The reporting system wasn’t designed to distinguish thyroid cancer subtypes.

Numerous subsequent studies didn’t confirm this relationship. The LEADER trial looked at liraglutide in patients with type 2 diabetes and showed no effect of GLP-1 receptor activation on human serum calcitonin levels, C-cell proliferation, or C-cell malignancy. Similarly, a large meta-analysis in patients with type 2 diabetes didn’t find a statistically increased risk for thyroid cancer with liraglutide, and no thyroid malignancies were reported with exenatide.

Two U.S. administrative databases from commercial health plans (a retrospective cohort study and a nested case-control study) compared type 2 diabetes patients who were taking exenatide vs. other antidiabetic drugs and found that exenatide was not significantly associated with an increased risk for thyroid cancer.

And a recent meta-analysis of 45 trials showed no significant effects on the occurrence of thyroid cancer with GLP-1 receptor agonists. Of note, it did find an increased risk for overall thyroid disorders, although there was no clear statistically significant finding pointing to a specific thyroid disorder.

Differing from prior studies, a recent nationwide French health care system study provided newer data suggesting a moderate increased risk for thyroid cancer in a cohort of patients with type 2 diabetes who were taking GLP-1 agonists. The increase in relative risk was noted for all types of thyroid cancer in patients using GLP-1 receptor agonists for 1-3 years.

An accompanying commentary by Caroline A. Thompson, PhD, and Til Stürmer, MD, provides perspective on this study’s potential limitations. These include detection bias, as the study results focused only on the statistically significant data. Also discussed were limitations to the case-control design, issues with claims-based tumor type classification (unavailability of surgical pathology), and an inability to adjust for family history and obesity, which is a risk factor alone for thyroid cancer. There was also no adjustment for exposure to head/neck radiation.

While this study has important findings to consider, it deserves further investigation, with future studies linking data to tumor registry data before a change is made in clinical practice.

No clear relationship has been drawn between GLP-1 receptor agonists and thyroid cancer in humans. Numerous confounding factors limit the data. Studies generally don’t specify the type of thyroid cancer, and they lump medullary thyroid cancer, the rarest form, with papillary thyroid cancer.

Is a detection bias present where weight loss makes nodules more visible on the neck among those treated with GLP-1 agonists? And/or are patients treated with GLP-1 agonists being screened more stringently for thyroid nodules and/or cancer?
 

How to advise our patients and respond to the EMR messages

The TikTok videos may continue, the celebrity chatter may increase, and we, as physicians, will continue to look to real-world data with randomized controlled trials to tailor our decision-making and guide our patients.

It’s prudent to advise patients that if they have a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2, in particular, they should avoid using this class of medication. Thyroid cancer remains a rare outcome, and GLP-1 receptor agonists remain a very important and beneficial treatment option for the right patient.

A version of this article first appeared on Medscape.com.

With #Ozempic and #ozempicweightloss continuing to trend on social media, along with the mainstream media focusing on celebrities who rely on Ozempic (semaglutide) for weight loss, the daily requests for this new medication have been increasing.

Accompanying these requests are concerns and questions about potential risks, including this most recent message from one of my patients: “Dr. P – I saw the warnings. Is this medication going to make me get thyroid cancer? Please let me know!”

Let’s look at what we know to date, including recent studies, and how to advise our patients on this very hot topic.
 

Using GLP-1 receptor agonists for obesity

We have extensive prior experience with glucagon-like peptide 1 (GLP-1) receptor agonists, such as semaglutide, for treating type 2 diabetes and now recently as agents for weight loss.

Large clinical trials have documented the benefits of this medication class not only for weight reduction but also for cardiovascular and renal benefits in patients with diabetes. The subcutaneously injectable medications work by promoting insulin secretion, slowing gastric emptying, and suppressing glucagon secretion, with a low risk for hypoglycemia.

The Food and Drug Administration approved daily-injection GLP-1 agonist liraglutide for weight loss in 2014, and weekly-injection semaglutide for chronic weight management in 2021, in patients with a body mass index ≥ 27 with at least one weight-related condition or a BMI ≥ 30.

The brand name for semaglutide approved for weight loss is Wegovy, and the dose is slightly higher (maximum 2.4 mg/wk) than that of Ozempic (maximum 2.0 mg/wk), which is semaglutide approved for type 2 diabetes.

In trials for weight loss, data showed a mean change in body weight of almost 15% in the semaglutide group at week 68 compared with placebo, which is very impressive, particularly compared with other FDA-approved oral long-term weight loss medications.

The newest synthetic dual-acting agent is tirzepatide, which targets GLP-1 but is also a glucose-dependent insulinotropic polypeptide (GIP) agonist. The weekly subcutaneous injection was approved in May 2022 as Mounjaro for treating type 2 diabetes and produced even greater weight loss than semaglutide in clinical trials. Tirzepatide is now in trials for obesity and is under expedited review by the FDA for weight loss.
 

Why the concern about thyroid cancer?

Early on with the FDA approvals of GLP-1 agonists, a warning accompanied the products’ labels to not use this class of medications in patients with medullary thyroid cancer, a family history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome type 2. This warning was based on data from animal studies.

Human pancreatic cells aren’t the only cells that express GLP-1 receptors. These receptors are also expressed by parafollicular cells (C cells) of the thyroid, which secrete calcitonin and are the cells involved in medullary thyroid cancer. A dose-related and duration-dependent increase in thyroid C-cell tumor incidence was noted in rodents. The same relationship was not demonstrated in monkeys. Humans have far fewer C cells than rats, and human C cells have very low expression of the GLP-1 receptor.

Over a decade ago, a study examining the FDA’s database of reported adverse events found an increased risk for thyroid cancer in patients treated with exenatide, another GLP-1 agonist. The reporting system wasn’t designed to distinguish thyroid cancer subtypes.

Numerous subsequent studies didn’t confirm this relationship. The LEADER trial looked at liraglutide in patients with type 2 diabetes and showed no effect of GLP-1 receptor activation on human serum calcitonin levels, C-cell proliferation, or C-cell malignancy. Similarly, a large meta-analysis in patients with type 2 diabetes didn’t find a statistically increased risk for thyroid cancer with liraglutide, and no thyroid malignancies were reported with exenatide.

Two U.S. administrative databases from commercial health plans (a retrospective cohort study and a nested case-control study) compared type 2 diabetes patients who were taking exenatide vs. other antidiabetic drugs and found that exenatide was not significantly associated with an increased risk for thyroid cancer.

And a recent meta-analysis of 45 trials showed no significant effects on the occurrence of thyroid cancer with GLP-1 receptor agonists. Of note, it did find an increased risk for overall thyroid disorders, although there was no clear statistically significant finding pointing to a specific thyroid disorder.

Differing from prior studies, a recent nationwide French health care system study provided newer data suggesting a moderate increased risk for thyroid cancer in a cohort of patients with type 2 diabetes who were taking GLP-1 agonists. The increase in relative risk was noted for all types of thyroid cancer in patients using GLP-1 receptor agonists for 1-3 years.

An accompanying commentary by Caroline A. Thompson, PhD, and Til Stürmer, MD, provides perspective on this study’s potential limitations. These include detection bias, as the study results focused only on the statistically significant data. Also discussed were limitations to the case-control design, issues with claims-based tumor type classification (unavailability of surgical pathology), and an inability to adjust for family history and obesity, which is a risk factor alone for thyroid cancer. There was also no adjustment for exposure to head/neck radiation.

While this study has important findings to consider, it deserves further investigation, with future studies linking data to tumor registry data before a change is made in clinical practice.

No clear relationship has been drawn between GLP-1 receptor agonists and thyroid cancer in humans. Numerous confounding factors limit the data. Studies generally don’t specify the type of thyroid cancer, and they lump medullary thyroid cancer, the rarest form, with papillary thyroid cancer.

Is a detection bias present where weight loss makes nodules more visible on the neck among those treated with GLP-1 agonists? And/or are patients treated with GLP-1 agonists being screened more stringently for thyroid nodules and/or cancer?
 

How to advise our patients and respond to the EMR messages

The TikTok videos may continue, the celebrity chatter may increase, and we, as physicians, will continue to look to real-world data with randomized controlled trials to tailor our decision-making and guide our patients.

It’s prudent to advise patients that if they have a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2, in particular, they should avoid using this class of medication. Thyroid cancer remains a rare outcome, and GLP-1 receptor agonists remain a very important and beneficial treatment option for the right patient.

A version of this article first appeared on Medscape.com.

With #Ozempic and #ozempicweightloss continuing to trend on social media, along with the mainstream media focusing on celebrities who rely on Ozempic (semaglutide) for weight loss, the daily requests for this new medication have been increasing.

Accompanying these requests are concerns and questions about potential risks, including this most recent message from one of my patients: “Dr. P – I saw the warnings. Is this medication going to make me get thyroid cancer? Please let me know!”

Let’s look at what we know to date, including recent studies, and how to advise our patients on this very hot topic.
 

Using GLP-1 receptor agonists for obesity

We have extensive prior experience with glucagon-like peptide 1 (GLP-1) receptor agonists, such as semaglutide, for treating type 2 diabetes and now recently as agents for weight loss.

Large clinical trials have documented the benefits of this medication class not only for weight reduction but also for cardiovascular and renal benefits in patients with diabetes. The subcutaneously injectable medications work by promoting insulin secretion, slowing gastric emptying, and suppressing glucagon secretion, with a low risk for hypoglycemia.

The Food and Drug Administration approved daily-injection GLP-1 agonist liraglutide for weight loss in 2014, and weekly-injection semaglutide for chronic weight management in 2021, in patients with a body mass index ≥ 27 with at least one weight-related condition or a BMI ≥ 30.

The brand name for semaglutide approved for weight loss is Wegovy, and the dose is slightly higher (maximum 2.4 mg/wk) than that of Ozempic (maximum 2.0 mg/wk), which is semaglutide approved for type 2 diabetes.

In trials for weight loss, data showed a mean change in body weight of almost 15% in the semaglutide group at week 68 compared with placebo, which is very impressive, particularly compared with other FDA-approved oral long-term weight loss medications.

The newest synthetic dual-acting agent is tirzepatide, which targets GLP-1 but is also a glucose-dependent insulinotropic polypeptide (GIP) agonist. The weekly subcutaneous injection was approved in May 2022 as Mounjaro for treating type 2 diabetes and produced even greater weight loss than semaglutide in clinical trials. Tirzepatide is now in trials for obesity and is under expedited review by the FDA for weight loss.
 

Why the concern about thyroid cancer?

Early on with the FDA approvals of GLP-1 agonists, a warning accompanied the products’ labels to not use this class of medications in patients with medullary thyroid cancer, a family history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome type 2. This warning was based on data from animal studies.

Human pancreatic cells aren’t the only cells that express GLP-1 receptors. These receptors are also expressed by parafollicular cells (C cells) of the thyroid, which secrete calcitonin and are the cells involved in medullary thyroid cancer. A dose-related and duration-dependent increase in thyroid C-cell tumor incidence was noted in rodents. The same relationship was not demonstrated in monkeys. Humans have far fewer C cells than rats, and human C cells have very low expression of the GLP-1 receptor.

Over a decade ago, a study examining the FDA’s database of reported adverse events found an increased risk for thyroid cancer in patients treated with exenatide, another GLP-1 agonist. The reporting system wasn’t designed to distinguish thyroid cancer subtypes.

Numerous subsequent studies didn’t confirm this relationship. The LEADER trial looked at liraglutide in patients with type 2 diabetes and showed no effect of GLP-1 receptor activation on human serum calcitonin levels, C-cell proliferation, or C-cell malignancy. Similarly, a large meta-analysis in patients with type 2 diabetes didn’t find a statistically increased risk for thyroid cancer with liraglutide, and no thyroid malignancies were reported with exenatide.

Two U.S. administrative databases from commercial health plans (a retrospective cohort study and a nested case-control study) compared type 2 diabetes patients who were taking exenatide vs. other antidiabetic drugs and found that exenatide was not significantly associated with an increased risk for thyroid cancer.

And a recent meta-analysis of 45 trials showed no significant effects on the occurrence of thyroid cancer with GLP-1 receptor agonists. Of note, it did find an increased risk for overall thyroid disorders, although there was no clear statistically significant finding pointing to a specific thyroid disorder.

Differing from prior studies, a recent nationwide French health care system study provided newer data suggesting a moderate increased risk for thyroid cancer in a cohort of patients with type 2 diabetes who were taking GLP-1 agonists. The increase in relative risk was noted for all types of thyroid cancer in patients using GLP-1 receptor agonists for 1-3 years.

An accompanying commentary by Caroline A. Thompson, PhD, and Til Stürmer, MD, provides perspective on this study’s potential limitations. These include detection bias, as the study results focused only on the statistically significant data. Also discussed were limitations to the case-control design, issues with claims-based tumor type classification (unavailability of surgical pathology), and an inability to adjust for family history and obesity, which is a risk factor alone for thyroid cancer. There was also no adjustment for exposure to head/neck radiation.

While this study has important findings to consider, it deserves further investigation, with future studies linking data to tumor registry data before a change is made in clinical practice.

No clear relationship has been drawn between GLP-1 receptor agonists and thyroid cancer in humans. Numerous confounding factors limit the data. Studies generally don’t specify the type of thyroid cancer, and they lump medullary thyroid cancer, the rarest form, with papillary thyroid cancer.

Is a detection bias present where weight loss makes nodules more visible on the neck among those treated with GLP-1 agonists? And/or are patients treated with GLP-1 agonists being screened more stringently for thyroid nodules and/or cancer?
 

How to advise our patients and respond to the EMR messages

The TikTok videos may continue, the celebrity chatter may increase, and we, as physicians, will continue to look to real-world data with randomized controlled trials to tailor our decision-making and guide our patients.

It’s prudent to advise patients that if they have a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2, in particular, they should avoid using this class of medication. Thyroid cancer remains a rare outcome, and GLP-1 receptor agonists remain a very important and beneficial treatment option for the right patient.

A version of this article first appeared on Medscape.com.

A qualitative study of breast cancer screening–age women finds that few women identified breast density as a risk factor for breast cancer.

Most women did not feel confident they knew what actions could mitigate breast cancer risk, leading researchers to the conclusion that comprehensive education about breast cancer risks and prevention strategies is needed.

The study was published earlier this year in JAMA Network Open.

“Forty [percent] to 50% of women who undergo mammography fall into the two highest breast density categories,” said the study’s lead author Christine Gunn, PhD, of the Dartmouth Institute for Health Policy and Clinical Practice, N.H. “Breast cancer risk increases from 1.2-4.0 times depending on the level of breast density. By comparison, a first-degree family history of breast cancer, particularly in premenopausal women, confers a two-fold higher breast cancer risk.”

Dr. Gunn’s study is based on a survey of 2,306 women (between 40 and 76 years old) that was conducted between 2019 and 2020. The goal was to determine how well women understood cancer risks associated with dense breast tissue. The final analysis included 1,858 women (9% Asian, 27% Black, 14% Hispanic, 43% White, and 7% other race or ethnicity).

Breast density was thought to be a greater risk than not having children, drinking daily, and having had a prior breast biopsy, according to 52%, 53%, and 48% of respondents, respectively. Breast density was believed to be a lesser breast cancer risk than having a first-degree relative with breast cancer by 93% of women, and 65% of women felt it was a lesser risk than being overweight or obese.

Of the 61 women who completed follow-up interviews, 6 described breast density as a contributing factor to breast cancer risk. And, 17 women did not know whether it was possible to reduce their breast cancer risk.
 

Doctors must notify patients in writing

Breast tissue falls under one of four categories: fatty tissue, scattered areas of dense fibroglandular tissue, many areas of glandular and connective tissue, or extremely dense tissue. The tissue is considered dense if it falls under heterogeneously dense or extremely dense, and in those cases, follow-up testing with ultrasound or MRI may be necessary. This is important, Dr. Gunn said, because dense tissue can make “it harder to find cancers because connective tissue appears white on the mammogram, potentially masking tumors.”

Prior studies have found that many clinicians are uncomfortable counseling patients on the implications of breast density and cancer risk, the authors wrote.

However, under the Mammography Quality Standards Act, which was updated on March 10, the Food and Drug Administration requires that patients be provided with a mammography report summary that “identifies whether the patient has dense or nondense breast tissue.” The report, which should be written in lay language, should also specify the “significance” of the dense tissue.

While some states mandate notification regardless of the density level, most only notify women if heterogeneously dense or extremely dense tissue has been identified, Dr. Gunn said. But the rules are inconsistent, she said. In some facilities in Massachusetts, for example, women may receive a mammography report letter and a separate breast density letter. “For some, it has been really confusing. They received a letter saying that their mammography was normal and then another one saying that they have dense breasts – resulting in a lot of uncertainty and anxiety. We don’t want to overly alarm people. We want them to understand their risk,” she said.

Breast density can be considered among other risk factors, including alcohol use, obesity, diet, parity, prior breast biopsy, and inherited unfavorable genetic mutations. “If the total lifetime risk is above 20%, that opens up further screening options, such as a breast MRI, which will catch more cancers than a breast mammogram by itself,” Dr. Gunn said.

“The challenges for physicians and patients around collecting and understanding breast density information in the context of other risk factors can potentially lead to disparities in who gets to know their risk and who doesn’t,” Dr. Gunn said. It would be possible, she speculated, to create or use existing risk calculators integrated into medical records and populated with information gathered in premammography visit questionnaires. Ideally, a radiologist could hand the patient results in real time at the end of the mammography visit, integrating risk estimates with mammography findings to make recommendations.

This study was supported by grant RSG-133017-CPHPS from the American Cancer Society.
 

A qualitative study of breast cancer screening–age women finds that few women identified breast density as a risk factor for breast cancer.

Most women did not feel confident they knew what actions could mitigate breast cancer risk, leading researchers to the conclusion that comprehensive education about breast cancer risks and prevention strategies is needed.

The study was published earlier this year in JAMA Network Open.

“Forty [percent] to 50% of women who undergo mammography fall into the two highest breast density categories,” said the study’s lead author Christine Gunn, PhD, of the Dartmouth Institute for Health Policy and Clinical Practice, N.H. “Breast cancer risk increases from 1.2-4.0 times depending on the level of breast density. By comparison, a first-degree family history of breast cancer, particularly in premenopausal women, confers a two-fold higher breast cancer risk.”

Dr. Gunn’s study is based on a survey of 2,306 women (between 40 and 76 years old) that was conducted between 2019 and 2020. The goal was to determine how well women understood cancer risks associated with dense breast tissue. The final analysis included 1,858 women (9% Asian, 27% Black, 14% Hispanic, 43% White, and 7% other race or ethnicity).

Breast density was thought to be a greater risk than not having children, drinking daily, and having had a prior breast biopsy, according to 52%, 53%, and 48% of respondents, respectively. Breast density was believed to be a lesser breast cancer risk than having a first-degree relative with breast cancer by 93% of women, and 65% of women felt it was a lesser risk than being overweight or obese.

Of the 61 women who completed follow-up interviews, 6 described breast density as a contributing factor to breast cancer risk. And, 17 women did not know whether it was possible to reduce their breast cancer risk.
 

Doctors must notify patients in writing

Breast tissue falls under one of four categories: fatty tissue, scattered areas of dense fibroglandular tissue, many areas of glandular and connective tissue, or extremely dense tissue. The tissue is considered dense if it falls under heterogeneously dense or extremely dense, and in those cases, follow-up testing with ultrasound or MRI may be necessary. This is important, Dr. Gunn said, because dense tissue can make “it harder to find cancers because connective tissue appears white on the mammogram, potentially masking tumors.”

Prior studies have found that many clinicians are uncomfortable counseling patients on the implications of breast density and cancer risk, the authors wrote.

However, under the Mammography Quality Standards Act, which was updated on March 10, the Food and Drug Administration requires that patients be provided with a mammography report summary that “identifies whether the patient has dense or nondense breast tissue.” The report, which should be written in lay language, should also specify the “significance” of the dense tissue.

While some states mandate notification regardless of the density level, most only notify women if heterogeneously dense or extremely dense tissue has been identified, Dr. Gunn said. But the rules are inconsistent, she said. In some facilities in Massachusetts, for example, women may receive a mammography report letter and a separate breast density letter. “For some, it has been really confusing. They received a letter saying that their mammography was normal and then another one saying that they have dense breasts – resulting in a lot of uncertainty and anxiety. We don’t want to overly alarm people. We want them to understand their risk,” she said.

Breast density can be considered among other risk factors, including alcohol use, obesity, diet, parity, prior breast biopsy, and inherited unfavorable genetic mutations. “If the total lifetime risk is above 20%, that opens up further screening options, such as a breast MRI, which will catch more cancers than a breast mammogram by itself,” Dr. Gunn said.

“The challenges for physicians and patients around collecting and understanding breast density information in the context of other risk factors can potentially lead to disparities in who gets to know their risk and who doesn’t,” Dr. Gunn said. It would be possible, she speculated, to create or use existing risk calculators integrated into medical records and populated with information gathered in premammography visit questionnaires. Ideally, a radiologist could hand the patient results in real time at the end of the mammography visit, integrating risk estimates with mammography findings to make recommendations.

This study was supported by grant RSG-133017-CPHPS from the American Cancer Society.
 

A qualitative study of breast cancer screening–age women finds that few women identified breast density as a risk factor for breast cancer.

Most women did not feel confident they knew what actions could mitigate breast cancer risk, leading researchers to the conclusion that comprehensive education about breast cancer risks and prevention strategies is needed.

The study was published earlier this year in JAMA Network Open.

“Forty [percent] to 50% of women who undergo mammography fall into the two highest breast density categories,” said the study’s lead author Christine Gunn, PhD, of the Dartmouth Institute for Health Policy and Clinical Practice, N.H. “Breast cancer risk increases from 1.2-4.0 times depending on the level of breast density. By comparison, a first-degree family history of breast cancer, particularly in premenopausal women, confers a two-fold higher breast cancer risk.”

Dr. Gunn’s study is based on a survey of 2,306 women (between 40 and 76 years old) that was conducted between 2019 and 2020. The goal was to determine how well women understood cancer risks associated with dense breast tissue. The final analysis included 1,858 women (9% Asian, 27% Black, 14% Hispanic, 43% White, and 7% other race or ethnicity).

Breast density was thought to be a greater risk than not having children, drinking daily, and having had a prior breast biopsy, according to 52%, 53%, and 48% of respondents, respectively. Breast density was believed to be a lesser breast cancer risk than having a first-degree relative with breast cancer by 93% of women, and 65% of women felt it was a lesser risk than being overweight or obese.

Of the 61 women who completed follow-up interviews, 6 described breast density as a contributing factor to breast cancer risk. And, 17 women did not know whether it was possible to reduce their breast cancer risk.
 

Doctors must notify patients in writing

Breast tissue falls under one of four categories: fatty tissue, scattered areas of dense fibroglandular tissue, many areas of glandular and connective tissue, or extremely dense tissue. The tissue is considered dense if it falls under heterogeneously dense or extremely dense, and in those cases, follow-up testing with ultrasound or MRI may be necessary. This is important, Dr. Gunn said, because dense tissue can make “it harder to find cancers because connective tissue appears white on the mammogram, potentially masking tumors.”

Prior studies have found that many clinicians are uncomfortable counseling patients on the implications of breast density and cancer risk, the authors wrote.

However, under the Mammography Quality Standards Act, which was updated on March 10, the Food and Drug Administration requires that patients be provided with a mammography report summary that “identifies whether the patient has dense or nondense breast tissue.” The report, which should be written in lay language, should also specify the “significance” of the dense tissue.

While some states mandate notification regardless of the density level, most only notify women if heterogeneously dense or extremely dense tissue has been identified, Dr. Gunn said. But the rules are inconsistent, she said. In some facilities in Massachusetts, for example, women may receive a mammography report letter and a separate breast density letter. “For some, it has been really confusing. They received a letter saying that their mammography was normal and then another one saying that they have dense breasts – resulting in a lot of uncertainty and anxiety. We don’t want to overly alarm people. We want them to understand their risk,” she said.

Breast density can be considered among other risk factors, including alcohol use, obesity, diet, parity, prior breast biopsy, and inherited unfavorable genetic mutations. “If the total lifetime risk is above 20%, that opens up further screening options, such as a breast MRI, which will catch more cancers than a breast mammogram by itself,” Dr. Gunn said.

“The challenges for physicians and patients around collecting and understanding breast density information in the context of other risk factors can potentially lead to disparities in who gets to know their risk and who doesn’t,” Dr. Gunn said. It would be possible, she speculated, to create or use existing risk calculators integrated into medical records and populated with information gathered in premammography visit questionnaires. Ideally, a radiologist could hand the patient results in real time at the end of the mammography visit, integrating risk estimates with mammography findings to make recommendations.

This study was supported by grant RSG-133017-CPHPS from the American Cancer Society.
 

In Western diets, dairy and beef are ubiquitous: Milk goes with coffee, melted cheese with pizza, and chili with rice. But what if dairy products and beef contained a new kind of pathogen that could infect you as a child and trigger cancer or multiple sclerosis (MS) 40-70 years later?

Researchers from the German Cancer Research Center (DKFZ) suspect that such zoonoses are possibly widespread and are therefore recommending that infants not be given dairy products until they are at least age 1 year. However, in two joint statements, the German Federal Institute for Risk Assessment (BfR) and the Max Rubner Institute (MRI) have rejected such theories.

In 2008, Harald zur Hausen, MD, DSc, received the Nobel Prize in Medicine for his discovery that human papillomaviruses cause cervical cancer. His starting point was the observation that sexually abstinent women, such as nuns, rarely develop this cancer. So it was possible to draw the conclusion that pathogens are transmitted during sexual intercourse, explain Dr. zur Hausen and his wife Ethel-Michele de Villiers, PhD, both of DKFZ Heidelberg.

Papillomaviruses, as well as human herpes and Epstein-Barr viruses (EBV), polyomaviruses, and retroviruses, cause cancer in a direct way: by inserting their genes into the DNA of human cells. With a latency of a few years to a few decades, the proteins formed through expression stimulate malignant growth by altering the regulating host gene.
 

Acid radicals

However, viruses – just like bacteria and parasites – can also indirectly trigger cancer. One mechanism for this triggering is the disruption of immune defenses, as shown by the sometimes drastically increased tumor incidence with AIDS or with immunosuppressants after transplants. Chronic inflammation is a second mechanism that generates acid radicals and thereby causes random mutations in replicating cells. Examples include stomach cancer caused by Helicobacter pylori and liver cancer caused by Schistosoma, liver fluke, and hepatitis B and C viruses.

According to Dr. de Villiers and Dr. zur Hausen, there are good reasons to believe that other pathogens could cause chronic inflammation and thereby lead to cancer. Epidemiologic data suggest that dairy and meat products from European cows (Bos taurus) are a potential source. This is because colon cancer and breast cancer commonly occur in places where these foods are heavily consumed (that is, in North America, Argentina, Europe, and Australia). In contrast, the rate is low in India, where cows are revered as holy animals. Also noteworthy is that women with a lactose intolerance rarely develop breast cancer.
 

Viral progeny

In fact, the researchers found single-stranded DNA rings that originated in viruses, which they named bovine meat and milk factors (BMMF), in the intestines of patients with colon cancer. They reported, “This new class of pathogen deserves, in our opinion at least, to become the focus of cancer development and further chronic diseases.” They also detected elevated levels of acid radicals in these areas (that is, oxidative stress), which is typical for chronic inflammation.

The researchers assume that infants, whose immune system is not yet fully matured, ingest the BMMF as soon as they have dairy. Therefore, there is no need for adults to avoid dairy or beef because everyone is infected anyway, said Dr. zur Hausen.
 

‘Breast milk is healthy’

Dr. De Villiers and Dr. zur Hausen outlined more evidence of cancer-triggering pathogens. Mothers who have breastfed are less likely, especially after multiple pregnancies, to develop tumors in various organs or to have MS and type 2 diabetes. The authors attribute the protective effect to oligosaccharides in breast milk, which begin to be formed midway through the pregnancy. They bind to lectin receptors and, in so doing, mask the terminal molecule onto which the viruses need to dock. As a result, their port of entry into the cells is blocked.

The oligosaccharides also protect the baby against life-threatening infections by blocking access by rotaviruses and noroviruses. In this way, especially if breastfeeding lasts a long time – around 1 year – the period of incomplete immunocompetence is bridged.
 

Colon cancer

To date, it has been assumed that around 20% of all cancerous diseases globally are caused by infections, said the researchers. But if the suspected BMMF cases are included, this figure rises to 50%, even to around 80%, for colon cancer. If the suspicion is confirmed, the consequences for prevention and therapy would be significant.

The voice of a Nobel prize winner undoubtedly carries weight, but at the time, Dr. zur Hausen still had to convince a host of skeptics with his discovery that a viral infection is a major cause of cervical cancer. Nonetheless, some indicators suggest that he and his wife have found a dead end this time.
 

Institutional skepticism

When his working group made the results public in February 2019, the DKFZ felt the need to give an all-clear signal in response to alarmed press reports. There is no reason to see dairy and meat consumption as something negative. Similarly, in their first joint statement, the BfR and the MRI judged the data to be insufficient and called for further studies. Multiple research teams began to focus on BMMF as a result. In what foods can they be found? Are they more common in patients with cancer than in healthy people? Are they infectious? Do they cause inflammation and cancer?

The findings presented in a second statement by the BfR and MRI at the end of November 2022 contradicted the claims made by the DKFZ scientists across the board. In no way do BMMF represent new pathogens. They are variants of already known DNA sequences. In addition, they are present in numerous animal-based and plant-based foods, including pork, fish, fruit, vegetables, and nuts.

BMMF do not possess the ability to infect human cells, the institutes said. The proof that they are damaging to one’s health was also absent. It is true that the incidence of intestinal tumors correlates positively with the consumption of red and processed meat – which in no way signifies causality – but dairy products are linked to a reduced risk. On the other hand, breast cancer cannot be associated with the consumption of beef or dairy.

Therefore, both institutes recommend continuing to use these products as supplementary diet for infants because of their micronutrients. They further stated that the products are safe for people of all ages.
 

Association with MS?

Unperturbed, Dr. de Villiers and Dr. zur Hausen went one step further in their current article. They posited that MS is also associated with the consumption of dairy products and beef. Here too geographic distribution prompted the idea to look for BMMF in the brain lesions of patients with MS. The researchers isolated ring-shaped DNA molecules that proved to be closely related to BMMF from dairy and cattle blood. “The result was electrifying for us.”

However, there are several other factors to consider, such as vitamin D3 deficiency. This is because the incidence of MS decreases the further you travel from the poles toward the equator (that is, as solar radiation increases). Also, EBV clearly plays a role because patients with MS display increased titers of EBV antibodies. One study also showed that people in Antarctica excreted reactivated EBV in their saliva during winter and that vitamin D3 stopped the viral secretion.

Under these conditions, the researchers hypothesized that MS is caused by a double infection of brain cells by EBV and BMMF. EBV is reactivated by a lack of vitamin D3, and the BMMF multiply and are eventually converted into proteins. A focal immunoreaction causes the Schwann cells and oligodendrocytes to malfunction, which leads to the destruction of the myelin sheaths around the nerve fibers.

This article was translated from the Medscape German Edition. A version appeared on Medscape.com.

In Western diets, dairy and beef are ubiquitous: Milk goes with coffee, melted cheese with pizza, and chili with rice. But what if dairy products and beef contained a new kind of pathogen that could infect you as a child and trigger cancer or multiple sclerosis (MS) 40-70 years later?

Researchers from the German Cancer Research Center (DKFZ) suspect that such zoonoses are possibly widespread and are therefore recommending that infants not be given dairy products until they are at least age 1 year. However, in two joint statements, the German Federal Institute for Risk Assessment (BfR) and the Max Rubner Institute (MRI) have rejected such theories.

In 2008, Harald zur Hausen, MD, DSc, received the Nobel Prize in Medicine for his discovery that human papillomaviruses cause cervical cancer. His starting point was the observation that sexually abstinent women, such as nuns, rarely develop this cancer. So it was possible to draw the conclusion that pathogens are transmitted during sexual intercourse, explain Dr. zur Hausen and his wife Ethel-Michele de Villiers, PhD, both of DKFZ Heidelberg.

Papillomaviruses, as well as human herpes and Epstein-Barr viruses (EBV), polyomaviruses, and retroviruses, cause cancer in a direct way: by inserting their genes into the DNA of human cells. With a latency of a few years to a few decades, the proteins formed through expression stimulate malignant growth by altering the regulating host gene.
 

Acid radicals

However, viruses – just like bacteria and parasites – can also indirectly trigger cancer. One mechanism for this triggering is the disruption of immune defenses, as shown by the sometimes drastically increased tumor incidence with AIDS or with immunosuppressants after transplants. Chronic inflammation is a second mechanism that generates acid radicals and thereby causes random mutations in replicating cells. Examples include stomach cancer caused by Helicobacter pylori and liver cancer caused by Schistosoma, liver fluke, and hepatitis B and C viruses.

According to Dr. de Villiers and Dr. zur Hausen, there are good reasons to believe that other pathogens could cause chronic inflammation and thereby lead to cancer. Epidemiologic data suggest that dairy and meat products from European cows (Bos taurus) are a potential source. This is because colon cancer and breast cancer commonly occur in places where these foods are heavily consumed (that is, in North America, Argentina, Europe, and Australia). In contrast, the rate is low in India, where cows are revered as holy animals. Also noteworthy is that women with a lactose intolerance rarely develop breast cancer.
 

Viral progeny

In fact, the researchers found single-stranded DNA rings that originated in viruses, which they named bovine meat and milk factors (BMMF), in the intestines of patients with colon cancer. They reported, “This new class of pathogen deserves, in our opinion at least, to become the focus of cancer development and further chronic diseases.” They also detected elevated levels of acid radicals in these areas (that is, oxidative stress), which is typical for chronic inflammation.

The researchers assume that infants, whose immune system is not yet fully matured, ingest the BMMF as soon as they have dairy. Therefore, there is no need for adults to avoid dairy or beef because everyone is infected anyway, said Dr. zur Hausen.
 

‘Breast milk is healthy’

Dr. De Villiers and Dr. zur Hausen outlined more evidence of cancer-triggering pathogens. Mothers who have breastfed are less likely, especially after multiple pregnancies, to develop tumors in various organs or to have MS and type 2 diabetes. The authors attribute the protective effect to oligosaccharides in breast milk, which begin to be formed midway through the pregnancy. They bind to lectin receptors and, in so doing, mask the terminal molecule onto which the viruses need to dock. As a result, their port of entry into the cells is blocked.

The oligosaccharides also protect the baby against life-threatening infections by blocking access by rotaviruses and noroviruses. In this way, especially if breastfeeding lasts a long time – around 1 year – the period of incomplete immunocompetence is bridged.
 

Colon cancer

To date, it has been assumed that around 20% of all cancerous diseases globally are caused by infections, said the researchers. But if the suspected BMMF cases are included, this figure rises to 50%, even to around 80%, for colon cancer. If the suspicion is confirmed, the consequences for prevention and therapy would be significant.

The voice of a Nobel prize winner undoubtedly carries weight, but at the time, Dr. zur Hausen still had to convince a host of skeptics with his discovery that a viral infection is a major cause of cervical cancer. Nonetheless, some indicators suggest that he and his wife have found a dead end this time.
 

Institutional skepticism

When his working group made the results public in February 2019, the DKFZ felt the need to give an all-clear signal in response to alarmed press reports. There is no reason to see dairy and meat consumption as something negative. Similarly, in their first joint statement, the BfR and the MRI judged the data to be insufficient and called for further studies. Multiple research teams began to focus on BMMF as a result. In what foods can they be found? Are they more common in patients with cancer than in healthy people? Are they infectious? Do they cause inflammation and cancer?

The findings presented in a second statement by the BfR and MRI at the end of November 2022 contradicted the claims made by the DKFZ scientists across the board. In no way do BMMF represent new pathogens. They are variants of already known DNA sequences. In addition, they are present in numerous animal-based and plant-based foods, including pork, fish, fruit, vegetables, and nuts.

BMMF do not possess the ability to infect human cells, the institutes said. The proof that they are damaging to one’s health was also absent. It is true that the incidence of intestinal tumors correlates positively with the consumption of red and processed meat – which in no way signifies causality – but dairy products are linked to a reduced risk. On the other hand, breast cancer cannot be associated with the consumption of beef or dairy.

Therefore, both institutes recommend continuing to use these products as supplementary diet for infants because of their micronutrients. They further stated that the products are safe for people of all ages.
 

Association with MS?

Unperturbed, Dr. de Villiers and Dr. zur Hausen went one step further in their current article. They posited that MS is also associated with the consumption of dairy products and beef. Here too geographic distribution prompted the idea to look for BMMF in the brain lesions of patients with MS. The researchers isolated ring-shaped DNA molecules that proved to be closely related to BMMF from dairy and cattle blood. “The result was electrifying for us.”

However, there are several other factors to consider, such as vitamin D3 deficiency. This is because the incidence of MS decreases the further you travel from the poles toward the equator (that is, as solar radiation increases). Also, EBV clearly plays a role because patients with MS display increased titers of EBV antibodies. One study also showed that people in Antarctica excreted reactivated EBV in their saliva during winter and that vitamin D3 stopped the viral secretion.

Under these conditions, the researchers hypothesized that MS is caused by a double infection of brain cells by EBV and BMMF. EBV is reactivated by a lack of vitamin D3, and the BMMF multiply and are eventually converted into proteins. A focal immunoreaction causes the Schwann cells and oligodendrocytes to malfunction, which leads to the destruction of the myelin sheaths around the nerve fibers.

This article was translated from the Medscape German Edition. A version appeared on Medscape.com.

In Western diets, dairy and beef are ubiquitous: Milk goes with coffee, melted cheese with pizza, and chili with rice. But what if dairy products and beef contained a new kind of pathogen that could infect you as a child and trigger cancer or multiple sclerosis (MS) 40-70 years later?

Researchers from the German Cancer Research Center (DKFZ) suspect that such zoonoses are possibly widespread and are therefore recommending that infants not be given dairy products until they are at least age 1 year. However, in two joint statements, the German Federal Institute for Risk Assessment (BfR) and the Max Rubner Institute (MRI) have rejected such theories.

In 2008, Harald zur Hausen, MD, DSc, received the Nobel Prize in Medicine for his discovery that human papillomaviruses cause cervical cancer. His starting point was the observation that sexually abstinent women, such as nuns, rarely develop this cancer. So it was possible to draw the conclusion that pathogens are transmitted during sexual intercourse, explain Dr. zur Hausen and his wife Ethel-Michele de Villiers, PhD, both of DKFZ Heidelberg.

Papillomaviruses, as well as human herpes and Epstein-Barr viruses (EBV), polyomaviruses, and retroviruses, cause cancer in a direct way: by inserting their genes into the DNA of human cells. With a latency of a few years to a few decades, the proteins formed through expression stimulate malignant growth by altering the regulating host gene.
 

Acid radicals

However, viruses – just like bacteria and parasites – can also indirectly trigger cancer. One mechanism for this triggering is the disruption of immune defenses, as shown by the sometimes drastically increased tumor incidence with AIDS or with immunosuppressants after transplants. Chronic inflammation is a second mechanism that generates acid radicals and thereby causes random mutations in replicating cells. Examples include stomach cancer caused by Helicobacter pylori and liver cancer caused by Schistosoma, liver fluke, and hepatitis B and C viruses.

According to Dr. de Villiers and Dr. zur Hausen, there are good reasons to believe that other pathogens could cause chronic inflammation and thereby lead to cancer. Epidemiologic data suggest that dairy and meat products from European cows (Bos taurus) are a potential source. This is because colon cancer and breast cancer commonly occur in places where these foods are heavily consumed (that is, in North America, Argentina, Europe, and Australia). In contrast, the rate is low in India, where cows are revered as holy animals. Also noteworthy is that women with a lactose intolerance rarely develop breast cancer.
 

Viral progeny

In fact, the researchers found single-stranded DNA rings that originated in viruses, which they named bovine meat and milk factors (BMMF), in the intestines of patients with colon cancer. They reported, “This new class of pathogen deserves, in our opinion at least, to become the focus of cancer development and further chronic diseases.” They also detected elevated levels of acid radicals in these areas (that is, oxidative stress), which is typical for chronic inflammation.

The researchers assume that infants, whose immune system is not yet fully matured, ingest the BMMF as soon as they have dairy. Therefore, there is no need for adults to avoid dairy or beef because everyone is infected anyway, said Dr. zur Hausen.
 

‘Breast milk is healthy’

Dr. De Villiers and Dr. zur Hausen outlined more evidence of cancer-triggering pathogens. Mothers who have breastfed are less likely, especially after multiple pregnancies, to develop tumors in various organs or to have MS and type 2 diabetes. The authors attribute the protective effect to oligosaccharides in breast milk, which begin to be formed midway through the pregnancy. They bind to lectin receptors and, in so doing, mask the terminal molecule onto which the viruses need to dock. As a result, their port of entry into the cells is blocked.

The oligosaccharides also protect the baby against life-threatening infections by blocking access by rotaviruses and noroviruses. In this way, especially if breastfeeding lasts a long time – around 1 year – the period of incomplete immunocompetence is bridged.
 

Colon cancer

To date, it has been assumed that around 20% of all cancerous diseases globally are caused by infections, said the researchers. But if the suspected BMMF cases are included, this figure rises to 50%, even to around 80%, for colon cancer. If the suspicion is confirmed, the consequences for prevention and therapy would be significant.

The voice of a Nobel prize winner undoubtedly carries weight, but at the time, Dr. zur Hausen still had to convince a host of skeptics with his discovery that a viral infection is a major cause of cervical cancer. Nonetheless, some indicators suggest that he and his wife have found a dead end this time.
 

Institutional skepticism

When his working group made the results public in February 2019, the DKFZ felt the need to give an all-clear signal in response to alarmed press reports. There is no reason to see dairy and meat consumption as something negative. Similarly, in their first joint statement, the BfR and the MRI judged the data to be insufficient and called for further studies. Multiple research teams began to focus on BMMF as a result. In what foods can they be found? Are they more common in patients with cancer than in healthy people? Are they infectious? Do they cause inflammation and cancer?

The findings presented in a second statement by the BfR and MRI at the end of November 2022 contradicted the claims made by the DKFZ scientists across the board. In no way do BMMF represent new pathogens. They are variants of already known DNA sequences. In addition, they are present in numerous animal-based and plant-based foods, including pork, fish, fruit, vegetables, and nuts.

BMMF do not possess the ability to infect human cells, the institutes said. The proof that they are damaging to one’s health was also absent. It is true that the incidence of intestinal tumors correlates positively with the consumption of red and processed meat – which in no way signifies causality – but dairy products are linked to a reduced risk. On the other hand, breast cancer cannot be associated with the consumption of beef or dairy.

Therefore, both institutes recommend continuing to use these products as supplementary diet for infants because of their micronutrients. They further stated that the products are safe for people of all ages.
 

Association with MS?

Unperturbed, Dr. de Villiers and Dr. zur Hausen went one step further in their current article. They posited that MS is also associated with the consumption of dairy products and beef. Here too geographic distribution prompted the idea to look for BMMF in the brain lesions of patients with MS. The researchers isolated ring-shaped DNA molecules that proved to be closely related to BMMF from dairy and cattle blood. “The result was electrifying for us.”

However, there are several other factors to consider, such as vitamin D3 deficiency. This is because the incidence of MS decreases the further you travel from the poles toward the equator (that is, as solar radiation increases). Also, EBV clearly plays a role because patients with MS display increased titers of EBV antibodies. One study also showed that people in Antarctica excreted reactivated EBV in their saliva during winter and that vitamin D3 stopped the viral secretion.

Under these conditions, the researchers hypothesized that MS is caused by a double infection of brain cells by EBV and BMMF. EBV is reactivated by a lack of vitamin D3, and the BMMF multiply and are eventually converted into proteins. A focal immunoreaction causes the Schwann cells and oligodendrocytes to malfunction, which leads to the destruction of the myelin sheaths around the nerve fibers.

This article was translated from the Medscape German Edition. A version appeared on Medscape.com.

Digital rectal examination (DRE) is neither helpful nor useful as a solitary prostate cancer screening tool in middle-aged men, say investigators reporting the PROBASE study.

The study compared risk-adapted screening measures in men who had prostate-specific antigen (PSA) measured at age 45 with those who had PSA measurements plus DRE at age 50.

The results show that as a solitary screening tool, 99% of DREs did not raise suspicion for prostate cancer, and among the 57 cases where DRE did raise suspicion, only three men were found to have cancer, all of which were low-grade, reported Agne Krilaviciute, PhD, from the German Cancer Research Center in Heidelberg, and colleagues.

“We also see that the cancer detection rate by PSA is four times higher compared to the DRE detection. Around 18% of the tumors are located in the part of the prostate where DRE cannot detect them,” she said in an oral presentation at the European Association of Urology Congress.

The investigators found that the majority of prostate cancers that occurred in this relatively young population were International Society of Urological Pathology grade 1 (Gleason score 3 + 3 = 6) or grade 2 (Gleason 3 + 4 = 7). DRE yields positive results in only about 12% of cases of ISUP grade 1 or 2, they noted.

“We conclude that DRE as a solitary screening test does not lead to a significant PCa [prostate cancer] detection rate in young men,” Dr. Krilaviciute said.
 

Falling by the wayside

The study adds to the growing body of evidence that DRE may not be especially helpful as either a screening tool or when used in active surveillance of men with prostate cancer.

An international consensus panel found that DRE could be safely skipped for active surveillance when MRI and other more accurate and objective measures, such as biomarkers, are available.

A prostate cancer expert who was not involved in the PROBASE study told this news organization that when he was in medical school, it would have been considered a serious lapse of practice not to perform a DRE, but that things have changed considerably over the past several years.

“We have PSA now, we have technology with MRI, and the yield of digital rectal examination is very low,” commented Julio Pow-Sang, MD, chief of the genitourinary oncology program at Moffitt Cancer Center in Tampa, Fla.

“Empirically, it’s very rare to find positive cancer through rectal exam in this day and age of PSA,” he said, adding that the examination itself is highly subjective, with varying results depending on the skills of the particular examiner.

“I think that in time, with good studies like this, digital rectal exam specifically for prostate cancer is going to slowly fade away,” Dr. Pow-Sang said.
 

PROBASE results

PROBASE was a randomized screening study enrolling men at age 45 to test a risk-adapted screening strategy using a baseline PSA value with the additional offer of DRE in a large subcohort of participants.

The study was conducted in Germany, and the authors note that the “German statutory early detection program recommends DRE as a stand-alone screening test starting annually at age 45.”

The PROBASE investigators enrolled 46,495 men from February 2014 through December 2019.

Among the first 23,194 men enrolled, 6,537 underwent DRE at enrollment without a study PSA test.

In this group, 6,480 DREs (99%) were not suspicious for cancer, and 57 (1%) were. Of those with suspected prostate cancer, 37 underwent biopsy and 20 did not. Of those biopsied, only two were found to have prostate cancer. This translated into a cancer detection rate of 0.03% for DRE.

After a median of 6.6 years of follow-up, only one additional case of ISUP grade 2 prostate cancer was detected among the 6,357 men who had DREs at enrollment, translating into a prostate cancer detection rate of .05%.

The investigators also looked at men who suspicious DRE findings at baseline. They assumed that a DRE-detectable tumor at age 45 would still be manifest 5 years later and should be detectable with PSA at age 50. Of the 57 men with initially suspicious findings, 11 returned for PSA screening but refused biopsy, and of this group only one had an elevated PSA level. He then underwent biopsy, but the findings were negative.

Of those who underwent biopsy on the basis of DRE, 16 had prostatitis, 14 had benign prostatic hyperplasia, 1 had high-grade prostatic intraepithelial neoplasia, 1 had atypical small acinar proliferation, and 3 had equivocal findings.

In total, the investigators found 24 tumors among men screened with DRE. Of these, 3 occurred in men with results deemed suspicious and 21 were in men with unsuspicious digital exams. All of the tumors were ISUP grade 1, 2, or 3 tumors.

Among 245 men who had biopsies for a PSA level equal to or higher than 3 ng/mL, primarily Prostate Imaging Reporting and Data System (PI-RADS) 3-5 tumors, DRE findings at the time of biopsy were unsuspicious in about 82% of cases, Dr. Krilaviciute said.

“We also used MRI data to determine what proportion of tumors would be potentially detectable by DRE. We estimated that around 18% of tumors are located in the upper part of the prostate, which is not detectable by DRE,” she said. “Even excluding those tumors, still the DRE detection rate is low in palpable tumors.”

Although DRE performed better in higher-grade tumors, 80% of the tumors in the PROBASE participants were ISUP grade 1 or 2 and were likely to be undetected by DRE, she added.

“In Germany, the recommendations for the screening still include 45-year-olds to go with annual DRE. The PROBASE trial allowed us to evaluate for the first time what was the diagnostic performance for DRE at such a young age, and we see that 99% of men undergoing DRE have no suspicious findings, and among the 1% of suspicious findings having cancers extremely unlikely,” she said.

The study was supported by Deutsche Krebshilfe (German Cancer Aid). Dr. Krilaviciute and Dr. Pow-Sang reported having no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

Digital rectal examination (DRE) is neither helpful nor useful as a solitary prostate cancer screening tool in middle-aged men, say investigators reporting the PROBASE study.

The study compared risk-adapted screening measures in men who had prostate-specific antigen (PSA) measured at age 45 with those who had PSA measurements plus DRE at age 50.

The results show that as a solitary screening tool, 99% of DREs did not raise suspicion for prostate cancer, and among the 57 cases where DRE did raise suspicion, only three men were found to have cancer, all of which were low-grade, reported Agne Krilaviciute, PhD, from the German Cancer Research Center in Heidelberg, and colleagues.

“We also see that the cancer detection rate by PSA is four times higher compared to the DRE detection. Around 18% of the tumors are located in the part of the prostate where DRE cannot detect them,” she said in an oral presentation at the European Association of Urology Congress.

The investigators found that the majority of prostate cancers that occurred in this relatively young population were International Society of Urological Pathology grade 1 (Gleason score 3 + 3 = 6) or grade 2 (Gleason 3 + 4 = 7). DRE yields positive results in only about 12% of cases of ISUP grade 1 or 2, they noted.

“We conclude that DRE as a solitary screening test does not lead to a significant PCa [prostate cancer] detection rate in young men,” Dr. Krilaviciute said.
 

Falling by the wayside

The study adds to the growing body of evidence that DRE may not be especially helpful as either a screening tool or when used in active surveillance of men with prostate cancer.

An international consensus panel found that DRE could be safely skipped for active surveillance when MRI and other more accurate and objective measures, such as biomarkers, are available.

A prostate cancer expert who was not involved in the PROBASE study told this news organization that when he was in medical school, it would have been considered a serious lapse of practice not to perform a DRE, but that things have changed considerably over the past several years.

“We have PSA now, we have technology with MRI, and the yield of digital rectal examination is very low,” commented Julio Pow-Sang, MD, chief of the genitourinary oncology program at Moffitt Cancer Center in Tampa, Fla.

“Empirically, it’s very rare to find positive cancer through rectal exam in this day and age of PSA,” he said, adding that the examination itself is highly subjective, with varying results depending on the skills of the particular examiner.

“I think that in time, with good studies like this, digital rectal exam specifically for prostate cancer is going to slowly fade away,” Dr. Pow-Sang said.
 

PROBASE results

PROBASE was a randomized screening study enrolling men at age 45 to test a risk-adapted screening strategy using a baseline PSA value with the additional offer of DRE in a large subcohort of participants.

The study was conducted in Germany, and the authors note that the “German statutory early detection program recommends DRE as a stand-alone screening test starting annually at age 45.”

The PROBASE investigators enrolled 46,495 men from February 2014 through December 2019.

Among the first 23,194 men enrolled, 6,537 underwent DRE at enrollment without a study PSA test.

In this group, 6,480 DREs (99%) were not suspicious for cancer, and 57 (1%) were. Of those with suspected prostate cancer, 37 underwent biopsy and 20 did not. Of those biopsied, only two were found to have prostate cancer. This translated into a cancer detection rate of 0.03% for DRE.

After a median of 6.6 years of follow-up, only one additional case of ISUP grade 2 prostate cancer was detected among the 6,357 men who had DREs at enrollment, translating into a prostate cancer detection rate of .05%.

The investigators also looked at men who suspicious DRE findings at baseline. They assumed that a DRE-detectable tumor at age 45 would still be manifest 5 years later and should be detectable with PSA at age 50. Of the 57 men with initially suspicious findings, 11 returned for PSA screening but refused biopsy, and of this group only one had an elevated PSA level. He then underwent biopsy, but the findings were negative.

Of those who underwent biopsy on the basis of DRE, 16 had prostatitis, 14 had benign prostatic hyperplasia, 1 had high-grade prostatic intraepithelial neoplasia, 1 had atypical small acinar proliferation, and 3 had equivocal findings.

In total, the investigators found 24 tumors among men screened with DRE. Of these, 3 occurred in men with results deemed suspicious and 21 were in men with unsuspicious digital exams. All of the tumors were ISUP grade 1, 2, or 3 tumors.

Among 245 men who had biopsies for a PSA level equal to or higher than 3 ng/mL, primarily Prostate Imaging Reporting and Data System (PI-RADS) 3-5 tumors, DRE findings at the time of biopsy were unsuspicious in about 82% of cases, Dr. Krilaviciute said.

“We also used MRI data to determine what proportion of tumors would be potentially detectable by DRE. We estimated that around 18% of tumors are located in the upper part of the prostate, which is not detectable by DRE,” she said. “Even excluding those tumors, still the DRE detection rate is low in palpable tumors.”

Although DRE performed better in higher-grade tumors, 80% of the tumors in the PROBASE participants were ISUP grade 1 or 2 and were likely to be undetected by DRE, she added.

“In Germany, the recommendations for the screening still include 45-year-olds to go with annual DRE. The PROBASE trial allowed us to evaluate for the first time what was the diagnostic performance for DRE at such a young age, and we see that 99% of men undergoing DRE have no suspicious findings, and among the 1% of suspicious findings having cancers extremely unlikely,” she said.

The study was supported by Deutsche Krebshilfe (German Cancer Aid). Dr. Krilaviciute and Dr. Pow-Sang reported having no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

Digital rectal examination (DRE) is neither helpful nor useful as a solitary prostate cancer screening tool in middle-aged men, say investigators reporting the PROBASE study.

The study compared risk-adapted screening measures in men who had prostate-specific antigen (PSA) measured at age 45 with those who had PSA measurements plus DRE at age 50.

The results show that as a solitary screening tool, 99% of DREs did not raise suspicion for prostate cancer, and among the 57 cases where DRE did raise suspicion, only three men were found to have cancer, all of which were low-grade, reported Agne Krilaviciute, PhD, from the German Cancer Research Center in Heidelberg, and colleagues.

“We also see that the cancer detection rate by PSA is four times higher compared to the DRE detection. Around 18% of the tumors are located in the part of the prostate where DRE cannot detect them,” she said in an oral presentation at the European Association of Urology Congress.

The investigators found that the majority of prostate cancers that occurred in this relatively young population were International Society of Urological Pathology grade 1 (Gleason score 3 + 3 = 6) or grade 2 (Gleason 3 + 4 = 7). DRE yields positive results in only about 12% of cases of ISUP grade 1 or 2, they noted.

“We conclude that DRE as a solitary screening test does not lead to a significant PCa [prostate cancer] detection rate in young men,” Dr. Krilaviciute said.
 

Falling by the wayside

The study adds to the growing body of evidence that DRE may not be especially helpful as either a screening tool or when used in active surveillance of men with prostate cancer.

An international consensus panel found that DRE could be safely skipped for active surveillance when MRI and other more accurate and objective measures, such as biomarkers, are available.

A prostate cancer expert who was not involved in the PROBASE study told this news organization that when he was in medical school, it would have been considered a serious lapse of practice not to perform a DRE, but that things have changed considerably over the past several years.

“We have PSA now, we have technology with MRI, and the yield of digital rectal examination is very low,” commented Julio Pow-Sang, MD, chief of the genitourinary oncology program at Moffitt Cancer Center in Tampa, Fla.

“Empirically, it’s very rare to find positive cancer through rectal exam in this day and age of PSA,” he said, adding that the examination itself is highly subjective, with varying results depending on the skills of the particular examiner.

“I think that in time, with good studies like this, digital rectal exam specifically for prostate cancer is going to slowly fade away,” Dr. Pow-Sang said.
 

PROBASE results

PROBASE was a randomized screening study enrolling men at age 45 to test a risk-adapted screening strategy using a baseline PSA value with the additional offer of DRE in a large subcohort of participants.

The study was conducted in Germany, and the authors note that the “German statutory early detection program recommends DRE as a stand-alone screening test starting annually at age 45.”

The PROBASE investigators enrolled 46,495 men from February 2014 through December 2019.

Among the first 23,194 men enrolled, 6,537 underwent DRE at enrollment without a study PSA test.

In this group, 6,480 DREs (99%) were not suspicious for cancer, and 57 (1%) were. Of those with suspected prostate cancer, 37 underwent biopsy and 20 did not. Of those biopsied, only two were found to have prostate cancer. This translated into a cancer detection rate of 0.03% for DRE.

After a median of 6.6 years of follow-up, only one additional case of ISUP grade 2 prostate cancer was detected among the 6,357 men who had DREs at enrollment, translating into a prostate cancer detection rate of .05%.

The investigators also looked at men who suspicious DRE findings at baseline. They assumed that a DRE-detectable tumor at age 45 would still be manifest 5 years later and should be detectable with PSA at age 50. Of the 57 men with initially suspicious findings, 11 returned for PSA screening but refused biopsy, and of this group only one had an elevated PSA level. He then underwent biopsy, but the findings were negative.

Of those who underwent biopsy on the basis of DRE, 16 had prostatitis, 14 had benign prostatic hyperplasia, 1 had high-grade prostatic intraepithelial neoplasia, 1 had atypical small acinar proliferation, and 3 had equivocal findings.

In total, the investigators found 24 tumors among men screened with DRE. Of these, 3 occurred in men with results deemed suspicious and 21 were in men with unsuspicious digital exams. All of the tumors were ISUP grade 1, 2, or 3 tumors.

Among 245 men who had biopsies for a PSA level equal to or higher than 3 ng/mL, primarily Prostate Imaging Reporting and Data System (PI-RADS) 3-5 tumors, DRE findings at the time of biopsy were unsuspicious in about 82% of cases, Dr. Krilaviciute said.

“We also used MRI data to determine what proportion of tumors would be potentially detectable by DRE. We estimated that around 18% of tumors are located in the upper part of the prostate, which is not detectable by DRE,” she said. “Even excluding those tumors, still the DRE detection rate is low in palpable tumors.”

Although DRE performed better in higher-grade tumors, 80% of the tumors in the PROBASE participants were ISUP grade 1 or 2 and were likely to be undetected by DRE, she added.

“In Germany, the recommendations for the screening still include 45-year-olds to go with annual DRE. The PROBASE trial allowed us to evaluate for the first time what was the diagnostic performance for DRE at such a young age, and we see that 99% of men undergoing DRE have no suspicious findings, and among the 1% of suspicious findings having cancers extremely unlikely,” she said.

The study was supported by Deutsche Krebshilfe (German Cancer Aid). Dr. Krilaviciute and Dr. Pow-Sang reported having no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.