AVAHO

A radical change in screening for colorectal cancer (CRC) is being proposed in the United States, where the default screening modality to date has been colonoscopy.

Instead, the American Gastroenterological Association is proposing new approaches that combine better risk assessment, more use of noninvasive testing (such as fecal occult blood tests), and more targeted referrals for colonoscopy. Such changes could increase patient compliance and “save countless lives.”

“We need to improve our strategies to curb the cancer that ranks second for deaths in the U.S.,” commented Srinadh Komanduri, MD, chair of the AGA Center for GI Innovation and Technology, in a statement.

“Approximately 67% of eligible Americans are screened for colorectal cancer,” he said, which means that a third (33%) are not.

During the COVID-19 pandemic, the proportion of individuals not being screened has increased. One report of medical claims data showed that colonoscopies dropped by 90% during April.

The proposed changes are outlined in an AGA white paper: “Roadmap for the Future of Colorectal Cancer Screening in the United States.”

The report, written following consultation with 60 gastroenterology and research experts, was published online in Clinical Gastroenterology and Hepatology.

It proposed that alternative testing modalities to colonoscopy will need to be integrated into organized screening programs.

Rather than offering colonoscopy as the default screening method for all patients at risk, the AGA advised that it be offered initially only to patients at high risk, which would increase access for those who need it most. For patients at lower risk, noninvasive screening methods, such as fecal occult blood testing, could be offered initially and then integrated with colonoscopy.

“If we offered tests that were convenient, accurate, and of lower cost, and we could help people choose the best option based on their individual cancer risks, we would save more lives,” Joshua E. Melson, MD, MPH, lead author of the AGA white paper and professor at Rush University Medical Center, Chicago, said in an interview.

Screening can reduce CRC mortality by more than 50%, he added.

“Screening should be thought of as a process over time, not a single test isolated in time,” Dr. Melson commented. A clinical practice that has historically used only colonoscopy will need an organized, structured program to incorporate noninvasive testing, he said.

To date, efforts to increase CRC screening uptake have met with limited success, the AGA says. In 2014, the National Colorectal Cancer Round Table set the bar high with a 2018 screening goal of 80% for adults 50 years of age and older. As of 2020, some states had almost reached this goal, but most had not.

“In the opportunistic screening environment in the U.S., where colonoscopy is the most prevalent method, CRC screening has not reached aspirational goals in terms of uptake, reduction in CRC incidence, and disease burden,” the AGA said. “It is questionable if 80% uptake is achievable in a primarily opportunistic screening environment.”

In the proposed revamping of the current CRC screening infrastructure, patients whose physicians recommend CRC screening would no longer be left to their own devices to follow up. Clinicians would initiate CRC screening and oversee follow-up testing at defined intervals and would employ ongoing surveillance.

Ensuring that appropriate screening is readily available to at-risk individuals with no social, racial, or economic disparities is crucial, the AGA says. Racial disparities in access to screening disproportionately burden Blacks and Latin Americans as well as people living in rural areas. Screening differences account for 42% of the disparity in CRC incidence between Black and White Americans and 19% of the disparity in CRC mortality.

Compared with colonoscopy, which requires bowel preparation, time off from work, and a hospital or clinic procedure, the fecal immunochemical test (FIT), for which a patient provides stool samples that are examined for the presence of blood, is much less stressful: it is noninvasive, and the patients collect the samples themselves in their own home. Studies show that, in diverse environments, patients prefer FIT over colonoscopy.

In a controlled trial that involved more than 55,000 patients who were randomly assigned to undergo either FIT or colonoscopy, the participation rate in the first cycle was greater for FIT than for colonoscopy (34.2% vs. 24.6%). This partially offset the lower single-application sensitivity for CRC of FIT, the researchers said.

Results from a study with a cluster randomized design showed that offering up-front stool testing as an option in addition to colonoscopy increased screening uptake. Of patients offered fecal occult blood testing or colonoscopy, 69% completed the noninvasive screening, compared with 38% of those offered colonoscopy alone. Notably, non-White participants were more adherent to stool testing.

The success of the AGA’s new initiative hinges largely upon the development of affordable, highly accurate, easy-to-use, noninvasive tests. In this regard, the organization has challenged scientists and industry partners with an aspirational target that is “far superior to current methodologies in terms of sensitivity and specificity,” said Dr. Melson, who is associate professor at Rush Medical College, Chicago, and a member of the AGA Center for GI Innovation and Technology.

The AGA wants new CRC screening tests that are capable of detecting advanced adenomas and advanced serrated lesions with a one-time sensitivity and specificity of 90% or higher, which is comparable with colonoscopy.

The FIT test has a sensitivity of less than 50% for detecting an advanced polyp of 10 mm or larger, said Dr. Melson.

The multitarget stool DNA (MT-sDNA) test may offer some improvement.

In a 2014 pivotal trial that compared FIT with the MT-sDNA in patients at average risk, the MT-sDNA test had higher sensitivity for detecting nonadvanced CRC lesions than FIT (92% vs. 74%) but less specificity (87% vs. 95%). The rate of detection of polyps with high-grade dysplasia was 69.2% with DNA testing and 46.2% with FIT.

However, the MT-sDNA test costs more than $500, compared with $25 for the FIT test, Dr. Melson pointed out.

To help identify the most appropriate screening for individual patients, better understanding and more thorough identification of risk factors are needed. “Risk assessment is definitely not where it could be,” Dr. Melson said.

The accuracy of risk assessment can be improved by sharing information from electronic health records on past colonoscopy polyp data, the presence of molecular markers, and family history, the AGA said. “With clearer risk assessment, shared decision-making on the most appropriate test becomes more clear and screening rates would benefit from patient buy-in and from easier access.”

The AGA recommended that research focus on the cost-effectiveness of screening younger patients, because the proportion of CRC cases in adults aged younger than 50 years has doubled since 1990.

This has raised the question as to whether the age for initial CRC screening should be lowered to 45 years (it already has been by the American Cancer Society), but there is much debate over this move.

Dr. Melson has received consulting fees from Clinical Genomics and research support from Boston Scientific Corporation and holds stocks in Virgo Imaging. A number of AGA white paper coauthors have disclosed relevant financial relationships.

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

A radical change in screening for colorectal cancer (CRC) is being proposed in the United States, where the default screening modality to date has been colonoscopy.

Instead, the American Gastroenterological Association is proposing new approaches that combine better risk assessment, more use of noninvasive testing (such as fecal occult blood tests), and more targeted referrals for colonoscopy. Such changes could increase patient compliance and “save countless lives.”

“We need to improve our strategies to curb the cancer that ranks second for deaths in the U.S.,” commented Srinadh Komanduri, MD, chair of the AGA Center for GI Innovation and Technology, in a statement.

“Approximately 67% of eligible Americans are screened for colorectal cancer,” he said, which means that a third (33%) are not.

During the COVID-19 pandemic, the proportion of individuals not being screened has increased. One report of medical claims data showed that colonoscopies dropped by 90% during April.

The proposed changes are outlined in an AGA white paper: “Roadmap for the Future of Colorectal Cancer Screening in the United States.”

The report, written following consultation with 60 gastroenterology and research experts, was published online in Clinical Gastroenterology and Hepatology.

It proposed that alternative testing modalities to colonoscopy will need to be integrated into organized screening programs.

Rather than offering colonoscopy as the default screening method for all patients at risk, the AGA advised that it be offered initially only to patients at high risk, which would increase access for those who need it most. For patients at lower risk, noninvasive screening methods, such as fecal occult blood testing, could be offered initially and then integrated with colonoscopy.

“If we offered tests that were convenient, accurate, and of lower cost, and we could help people choose the best option based on their individual cancer risks, we would save more lives,” Joshua E. Melson, MD, MPH, lead author of the AGA white paper and professor at Rush University Medical Center, Chicago, said in an interview.

Screening can reduce CRC mortality by more than 50%, he added.

“Screening should be thought of as a process over time, not a single test isolated in time,” Dr. Melson commented. A clinical practice that has historically used only colonoscopy will need an organized, structured program to incorporate noninvasive testing, he said.

To date, efforts to increase CRC screening uptake have met with limited success, the AGA says. In 2014, the National Colorectal Cancer Round Table set the bar high with a 2018 screening goal of 80% for adults 50 years of age and older. As of 2020, some states had almost reached this goal, but most had not.

“In the opportunistic screening environment in the U.S., where colonoscopy is the most prevalent method, CRC screening has not reached aspirational goals in terms of uptake, reduction in CRC incidence, and disease burden,” the AGA said. “It is questionable if 80% uptake is achievable in a primarily opportunistic screening environment.”

In the proposed revamping of the current CRC screening infrastructure, patients whose physicians recommend CRC screening would no longer be left to their own devices to follow up. Clinicians would initiate CRC screening and oversee follow-up testing at defined intervals and would employ ongoing surveillance.

Ensuring that appropriate screening is readily available to at-risk individuals with no social, racial, or economic disparities is crucial, the AGA says. Racial disparities in access to screening disproportionately burden Blacks and Latin Americans as well as people living in rural areas. Screening differences account for 42% of the disparity in CRC incidence between Black and White Americans and 19% of the disparity in CRC mortality.

Compared with colonoscopy, which requires bowel preparation, time off from work, and a hospital or clinic procedure, the fecal immunochemical test (FIT), for which a patient provides stool samples that are examined for the presence of blood, is much less stressful: it is noninvasive, and the patients collect the samples themselves in their own home. Studies show that, in diverse environments, patients prefer FIT over colonoscopy.

In a controlled trial that involved more than 55,000 patients who were randomly assigned to undergo either FIT or colonoscopy, the participation rate in the first cycle was greater for FIT than for colonoscopy (34.2% vs. 24.6%). This partially offset the lower single-application sensitivity for CRC of FIT, the researchers said.

Results from a study with a cluster randomized design showed that offering up-front stool testing as an option in addition to colonoscopy increased screening uptake. Of patients offered fecal occult blood testing or colonoscopy, 69% completed the noninvasive screening, compared with 38% of those offered colonoscopy alone. Notably, non-White participants were more adherent to stool testing.

The success of the AGA’s new initiative hinges largely upon the development of affordable, highly accurate, easy-to-use, noninvasive tests. In this regard, the organization has challenged scientists and industry partners with an aspirational target that is “far superior to current methodologies in terms of sensitivity and specificity,” said Dr. Melson, who is associate professor at Rush Medical College, Chicago, and a member of the AGA Center for GI Innovation and Technology.

The AGA wants new CRC screening tests that are capable of detecting advanced adenomas and advanced serrated lesions with a one-time sensitivity and specificity of 90% or higher, which is comparable with colonoscopy.

The FIT test has a sensitivity of less than 50% for detecting an advanced polyp of 10 mm or larger, said Dr. Melson.

The multitarget stool DNA (MT-sDNA) test may offer some improvement.

In a 2014 pivotal trial that compared FIT with the MT-sDNA in patients at average risk, the MT-sDNA test had higher sensitivity for detecting nonadvanced CRC lesions than FIT (92% vs. 74%) but less specificity (87% vs. 95%). The rate of detection of polyps with high-grade dysplasia was 69.2% with DNA testing and 46.2% with FIT.

However, the MT-sDNA test costs more than $500, compared with $25 for the FIT test, Dr. Melson pointed out.

To help identify the most appropriate screening for individual patients, better understanding and more thorough identification of risk factors are needed. “Risk assessment is definitely not where it could be,” Dr. Melson said.

The accuracy of risk assessment can be improved by sharing information from electronic health records on past colonoscopy polyp data, the presence of molecular markers, and family history, the AGA said. “With clearer risk assessment, shared decision-making on the most appropriate test becomes more clear and screening rates would benefit from patient buy-in and from easier access.”

The AGA recommended that research focus on the cost-effectiveness of screening younger patients, because the proportion of CRC cases in adults aged younger than 50 years has doubled since 1990.

This has raised the question as to whether the age for initial CRC screening should be lowered to 45 years (it already has been by the American Cancer Society), but there is much debate over this move.

Dr. Melson has received consulting fees from Clinical Genomics and research support from Boston Scientific Corporation and holds stocks in Virgo Imaging. A number of AGA white paper coauthors have disclosed relevant financial relationships.

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

A radical change in screening for colorectal cancer (CRC) is being proposed in the United States, where the default screening modality to date has been colonoscopy.

Instead, the American Gastroenterological Association is proposing new approaches that combine better risk assessment, more use of noninvasive testing (such as fecal occult blood tests), and more targeted referrals for colonoscopy. Such changes could increase patient compliance and “save countless lives.”

“We need to improve our strategies to curb the cancer that ranks second for deaths in the U.S.,” commented Srinadh Komanduri, MD, chair of the AGA Center for GI Innovation and Technology, in a statement.

“Approximately 67% of eligible Americans are screened for colorectal cancer,” he said, which means that a third (33%) are not.

During the COVID-19 pandemic, the proportion of individuals not being screened has increased. One report of medical claims data showed that colonoscopies dropped by 90% during April.

The proposed changes are outlined in an AGA white paper: “Roadmap for the Future of Colorectal Cancer Screening in the United States.”

The report, written following consultation with 60 gastroenterology and research experts, was published online in Clinical Gastroenterology and Hepatology.

It proposed that alternative testing modalities to colonoscopy will need to be integrated into organized screening programs.

Rather than offering colonoscopy as the default screening method for all patients at risk, the AGA advised that it be offered initially only to patients at high risk, which would increase access for those who need it most. For patients at lower risk, noninvasive screening methods, such as fecal occult blood testing, could be offered initially and then integrated with colonoscopy.

“If we offered tests that were convenient, accurate, and of lower cost, and we could help people choose the best option based on their individual cancer risks, we would save more lives,” Joshua E. Melson, MD, MPH, lead author of the AGA white paper and professor at Rush University Medical Center, Chicago, said in an interview.

Screening can reduce CRC mortality by more than 50%, he added.

“Screening should be thought of as a process over time, not a single test isolated in time,” Dr. Melson commented. A clinical practice that has historically used only colonoscopy will need an organized, structured program to incorporate noninvasive testing, he said.

To date, efforts to increase CRC screening uptake have met with limited success, the AGA says. In 2014, the National Colorectal Cancer Round Table set the bar high with a 2018 screening goal of 80% for adults 50 years of age and older. As of 2020, some states had almost reached this goal, but most had not.

“In the opportunistic screening environment in the U.S., where colonoscopy is the most prevalent method, CRC screening has not reached aspirational goals in terms of uptake, reduction in CRC incidence, and disease burden,” the AGA said. “It is questionable if 80% uptake is achievable in a primarily opportunistic screening environment.”

In the proposed revamping of the current CRC screening infrastructure, patients whose physicians recommend CRC screening would no longer be left to their own devices to follow up. Clinicians would initiate CRC screening and oversee follow-up testing at defined intervals and would employ ongoing surveillance.

Ensuring that appropriate screening is readily available to at-risk individuals with no social, racial, or economic disparities is crucial, the AGA says. Racial disparities in access to screening disproportionately burden Blacks and Latin Americans as well as people living in rural areas. Screening differences account for 42% of the disparity in CRC incidence between Black and White Americans and 19% of the disparity in CRC mortality.

Compared with colonoscopy, which requires bowel preparation, time off from work, and a hospital or clinic procedure, the fecal immunochemical test (FIT), for which a patient provides stool samples that are examined for the presence of blood, is much less stressful: it is noninvasive, and the patients collect the samples themselves in their own home. Studies show that, in diverse environments, patients prefer FIT over colonoscopy.

In a controlled trial that involved more than 55,000 patients who were randomly assigned to undergo either FIT or colonoscopy, the participation rate in the first cycle was greater for FIT than for colonoscopy (34.2% vs. 24.6%). This partially offset the lower single-application sensitivity for CRC of FIT, the researchers said.

Results from a study with a cluster randomized design showed that offering up-front stool testing as an option in addition to colonoscopy increased screening uptake. Of patients offered fecal occult blood testing or colonoscopy, 69% completed the noninvasive screening, compared with 38% of those offered colonoscopy alone. Notably, non-White participants were more adherent to stool testing.

The success of the AGA’s new initiative hinges largely upon the development of affordable, highly accurate, easy-to-use, noninvasive tests. In this regard, the organization has challenged scientists and industry partners with an aspirational target that is “far superior to current methodologies in terms of sensitivity and specificity,” said Dr. Melson, who is associate professor at Rush Medical College, Chicago, and a member of the AGA Center for GI Innovation and Technology.

The AGA wants new CRC screening tests that are capable of detecting advanced adenomas and advanced serrated lesions with a one-time sensitivity and specificity of 90% or higher, which is comparable with colonoscopy.

The FIT test has a sensitivity of less than 50% for detecting an advanced polyp of 10 mm or larger, said Dr. Melson.

The multitarget stool DNA (MT-sDNA) test may offer some improvement.

In a 2014 pivotal trial that compared FIT with the MT-sDNA in patients at average risk, the MT-sDNA test had higher sensitivity for detecting nonadvanced CRC lesions than FIT (92% vs. 74%) but less specificity (87% vs. 95%). The rate of detection of polyps with high-grade dysplasia was 69.2% with DNA testing and 46.2% with FIT.

However, the MT-sDNA test costs more than $500, compared with $25 for the FIT test, Dr. Melson pointed out.

To help identify the most appropriate screening for individual patients, better understanding and more thorough identification of risk factors are needed. “Risk assessment is definitely not where it could be,” Dr. Melson said.

The accuracy of risk assessment can be improved by sharing information from electronic health records on past colonoscopy polyp data, the presence of molecular markers, and family history, the AGA said. “With clearer risk assessment, shared decision-making on the most appropriate test becomes more clear and screening rates would benefit from patient buy-in and from easier access.”

The AGA recommended that research focus on the cost-effectiveness of screening younger patients, because the proportion of CRC cases in adults aged younger than 50 years has doubled since 1990.

This has raised the question as to whether the age for initial CRC screening should be lowered to 45 years (it already has been by the American Cancer Society), but there is much debate over this move.

Dr. Melson has received consulting fees from Clinical Genomics and research support from Boston Scientific Corporation and holds stocks in Virgo Imaging. A number of AGA white paper coauthors have disclosed relevant financial relationships.

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

Immune checkpoint inhibition was not associated with an increased mortality risk from COVID-19 in patients with cancer in an international observational study.

The study included 113 cancer patients who had laboratory-confirmed COVID-19 within 12 months of receiving immune checkpoint inhibitor therapy. The patients did not receive chemotherapy within 3 months of testing positive for COVID-19.

In all, 33 patients were admitted to the hospital, including 6 who were admitted to the ICU, and 9 patients died.

“Nine out of 113 patients is a mortality rate of 8%, which is in the middle of the earlier reported rates for cancer patients in general [7.6%-12%],” said Aljosja Rogiers, MD, PhD, of the Melanoma Institute Australia in Sydney.

COVID-19 was the primary cause of death in seven of the patients, including three of those who were admitted to the ICU, Dr. Rogiers noted.

He reported these results during the AACR virtual meeting: COVID-19 and Cancer.
 

Study details

Patients in this study were treated at 19 hospitals in North America, Europe, and Australia, and the data cutoff was May 15, 2020. Most patients (64%) were treated in Europe, which was the epicenter for the COVID-19 pandemic at the time of data collection, Dr. Rogiers noted. A third of patients were in North America, and 3% were in Australia.

The patients’ median age was 63 years (range, 27-86 years). Most patients were men (65%), and most had Eastern Cooperative Oncology Group performance scores of 0-1 (90%).

The most common malignancies were melanoma (57%), non–small cell lung cancer (17%), and renal cell carcinoma (9%). Treatment was for early cancer in 26% of patients and for advanced cancer in 74%. Comorbidities included cardiovascular disease in 27% of patients, diabetes in 15%, pulmonary disease in 12%, and renal disease in 5%.

Immunosuppressive therapy equivalent to a prednisone dose of 10 mg or greater daily was given in 13% of patients, and other immunosuppressive therapies, such as infliximab, were given in 3%.

Among the 60% of patients with COVID-19 symptoms, 68% had fever, 59% had cough, 34% had dyspnea, and 15% had myalgia. Most of the 40% of asymptomatic patients were tested because they had COVID-19–positive contact, Dr. Rogiers noted.

Immune checkpoint inhibitor treatment included monotherapy with a programmed death–1/PD–ligand 1 inhibitor in 82% of patients, combination anti-PD-1 and anti-CTLA4 therapy in 13%, and other therapy – usually a checkpoint inhibitor combined with a different type of targeted agent – in 5%.

At the time of COVID-19 diagnosis, 30% of patients had achieved a partial response, complete response, or had no evidence of disease, 18% had stable disease, and 15% had progression. Response data were not available in 37% of cases, usually because treatment was only recently started prior to COVID-19 diagnosis, Dr. Rogiers said.

Treatments administered for COVID-19 included antibiotic therapy in 25% of patients, oxygen therapy in 20%, glucocorticoids in 10%, antiviral drugs in 6%, and intravenous immunoglobulin or anti–interleukin-6 in 2% each.

Among patients admitted to the ICU, 3% required mechanical ventilation, 2% had vasopressin, and 1% received renal replacement therapy.

At the data cutoff, 20 of 33 hospitalized patients (61%) had been discharged, and 4 (12%) were still in the hospital.
 

Mortality results

Nine patients died. The rate of death was 8% overall and 27% among hospitalized patients.

“The mortality rate of COVID-19 in the general population without comorbidities is about 1.4%,” Dr. Rogiers said. “For cancer patients, this is reported to be in the range of 7.6%-12%. To what extent patients on immune checkpoint inhibition are at a higher risk of mortality is currently unknown.”

Theoretically, immune checkpoint inhibition could either mitigate or exacerbate COVID-19 infection. It has been hypothesized that immune checkpoint inhibitors could increase the risk of severe acute lung injury or other complications of COVID-19, Dr. Rogiers said, explaining the rationale for the study.

The study shows that the patients who died had a median age of 72 years (range, 49-81 years), which is slightly higher than the median overall age of 63 years. Six patients were from North America, and three were from Italy.

“Two melanoma patients and two non–small cell lung cancer patients died,” Dr. Rogiers said. He noted that two other deaths were in patients with renal cell carcinoma, and three deaths were in other cancer types. All patients had advanced or metastatic disease.

Given that 57% of patients in the study had melanoma and 17% had NSCLC, this finding may indicate that COVID-19 has a slightly higher mortality rate in NSCLC patients than in melanoma patients, but the numbers are small, Dr. Rogiers said.

Notably, six of the patients who died were not admitted to the ICU. In four cases, this was because of underlying malignancy; in the other two cases, it was because of a constrained health care system, Dr. Rogiers said.

Overall, the findings show that the mortality rate of patients with COVID-19 and cancer treated with immune checkpoint inhibitors is similar to the mortality rate reported in the general cancer population, Dr. Rogiers said.

“Treatment with immune checkpoint inhibition does not seem to pose an additional mortality risk for cancer patients with COVID-19,” he concluded.

Dr. Rogiers reported having no conflicts of interest. There was no funding disclosed for the study.

[email protected]

SOURCE: Rogiers A et al. AACR: COVID-19 and Cancer, Abstract S02-01.

Immune checkpoint inhibition was not associated with an increased mortality risk from COVID-19 in patients with cancer in an international observational study.

The study included 113 cancer patients who had laboratory-confirmed COVID-19 within 12 months of receiving immune checkpoint inhibitor therapy. The patients did not receive chemotherapy within 3 months of testing positive for COVID-19.

In all, 33 patients were admitted to the hospital, including 6 who were admitted to the ICU, and 9 patients died.

“Nine out of 113 patients is a mortality rate of 8%, which is in the middle of the earlier reported rates for cancer patients in general [7.6%-12%],” said Aljosja Rogiers, MD, PhD, of the Melanoma Institute Australia in Sydney.

COVID-19 was the primary cause of death in seven of the patients, including three of those who were admitted to the ICU, Dr. Rogiers noted.

He reported these results during the AACR virtual meeting: COVID-19 and Cancer.
 

Study details

Patients in this study were treated at 19 hospitals in North America, Europe, and Australia, and the data cutoff was May 15, 2020. Most patients (64%) were treated in Europe, which was the epicenter for the COVID-19 pandemic at the time of data collection, Dr. Rogiers noted. A third of patients were in North America, and 3% were in Australia.

The patients’ median age was 63 years (range, 27-86 years). Most patients were men (65%), and most had Eastern Cooperative Oncology Group performance scores of 0-1 (90%).

The most common malignancies were melanoma (57%), non–small cell lung cancer (17%), and renal cell carcinoma (9%). Treatment was for early cancer in 26% of patients and for advanced cancer in 74%. Comorbidities included cardiovascular disease in 27% of patients, diabetes in 15%, pulmonary disease in 12%, and renal disease in 5%.

Immunosuppressive therapy equivalent to a prednisone dose of 10 mg or greater daily was given in 13% of patients, and other immunosuppressive therapies, such as infliximab, were given in 3%.

Among the 60% of patients with COVID-19 symptoms, 68% had fever, 59% had cough, 34% had dyspnea, and 15% had myalgia. Most of the 40% of asymptomatic patients were tested because they had COVID-19–positive contact, Dr. Rogiers noted.

Immune checkpoint inhibitor treatment included monotherapy with a programmed death–1/PD–ligand 1 inhibitor in 82% of patients, combination anti-PD-1 and anti-CTLA4 therapy in 13%, and other therapy – usually a checkpoint inhibitor combined with a different type of targeted agent – in 5%.

At the time of COVID-19 diagnosis, 30% of patients had achieved a partial response, complete response, or had no evidence of disease, 18% had stable disease, and 15% had progression. Response data were not available in 37% of cases, usually because treatment was only recently started prior to COVID-19 diagnosis, Dr. Rogiers said.

Treatments administered for COVID-19 included antibiotic therapy in 25% of patients, oxygen therapy in 20%, glucocorticoids in 10%, antiviral drugs in 6%, and intravenous immunoglobulin or anti–interleukin-6 in 2% each.

Among patients admitted to the ICU, 3% required mechanical ventilation, 2% had vasopressin, and 1% received renal replacement therapy.

At the data cutoff, 20 of 33 hospitalized patients (61%) had been discharged, and 4 (12%) were still in the hospital.
 

Mortality results

Nine patients died. The rate of death was 8% overall and 27% among hospitalized patients.

“The mortality rate of COVID-19 in the general population without comorbidities is about 1.4%,” Dr. Rogiers said. “For cancer patients, this is reported to be in the range of 7.6%-12%. To what extent patients on immune checkpoint inhibition are at a higher risk of mortality is currently unknown.”

Theoretically, immune checkpoint inhibition could either mitigate or exacerbate COVID-19 infection. It has been hypothesized that immune checkpoint inhibitors could increase the risk of severe acute lung injury or other complications of COVID-19, Dr. Rogiers said, explaining the rationale for the study.

The study shows that the patients who died had a median age of 72 years (range, 49-81 years), which is slightly higher than the median overall age of 63 years. Six patients were from North America, and three were from Italy.

“Two melanoma patients and two non–small cell lung cancer patients died,” Dr. Rogiers said. He noted that two other deaths were in patients with renal cell carcinoma, and three deaths were in other cancer types. All patients had advanced or metastatic disease.

Given that 57% of patients in the study had melanoma and 17% had NSCLC, this finding may indicate that COVID-19 has a slightly higher mortality rate in NSCLC patients than in melanoma patients, but the numbers are small, Dr. Rogiers said.

Notably, six of the patients who died were not admitted to the ICU. In four cases, this was because of underlying malignancy; in the other two cases, it was because of a constrained health care system, Dr. Rogiers said.

Overall, the findings show that the mortality rate of patients with COVID-19 and cancer treated with immune checkpoint inhibitors is similar to the mortality rate reported in the general cancer population, Dr. Rogiers said.

“Treatment with immune checkpoint inhibition does not seem to pose an additional mortality risk for cancer patients with COVID-19,” he concluded.

Dr. Rogiers reported having no conflicts of interest. There was no funding disclosed for the study.

[email protected]

SOURCE: Rogiers A et al. AACR: COVID-19 and Cancer, Abstract S02-01.

Immune checkpoint inhibition was not associated with an increased mortality risk from COVID-19 in patients with cancer in an international observational study.

The study included 113 cancer patients who had laboratory-confirmed COVID-19 within 12 months of receiving immune checkpoint inhibitor therapy. The patients did not receive chemotherapy within 3 months of testing positive for COVID-19.

In all, 33 patients were admitted to the hospital, including 6 who were admitted to the ICU, and 9 patients died.

“Nine out of 113 patients is a mortality rate of 8%, which is in the middle of the earlier reported rates for cancer patients in general [7.6%-12%],” said Aljosja Rogiers, MD, PhD, of the Melanoma Institute Australia in Sydney.

COVID-19 was the primary cause of death in seven of the patients, including three of those who were admitted to the ICU, Dr. Rogiers noted.

He reported these results during the AACR virtual meeting: COVID-19 and Cancer.
 

Study details

Patients in this study were treated at 19 hospitals in North America, Europe, and Australia, and the data cutoff was May 15, 2020. Most patients (64%) were treated in Europe, which was the epicenter for the COVID-19 pandemic at the time of data collection, Dr. Rogiers noted. A third of patients were in North America, and 3% were in Australia.

The patients’ median age was 63 years (range, 27-86 years). Most patients were men (65%), and most had Eastern Cooperative Oncology Group performance scores of 0-1 (90%).

The most common malignancies were melanoma (57%), non–small cell lung cancer (17%), and renal cell carcinoma (9%). Treatment was for early cancer in 26% of patients and for advanced cancer in 74%. Comorbidities included cardiovascular disease in 27% of patients, diabetes in 15%, pulmonary disease in 12%, and renal disease in 5%.

Immunosuppressive therapy equivalent to a prednisone dose of 10 mg or greater daily was given in 13% of patients, and other immunosuppressive therapies, such as infliximab, were given in 3%.

Among the 60% of patients with COVID-19 symptoms, 68% had fever, 59% had cough, 34% had dyspnea, and 15% had myalgia. Most of the 40% of asymptomatic patients were tested because they had COVID-19–positive contact, Dr. Rogiers noted.

Immune checkpoint inhibitor treatment included monotherapy with a programmed death–1/PD–ligand 1 inhibitor in 82% of patients, combination anti-PD-1 and anti-CTLA4 therapy in 13%, and other therapy – usually a checkpoint inhibitor combined with a different type of targeted agent – in 5%.

At the time of COVID-19 diagnosis, 30% of patients had achieved a partial response, complete response, or had no evidence of disease, 18% had stable disease, and 15% had progression. Response data were not available in 37% of cases, usually because treatment was only recently started prior to COVID-19 diagnosis, Dr. Rogiers said.

Treatments administered for COVID-19 included antibiotic therapy in 25% of patients, oxygen therapy in 20%, glucocorticoids in 10%, antiviral drugs in 6%, and intravenous immunoglobulin or anti–interleukin-6 in 2% each.

Among patients admitted to the ICU, 3% required mechanical ventilation, 2% had vasopressin, and 1% received renal replacement therapy.

At the data cutoff, 20 of 33 hospitalized patients (61%) had been discharged, and 4 (12%) were still in the hospital.
 

Mortality results

Nine patients died. The rate of death was 8% overall and 27% among hospitalized patients.

“The mortality rate of COVID-19 in the general population without comorbidities is about 1.4%,” Dr. Rogiers said. “For cancer patients, this is reported to be in the range of 7.6%-12%. To what extent patients on immune checkpoint inhibition are at a higher risk of mortality is currently unknown.”

Theoretically, immune checkpoint inhibition could either mitigate or exacerbate COVID-19 infection. It has been hypothesized that immune checkpoint inhibitors could increase the risk of severe acute lung injury or other complications of COVID-19, Dr. Rogiers said, explaining the rationale for the study.

The study shows that the patients who died had a median age of 72 years (range, 49-81 years), which is slightly higher than the median overall age of 63 years. Six patients were from North America, and three were from Italy.

“Two melanoma patients and two non–small cell lung cancer patients died,” Dr. Rogiers said. He noted that two other deaths were in patients with renal cell carcinoma, and three deaths were in other cancer types. All patients had advanced or metastatic disease.

Given that 57% of patients in the study had melanoma and 17% had NSCLC, this finding may indicate that COVID-19 has a slightly higher mortality rate in NSCLC patients than in melanoma patients, but the numbers are small, Dr. Rogiers said.

Notably, six of the patients who died were not admitted to the ICU. In four cases, this was because of underlying malignancy; in the other two cases, it was because of a constrained health care system, Dr. Rogiers said.

Overall, the findings show that the mortality rate of patients with COVID-19 and cancer treated with immune checkpoint inhibitors is similar to the mortality rate reported in the general cancer population, Dr. Rogiers said.

“Treatment with immune checkpoint inhibition does not seem to pose an additional mortality risk for cancer patients with COVID-19,” he concluded.

Dr. Rogiers reported having no conflicts of interest. There was no funding disclosed for the study.

[email protected]

SOURCE: Rogiers A et al. AACR: COVID-19 and Cancer, Abstract S02-01.

The American Cancer Society (ACS) has released updated guidelines for cervical cancer screening. The key recommendation is that primary human papillomavirus (HPV) testing is the preferred screening method, starting at the age of 25 and repeated every 5 years.

In the past, guidelines for cervical cancer screening recommended cytology (the Pap test) starting at 21 years of age and repeated every 3 years. In more recent years, cotesting (with both Pap and HPV tests) has been recommended.

Since the last ACS guidelines on cervical cancer screening were published in 2012, two HPV tests have been approved by the Food and Drug Administration (FDA) for use in primary HPV screening.

The new “streamlined recommendations can improve compliance and reduce potential harms,” commented Debbie Saslow, PhD, managing director, HPV/GYN Cancers, American Cancer Society.

The updated guidelines were published online July 30 in CA: A Cancer Journal for Clinicians.

“We now have stronger evidence to support starting cervical cancer screening at a later age and to recommend screening with the HPV test as the preferred test,” Saslow told Medscape Medical News. This also reflects the phasing out of cytology and cotesting, she added.

“This update is based on decades of studies comparing the effectiveness of HPV testing to cytology and is bolstered by evidence of the impact of HPV vaccination, including a dramatic decline in cervical precancers and, more recently, cervical cancers among young women,” she said.

The American Society for Colposcopy and Cervical Pathology (ASCCP) said that it was preparing a response to these new guidelines, as is the American College of Obstetricians and Gynecologists (ACOG).
 

Cotesting or cytology alone

The updated guidelines recommend primary HPV testing as the preferred screening method for all women with a cervix. If primary HPV testing is not available, women should be screened with cotesting, which should also be performed every 5 years.

If only cytology is available, then women should be screened every 3 years.

The ACS authors point out that cotesting or cytology testing alone is still an acceptable option for cervical cancer screening, insofar as primary HPV testing using FDA-approved tests may not be available in some settings.

As more laboratories in the United States transition to FDA-approved tests for primary HPV testing, it is expected that the use of cotesting or cytology alone will be phased out.

The new guidelines also emphasize that women may discontinue screening at the age of 65 if they have not had cervical intraepitheal neoplasia of grade 2 or higher within the past 25 years and if they have tested negative over the past 10 years on all past screens.

The authors caution that past screens should only be considered negative if the patient has had two consecutive negative HPV tests or two consecutive negative cotests or three consecutive negative cytology tests within the past 10 years.

“These criteria do not apply to individuals who are currently under surveillance for abnormal screening results,” the authors state.

Women older than 65 for whom adequate documentation of prior screening is not available should continue to be screened until criteria for screening discontinuation are met, they add.

Screening may be discontinued among women with a limited life expectancy.
 

HPV vaccination

The authors note that HPV vaccination is expected to substantially change cervical cancer screening strategies.

In 2018, the National Immunization Survey–Teen, involving adolescents aged 13 to 17 years, showed that 68.1% of female patients were up to date on HPV vaccine recommendations, as were 51.1% of male patients.

“Cytology-based screening is much less efficient in vaccinated populations, as abnormal cytology disproportionately identifies minor abnormalities resulting from HPV types that are associated with lower cancer risk,” the reports’ authors point out.

As the prevalence of high-grade cervical abnormalities and the incidence of cervical cancer continue to decline, “the proportion of false-positive findings [on cytology alone] is expected to increase significantly,” they caution.

As a result, the ACS suggests that physicians will likely have to consider a patient’s vaccination status in tandem with cervical cancer screening results to arrive at an accurate assessment.
 

Raising starting age to 25 years

Saslow also noted that there were several reasons why it is now recommended that screening begin at the age of 25 instead of the age of 21, as in earlier guidelines.

“Firstly, less than 1% of cervical cancers are diagnosed before the age of 25 – so this is about 130 cases per year,” she explained.

Thanks to HPV vaccination, this percentage is further declining, “so screening is just not beneficial at this age,” Saslow emphasized.

Furthermore, the rate of false positives is much higher in younger patients, and a false-positive result can have a negative impact on pregnancy outcomes, she added.

Saslow also dismissed an article in favor of cotesting instead of HPV testing alone. That study, carried out by researchers at Quest Diagnostics and the University of Pittsburgh Medical Center, recommended cotesting, claiming that primary HPV testing is significantly less likely to detect cervical precancers or cervical cancer than cotesting.

“These data come from parties with a vested interest in preserving cytology as a screening test,” Saslow told Medscape Medical News. She noted that “these findings are not at all credible as judged by the scientific community.”

On the basis of their own modeling, ACS researchers estimate that “starting with primary HPV testing at age 25 will prevent 13% more cervical cancers and 7% more cervical cancer deaths” in comparison with cytology (Pap testing alone) beginning at the age of 21, then cotesting at the age of 30, Saslow said in a statement.

“Our model showed we could do that with a 9% increase in follow-up procedures but with 45% fewer tests required overall,” she added.

The new recommendations are not expected to create any change in the type or amount of care required by providers, and patients will not notice any difference, inasmuch as cotesting and primary HPV testing are performed the same way in the examination room, she added.

“Resistance [to the changes] is expected – and is already occurring – from laboratories and manufacturers of tests that will no longer be used once we transition from cotesting and, less commonly, Pap testing to primary HPV testing,” Saslow said.

However, providers need to be aware that HPV infection, as with any sexually transmitted disease, is associated with a certain stigma, and they need to take care in discussing potential HPV infection with their patients.
 

Good method

Medscape Medical News approached Mark Einstein, MD, president of the ASCCP and professor and chair of obstetrics, gynecology, and reproductive health at Rutgers Biomedical and Health Sciences, Newark, New Jersey, to comment on the new guidelines.

“First and foremost,” he said, “everything we want to do when it comes to screening is to maximize the identification of picking up a cancer and minimize the risk or potential harm of not only screening itself but of missing cancers, so any strategy that improves on the sensitivity of picking up a cancer is a good method.”

Nevertheless, inasmuch as the ASCCP is one of the foremost organizations involved in cervical cancer screening and management, its members need more time to take a closer look at the updated ACS guidelines before they, together with sister organizations, such as the ACOG, release an official statement as to whether or not they fully endorse the new guidelines.

The United States Preventive Services Task Force recently endorsed primary HPV testing (starting at age 30), but it also said that an alternative strategy is cotesting for women between 30 and 65 years of age, Einstein observed.

Asked to comment on the article from Quest Diagnostics and the University of Pittsburgh that recommended cotesting instead of primary HPV testing, Einstein said that suggestion should not be dismissed out of hand.

The ASCCP has asked the authors of that study for their data in order conduct an independent assessment of it, largely because the study was retrospective in nature. Because of that, “there may have been a few pieces of information that were missing in true real-time fashion,” he said. “Not having [both the primary HPV testing and the cytology results] in front of me might change the next thing I might recommend to the patient,” Einstein explained.

The bottom line is that, when comparing primary HPV testing alone, cytology alone, and cotesting and rates of cervical cancer at 5 years, “the biggest driver for true performance of positive predictive value is HPV,” Einstein said.

Nevertheless, cotesting does bring more information into the equation compared with primary HPV testing alone, although it also increases the potential for harm, including the harm of overtesting and conducting needless colposcopies, he added.

That said, starting primary HPV testing at the age of 25 rather than the age of 30, as was previously recommended, is very likely to lead to detection of spurious HPV infections because HPV infections are very common among women in their 20s, Einstein pointed out.

“This, too, could potentially lead to more colposcopies, which may cause harm from the procedure itself but also create a certain amount of anxiety and concern, so there is some harm in testing for HPV at an earlier age as well,” Einstein said.

Saslow and Einstein have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The American Cancer Society (ACS) has released updated guidelines for cervical cancer screening. The key recommendation is that primary human papillomavirus (HPV) testing is the preferred screening method, starting at the age of 25 and repeated every 5 years.

In the past, guidelines for cervical cancer screening recommended cytology (the Pap test) starting at 21 years of age and repeated every 3 years. In more recent years, cotesting (with both Pap and HPV tests) has been recommended.

Since the last ACS guidelines on cervical cancer screening were published in 2012, two HPV tests have been approved by the Food and Drug Administration (FDA) for use in primary HPV screening.

The new “streamlined recommendations can improve compliance and reduce potential harms,” commented Debbie Saslow, PhD, managing director, HPV/GYN Cancers, American Cancer Society.

The updated guidelines were published online July 30 in CA: A Cancer Journal for Clinicians.

“We now have stronger evidence to support starting cervical cancer screening at a later age and to recommend screening with the HPV test as the preferred test,” Saslow told Medscape Medical News. This also reflects the phasing out of cytology and cotesting, she added.

“This update is based on decades of studies comparing the effectiveness of HPV testing to cytology and is bolstered by evidence of the impact of HPV vaccination, including a dramatic decline in cervical precancers and, more recently, cervical cancers among young women,” she said.

The American Society for Colposcopy and Cervical Pathology (ASCCP) said that it was preparing a response to these new guidelines, as is the American College of Obstetricians and Gynecologists (ACOG).
 

Cotesting or cytology alone

The updated guidelines recommend primary HPV testing as the preferred screening method for all women with a cervix. If primary HPV testing is not available, women should be screened with cotesting, which should also be performed every 5 years.

If only cytology is available, then women should be screened every 3 years.

The ACS authors point out that cotesting or cytology testing alone is still an acceptable option for cervical cancer screening, insofar as primary HPV testing using FDA-approved tests may not be available in some settings.

As more laboratories in the United States transition to FDA-approved tests for primary HPV testing, it is expected that the use of cotesting or cytology alone will be phased out.

The new guidelines also emphasize that women may discontinue screening at the age of 65 if they have not had cervical intraepitheal neoplasia of grade 2 or higher within the past 25 years and if they have tested negative over the past 10 years on all past screens.

The authors caution that past screens should only be considered negative if the patient has had two consecutive negative HPV tests or two consecutive negative cotests or three consecutive negative cytology tests within the past 10 years.

“These criteria do not apply to individuals who are currently under surveillance for abnormal screening results,” the authors state.

Women older than 65 for whom adequate documentation of prior screening is not available should continue to be screened until criteria for screening discontinuation are met, they add.

Screening may be discontinued among women with a limited life expectancy.
 

HPV vaccination

The authors note that HPV vaccination is expected to substantially change cervical cancer screening strategies.

In 2018, the National Immunization Survey–Teen, involving adolescents aged 13 to 17 years, showed that 68.1% of female patients were up to date on HPV vaccine recommendations, as were 51.1% of male patients.

“Cytology-based screening is much less efficient in vaccinated populations, as abnormal cytology disproportionately identifies minor abnormalities resulting from HPV types that are associated with lower cancer risk,” the reports’ authors point out.

As the prevalence of high-grade cervical abnormalities and the incidence of cervical cancer continue to decline, “the proportion of false-positive findings [on cytology alone] is expected to increase significantly,” they caution.

As a result, the ACS suggests that physicians will likely have to consider a patient’s vaccination status in tandem with cervical cancer screening results to arrive at an accurate assessment.
 

Raising starting age to 25 years

Saslow also noted that there were several reasons why it is now recommended that screening begin at the age of 25 instead of the age of 21, as in earlier guidelines.

“Firstly, less than 1% of cervical cancers are diagnosed before the age of 25 – so this is about 130 cases per year,” she explained.

Thanks to HPV vaccination, this percentage is further declining, “so screening is just not beneficial at this age,” Saslow emphasized.

Furthermore, the rate of false positives is much higher in younger patients, and a false-positive result can have a negative impact on pregnancy outcomes, she added.

Saslow also dismissed an article in favor of cotesting instead of HPV testing alone. That study, carried out by researchers at Quest Diagnostics and the University of Pittsburgh Medical Center, recommended cotesting, claiming that primary HPV testing is significantly less likely to detect cervical precancers or cervical cancer than cotesting.

“These data come from parties with a vested interest in preserving cytology as a screening test,” Saslow told Medscape Medical News. She noted that “these findings are not at all credible as judged by the scientific community.”

On the basis of their own modeling, ACS researchers estimate that “starting with primary HPV testing at age 25 will prevent 13% more cervical cancers and 7% more cervical cancer deaths” in comparison with cytology (Pap testing alone) beginning at the age of 21, then cotesting at the age of 30, Saslow said in a statement.

“Our model showed we could do that with a 9% increase in follow-up procedures but with 45% fewer tests required overall,” she added.

The new recommendations are not expected to create any change in the type or amount of care required by providers, and patients will not notice any difference, inasmuch as cotesting and primary HPV testing are performed the same way in the examination room, she added.

“Resistance [to the changes] is expected – and is already occurring – from laboratories and manufacturers of tests that will no longer be used once we transition from cotesting and, less commonly, Pap testing to primary HPV testing,” Saslow said.

However, providers need to be aware that HPV infection, as with any sexually transmitted disease, is associated with a certain stigma, and they need to take care in discussing potential HPV infection with their patients.
 

Good method

Medscape Medical News approached Mark Einstein, MD, president of the ASCCP and professor and chair of obstetrics, gynecology, and reproductive health at Rutgers Biomedical and Health Sciences, Newark, New Jersey, to comment on the new guidelines.

“First and foremost,” he said, “everything we want to do when it comes to screening is to maximize the identification of picking up a cancer and minimize the risk or potential harm of not only screening itself but of missing cancers, so any strategy that improves on the sensitivity of picking up a cancer is a good method.”

Nevertheless, inasmuch as the ASCCP is one of the foremost organizations involved in cervical cancer screening and management, its members need more time to take a closer look at the updated ACS guidelines before they, together with sister organizations, such as the ACOG, release an official statement as to whether or not they fully endorse the new guidelines.

The United States Preventive Services Task Force recently endorsed primary HPV testing (starting at age 30), but it also said that an alternative strategy is cotesting for women between 30 and 65 years of age, Einstein observed.

Asked to comment on the article from Quest Diagnostics and the University of Pittsburgh that recommended cotesting instead of primary HPV testing, Einstein said that suggestion should not be dismissed out of hand.

The ASCCP has asked the authors of that study for their data in order conduct an independent assessment of it, largely because the study was retrospective in nature. Because of that, “there may have been a few pieces of information that were missing in true real-time fashion,” he said. “Not having [both the primary HPV testing and the cytology results] in front of me might change the next thing I might recommend to the patient,” Einstein explained.

The bottom line is that, when comparing primary HPV testing alone, cytology alone, and cotesting and rates of cervical cancer at 5 years, “the biggest driver for true performance of positive predictive value is HPV,” Einstein said.

Nevertheless, cotesting does bring more information into the equation compared with primary HPV testing alone, although it also increases the potential for harm, including the harm of overtesting and conducting needless colposcopies, he added.

That said, starting primary HPV testing at the age of 25 rather than the age of 30, as was previously recommended, is very likely to lead to detection of spurious HPV infections because HPV infections are very common among women in their 20s, Einstein pointed out.

“This, too, could potentially lead to more colposcopies, which may cause harm from the procedure itself but also create a certain amount of anxiety and concern, so there is some harm in testing for HPV at an earlier age as well,” Einstein said.

Saslow and Einstein have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The American Cancer Society (ACS) has released updated guidelines for cervical cancer screening. The key recommendation is that primary human papillomavirus (HPV) testing is the preferred screening method, starting at the age of 25 and repeated every 5 years.

In the past, guidelines for cervical cancer screening recommended cytology (the Pap test) starting at 21 years of age and repeated every 3 years. In more recent years, cotesting (with both Pap and HPV tests) has been recommended.

Since the last ACS guidelines on cervical cancer screening were published in 2012, two HPV tests have been approved by the Food and Drug Administration (FDA) for use in primary HPV screening.

The new “streamlined recommendations can improve compliance and reduce potential harms,” commented Debbie Saslow, PhD, managing director, HPV/GYN Cancers, American Cancer Society.

The updated guidelines were published online July 30 in CA: A Cancer Journal for Clinicians.

“We now have stronger evidence to support starting cervical cancer screening at a later age and to recommend screening with the HPV test as the preferred test,” Saslow told Medscape Medical News. This also reflects the phasing out of cytology and cotesting, she added.

“This update is based on decades of studies comparing the effectiveness of HPV testing to cytology and is bolstered by evidence of the impact of HPV vaccination, including a dramatic decline in cervical precancers and, more recently, cervical cancers among young women,” she said.

The American Society for Colposcopy and Cervical Pathology (ASCCP) said that it was preparing a response to these new guidelines, as is the American College of Obstetricians and Gynecologists (ACOG).
 

Cotesting or cytology alone

The updated guidelines recommend primary HPV testing as the preferred screening method for all women with a cervix. If primary HPV testing is not available, women should be screened with cotesting, which should also be performed every 5 years.

If only cytology is available, then women should be screened every 3 years.

The ACS authors point out that cotesting or cytology testing alone is still an acceptable option for cervical cancer screening, insofar as primary HPV testing using FDA-approved tests may not be available in some settings.

As more laboratories in the United States transition to FDA-approved tests for primary HPV testing, it is expected that the use of cotesting or cytology alone will be phased out.

The new guidelines also emphasize that women may discontinue screening at the age of 65 if they have not had cervical intraepitheal neoplasia of grade 2 or higher within the past 25 years and if they have tested negative over the past 10 years on all past screens.

The authors caution that past screens should only be considered negative if the patient has had two consecutive negative HPV tests or two consecutive negative cotests or three consecutive negative cytology tests within the past 10 years.

“These criteria do not apply to individuals who are currently under surveillance for abnormal screening results,” the authors state.

Women older than 65 for whom adequate documentation of prior screening is not available should continue to be screened until criteria for screening discontinuation are met, they add.

Screening may be discontinued among women with a limited life expectancy.
 

HPV vaccination

The authors note that HPV vaccination is expected to substantially change cervical cancer screening strategies.

In 2018, the National Immunization Survey–Teen, involving adolescents aged 13 to 17 years, showed that 68.1% of female patients were up to date on HPV vaccine recommendations, as were 51.1% of male patients.

“Cytology-based screening is much less efficient in vaccinated populations, as abnormal cytology disproportionately identifies minor abnormalities resulting from HPV types that are associated with lower cancer risk,” the reports’ authors point out.

As the prevalence of high-grade cervical abnormalities and the incidence of cervical cancer continue to decline, “the proportion of false-positive findings [on cytology alone] is expected to increase significantly,” they caution.

As a result, the ACS suggests that physicians will likely have to consider a patient’s vaccination status in tandem with cervical cancer screening results to arrive at an accurate assessment.
 

Raising starting age to 25 years

Saslow also noted that there were several reasons why it is now recommended that screening begin at the age of 25 instead of the age of 21, as in earlier guidelines.

“Firstly, less than 1% of cervical cancers are diagnosed before the age of 25 – so this is about 130 cases per year,” she explained.

Thanks to HPV vaccination, this percentage is further declining, “so screening is just not beneficial at this age,” Saslow emphasized.

Furthermore, the rate of false positives is much higher in younger patients, and a false-positive result can have a negative impact on pregnancy outcomes, she added.

Saslow also dismissed an article in favor of cotesting instead of HPV testing alone. That study, carried out by researchers at Quest Diagnostics and the University of Pittsburgh Medical Center, recommended cotesting, claiming that primary HPV testing is significantly less likely to detect cervical precancers or cervical cancer than cotesting.

“These data come from parties with a vested interest in preserving cytology as a screening test,” Saslow told Medscape Medical News. She noted that “these findings are not at all credible as judged by the scientific community.”

On the basis of their own modeling, ACS researchers estimate that “starting with primary HPV testing at age 25 will prevent 13% more cervical cancers and 7% more cervical cancer deaths” in comparison with cytology (Pap testing alone) beginning at the age of 21, then cotesting at the age of 30, Saslow said in a statement.

“Our model showed we could do that with a 9% increase in follow-up procedures but with 45% fewer tests required overall,” she added.

The new recommendations are not expected to create any change in the type or amount of care required by providers, and patients will not notice any difference, inasmuch as cotesting and primary HPV testing are performed the same way in the examination room, she added.

“Resistance [to the changes] is expected – and is already occurring – from laboratories and manufacturers of tests that will no longer be used once we transition from cotesting and, less commonly, Pap testing to primary HPV testing,” Saslow said.

However, providers need to be aware that HPV infection, as with any sexually transmitted disease, is associated with a certain stigma, and they need to take care in discussing potential HPV infection with their patients.
 

Good method

Medscape Medical News approached Mark Einstein, MD, president of the ASCCP and professor and chair of obstetrics, gynecology, and reproductive health at Rutgers Biomedical and Health Sciences, Newark, New Jersey, to comment on the new guidelines.

“First and foremost,” he said, “everything we want to do when it comes to screening is to maximize the identification of picking up a cancer and minimize the risk or potential harm of not only screening itself but of missing cancers, so any strategy that improves on the sensitivity of picking up a cancer is a good method.”

Nevertheless, inasmuch as the ASCCP is one of the foremost organizations involved in cervical cancer screening and management, its members need more time to take a closer look at the updated ACS guidelines before they, together with sister organizations, such as the ACOG, release an official statement as to whether or not they fully endorse the new guidelines.

The United States Preventive Services Task Force recently endorsed primary HPV testing (starting at age 30), but it also said that an alternative strategy is cotesting for women between 30 and 65 years of age, Einstein observed.

Asked to comment on the article from Quest Diagnostics and the University of Pittsburgh that recommended cotesting instead of primary HPV testing, Einstein said that suggestion should not be dismissed out of hand.

The ASCCP has asked the authors of that study for their data in order conduct an independent assessment of it, largely because the study was retrospective in nature. Because of that, “there may have been a few pieces of information that were missing in true real-time fashion,” he said. “Not having [both the primary HPV testing and the cytology results] in front of me might change the next thing I might recommend to the patient,” Einstein explained.

The bottom line is that, when comparing primary HPV testing alone, cytology alone, and cotesting and rates of cervical cancer at 5 years, “the biggest driver for true performance of positive predictive value is HPV,” Einstein said.

Nevertheless, cotesting does bring more information into the equation compared with primary HPV testing alone, although it also increases the potential for harm, including the harm of overtesting and conducting needless colposcopies, he added.

That said, starting primary HPV testing at the age of 25 rather than the age of 30, as was previously recommended, is very likely to lead to detection of spurious HPV infections because HPV infections are very common among women in their 20s, Einstein pointed out.

“This, too, could potentially lead to more colposcopies, which may cause harm from the procedure itself but also create a certain amount of anxiety and concern, so there is some harm in testing for HPV at an earlier age as well,” Einstein said.

Saslow and Einstein have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Older adults are being “overscreened” for cancer, say researchers who discovered that many patients reported undergoing screening for cancer even though they were older than the upper age limit recommended.

The U.S. Preventive Services Task Force recommends an upper age limit on cancer screening that varies by cancer type – 75 years old for colorectal cancer, 74 for breast cancer, and 65 for cervical cancer.

The study found that 59.3% of men and 56.2% of women being screening for colorectal cancer were above that cut-off age, as were 45.8% of women being screened for cervical cancer and 74.1% of women being screened for breast cancer.    

Overscreening was particularly high for women living in metropolitan areas.

The finding is of concern, say the researchers, because “continuing to screen patients who are older and/or who have limited life expectancy may cause more harms than benefits.”

“The development of successful interventions to address this problem are thus essential,” they write.

The study was published online July 27 in JAMA Network Open.

Clinicians, patients, and health care systems can be changed – and should be changed – to minimize overscreening,” said lead author Jennifer L. Moss, PhD, assistant professor of family and community medicine and public health sciences at Penn State University, Hershey.

“It will probably take many changes to meaningfully decrease overscreening,” she told Medscape Medical News.

One change that would help is if health insurance companies stopped reimbursing providers for screening after the recommended upper age limit, she continued. “Another change is if providers had evidence-based tools to guide conversations about stopping screening, given an individual patient’s demographics, health status, and risks and benefits of the screening test.”

Approached for comment on the study, Nancy Schoenborn, MD, MHS, an associate professor of medicine in the Division of Geriatric Medicine and Gerontology at Johns Hopkins University, Baltimore, noted that the finding of high overscreening is not surprising and is consistent with prior works that found similar results.

“One value of this paper is that the timing of the study is more recent and confirms that the issue of overscreening is one that is still ongoing,” she told Medscape Medical News. Schoenborn was not associated with the study.

As for what physicians should do about the findings in this study, Schoenborn suggested the first step is to simply recognize that overscreening is likely a problem and “to reflect if there are instances in one’s own practice where overscreening may occur.”

In her own work, Schoenborn continued, “I was recently surprised that a substantial minority of clinicians actually do not believe overscreening to be a problem in older adults, and they have a number of concerns about how overscreening is defined and about unintended consequences that can occur from efforts to reduce overscreening.”

She added that there are a number of reasons why overscreening occurs. These include guideline inconsistencies, inertia, patient request, clinician knowledge gaps, and discomfort with discussing stopping. “A lot of work is ongoing to address each of these issues, but I think the first step would be the clinician recognizing and agreeing that this is a problem that needs to be addressed,” she said.

Unnecessary screening

The authors note that the prevalence estimates for overscreening have not been reported on a national level, and it is also unclear how overscreening may vary among subgroups.

“The reason I focused on colorectal, cervical, and breast cancers is because USPSTF has very clear, age-based recommendations for these cancers in terms of who should and should not get screened routinely,” explained Moss. “This was important because it allowed me and my coauthors to clearly say, based on age alone, this person probably was screened unnecessarily, and this person was not.”

She noted that the age-based recommendations for routine screening are based on very large clinical trials to examine the effectiveness of the screening tool. “The recommendations for lung and prostate cancer screening are not so clear cut, and we would not be able to tell, based only on the available survey data, if someone was overscreened,” she said.

For their study, the team used data from the 2018 Behavioral Risk Factor Surveillance System, administered by the Centers for Disease Control and Prevention.

Overscreening was assessed in a cohort of 20,937 men and 34,244 women for colorectal cancer, 82,811 women for cervical cancer, and 38,356 women for breast cancer. Most the participants lived in a metropolitan area (about 80%) and were white (about 80%).

Being overscreened was also more common in metropolitan vs. nonmetropolitan areas for colorectal cancer in women (adjusted odds ratio, 1.23), cervical cancer (aOR, 1.20), and breast cancer (aOR, 1.36).

Overscreening for cervical and breast cancers was also associated with having a usual source of care, good/very good/excellent self-reported health, education beyond a high school diploma, and being married or living as married.

The study was carried out in 2018, and the situation is likely to have changed over recent months during the COVID-19 pandemic.

“We have already seen dramatic reductions in routine cancer screening among age-eligible adults, so part of this problem of overscreening among older adults will likely diminish,” said Moss. “State and national cancer surveillance systems will continue to monitor trends in cancer screening, including overscreening, cancer incidence, and cancer mortality.”

Johns Hopkins’ Schoenborn said one finding of particular interest was that the colorectal cancer overscreening rate was higher in those older than 80 and in those with higher mortality risk.

“It makes me wonder if this is due to the increasing use of noninvasive colorectal cancer screening modalities, such as the fecal immunochemical test FIT or Cologuard,” Schoenborn commented. “It would be important for clinicians to consider downstream effects even when the initial test is low risk, such as if the stool test screens positive, would the patient still need a colonoscopy, and is that something the patient can undergo and wants to undergo?”

The study was funded by the National Cancer Institute and American Cancer Society. Moss, study coauthors, and Schoenborn have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Older adults are being “overscreened” for cancer, say researchers who discovered that many patients reported undergoing screening for cancer even though they were older than the upper age limit recommended.

The U.S. Preventive Services Task Force recommends an upper age limit on cancer screening that varies by cancer type – 75 years old for colorectal cancer, 74 for breast cancer, and 65 for cervical cancer.

The study found that 59.3% of men and 56.2% of women being screening for colorectal cancer were above that cut-off age, as were 45.8% of women being screened for cervical cancer and 74.1% of women being screened for breast cancer.    

Overscreening was particularly high for women living in metropolitan areas.

The finding is of concern, say the researchers, because “continuing to screen patients who are older and/or who have limited life expectancy may cause more harms than benefits.”

“The development of successful interventions to address this problem are thus essential,” they write.

The study was published online July 27 in JAMA Network Open.

Clinicians, patients, and health care systems can be changed – and should be changed – to minimize overscreening,” said lead author Jennifer L. Moss, PhD, assistant professor of family and community medicine and public health sciences at Penn State University, Hershey.

“It will probably take many changes to meaningfully decrease overscreening,” she told Medscape Medical News.

One change that would help is if health insurance companies stopped reimbursing providers for screening after the recommended upper age limit, she continued. “Another change is if providers had evidence-based tools to guide conversations about stopping screening, given an individual patient’s demographics, health status, and risks and benefits of the screening test.”

Approached for comment on the study, Nancy Schoenborn, MD, MHS, an associate professor of medicine in the Division of Geriatric Medicine and Gerontology at Johns Hopkins University, Baltimore, noted that the finding of high overscreening is not surprising and is consistent with prior works that found similar results.

“One value of this paper is that the timing of the study is more recent and confirms that the issue of overscreening is one that is still ongoing,” she told Medscape Medical News. Schoenborn was not associated with the study.

As for what physicians should do about the findings in this study, Schoenborn suggested the first step is to simply recognize that overscreening is likely a problem and “to reflect if there are instances in one’s own practice where overscreening may occur.”

In her own work, Schoenborn continued, “I was recently surprised that a substantial minority of clinicians actually do not believe overscreening to be a problem in older adults, and they have a number of concerns about how overscreening is defined and about unintended consequences that can occur from efforts to reduce overscreening.”

She added that there are a number of reasons why overscreening occurs. These include guideline inconsistencies, inertia, patient request, clinician knowledge gaps, and discomfort with discussing stopping. “A lot of work is ongoing to address each of these issues, but I think the first step would be the clinician recognizing and agreeing that this is a problem that needs to be addressed,” she said.

Unnecessary screening

The authors note that the prevalence estimates for overscreening have not been reported on a national level, and it is also unclear how overscreening may vary among subgroups.

“The reason I focused on colorectal, cervical, and breast cancers is because USPSTF has very clear, age-based recommendations for these cancers in terms of who should and should not get screened routinely,” explained Moss. “This was important because it allowed me and my coauthors to clearly say, based on age alone, this person probably was screened unnecessarily, and this person was not.”

She noted that the age-based recommendations for routine screening are based on very large clinical trials to examine the effectiveness of the screening tool. “The recommendations for lung and prostate cancer screening are not so clear cut, and we would not be able to tell, based only on the available survey data, if someone was overscreened,” she said.

For their study, the team used data from the 2018 Behavioral Risk Factor Surveillance System, administered by the Centers for Disease Control and Prevention.

Overscreening was assessed in a cohort of 20,937 men and 34,244 women for colorectal cancer, 82,811 women for cervical cancer, and 38,356 women for breast cancer. Most the participants lived in a metropolitan area (about 80%) and were white (about 80%).

Being overscreened was also more common in metropolitan vs. nonmetropolitan areas for colorectal cancer in women (adjusted odds ratio, 1.23), cervical cancer (aOR, 1.20), and breast cancer (aOR, 1.36).

Overscreening for cervical and breast cancers was also associated with having a usual source of care, good/very good/excellent self-reported health, education beyond a high school diploma, and being married or living as married.

The study was carried out in 2018, and the situation is likely to have changed over recent months during the COVID-19 pandemic.

“We have already seen dramatic reductions in routine cancer screening among age-eligible adults, so part of this problem of overscreening among older adults will likely diminish,” said Moss. “State and national cancer surveillance systems will continue to monitor trends in cancer screening, including overscreening, cancer incidence, and cancer mortality.”

Johns Hopkins’ Schoenborn said one finding of particular interest was that the colorectal cancer overscreening rate was higher in those older than 80 and in those with higher mortality risk.

“It makes me wonder if this is due to the increasing use of noninvasive colorectal cancer screening modalities, such as the fecal immunochemical test FIT or Cologuard,” Schoenborn commented. “It would be important for clinicians to consider downstream effects even when the initial test is low risk, such as if the stool test screens positive, would the patient still need a colonoscopy, and is that something the patient can undergo and wants to undergo?”

The study was funded by the National Cancer Institute and American Cancer Society. Moss, study coauthors, and Schoenborn have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Older adults are being “overscreened” for cancer, say researchers who discovered that many patients reported undergoing screening for cancer even though they were older than the upper age limit recommended.

The U.S. Preventive Services Task Force recommends an upper age limit on cancer screening that varies by cancer type – 75 years old for colorectal cancer, 74 for breast cancer, and 65 for cervical cancer.

The study found that 59.3% of men and 56.2% of women being screening for colorectal cancer were above that cut-off age, as were 45.8% of women being screened for cervical cancer and 74.1% of women being screened for breast cancer.    

Overscreening was particularly high for women living in metropolitan areas.

The finding is of concern, say the researchers, because “continuing to screen patients who are older and/or who have limited life expectancy may cause more harms than benefits.”

“The development of successful interventions to address this problem are thus essential,” they write.

The study was published online July 27 in JAMA Network Open.

Clinicians, patients, and health care systems can be changed – and should be changed – to minimize overscreening,” said lead author Jennifer L. Moss, PhD, assistant professor of family and community medicine and public health sciences at Penn State University, Hershey.

“It will probably take many changes to meaningfully decrease overscreening,” she told Medscape Medical News.

One change that would help is if health insurance companies stopped reimbursing providers for screening after the recommended upper age limit, she continued. “Another change is if providers had evidence-based tools to guide conversations about stopping screening, given an individual patient’s demographics, health status, and risks and benefits of the screening test.”

Approached for comment on the study, Nancy Schoenborn, MD, MHS, an associate professor of medicine in the Division of Geriatric Medicine and Gerontology at Johns Hopkins University, Baltimore, noted that the finding of high overscreening is not surprising and is consistent with prior works that found similar results.

“One value of this paper is that the timing of the study is more recent and confirms that the issue of overscreening is one that is still ongoing,” she told Medscape Medical News. Schoenborn was not associated with the study.

As for what physicians should do about the findings in this study, Schoenborn suggested the first step is to simply recognize that overscreening is likely a problem and “to reflect if there are instances in one’s own practice where overscreening may occur.”

In her own work, Schoenborn continued, “I was recently surprised that a substantial minority of clinicians actually do not believe overscreening to be a problem in older adults, and they have a number of concerns about how overscreening is defined and about unintended consequences that can occur from efforts to reduce overscreening.”

She added that there are a number of reasons why overscreening occurs. These include guideline inconsistencies, inertia, patient request, clinician knowledge gaps, and discomfort with discussing stopping. “A lot of work is ongoing to address each of these issues, but I think the first step would be the clinician recognizing and agreeing that this is a problem that needs to be addressed,” she said.

Unnecessary screening

The authors note that the prevalence estimates for overscreening have not been reported on a national level, and it is also unclear how overscreening may vary among subgroups.

“The reason I focused on colorectal, cervical, and breast cancers is because USPSTF has very clear, age-based recommendations for these cancers in terms of who should and should not get screened routinely,” explained Moss. “This was important because it allowed me and my coauthors to clearly say, based on age alone, this person probably was screened unnecessarily, and this person was not.”

She noted that the age-based recommendations for routine screening are based on very large clinical trials to examine the effectiveness of the screening tool. “The recommendations for lung and prostate cancer screening are not so clear cut, and we would not be able to tell, based only on the available survey data, if someone was overscreened,” she said.

For their study, the team used data from the 2018 Behavioral Risk Factor Surveillance System, administered by the Centers for Disease Control and Prevention.

Overscreening was assessed in a cohort of 20,937 men and 34,244 women for colorectal cancer, 82,811 women for cervical cancer, and 38,356 women for breast cancer. Most the participants lived in a metropolitan area (about 80%) and were white (about 80%).

Being overscreened was also more common in metropolitan vs. nonmetropolitan areas for colorectal cancer in women (adjusted odds ratio, 1.23), cervical cancer (aOR, 1.20), and breast cancer (aOR, 1.36).

Overscreening for cervical and breast cancers was also associated with having a usual source of care, good/very good/excellent self-reported health, education beyond a high school diploma, and being married or living as married.

The study was carried out in 2018, and the situation is likely to have changed over recent months during the COVID-19 pandemic.

“We have already seen dramatic reductions in routine cancer screening among age-eligible adults, so part of this problem of overscreening among older adults will likely diminish,” said Moss. “State and national cancer surveillance systems will continue to monitor trends in cancer screening, including overscreening, cancer incidence, and cancer mortality.”

Johns Hopkins’ Schoenborn said one finding of particular interest was that the colorectal cancer overscreening rate was higher in those older than 80 and in those with higher mortality risk.

“It makes me wonder if this is due to the increasing use of noninvasive colorectal cancer screening modalities, such as the fecal immunochemical test FIT or Cologuard,” Schoenborn commented. “It would be important for clinicians to consider downstream effects even when the initial test is low risk, such as if the stool test screens positive, would the patient still need a colonoscopy, and is that something the patient can undergo and wants to undergo?”

The study was funded by the National Cancer Institute and American Cancer Society. Moss, study coauthors, and Schoenborn have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

A strategy that includes a urine steroid test along with imaging characteristics and tumor size criteria can significantly improve the challenging diagnosis of adrenocortical cancer, helping to avoid unnecessary, and often unsuccessful, further imaging and even surgery, new research shows.

“A triple-test strategy of tumor diameter, imaging characteristics, and urine steroid metabolomics improves detection of adrenocortical carcinoma, which could shorten time to surgery for patients with ... carcinoma and help to avoid unnecessary surgery in patients with benign tumors,” the authors say in research published online July 23 in The Lancet Diabetes & Endocrinology.

The triple-test strategy can be expected to make its way into international guidelines, notes joint lead author Irina Bancos, MD, an associate professor of endocrinology at the Mayo Clinic, Rochester, Minn., in a press statement issued by the University of Birmingham (England), which also had a number of researchers involved in the study.

“The findings of this study will feed into the next international guidelines on the management of adrenal tumors and the implementation of the new test will hopefully improve the overall outlook for patients diagnosed with adrenal tumors,” Dr. Bancos emphasized.

More imaging has led to detection of more adrenal tumors

Advances in CT and MRI imaging have increased the ability to detect adrenal incidentalomas, which are now picked up on about 5% of scans, and the widespread use of imaging has compounded the prevalence of such findings, particularly in older people.

Adrenocortical carcinomas represent only about 2%-12% of adrenal incidentalomas, but the prognosis is very poor, and early detection and surgery can improve outcomes, so findings of any adrenal tumor typically trigger additional multimodal imaging to rule out malignancy.

Evidence is lacking on the accuracy of imaging in determining whether such masses are truly cancerous, or benign, and such procedures add costs, as well as expose patients to radiation that may ultimately have no benefit. However, a previous proof-of-concept study from the same authors did show that the presence of excess adrenal steroid hormones in the urine is a key indicator of adrenal tumors, and other research has supported the findings.

All three tests together give best predictive value: EURINE-ACT

To further validate this work, the authors conducted the EURINE-ACT trial, a prospective 14-center study that is the first of its kind to evaluate the efficacy of a screening strategy for adrenocortical carcinoma that combines urine steroid profiling with tumor size and imaging characteristics.

The study of 2,017 participants with newly diagnosed adrenal masses, recruited from January 2011 to July 2016 from specialist centers in 11 different countries, assessed the diagnostic accuracy of three components: maximum tumor diameter (≥4 cm vs. <4 cm), imaging characteristics (positive vs. negative), and urine steroid metabolomics (low, medium, or high risk of adrenocortical carcinoma), separately and in combination.

Of the patients, 98 (4.9%) had adrenocortical carcinoma confirmed clinically, histopathologically, or biochemically.

Tumors with diameters of 4 cm or larger were identified in 488 patients (24.2%) and were observed in the vast majority of patients with adrenocortical carcinoma (96 of 98), for a positive predictive value (PPV) of 19.7%.

Likewise, the PPV for imaging characteristics was 19.7%. However, increasing the unenhanced CT tumor attenuation threshold to 20 Hounsfield units (HU) from the recommended 10 HU increased specificity for adrenocortical carcinoma (80.0% vs. 64.0%) while maintaining sensitivity (99.0% vs. 100.0%).

Comparatively, a urine steroid metabolomics result suggesting a high risk of adrenocortical carcinoma had a PPV of 34.6%.

A total of 106 patients (5.3%) met the criteria for all three measures, and the PPV for all three was 76.4%.

Using the criteria, 70 patients (3.5%) were classified as being at moderate risk of adrenocortical carcinoma and 1,841 (91.3%) at low risk, for a negative predictive value (NPV) of 99.7%.

“Use of radiation-free, noninvasive urine steroid metabolomics has a higher PPV than two standard imaging tests, and best performance was seen with the combination of all three tests,” the authors state.

Limit urine test to patients with larger tumors

They note that the use of the combined diagnostic strategy would have led to additional imaging in only 488 (24.2%) of the study’s 2,017 patients, compared with the 2,737 scans that were actually conducted before reaching a diagnostic decision.

“Implementation of urine steroid metabolomics in the routine diagnostic assessment of newly discovered adrenal masses could reduce the number of imaging procedures required to diagnose adrenocortical carcinoma and avoid unnecessary surgery of benign adrenal tumors, potentially yielding beneficial effects with respect to patient burden and health care costs,” they stress.

And regarding imaging parameters, “we also showed that using a cutoff of 20 HU for unenhanced CT tumor attenuation increases the accuracy of imaging characteristic assessment for exclusion of adrenocortical carcinoma, compared with the currently recommended cutoff of 10 HU, which has immediate implications for clinical practice,” they emphasize.

In an accompanying editorial, Adina F. Turcu, MD, of the division of metabolism, endocrinology, and diabetes, University of Michigan, Ann Arbor, and Axel K. Walch, MD, of the Helmholtz Zentrum München–German Research Centre for Environmental Health, agree. “The introduction of urine steroid metabolomics into routine clinical practice would provide major advantages,” they state.

However, they point out that, although the overall negative predictive value of the test was excellent, the specificity was weak.

“Thus, urine steroid metabolomics should be limited to patients who have adrenal nodules larger than 4 cm and have qualitative imaging characteristics suggestive of malignancy,” say Dr. Turcu and Dr. Walch.

The EURINE-ACT study results suggest this subgroup would represent roughly only 12% of all patients with adrenal incidentalomas, they add.

Issues that remain to be addressed with regard to the implementation of the screening strategy include how to best respond to patients who are classified as having intermediate or moderate risk of malignancy, and whether the diagnostic value of steroid metabolomics could be refined by adding analytes or parameters, the editorialists conclude.

The study was funded by the European Commission, U.K. Medical Research Council, Wellcome Trust, U.K. National Institute for Health Research, U.S. National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research.
 

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

A strategy that includes a urine steroid test along with imaging characteristics and tumor size criteria can significantly improve the challenging diagnosis of adrenocortical cancer, helping to avoid unnecessary, and often unsuccessful, further imaging and even surgery, new research shows.

“A triple-test strategy of tumor diameter, imaging characteristics, and urine steroid metabolomics improves detection of adrenocortical carcinoma, which could shorten time to surgery for patients with ... carcinoma and help to avoid unnecessary surgery in patients with benign tumors,” the authors say in research published online July 23 in The Lancet Diabetes & Endocrinology.

The triple-test strategy can be expected to make its way into international guidelines, notes joint lead author Irina Bancos, MD, an associate professor of endocrinology at the Mayo Clinic, Rochester, Minn., in a press statement issued by the University of Birmingham (England), which also had a number of researchers involved in the study.

“The findings of this study will feed into the next international guidelines on the management of adrenal tumors and the implementation of the new test will hopefully improve the overall outlook for patients diagnosed with adrenal tumors,” Dr. Bancos emphasized.

More imaging has led to detection of more adrenal tumors

Advances in CT and MRI imaging have increased the ability to detect adrenal incidentalomas, which are now picked up on about 5% of scans, and the widespread use of imaging has compounded the prevalence of such findings, particularly in older people.

Adrenocortical carcinomas represent only about 2%-12% of adrenal incidentalomas, but the prognosis is very poor, and early detection and surgery can improve outcomes, so findings of any adrenal tumor typically trigger additional multimodal imaging to rule out malignancy.

Evidence is lacking on the accuracy of imaging in determining whether such masses are truly cancerous, or benign, and such procedures add costs, as well as expose patients to radiation that may ultimately have no benefit. However, a previous proof-of-concept study from the same authors did show that the presence of excess adrenal steroid hormones in the urine is a key indicator of adrenal tumors, and other research has supported the findings.

All three tests together give best predictive value: EURINE-ACT

To further validate this work, the authors conducted the EURINE-ACT trial, a prospective 14-center study that is the first of its kind to evaluate the efficacy of a screening strategy for adrenocortical carcinoma that combines urine steroid profiling with tumor size and imaging characteristics.

The study of 2,017 participants with newly diagnosed adrenal masses, recruited from January 2011 to July 2016 from specialist centers in 11 different countries, assessed the diagnostic accuracy of three components: maximum tumor diameter (≥4 cm vs. <4 cm), imaging characteristics (positive vs. negative), and urine steroid metabolomics (low, medium, or high risk of adrenocortical carcinoma), separately and in combination.

Of the patients, 98 (4.9%) had adrenocortical carcinoma confirmed clinically, histopathologically, or biochemically.

Tumors with diameters of 4 cm or larger were identified in 488 patients (24.2%) and were observed in the vast majority of patients with adrenocortical carcinoma (96 of 98), for a positive predictive value (PPV) of 19.7%.

Likewise, the PPV for imaging characteristics was 19.7%. However, increasing the unenhanced CT tumor attenuation threshold to 20 Hounsfield units (HU) from the recommended 10 HU increased specificity for adrenocortical carcinoma (80.0% vs. 64.0%) while maintaining sensitivity (99.0% vs. 100.0%).

Comparatively, a urine steroid metabolomics result suggesting a high risk of adrenocortical carcinoma had a PPV of 34.6%.

A total of 106 patients (5.3%) met the criteria for all three measures, and the PPV for all three was 76.4%.

Using the criteria, 70 patients (3.5%) were classified as being at moderate risk of adrenocortical carcinoma and 1,841 (91.3%) at low risk, for a negative predictive value (NPV) of 99.7%.

“Use of radiation-free, noninvasive urine steroid metabolomics has a higher PPV than two standard imaging tests, and best performance was seen with the combination of all three tests,” the authors state.

Limit urine test to patients with larger tumors

They note that the use of the combined diagnostic strategy would have led to additional imaging in only 488 (24.2%) of the study’s 2,017 patients, compared with the 2,737 scans that were actually conducted before reaching a diagnostic decision.

“Implementation of urine steroid metabolomics in the routine diagnostic assessment of newly discovered adrenal masses could reduce the number of imaging procedures required to diagnose adrenocortical carcinoma and avoid unnecessary surgery of benign adrenal tumors, potentially yielding beneficial effects with respect to patient burden and health care costs,” they stress.

And regarding imaging parameters, “we also showed that using a cutoff of 20 HU for unenhanced CT tumor attenuation increases the accuracy of imaging characteristic assessment for exclusion of adrenocortical carcinoma, compared with the currently recommended cutoff of 10 HU, which has immediate implications for clinical practice,” they emphasize.

In an accompanying editorial, Adina F. Turcu, MD, of the division of metabolism, endocrinology, and diabetes, University of Michigan, Ann Arbor, and Axel K. Walch, MD, of the Helmholtz Zentrum München–German Research Centre for Environmental Health, agree. “The introduction of urine steroid metabolomics into routine clinical practice would provide major advantages,” they state.

However, they point out that, although the overall negative predictive value of the test was excellent, the specificity was weak.

“Thus, urine steroid metabolomics should be limited to patients who have adrenal nodules larger than 4 cm and have qualitative imaging characteristics suggestive of malignancy,” say Dr. Turcu and Dr. Walch.

The EURINE-ACT study results suggest this subgroup would represent roughly only 12% of all patients with adrenal incidentalomas, they add.

Issues that remain to be addressed with regard to the implementation of the screening strategy include how to best respond to patients who are classified as having intermediate or moderate risk of malignancy, and whether the diagnostic value of steroid metabolomics could be refined by adding analytes or parameters, the editorialists conclude.

The study was funded by the European Commission, U.K. Medical Research Council, Wellcome Trust, U.K. National Institute for Health Research, U.S. National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research.
 

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

A strategy that includes a urine steroid test along with imaging characteristics and tumor size criteria can significantly improve the challenging diagnosis of adrenocortical cancer, helping to avoid unnecessary, and often unsuccessful, further imaging and even surgery, new research shows.

“A triple-test strategy of tumor diameter, imaging characteristics, and urine steroid metabolomics improves detection of adrenocortical carcinoma, which could shorten time to surgery for patients with ... carcinoma and help to avoid unnecessary surgery in patients with benign tumors,” the authors say in research published online July 23 in The Lancet Diabetes & Endocrinology.

The triple-test strategy can be expected to make its way into international guidelines, notes joint lead author Irina Bancos, MD, an associate professor of endocrinology at the Mayo Clinic, Rochester, Minn., in a press statement issued by the University of Birmingham (England), which also had a number of researchers involved in the study.

“The findings of this study will feed into the next international guidelines on the management of adrenal tumors and the implementation of the new test will hopefully improve the overall outlook for patients diagnosed with adrenal tumors,” Dr. Bancos emphasized.

More imaging has led to detection of more adrenal tumors

Advances in CT and MRI imaging have increased the ability to detect adrenal incidentalomas, which are now picked up on about 5% of scans, and the widespread use of imaging has compounded the prevalence of such findings, particularly in older people.

Adrenocortical carcinomas represent only about 2%-12% of adrenal incidentalomas, but the prognosis is very poor, and early detection and surgery can improve outcomes, so findings of any adrenal tumor typically trigger additional multimodal imaging to rule out malignancy.

Evidence is lacking on the accuracy of imaging in determining whether such masses are truly cancerous, or benign, and such procedures add costs, as well as expose patients to radiation that may ultimately have no benefit. However, a previous proof-of-concept study from the same authors did show that the presence of excess adrenal steroid hormones in the urine is a key indicator of adrenal tumors, and other research has supported the findings.

All three tests together give best predictive value: EURINE-ACT

To further validate this work, the authors conducted the EURINE-ACT trial, a prospective 14-center study that is the first of its kind to evaluate the efficacy of a screening strategy for adrenocortical carcinoma that combines urine steroid profiling with tumor size and imaging characteristics.

The study of 2,017 participants with newly diagnosed adrenal masses, recruited from January 2011 to July 2016 from specialist centers in 11 different countries, assessed the diagnostic accuracy of three components: maximum tumor diameter (≥4 cm vs. <4 cm), imaging characteristics (positive vs. negative), and urine steroid metabolomics (low, medium, or high risk of adrenocortical carcinoma), separately and in combination.

Of the patients, 98 (4.9%) had adrenocortical carcinoma confirmed clinically, histopathologically, or biochemically.

Tumors with diameters of 4 cm or larger were identified in 488 patients (24.2%) and were observed in the vast majority of patients with adrenocortical carcinoma (96 of 98), for a positive predictive value (PPV) of 19.7%.

Likewise, the PPV for imaging characteristics was 19.7%. However, increasing the unenhanced CT tumor attenuation threshold to 20 Hounsfield units (HU) from the recommended 10 HU increased specificity for adrenocortical carcinoma (80.0% vs. 64.0%) while maintaining sensitivity (99.0% vs. 100.0%).

Comparatively, a urine steroid metabolomics result suggesting a high risk of adrenocortical carcinoma had a PPV of 34.6%.

A total of 106 patients (5.3%) met the criteria for all three measures, and the PPV for all three was 76.4%.

Using the criteria, 70 patients (3.5%) were classified as being at moderate risk of adrenocortical carcinoma and 1,841 (91.3%) at low risk, for a negative predictive value (NPV) of 99.7%.

“Use of radiation-free, noninvasive urine steroid metabolomics has a higher PPV than two standard imaging tests, and best performance was seen with the combination of all three tests,” the authors state.

Limit urine test to patients with larger tumors

They note that the use of the combined diagnostic strategy would have led to additional imaging in only 488 (24.2%) of the study’s 2,017 patients, compared with the 2,737 scans that were actually conducted before reaching a diagnostic decision.

“Implementation of urine steroid metabolomics in the routine diagnostic assessment of newly discovered adrenal masses could reduce the number of imaging procedures required to diagnose adrenocortical carcinoma and avoid unnecessary surgery of benign adrenal tumors, potentially yielding beneficial effects with respect to patient burden and health care costs,” they stress.

And regarding imaging parameters, “we also showed that using a cutoff of 20 HU for unenhanced CT tumor attenuation increases the accuracy of imaging characteristic assessment for exclusion of adrenocortical carcinoma, compared with the currently recommended cutoff of 10 HU, which has immediate implications for clinical practice,” they emphasize.

In an accompanying editorial, Adina F. Turcu, MD, of the division of metabolism, endocrinology, and diabetes, University of Michigan, Ann Arbor, and Axel K. Walch, MD, of the Helmholtz Zentrum München–German Research Centre for Environmental Health, agree. “The introduction of urine steroid metabolomics into routine clinical practice would provide major advantages,” they state.

However, they point out that, although the overall negative predictive value of the test was excellent, the specificity was weak.

“Thus, urine steroid metabolomics should be limited to patients who have adrenal nodules larger than 4 cm and have qualitative imaging characteristics suggestive of malignancy,” say Dr. Turcu and Dr. Walch.

The EURINE-ACT study results suggest this subgroup would represent roughly only 12% of all patients with adrenal incidentalomas, they add.

Issues that remain to be addressed with regard to the implementation of the screening strategy include how to best respond to patients who are classified as having intermediate or moderate risk of malignancy, and whether the diagnostic value of steroid metabolomics could be refined by adding analytes or parameters, the editorialists conclude.

The study was funded by the European Commission, U.K. Medical Research Council, Wellcome Trust, U.K. National Institute for Health Research, U.S. National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research.
 

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

In the era of COVID-19, cancer treatment should not be discontinued or delayed if it can affect overall survival, according to new recommendations from an international team of experts.

Another important recommendation is to stop labeling all patients with cancer as being vulnerable to infection with the virus as it can lead to inappropriate care with potential negative outcomes.

“Although it was reasonable to adopt over-protective measures for our patients at the outbreak of a novel infective disease which was not previously observed in humans, we now need to step away from the assumption that all cancer patients are vulnerable to COVID-19,” said first author of the consensus article Giuseppe Curigliano, MD, PhD, of the European Institute of Oncology, Milan, Italy, in a statement. “The implications have been important because for some patients treatment was delayed or interrupted over the last few months, and I believe that we will see the impact of this over-precautionary approach in the...future.”

The recommendations were issued by the European Society of Medical Oncology (ESMO) to help guide physicians in “optimizing the pathway to cancer care” as well as to improve outcomes during the pandemic. The recommendations were published online July 31 in Annals of Oncology.

Studies have found that patients with cancer face a higher risk of serious complications and death if they develop COVID-19. Data from the COVID-19 and Cancer Consortium registry, for example, showed that patients with progressing cancer and COVID-19 infection had a fivefold increase in the risk of 30-day mortality compared with COVID-19–positive cancer patients who were in remission or had no evidence of cancer.

But while this may be true for some patients, Curigliano and colleagues emphasize that individuals with cancer are not a heterogeneous group and that the term “cancer” itself represents myriad different diseases. The European experts note that current evidence suggests many patients with solid tumors are not more vulnerable to serious complications than the general population.

Thus, cancer prognoses vary considerably, and addressing all patients with cancer as being “COVID-19-vulnerable is probably neither reasonable nor informative,” say the authors.

Dramatic changes were initiated in cancer management for all cancer types, nevertheless, and although these changes seemed reasonable in an acute pandemic situation, note the authors, they were made in the absence of strong supportive evidence. Attempts to define the individualized risk for a given patient, taking into account their primary tumor subtype, stage, age, and gender, have been limited.

“Based on current evidence, only patients who are elderly, with multiple comorbidities, and receiving chemotherapy are vulnerable to the infection,” explained Curigliano.

However, on a positive note, a recently published prospective cohort study looked at approximately 800 patients with cancer – who had symptomatic COVID-19 – in the United Kingdom. The analysis showed no association at all between the risk for death and receiving chemotherapy or immunotherapy, points out Medscape commentator David Kerr, MD, of the University of Oxford, UK, in a recent commentary.

Key recommendations

An international consortium was established by ESMO, and the interdisciplinary expert panel consisted of 64 experts and one voting patient advocate. They agreed on 28 statements that can be used to help with many of the current clinical and technical areas of uncertainty that range from diagnosis to treatment decisions.

The following are several of the key recommendations:

• Patients with cancer who face the highest risk of severe COVID-19 are characterized by active and progressive cancer, advanced age, poor performance status, smoking status, comorbidities, and possibly type of cancer.
• Telehealth and digital health can be excellent tools for some types of care such as primary care triage and counseling, but meeting in person may be more effective for situations that include delivery of key cancer-related information and for patients with complex cancer needs.
• Prior to hospital admission, patients with cancer should be tested for COVID-19, if feasible, and if they are considered at high risk, regardless of symptoms or chest radiological findings.
• Patients with cancer and COVID-19 have a higher risk of thromboembolic events, and prophylaxis using low molecular weight  or novel oral anticoagulants is recommended.
• Immune checkpoint inhibitors should not be withheld or delayed when there is a significant survival benefit, but use should be postponed in patients who test positive for COVID-19 until they recover.
• Use of high-dose steroids in patients with cancer infected with COVID-19 could potentially increase the risk of mortality, and a switch should be made to another immunosuppressant, if possible.
• The decision to use tyrosine kinase inhibitors (TKIs) of the PI3K/AKT/mTOR or RAS/RAF/MEK axis is complex, as they interfere with critical pathways involved in innate or adaptive immune responses. Stopping or withholding therapy depends on the risk-benefit balance, and the magnitude of benefit from the TKI needs to be considered.

The authors conclude that “ultimately, this set of statements will serve as a dynamic knowledge repository that will be better informed by accumulating data on SARS-CoV-2 biology, COVID-19 pandemic characteristics, on the risk of cancer patients for COVID-19 and its modulating factors, and finally, on optimal cancer care in the presence of the virus.”

No funding was reported for the current study. Several authors have disclosed relationships with industry, which are listed in the article.
 

This article first appeared on Medscape.com.

In the era of COVID-19, cancer treatment should not be discontinued or delayed if it can affect overall survival, according to new recommendations from an international team of experts.

Another important recommendation is to stop labeling all patients with cancer as being vulnerable to infection with the virus as it can lead to inappropriate care with potential negative outcomes.

“Although it was reasonable to adopt over-protective measures for our patients at the outbreak of a novel infective disease which was not previously observed in humans, we now need to step away from the assumption that all cancer patients are vulnerable to COVID-19,” said first author of the consensus article Giuseppe Curigliano, MD, PhD, of the European Institute of Oncology, Milan, Italy, in a statement. “The implications have been important because for some patients treatment was delayed or interrupted over the last few months, and I believe that we will see the impact of this over-precautionary approach in the...future.”

The recommendations were issued by the European Society of Medical Oncology (ESMO) to help guide physicians in “optimizing the pathway to cancer care” as well as to improve outcomes during the pandemic. The recommendations were published online July 31 in Annals of Oncology.

Studies have found that patients with cancer face a higher risk of serious complications and death if they develop COVID-19. Data from the COVID-19 and Cancer Consortium registry, for example, showed that patients with progressing cancer and COVID-19 infection had a fivefold increase in the risk of 30-day mortality compared with COVID-19–positive cancer patients who were in remission or had no evidence of cancer.

But while this may be true for some patients, Curigliano and colleagues emphasize that individuals with cancer are not a heterogeneous group and that the term “cancer” itself represents myriad different diseases. The European experts note that current evidence suggests many patients with solid tumors are not more vulnerable to serious complications than the general population.

Thus, cancer prognoses vary considerably, and addressing all patients with cancer as being “COVID-19-vulnerable is probably neither reasonable nor informative,” say the authors.

Dramatic changes were initiated in cancer management for all cancer types, nevertheless, and although these changes seemed reasonable in an acute pandemic situation, note the authors, they were made in the absence of strong supportive evidence. Attempts to define the individualized risk for a given patient, taking into account their primary tumor subtype, stage, age, and gender, have been limited.

“Based on current evidence, only patients who are elderly, with multiple comorbidities, and receiving chemotherapy are vulnerable to the infection,” explained Curigliano.

However, on a positive note, a recently published prospective cohort study looked at approximately 800 patients with cancer – who had symptomatic COVID-19 – in the United Kingdom. The analysis showed no association at all between the risk for death and receiving chemotherapy or immunotherapy, points out Medscape commentator David Kerr, MD, of the University of Oxford, UK, in a recent commentary.

Key recommendations

An international consortium was established by ESMO, and the interdisciplinary expert panel consisted of 64 experts and one voting patient advocate. They agreed on 28 statements that can be used to help with many of the current clinical and technical areas of uncertainty that range from diagnosis to treatment decisions.

The following are several of the key recommendations:

• Patients with cancer who face the highest risk of severe COVID-19 are characterized by active and progressive cancer, advanced age, poor performance status, smoking status, comorbidities, and possibly type of cancer.
• Telehealth and digital health can be excellent tools for some types of care such as primary care triage and counseling, but meeting in person may be more effective for situations that include delivery of key cancer-related information and for patients with complex cancer needs.
• Prior to hospital admission, patients with cancer should be tested for COVID-19, if feasible, and if they are considered at high risk, regardless of symptoms or chest radiological findings.
• Patients with cancer and COVID-19 have a higher risk of thromboembolic events, and prophylaxis using low molecular weight  or novel oral anticoagulants is recommended.
• Immune checkpoint inhibitors should not be withheld or delayed when there is a significant survival benefit, but use should be postponed in patients who test positive for COVID-19 until they recover.
• Use of high-dose steroids in patients with cancer infected with COVID-19 could potentially increase the risk of mortality, and a switch should be made to another immunosuppressant, if possible.
• The decision to use tyrosine kinase inhibitors (TKIs) of the PI3K/AKT/mTOR or RAS/RAF/MEK axis is complex, as they interfere with critical pathways involved in innate or adaptive immune responses. Stopping or withholding therapy depends on the risk-benefit balance, and the magnitude of benefit from the TKI needs to be considered.

The authors conclude that “ultimately, this set of statements will serve as a dynamic knowledge repository that will be better informed by accumulating data on SARS-CoV-2 biology, COVID-19 pandemic characteristics, on the risk of cancer patients for COVID-19 and its modulating factors, and finally, on optimal cancer care in the presence of the virus.”

No funding was reported for the current study. Several authors have disclosed relationships with industry, which are listed in the article.
 

This article first appeared on Medscape.com.

In the era of COVID-19, cancer treatment should not be discontinued or delayed if it can affect overall survival, according to new recommendations from an international team of experts.

Another important recommendation is to stop labeling all patients with cancer as being vulnerable to infection with the virus as it can lead to inappropriate care with potential negative outcomes.

“Although it was reasonable to adopt over-protective measures for our patients at the outbreak of a novel infective disease which was not previously observed in humans, we now need to step away from the assumption that all cancer patients are vulnerable to COVID-19,” said first author of the consensus article Giuseppe Curigliano, MD, PhD, of the European Institute of Oncology, Milan, Italy, in a statement. “The implications have been important because for some patients treatment was delayed or interrupted over the last few months, and I believe that we will see the impact of this over-precautionary approach in the...future.”

The recommendations were issued by the European Society of Medical Oncology (ESMO) to help guide physicians in “optimizing the pathway to cancer care” as well as to improve outcomes during the pandemic. The recommendations were published online July 31 in Annals of Oncology.

Studies have found that patients with cancer face a higher risk of serious complications and death if they develop COVID-19. Data from the COVID-19 and Cancer Consortium registry, for example, showed that patients with progressing cancer and COVID-19 infection had a fivefold increase in the risk of 30-day mortality compared with COVID-19–positive cancer patients who were in remission or had no evidence of cancer.

But while this may be true for some patients, Curigliano and colleagues emphasize that individuals with cancer are not a heterogeneous group and that the term “cancer” itself represents myriad different diseases. The European experts note that current evidence suggests many patients with solid tumors are not more vulnerable to serious complications than the general population.

Thus, cancer prognoses vary considerably, and addressing all patients with cancer as being “COVID-19-vulnerable is probably neither reasonable nor informative,” say the authors.

Dramatic changes were initiated in cancer management for all cancer types, nevertheless, and although these changes seemed reasonable in an acute pandemic situation, note the authors, they were made in the absence of strong supportive evidence. Attempts to define the individualized risk for a given patient, taking into account their primary tumor subtype, stage, age, and gender, have been limited.

“Based on current evidence, only patients who are elderly, with multiple comorbidities, and receiving chemotherapy are vulnerable to the infection,” explained Curigliano.

However, on a positive note, a recently published prospective cohort study looked at approximately 800 patients with cancer – who had symptomatic COVID-19 – in the United Kingdom. The analysis showed no association at all between the risk for death and receiving chemotherapy or immunotherapy, points out Medscape commentator David Kerr, MD, of the University of Oxford, UK, in a recent commentary.

Key recommendations

An international consortium was established by ESMO, and the interdisciplinary expert panel consisted of 64 experts and one voting patient advocate. They agreed on 28 statements that can be used to help with many of the current clinical and technical areas of uncertainty that range from diagnosis to treatment decisions.

The following are several of the key recommendations:

• Patients with cancer who face the highest risk of severe COVID-19 are characterized by active and progressive cancer, advanced age, poor performance status, smoking status, comorbidities, and possibly type of cancer.
• Telehealth and digital health can be excellent tools for some types of care such as primary care triage and counseling, but meeting in person may be more effective for situations that include delivery of key cancer-related information and for patients with complex cancer needs.
• Prior to hospital admission, patients with cancer should be tested for COVID-19, if feasible, and if they are considered at high risk, regardless of symptoms or chest radiological findings.
• Patients with cancer and COVID-19 have a higher risk of thromboembolic events, and prophylaxis using low molecular weight  or novel oral anticoagulants is recommended.
• Immune checkpoint inhibitors should not be withheld or delayed when there is a significant survival benefit, but use should be postponed in patients who test positive for COVID-19 until they recover.
• Use of high-dose steroids in patients with cancer infected with COVID-19 could potentially increase the risk of mortality, and a switch should be made to another immunosuppressant, if possible.
• The decision to use tyrosine kinase inhibitors (TKIs) of the PI3K/AKT/mTOR or RAS/RAF/MEK axis is complex, as they interfere with critical pathways involved in innate or adaptive immune responses. Stopping or withholding therapy depends on the risk-benefit balance, and the magnitude of benefit from the TKI needs to be considered.

The authors conclude that “ultimately, this set of statements will serve as a dynamic knowledge repository that will be better informed by accumulating data on SARS-CoV-2 biology, COVID-19 pandemic characteristics, on the risk of cancer patients for COVID-19 and its modulating factors, and finally, on optimal cancer care in the presence of the virus.”

No funding was reported for the current study. Several authors have disclosed relationships with industry, which are listed in the article.
 

This article first appeared on Medscape.com.

Higher continence rates were seen after robot-assisted radical prostatectomy (RARP) than after laparoscopic radical prostatectomy (LRP) in the first large-scale, prospective, multicenter, randomized trial to compare the two surgical approaches.

At 3 months, 54.3% of prostate cancer patients who underwent RARP and 45.6% of those who had LRP were continent after catheter removal (P = .027).

“We did use a very strong definition for continence, meaning no pad or safety pad; patients wearing one pad per day we’re not classified as continent,” said study investigator Jens-Uwe Stolzenburg, MD, PhD, professor and head of urology at the University of Leipzig Hospital in Germany.

Dr. Stolzenburg presented these findings at the European Association of Urology virtual annual congress.

The findings fit with previous research showing higher continence rates with RARP (69%-80%) than with LRP (62%-63%), although those studies did not always find the difference to be statistically significant, and higher quality evidence was needed (J Sex Med. 2011 May;8[5]:1503-12; Eur Urol. 2013 Apr;63[4]:606-14). “Up to now, there are only two randomized studies published in the literature comparing robotic and classical laparoscopic prostatectomy, and my point of view is that there are strong limitations of both studies,” Dr. Stolzenburg said.

“First of all, both studies are based on the single experience of surgeons, so only one surgeon has performed surgery. The second limitation is the limited numbers of patients included,” he observed. One study had 64 patients in each arm, and the other had 60 patients in each arm.
 

Providing higher quality evidence

Dr. Stolzenburg presented results of the LAP-01 study, which was designed to close the knowledge gap and determine if there really was an advantage for RARP over LRP for preserving continence.

The trial was conducted at three academic centers and one public hospital in Germany. The final analysis included 718 patients with prostate cancer referred for prostate surgery. They were randomized, in a ratio of three to one, to undergo RARP (n = 530) or LRP (n = 188), being unaware themselves of which surgery they would be having until the 3-month primary endpoint.

In addition to improved continence over LRP, RARP was associated with significantly better erectile function at 3 months (P = .016), as measured by the International Index of Erectile Function (IIEF).

That said, erectile function was still severely affected by both surgical procedures. Total IIEF scores were 6.0 with RARP and 4.7 with LRP, compared with 15.9 and 16.2, respectively, at baseline.

A higher percentage of men who had nerve-sparing procedures reported having an erection suitable for sexual intercourse at 2 months in the RARP group than in the LRP group (17.7% vs. 6.7%, P = .007).

The complication rate was “a little bit higher” in the LRP group than in the RARP group, “but the difference was not statistically significant,” Dr. Stolzenburg said. He added that “the most frequent complication was anastomotic leakage, and most complications overall were low-grade complications in both groups.”
 

Multicenter experience

The potential for prostatectomy to have effects on urinary continence and sexual function are important issues that need to be discussed upfront with patients, observed Alexandre de la Taille, MD, PhD, who was invited to discuss the study.

Current European guidance says “there is no surgical approach – open, laparoscopic, or robotic radical prostatectomy – that has proven superiority in terms of functional or oncological results,” he said. However, the LAP-01 study “found that the continence rate was better when we use a robotic approach compared to a laparoscopic approach.”

Dr. de la Taille, who is professor and chair of the urology service at CHU Mondor in Cretéil, France, also highlighted that this result was achieved with no increase in the morbidity profile or compromise of cancer control.

“My very first impression is that we are missing a little bit, some granularity of the data in terms of one key question, which is volume of surgery,” said the chair of the session Alberto Briganti, MD, PhD, associate professor of urology at Università Vita-Salute San Raffaele, and deputy director of the Urological Research Institute of IRCCS Ospedale San Raffaele, both in Milan.

“We know that recovery of outcomes is volume-dependent, both in the laparoscopic and robotic setting,” Dr. Briganti added.

“This is really a multicenter study including a lot of surgeons,” Dr. de la Taille countered, agreeing that the volume of surgeries might be something the LAP-01 study investigators could look at in a sub-analysis.

“Of course, some of them have a huge experience in the robotic approach and some of them a lower experience of the robotic approach, but when you put all together, there is a better continence recovery at 3 months when compared to the laparoscopic approach,” Dr. de la Taille said.

Calling the study a “real-life practice study,” he noted that urinary continence at 12 months might be a stronger endpoint, and the difference between the two surgical approaches may become less with time.

“But for the patient, again, daily practice, it’s better to have early urinary continence recovery compared to a late recovery,” Dr. de la Taille said.

This study was funded by the University of Leipzig via a German Cancer Aid grant. All speakers declared no conflicts of interest.

SOURCE: Stolzenburg J-E. EAU20, Abstract.

Higher continence rates were seen after robot-assisted radical prostatectomy (RARP) than after laparoscopic radical prostatectomy (LRP) in the first large-scale, prospective, multicenter, randomized trial to compare the two surgical approaches.

At 3 months, 54.3% of prostate cancer patients who underwent RARP and 45.6% of those who had LRP were continent after catheter removal (P = .027).

“We did use a very strong definition for continence, meaning no pad or safety pad; patients wearing one pad per day we’re not classified as continent,” said study investigator Jens-Uwe Stolzenburg, MD, PhD, professor and head of urology at the University of Leipzig Hospital in Germany.

Dr. Stolzenburg presented these findings at the European Association of Urology virtual annual congress.

The findings fit with previous research showing higher continence rates with RARP (69%-80%) than with LRP (62%-63%), although those studies did not always find the difference to be statistically significant, and higher quality evidence was needed (J Sex Med. 2011 May;8[5]:1503-12; Eur Urol. 2013 Apr;63[4]:606-14). “Up to now, there are only two randomized studies published in the literature comparing robotic and classical laparoscopic prostatectomy, and my point of view is that there are strong limitations of both studies,” Dr. Stolzenburg said.

“First of all, both studies are based on the single experience of surgeons, so only one surgeon has performed surgery. The second limitation is the limited numbers of patients included,” he observed. One study had 64 patients in each arm, and the other had 60 patients in each arm.
 

Providing higher quality evidence

Dr. Stolzenburg presented results of the LAP-01 study, which was designed to close the knowledge gap and determine if there really was an advantage for RARP over LRP for preserving continence.

The trial was conducted at three academic centers and one public hospital in Germany. The final analysis included 718 patients with prostate cancer referred for prostate surgery. They were randomized, in a ratio of three to one, to undergo RARP (n = 530) or LRP (n = 188), being unaware themselves of which surgery they would be having until the 3-month primary endpoint.

In addition to improved continence over LRP, RARP was associated with significantly better erectile function at 3 months (P = .016), as measured by the International Index of Erectile Function (IIEF).

That said, erectile function was still severely affected by both surgical procedures. Total IIEF scores were 6.0 with RARP and 4.7 with LRP, compared with 15.9 and 16.2, respectively, at baseline.

A higher percentage of men who had nerve-sparing procedures reported having an erection suitable for sexual intercourse at 2 months in the RARP group than in the LRP group (17.7% vs. 6.7%, P = .007).

The complication rate was “a little bit higher” in the LRP group than in the RARP group, “but the difference was not statistically significant,” Dr. Stolzenburg said. He added that “the most frequent complication was anastomotic leakage, and most complications overall were low-grade complications in both groups.”
 

Multicenter experience

The potential for prostatectomy to have effects on urinary continence and sexual function are important issues that need to be discussed upfront with patients, observed Alexandre de la Taille, MD, PhD, who was invited to discuss the study.

Current European guidance says “there is no surgical approach – open, laparoscopic, or robotic radical prostatectomy – that has proven superiority in terms of functional or oncological results,” he said. However, the LAP-01 study “found that the continence rate was better when we use a robotic approach compared to a laparoscopic approach.”

Dr. de la Taille, who is professor and chair of the urology service at CHU Mondor in Cretéil, France, also highlighted that this result was achieved with no increase in the morbidity profile or compromise of cancer control.

“My very first impression is that we are missing a little bit, some granularity of the data in terms of one key question, which is volume of surgery,” said the chair of the session Alberto Briganti, MD, PhD, associate professor of urology at Università Vita-Salute San Raffaele, and deputy director of the Urological Research Institute of IRCCS Ospedale San Raffaele, both in Milan.

“We know that recovery of outcomes is volume-dependent, both in the laparoscopic and robotic setting,” Dr. Briganti added.

“This is really a multicenter study including a lot of surgeons,” Dr. de la Taille countered, agreeing that the volume of surgeries might be something the LAP-01 study investigators could look at in a sub-analysis.

“Of course, some of them have a huge experience in the robotic approach and some of them a lower experience of the robotic approach, but when you put all together, there is a better continence recovery at 3 months when compared to the laparoscopic approach,” Dr. de la Taille said.

Calling the study a “real-life practice study,” he noted that urinary continence at 12 months might be a stronger endpoint, and the difference between the two surgical approaches may become less with time.

“But for the patient, again, daily practice, it’s better to have early urinary continence recovery compared to a late recovery,” Dr. de la Taille said.

This study was funded by the University of Leipzig via a German Cancer Aid grant. All speakers declared no conflicts of interest.

SOURCE: Stolzenburg J-E. EAU20, Abstract.

Higher continence rates were seen after robot-assisted radical prostatectomy (RARP) than after laparoscopic radical prostatectomy (LRP) in the first large-scale, prospective, multicenter, randomized trial to compare the two surgical approaches.

At 3 months, 54.3% of prostate cancer patients who underwent RARP and 45.6% of those who had LRP were continent after catheter removal (P = .027).

“We did use a very strong definition for continence, meaning no pad or safety pad; patients wearing one pad per day we’re not classified as continent,” said study investigator Jens-Uwe Stolzenburg, MD, PhD, professor and head of urology at the University of Leipzig Hospital in Germany.

Dr. Stolzenburg presented these findings at the European Association of Urology virtual annual congress.

The findings fit with previous research showing higher continence rates with RARP (69%-80%) than with LRP (62%-63%), although those studies did not always find the difference to be statistically significant, and higher quality evidence was needed (J Sex Med. 2011 May;8[5]:1503-12; Eur Urol. 2013 Apr;63[4]:606-14). “Up to now, there are only two randomized studies published in the literature comparing robotic and classical laparoscopic prostatectomy, and my point of view is that there are strong limitations of both studies,” Dr. Stolzenburg said.

“First of all, both studies are based on the single experience of surgeons, so only one surgeon has performed surgery. The second limitation is the limited numbers of patients included,” he observed. One study had 64 patients in each arm, and the other had 60 patients in each arm.
 

Providing higher quality evidence

Dr. Stolzenburg presented results of the LAP-01 study, which was designed to close the knowledge gap and determine if there really was an advantage for RARP over LRP for preserving continence.

The trial was conducted at three academic centers and one public hospital in Germany. The final analysis included 718 patients with prostate cancer referred for prostate surgery. They were randomized, in a ratio of three to one, to undergo RARP (n = 530) or LRP (n = 188), being unaware themselves of which surgery they would be having until the 3-month primary endpoint.

In addition to improved continence over LRP, RARP was associated with significantly better erectile function at 3 months (P = .016), as measured by the International Index of Erectile Function (IIEF).

That said, erectile function was still severely affected by both surgical procedures. Total IIEF scores were 6.0 with RARP and 4.7 with LRP, compared with 15.9 and 16.2, respectively, at baseline.

A higher percentage of men who had nerve-sparing procedures reported having an erection suitable for sexual intercourse at 2 months in the RARP group than in the LRP group (17.7% vs. 6.7%, P = .007).

The complication rate was “a little bit higher” in the LRP group than in the RARP group, “but the difference was not statistically significant,” Dr. Stolzenburg said. He added that “the most frequent complication was anastomotic leakage, and most complications overall were low-grade complications in both groups.”
 

Multicenter experience

The potential for prostatectomy to have effects on urinary continence and sexual function are important issues that need to be discussed upfront with patients, observed Alexandre de la Taille, MD, PhD, who was invited to discuss the study.

Current European guidance says “there is no surgical approach – open, laparoscopic, or robotic radical prostatectomy – that has proven superiority in terms of functional or oncological results,” he said. However, the LAP-01 study “found that the continence rate was better when we use a robotic approach compared to a laparoscopic approach.”

Dr. de la Taille, who is professor and chair of the urology service at CHU Mondor in Cretéil, France, also highlighted that this result was achieved with no increase in the morbidity profile or compromise of cancer control.

“My very first impression is that we are missing a little bit, some granularity of the data in terms of one key question, which is volume of surgery,” said the chair of the session Alberto Briganti, MD, PhD, associate professor of urology at Università Vita-Salute San Raffaele, and deputy director of the Urological Research Institute of IRCCS Ospedale San Raffaele, both in Milan.

“We know that recovery of outcomes is volume-dependent, both in the laparoscopic and robotic setting,” Dr. Briganti added.

“This is really a multicenter study including a lot of surgeons,” Dr. de la Taille countered, agreeing that the volume of surgeries might be something the LAP-01 study investigators could look at in a sub-analysis.

“Of course, some of them have a huge experience in the robotic approach and some of them a lower experience of the robotic approach, but when you put all together, there is a better continence recovery at 3 months when compared to the laparoscopic approach,” Dr. de la Taille said.

Calling the study a “real-life practice study,” he noted that urinary continence at 12 months might be a stronger endpoint, and the difference between the two surgical approaches may become less with time.

“But for the patient, again, daily practice, it’s better to have early urinary continence recovery compared to a late recovery,” Dr. de la Taille said.

This study was funded by the University of Leipzig via a German Cancer Aid grant. All speakers declared no conflicts of interest.

SOURCE: Stolzenburg J-E. EAU20, Abstract.

Hospitalized cancer patients have a high risk of nosocomial COVID-19 that is associated with increased mortality, so these patients should be treated in COVID-free zones, according to researchers.

In an observational study of patients with COVID-19 and cancer, 19% of patients had COVID-19 acquired during a non-COVID-related hospital stay, and 81% had community-acquired COVID-19.

At a median follow-up of 23 days, the overall mortality rate was 28%. However, the all-cause mortality rate in patients with nosocomial COVID-19 was more than double that of patients with community-acquired COVID-19, at 47% and 23%, respectively.

Arielle Elkrief, MD, of the University of Montreal, reported these results during the AACR virtual meeting: COVID-19 and Cancer.

“This is the first report that describes a high rate of hospital-acquired COVID-19 in patients with cancer, at a rate of 19%,” Dr. Elkrief said. “This was associated with high mortality in both univariate and multivariate analyses.”

The study included 250 adults and 3 children with COVID-19 and cancer who were identified between March 3 and May 23, 2020. They ranged in age from 4 to 95 years, but the median age was 73 years.

All patients had either laboratory-confirmed (95%) or presumed COVID-19 (5%) and invasive cancer. The most common cancer types were similar to those seen in the general population. Lung and breast cancer were the most common, followed by lymphoma, prostate cancer, and colorectal cancer. Most patients were on active anticancer therapy, most often chemotherapy.

Most patients (n = 236) were residents of Quebec, but 17 patients were residents of British Columbia.

“It is important to note that Quebec was one of the most heavily affected areas in North America at the time of the study,” Dr. Elkrief said.
 

Outcomes by group

There were 206 patients (81%) who had community-acquired COVID-19 and 47 (19%) who had nosocomial COVID-19. The two groups were similar with respect to sex, performance status, and cancer stage. A small trend toward more patients on active therapy was seen in the nosocomial group, but the difference did not reach statistical significance.

The median overall survival was 27 days in the nosocomial group and 71 days in the community-acquired group (hazard ratio, 2.2; P = .002).

A multivariate analysis showed that nosocomial infection was “strongly and independently associated with death,” Dr. Elkrief said. “Other risk factors for poor prognosis included age, poor [performance] status, and advanced stage of cancer.”

There were no significant differences between the hospital-acquired and community-acquired groups for other outcomes, including oxygen requirements (43% and 47%, respectively), ICU admission (13% and 11%), need for mechanical ventilation (6% and 5%), or length of stay (median, 9.5 days and 8.5 days).

The low rate of ICU admission, considering the mortality rate of 28%, “could reflect that patients with cancer are less likely to be admitted to the ICU,” Dr. Elkrief noted.
 

Applying the findings to practice

The findings reinforce the importance of adherence to stringent infection control guidelines to protect vulnerable patients, such as those with cancer, Dr. Elkrief said.

In ambulatory settings, this means decreasing in-person visits through increased use of teleconsultations, and for those who need to be seen in person, screening for symptoms or use of polymerase chain reaction testing should be used when resources are available, she said.

“Similar principles apply to chemotherapy treatment units,” Dr. Elkrief said. She added that staff must avoid cross-contamination between COVID and COVID-free zones, and that “dedicated personnel and equipment should be maintained and separate between these two zones.

“Adequate protective personal equipment and strict hand hygiene protocols are also of utmost importance,” Dr. Elkrief said. “The threat of COVID-19 is not behind us, and so we continue to enforce these strategies to protect our patients.”

Session moderator Gypsyamber D’Souza, PhD, an infectious disease epidemiologist at Johns Hopkins University in Baltimore, raised the question of whether the high nosocomial infection and death rate in this study was related to patients having more severe disease because of underlying comorbidities.

Dr. Elkrief explained that the overall mortality rate was indeed higher than the 13% reported in other studies, and it may reflect an overrepresentation of hospitalized or more severely ill patients in the cohort.

However, the investigators made every effort to include all patients with both cancer and COVID-19 by using systematic screening of inpatient and outpatients lists and registries.

Further, the multivariate analysis included both inpatients and outpatients and adjusted for known negative prognostic factors for COVID-19 outcomes. These included increasing age, poor performance status, and different comorbidities.

The finding that nosocomial infection was an independent predictor of death “pushed us to look at nosocomial infection as a new independent risk factor,” Dr. Elkrief said.

Dr. Elkrief reported grant support from AstraZeneca. Dr. D’Souza did not report any disclosures.

[email protected]

SOURCE: Elkrief A et al. AACR: COVID and Cancer, Abstract S12-01.

Hospitalized cancer patients have a high risk of nosocomial COVID-19 that is associated with increased mortality, so these patients should be treated in COVID-free zones, according to researchers.

In an observational study of patients with COVID-19 and cancer, 19% of patients had COVID-19 acquired during a non-COVID-related hospital stay, and 81% had community-acquired COVID-19.

At a median follow-up of 23 days, the overall mortality rate was 28%. However, the all-cause mortality rate in patients with nosocomial COVID-19 was more than double that of patients with community-acquired COVID-19, at 47% and 23%, respectively.

Arielle Elkrief, MD, of the University of Montreal, reported these results during the AACR virtual meeting: COVID-19 and Cancer.

“This is the first report that describes a high rate of hospital-acquired COVID-19 in patients with cancer, at a rate of 19%,” Dr. Elkrief said. “This was associated with high mortality in both univariate and multivariate analyses.”

The study included 250 adults and 3 children with COVID-19 and cancer who were identified between March 3 and May 23, 2020. They ranged in age from 4 to 95 years, but the median age was 73 years.

All patients had either laboratory-confirmed (95%) or presumed COVID-19 (5%) and invasive cancer. The most common cancer types were similar to those seen in the general population. Lung and breast cancer were the most common, followed by lymphoma, prostate cancer, and colorectal cancer. Most patients were on active anticancer therapy, most often chemotherapy.

Most patients (n = 236) were residents of Quebec, but 17 patients were residents of British Columbia.

“It is important to note that Quebec was one of the most heavily affected areas in North America at the time of the study,” Dr. Elkrief said.
 

Outcomes by group

There were 206 patients (81%) who had community-acquired COVID-19 and 47 (19%) who had nosocomial COVID-19. The two groups were similar with respect to sex, performance status, and cancer stage. A small trend toward more patients on active therapy was seen in the nosocomial group, but the difference did not reach statistical significance.

The median overall survival was 27 days in the nosocomial group and 71 days in the community-acquired group (hazard ratio, 2.2; P = .002).

A multivariate analysis showed that nosocomial infection was “strongly and independently associated with death,” Dr. Elkrief said. “Other risk factors for poor prognosis included age, poor [performance] status, and advanced stage of cancer.”

There were no significant differences between the hospital-acquired and community-acquired groups for other outcomes, including oxygen requirements (43% and 47%, respectively), ICU admission (13% and 11%), need for mechanical ventilation (6% and 5%), or length of stay (median, 9.5 days and 8.5 days).

The low rate of ICU admission, considering the mortality rate of 28%, “could reflect that patients with cancer are less likely to be admitted to the ICU,” Dr. Elkrief noted.
 

Applying the findings to practice

The findings reinforce the importance of adherence to stringent infection control guidelines to protect vulnerable patients, such as those with cancer, Dr. Elkrief said.

In ambulatory settings, this means decreasing in-person visits through increased use of teleconsultations, and for those who need to be seen in person, screening for symptoms or use of polymerase chain reaction testing should be used when resources are available, she said.

“Similar principles apply to chemotherapy treatment units,” Dr. Elkrief said. She added that staff must avoid cross-contamination between COVID and COVID-free zones, and that “dedicated personnel and equipment should be maintained and separate between these two zones.

“Adequate protective personal equipment and strict hand hygiene protocols are also of utmost importance,” Dr. Elkrief said. “The threat of COVID-19 is not behind us, and so we continue to enforce these strategies to protect our patients.”

Session moderator Gypsyamber D’Souza, PhD, an infectious disease epidemiologist at Johns Hopkins University in Baltimore, raised the question of whether the high nosocomial infection and death rate in this study was related to patients having more severe disease because of underlying comorbidities.

Dr. Elkrief explained that the overall mortality rate was indeed higher than the 13% reported in other studies, and it may reflect an overrepresentation of hospitalized or more severely ill patients in the cohort.

However, the investigators made every effort to include all patients with both cancer and COVID-19 by using systematic screening of inpatient and outpatients lists and registries.

Further, the multivariate analysis included both inpatients and outpatients and adjusted for known negative prognostic factors for COVID-19 outcomes. These included increasing age, poor performance status, and different comorbidities.

The finding that nosocomial infection was an independent predictor of death “pushed us to look at nosocomial infection as a new independent risk factor,” Dr. Elkrief said.

Dr. Elkrief reported grant support from AstraZeneca. Dr. D’Souza did not report any disclosures.

[email protected]

SOURCE: Elkrief A et al. AACR: COVID and Cancer, Abstract S12-01.

Hospitalized cancer patients have a high risk of nosocomial COVID-19 that is associated with increased mortality, so these patients should be treated in COVID-free zones, according to researchers.

In an observational study of patients with COVID-19 and cancer, 19% of patients had COVID-19 acquired during a non-COVID-related hospital stay, and 81% had community-acquired COVID-19.

At a median follow-up of 23 days, the overall mortality rate was 28%. However, the all-cause mortality rate in patients with nosocomial COVID-19 was more than double that of patients with community-acquired COVID-19, at 47% and 23%, respectively.

Arielle Elkrief, MD, of the University of Montreal, reported these results during the AACR virtual meeting: COVID-19 and Cancer.

“This is the first report that describes a high rate of hospital-acquired COVID-19 in patients with cancer, at a rate of 19%,” Dr. Elkrief said. “This was associated with high mortality in both univariate and multivariate analyses.”

The study included 250 adults and 3 children with COVID-19 and cancer who were identified between March 3 and May 23, 2020. They ranged in age from 4 to 95 years, but the median age was 73 years.

All patients had either laboratory-confirmed (95%) or presumed COVID-19 (5%) and invasive cancer. The most common cancer types were similar to those seen in the general population. Lung and breast cancer were the most common, followed by lymphoma, prostate cancer, and colorectal cancer. Most patients were on active anticancer therapy, most often chemotherapy.

Most patients (n = 236) were residents of Quebec, but 17 patients were residents of British Columbia.

“It is important to note that Quebec was one of the most heavily affected areas in North America at the time of the study,” Dr. Elkrief said.
 

Outcomes by group

There were 206 patients (81%) who had community-acquired COVID-19 and 47 (19%) who had nosocomial COVID-19. The two groups were similar with respect to sex, performance status, and cancer stage. A small trend toward more patients on active therapy was seen in the nosocomial group, but the difference did not reach statistical significance.

The median overall survival was 27 days in the nosocomial group and 71 days in the community-acquired group (hazard ratio, 2.2; P = .002).

A multivariate analysis showed that nosocomial infection was “strongly and independently associated with death,” Dr. Elkrief said. “Other risk factors for poor prognosis included age, poor [performance] status, and advanced stage of cancer.”

There were no significant differences between the hospital-acquired and community-acquired groups for other outcomes, including oxygen requirements (43% and 47%, respectively), ICU admission (13% and 11%), need for mechanical ventilation (6% and 5%), or length of stay (median, 9.5 days and 8.5 days).

The low rate of ICU admission, considering the mortality rate of 28%, “could reflect that patients with cancer are less likely to be admitted to the ICU,” Dr. Elkrief noted.
 

Applying the findings to practice

The findings reinforce the importance of adherence to stringent infection control guidelines to protect vulnerable patients, such as those with cancer, Dr. Elkrief said.

In ambulatory settings, this means decreasing in-person visits through increased use of teleconsultations, and for those who need to be seen in person, screening for symptoms or use of polymerase chain reaction testing should be used when resources are available, she said.

“Similar principles apply to chemotherapy treatment units,” Dr. Elkrief said. She added that staff must avoid cross-contamination between COVID and COVID-free zones, and that “dedicated personnel and equipment should be maintained and separate between these two zones.

“Adequate protective personal equipment and strict hand hygiene protocols are also of utmost importance,” Dr. Elkrief said. “The threat of COVID-19 is not behind us, and so we continue to enforce these strategies to protect our patients.”

Session moderator Gypsyamber D’Souza, PhD, an infectious disease epidemiologist at Johns Hopkins University in Baltimore, raised the question of whether the high nosocomial infection and death rate in this study was related to patients having more severe disease because of underlying comorbidities.

Dr. Elkrief explained that the overall mortality rate was indeed higher than the 13% reported in other studies, and it may reflect an overrepresentation of hospitalized or more severely ill patients in the cohort.

However, the investigators made every effort to include all patients with both cancer and COVID-19 by using systematic screening of inpatient and outpatients lists and registries.

Further, the multivariate analysis included both inpatients and outpatients and adjusted for known negative prognostic factors for COVID-19 outcomes. These included increasing age, poor performance status, and different comorbidities.

The finding that nosocomial infection was an independent predictor of death “pushed us to look at nosocomial infection as a new independent risk factor,” Dr. Elkrief said.

Dr. Elkrief reported grant support from AstraZeneca. Dr. D’Souza did not report any disclosures.

[email protected]

SOURCE: Elkrief A et al. AACR: COVID and Cancer, Abstract S12-01.

While SARS-CoV-2 causes frequent and potentially severe pulmonary disease, extrapulmonary manifestations may be a prominent part of the clinical spectrum, according to a review published in Nature Medicine.

In this comprehensive literature review, Aakriti Gupta, MD, of New York-Presbyterian/Columbia University Irving Medical Center and colleagues detailed the epidemiologic and clinical multisystem effects of COVID-19. The authors explained what is known and/or suspected about the pathophysiology of those effects and outlined the resultant management considerations.

Key mechanisms for multiorgan injury include direct viral toxicity, endothelial cell damage with inflammatory mediation of thrombosis, aberrant immune response, and dysregulation of the renin-angiotensin-aldosterone system.

The relative importance of each pathway in the clinical presentation of COVID-19 and the mechanism for extrapulmonary spread of SARS-CoV-2 infection are imperfectly understood, Dr. Gupta and colleagues noted.

As for the hematologic effects of COVID-19, patients may present with several laboratory abnormalities, but the most clinically relevant complications are thromboembolic.
 

COVID-19-associated coagulopathy

Dr. Gupta and colleagues noted that COVID-19–associated coagulopathy (CAC) is accompanied by elevated levels of D-dimer and fibrinogen, with minor abnormalities in prothrombin time, activated partial thromboplastin time, and platelet counts in the initial stage of infection.

Elevated D-dimer levels have been reported in up to 46% of hospitalized patients, and a longitudinal increase while hospitalized is associated with higher mortality.

In initial reports from China and the Netherlands, thrombotic complications were seen in up to 30% of COVID-19 patients in ICUs. Thromboembolic events have been reported in 17%-22% of critically ill COVID-19 patients in studies from Italy and France.

Globally, in severely affected COVID-19 patients, there have been reports of thromboses in intravenous catheters and extracorporeal circuits as well as arterial vascular occlusive events, including myocardial infarction, acute limb ischemia, and stroke.

There have been multiple small studies in which critically ill COVID-19 patients were routinely screened for thrombotic disease. In these studies, rates of thrombotic complications ranged from 69% to 85%, despite thromboprophylaxis. Variability in prophylactic and screening protocols explain discrepancies in event rates.
 

Pathophysiology

The abnormally high blood levels of D-dimer and fibrinogen during the early stages of SARS-CoV-2 infection are reflective of excessive inflammation rather than overt disseminated intravascular coagulation (DIC), which may develop in later stages of illness, according to Dr. Gupta and colleagues. The authors theorized that uninhibited inflammation, along with hypoxia and direct viral-mediated cellular injury, contribute to thrombotic complications in COVID-19 patients.

“The increased expression of ACE2 in endothelial cells after infection with SARS-CoV-2 may perpetuate a vicious cycle of endothelialitis that promotes thromboinflammation,” the authors wrote. “Collectively, hemostatic and inflammatory changes, which reflect endothelial damage and activation as well as critical illness, constitute a prothrombotic milieu.”

The authors noted that small autopsy series have shown high rates of microvascular and macrovascular thromboses, particularly in the pulmonary circulation, in COVID-19 patients.
 

Management considerations

Dr. Gupta and colleagues referenced interim guidelines from the International Society of Thrombosis and Haemostasis that recommend serial complete blood counts, with white blood cell differential and assessment of D-dimer, prothrombin time, and fibrinogen for hospitalized patients with COVID-19. The authors also cited guidelines published in the Journal of the American College of Cardiology that recommend routine risk assessment for venous thromboembolism in all hospitalized patients with COVID-19 and the consideration of standard-dose pharmaco-prophylaxis in patients who lack absolute contraindications.

Empiric use of higher-than-routine prophylactic-dose or therapeutic-dose anticoagulation in ICU patients in the absence of proven thromboses has been implemented in some institutions, Dr. Gupta and colleagues noted. Parenteral anticoagulants (such as low-molecular-weight or unfractionated heparin) are preferred to oral anticoagulants because of short half-life, available reversal agents, and the potential for drug interactions between oral agents and antiviral and/or antibacterial treatment, according to the authors.

They wrote that randomized clinical trials “will be crucial to establishing effective and safe strategies” for anticoagulation in COVID-19 patients. To this point, few randomized trials have been published to guide management of COVID-19–associated extrapulmonary manifestations, including CAC.
 

Research priorities

A more complete understanding of the organ-specific pathophysiology of this multisystem disease is vital, according to Dr. Gupta and colleagues.

“Regional, national, and international collaborations of clinicians and scientists focused on high-quality, transparent, ethical, and evidence-based research practices would help propel the global community toward achieving success against this pandemic,” the authors wrote.

They noted that common definitions and data standards for research are key for cross-institutional and international collaborations.

Initial attention to high-quality prospective scientific documentation standards would have been valuable and will be required for dedicated trials to address the multisystem effects of COVID-19.
 

Community of learners

As much as at any prior time in their careers, during the COVID-19 pandemic, health care providers have been enveloped in a community of learners – a group of people who share values and beliefs and who actively engage in learning from one another.

Through a patchwork of sources – news media, social media, traditional medical journals, general and COVID-focused meetings, and, most importantly, patients – we have been living in a learning-centered environment. Academicians, clinicians, practicing physicians, researchers, patients, family members, and caregivers have been actively and intentionally building a knowledge base together.

Through their published review, Dr. Gupta and colleagues have contributed meaningfully to the understanding our learning community has of the various extrapulmonary manifestations of COVID-19. The authors have provided a nice template for further research and clinical advances.

Dr. Gupta and colleagues disclosed financial relationships with a range of pharmaceutical companies and other organizations.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Source: Gupta A et al. Nat Med. 2020 Jul;26(7):1017-32.

While SARS-CoV-2 causes frequent and potentially severe pulmonary disease, extrapulmonary manifestations may be a prominent part of the clinical spectrum, according to a review published in Nature Medicine.

In this comprehensive literature review, Aakriti Gupta, MD, of New York-Presbyterian/Columbia University Irving Medical Center and colleagues detailed the epidemiologic and clinical multisystem effects of COVID-19. The authors explained what is known and/or suspected about the pathophysiology of those effects and outlined the resultant management considerations.

Key mechanisms for multiorgan injury include direct viral toxicity, endothelial cell damage with inflammatory mediation of thrombosis, aberrant immune response, and dysregulation of the renin-angiotensin-aldosterone system.

The relative importance of each pathway in the clinical presentation of COVID-19 and the mechanism for extrapulmonary spread of SARS-CoV-2 infection are imperfectly understood, Dr. Gupta and colleagues noted.

As for the hematologic effects of COVID-19, patients may present with several laboratory abnormalities, but the most clinically relevant complications are thromboembolic.
 

COVID-19-associated coagulopathy

Dr. Gupta and colleagues noted that COVID-19–associated coagulopathy (CAC) is accompanied by elevated levels of D-dimer and fibrinogen, with minor abnormalities in prothrombin time, activated partial thromboplastin time, and platelet counts in the initial stage of infection.

Elevated D-dimer levels have been reported in up to 46% of hospitalized patients, and a longitudinal increase while hospitalized is associated with higher mortality.

In initial reports from China and the Netherlands, thrombotic complications were seen in up to 30% of COVID-19 patients in ICUs. Thromboembolic events have been reported in 17%-22% of critically ill COVID-19 patients in studies from Italy and France.

Globally, in severely affected COVID-19 patients, there have been reports of thromboses in intravenous catheters and extracorporeal circuits as well as arterial vascular occlusive events, including myocardial infarction, acute limb ischemia, and stroke.

There have been multiple small studies in which critically ill COVID-19 patients were routinely screened for thrombotic disease. In these studies, rates of thrombotic complications ranged from 69% to 85%, despite thromboprophylaxis. Variability in prophylactic and screening protocols explain discrepancies in event rates.
 

Pathophysiology

The abnormally high blood levels of D-dimer and fibrinogen during the early stages of SARS-CoV-2 infection are reflective of excessive inflammation rather than overt disseminated intravascular coagulation (DIC), which may develop in later stages of illness, according to Dr. Gupta and colleagues. The authors theorized that uninhibited inflammation, along with hypoxia and direct viral-mediated cellular injury, contribute to thrombotic complications in COVID-19 patients.

“The increased expression of ACE2 in endothelial cells after infection with SARS-CoV-2 may perpetuate a vicious cycle of endothelialitis that promotes thromboinflammation,” the authors wrote. “Collectively, hemostatic and inflammatory changes, which reflect endothelial damage and activation as well as critical illness, constitute a prothrombotic milieu.”

The authors noted that small autopsy series have shown high rates of microvascular and macrovascular thromboses, particularly in the pulmonary circulation, in COVID-19 patients.
 

Management considerations

Dr. Gupta and colleagues referenced interim guidelines from the International Society of Thrombosis and Haemostasis that recommend serial complete blood counts, with white blood cell differential and assessment of D-dimer, prothrombin time, and fibrinogen for hospitalized patients with COVID-19. The authors also cited guidelines published in the Journal of the American College of Cardiology that recommend routine risk assessment for venous thromboembolism in all hospitalized patients with COVID-19 and the consideration of standard-dose pharmaco-prophylaxis in patients who lack absolute contraindications.

Empiric use of higher-than-routine prophylactic-dose or therapeutic-dose anticoagulation in ICU patients in the absence of proven thromboses has been implemented in some institutions, Dr. Gupta and colleagues noted. Parenteral anticoagulants (such as low-molecular-weight or unfractionated heparin) are preferred to oral anticoagulants because of short half-life, available reversal agents, and the potential for drug interactions between oral agents and antiviral and/or antibacterial treatment, according to the authors.

They wrote that randomized clinical trials “will be crucial to establishing effective and safe strategies” for anticoagulation in COVID-19 patients. To this point, few randomized trials have been published to guide management of COVID-19–associated extrapulmonary manifestations, including CAC.
 

Research priorities

A more complete understanding of the organ-specific pathophysiology of this multisystem disease is vital, according to Dr. Gupta and colleagues.

“Regional, national, and international collaborations of clinicians and scientists focused on high-quality, transparent, ethical, and evidence-based research practices would help propel the global community toward achieving success against this pandemic,” the authors wrote.

They noted that common definitions and data standards for research are key for cross-institutional and international collaborations.

Initial attention to high-quality prospective scientific documentation standards would have been valuable and will be required for dedicated trials to address the multisystem effects of COVID-19.
 

Community of learners

As much as at any prior time in their careers, during the COVID-19 pandemic, health care providers have been enveloped in a community of learners – a group of people who share values and beliefs and who actively engage in learning from one another.

Through a patchwork of sources – news media, social media, traditional medical journals, general and COVID-focused meetings, and, most importantly, patients – we have been living in a learning-centered environment. Academicians, clinicians, practicing physicians, researchers, patients, family members, and caregivers have been actively and intentionally building a knowledge base together.

Through their published review, Dr. Gupta and colleagues have contributed meaningfully to the understanding our learning community has of the various extrapulmonary manifestations of COVID-19. The authors have provided a nice template for further research and clinical advances.

Dr. Gupta and colleagues disclosed financial relationships with a range of pharmaceutical companies and other organizations.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Source: Gupta A et al. Nat Med. 2020 Jul;26(7):1017-32.

While SARS-CoV-2 causes frequent and potentially severe pulmonary disease, extrapulmonary manifestations may be a prominent part of the clinical spectrum, according to a review published in Nature Medicine.

In this comprehensive literature review, Aakriti Gupta, MD, of New York-Presbyterian/Columbia University Irving Medical Center and colleagues detailed the epidemiologic and clinical multisystem effects of COVID-19. The authors explained what is known and/or suspected about the pathophysiology of those effects and outlined the resultant management considerations.

Key mechanisms for multiorgan injury include direct viral toxicity, endothelial cell damage with inflammatory mediation of thrombosis, aberrant immune response, and dysregulation of the renin-angiotensin-aldosterone system.

The relative importance of each pathway in the clinical presentation of COVID-19 and the mechanism for extrapulmonary spread of SARS-CoV-2 infection are imperfectly understood, Dr. Gupta and colleagues noted.

As for the hematologic effects of COVID-19, patients may present with several laboratory abnormalities, but the most clinically relevant complications are thromboembolic.
 

COVID-19-associated coagulopathy

Dr. Gupta and colleagues noted that COVID-19–associated coagulopathy (CAC) is accompanied by elevated levels of D-dimer and fibrinogen, with minor abnormalities in prothrombin time, activated partial thromboplastin time, and platelet counts in the initial stage of infection.

Elevated D-dimer levels have been reported in up to 46% of hospitalized patients, and a longitudinal increase while hospitalized is associated with higher mortality.

In initial reports from China and the Netherlands, thrombotic complications were seen in up to 30% of COVID-19 patients in ICUs. Thromboembolic events have been reported in 17%-22% of critically ill COVID-19 patients in studies from Italy and France.

Globally, in severely affected COVID-19 patients, there have been reports of thromboses in intravenous catheters and extracorporeal circuits as well as arterial vascular occlusive events, including myocardial infarction, acute limb ischemia, and stroke.

There have been multiple small studies in which critically ill COVID-19 patients were routinely screened for thrombotic disease. In these studies, rates of thrombotic complications ranged from 69% to 85%, despite thromboprophylaxis. Variability in prophylactic and screening protocols explain discrepancies in event rates.
 

Pathophysiology

The abnormally high blood levels of D-dimer and fibrinogen during the early stages of SARS-CoV-2 infection are reflective of excessive inflammation rather than overt disseminated intravascular coagulation (DIC), which may develop in later stages of illness, according to Dr. Gupta and colleagues. The authors theorized that uninhibited inflammation, along with hypoxia and direct viral-mediated cellular injury, contribute to thrombotic complications in COVID-19 patients.

“The increased expression of ACE2 in endothelial cells after infection with SARS-CoV-2 may perpetuate a vicious cycle of endothelialitis that promotes thromboinflammation,” the authors wrote. “Collectively, hemostatic and inflammatory changes, which reflect endothelial damage and activation as well as critical illness, constitute a prothrombotic milieu.”

The authors noted that small autopsy series have shown high rates of microvascular and macrovascular thromboses, particularly in the pulmonary circulation, in COVID-19 patients.
 

Management considerations

Dr. Gupta and colleagues referenced interim guidelines from the International Society of Thrombosis and Haemostasis that recommend serial complete blood counts, with white blood cell differential and assessment of D-dimer, prothrombin time, and fibrinogen for hospitalized patients with COVID-19. The authors also cited guidelines published in the Journal of the American College of Cardiology that recommend routine risk assessment for venous thromboembolism in all hospitalized patients with COVID-19 and the consideration of standard-dose pharmaco-prophylaxis in patients who lack absolute contraindications.

Empiric use of higher-than-routine prophylactic-dose or therapeutic-dose anticoagulation in ICU patients in the absence of proven thromboses has been implemented in some institutions, Dr. Gupta and colleagues noted. Parenteral anticoagulants (such as low-molecular-weight or unfractionated heparin) are preferred to oral anticoagulants because of short half-life, available reversal agents, and the potential for drug interactions between oral agents and antiviral and/or antibacterial treatment, according to the authors.

They wrote that randomized clinical trials “will be crucial to establishing effective and safe strategies” for anticoagulation in COVID-19 patients. To this point, few randomized trials have been published to guide management of COVID-19–associated extrapulmonary manifestations, including CAC.
 

Research priorities

A more complete understanding of the organ-specific pathophysiology of this multisystem disease is vital, according to Dr. Gupta and colleagues.

“Regional, national, and international collaborations of clinicians and scientists focused on high-quality, transparent, ethical, and evidence-based research practices would help propel the global community toward achieving success against this pandemic,” the authors wrote.

They noted that common definitions and data standards for research are key for cross-institutional and international collaborations.

Initial attention to high-quality prospective scientific documentation standards would have been valuable and will be required for dedicated trials to address the multisystem effects of COVID-19.
 

Community of learners

As much as at any prior time in their careers, during the COVID-19 pandemic, health care providers have been enveloped in a community of learners – a group of people who share values and beliefs and who actively engage in learning from one another.

Through a patchwork of sources – news media, social media, traditional medical journals, general and COVID-focused meetings, and, most importantly, patients – we have been living in a learning-centered environment. Academicians, clinicians, practicing physicians, researchers, patients, family members, and caregivers have been actively and intentionally building a knowledge base together.

Through their published review, Dr. Gupta and colleagues have contributed meaningfully to the understanding our learning community has of the various extrapulmonary manifestations of COVID-19. The authors have provided a nice template for further research and clinical advances.

Dr. Gupta and colleagues disclosed financial relationships with a range of pharmaceutical companies and other organizations.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Source: Gupta A et al. Nat Med. 2020 Jul;26(7):1017-32.

The Food and Drug Administration granted accelerated approval to brexucabtagene autoleucel (Tecartus, Kite Pharma), the first approved chimeric antigen receptor (CAR) T cell therapy for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL).

The new agent is the second approved CAR T cell product developed by Kite and follows the 2017 approval of axicabtagene ciloleucel (Yescarta) for diffuse large B-cell lymphoma.

“Despite promising advances, there are still major gaps in treatment for patients with MCL who progress following initial therapy,” investigator Michael Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston, said in a company statement. “Many patients have high-risk disease and are more likely to keep progressing, even after subsequent treatments.”

In the same press statement, Meghan Gutierrez, chief executive officer, Lymphoma Research Foundation, said: “This approval marks the first CAR T cell therapy approved for mantle cell lymphoma patients and represents a new frontier in the treatment of this disease.”

The approval of the single-infusion therapy is based on efficacy and safety data from the ongoing, single-arm ZUMA-2 pivotal trial, which enrolled 74 adult patients. All patients had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody therapy and a Bruton tyrosine kinase inhibitor (ibrutinib or acalabrutinib).

In the trial, there was an objective response rate, which was the primary outcome measure, of 87% among 60 patients who were evaluable for efficacy analysis; 62% had a complete response. 

Among all patients, follow-up was at least 6 months after their first objective disease response. Median duration of response has not yet been reached.

In terms of adverse events, 18% of the 82 patients evaluable for safety experienced > grade 3 cytokine release syndrome and 37% experienced neurologic events, per the company statement. The most common (≥ 10%) grade 3 or higher adverse reactions were anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, infection-pathogen unspecified, pneumonia, hypocalcemia, and lymphopenia.

Brexucabtagene autoleucel will be manufactured in Kite’s facility in California. In the pivotal trial, there was a 96% manufacturing success rate and a median manufacturing turnaround time of 15 days from leukapheresis to product delivery.  
 

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

The Food and Drug Administration granted accelerated approval to brexucabtagene autoleucel (Tecartus, Kite Pharma), the first approved chimeric antigen receptor (CAR) T cell therapy for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL).

The new agent is the second approved CAR T cell product developed by Kite and follows the 2017 approval of axicabtagene ciloleucel (Yescarta) for diffuse large B-cell lymphoma.

“Despite promising advances, there are still major gaps in treatment for patients with MCL who progress following initial therapy,” investigator Michael Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston, said in a company statement. “Many patients have high-risk disease and are more likely to keep progressing, even after subsequent treatments.”

In the same press statement, Meghan Gutierrez, chief executive officer, Lymphoma Research Foundation, said: “This approval marks the first CAR T cell therapy approved for mantle cell lymphoma patients and represents a new frontier in the treatment of this disease.”

The approval of the single-infusion therapy is based on efficacy and safety data from the ongoing, single-arm ZUMA-2 pivotal trial, which enrolled 74 adult patients. All patients had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody therapy and a Bruton tyrosine kinase inhibitor (ibrutinib or acalabrutinib).

In the trial, there was an objective response rate, which was the primary outcome measure, of 87% among 60 patients who were evaluable for efficacy analysis; 62% had a complete response. 

Among all patients, follow-up was at least 6 months after their first objective disease response. Median duration of response has not yet been reached.

In terms of adverse events, 18% of the 82 patients evaluable for safety experienced > grade 3 cytokine release syndrome and 37% experienced neurologic events, per the company statement. The most common (≥ 10%) grade 3 or higher adverse reactions were anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, infection-pathogen unspecified, pneumonia, hypocalcemia, and lymphopenia.

Brexucabtagene autoleucel will be manufactured in Kite’s facility in California. In the pivotal trial, there was a 96% manufacturing success rate and a median manufacturing turnaround time of 15 days from leukapheresis to product delivery.  
 

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

The Food and Drug Administration granted accelerated approval to brexucabtagene autoleucel (Tecartus, Kite Pharma), the first approved chimeric antigen receptor (CAR) T cell therapy for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL).

The new agent is the second approved CAR T cell product developed by Kite and follows the 2017 approval of axicabtagene ciloleucel (Yescarta) for diffuse large B-cell lymphoma.

“Despite promising advances, there are still major gaps in treatment for patients with MCL who progress following initial therapy,” investigator Michael Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston, said in a company statement. “Many patients have high-risk disease and are more likely to keep progressing, even after subsequent treatments.”

In the same press statement, Meghan Gutierrez, chief executive officer, Lymphoma Research Foundation, said: “This approval marks the first CAR T cell therapy approved for mantle cell lymphoma patients and represents a new frontier in the treatment of this disease.”

The approval of the single-infusion therapy is based on efficacy and safety data from the ongoing, single-arm ZUMA-2 pivotal trial, which enrolled 74 adult patients. All patients had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody therapy and a Bruton tyrosine kinase inhibitor (ibrutinib or acalabrutinib).

In the trial, there was an objective response rate, which was the primary outcome measure, of 87% among 60 patients who were evaluable for efficacy analysis; 62% had a complete response. 

Among all patients, follow-up was at least 6 months after their first objective disease response. Median duration of response has not yet been reached.

In terms of adverse events, 18% of the 82 patients evaluable for safety experienced > grade 3 cytokine release syndrome and 37% experienced neurologic events, per the company statement. The most common (≥ 10%) grade 3 or higher adverse reactions were anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, infection-pathogen unspecified, pneumonia, hypocalcemia, and lymphopenia.

Brexucabtagene autoleucel will be manufactured in Kite’s facility in California. In the pivotal trial, there was a 96% manufacturing success rate and a median manufacturing turnaround time of 15 days from leukapheresis to product delivery.  
 

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