AVAHO

A substantial number of older women may experience worsening frailty after undergoing surgery and radiation therapy for early-stage breast cancer, according to a new study.

About 1 in 5 experienced clinically significant deterioration in frailty status after treatment, the study team found. Women at highest risk for declines in frailty following treatment had “robust” baseline frailty status at diagnosis and underwent more invasive mastectomy compared with lumpectomy.

The fact that “robust” older women were more likely to become frail after locoregional therapy suggests that “thoughtful treatment decisions should be undertaken in all older women, not simply those who have frailty at diagnosis,” said the investigators, led by Christina Minami, MD, of Dana-Farber/Brigham and Women’s Cancer Center in Boston.

The study findings emphasize that there is no one-size-fits-all approach to breast cancer treatment in the elderly, said Sarah P. Cate, MD, director, Breast Surgery Quality Program, Mount Sinai Health System, New York, who wasn’t involved in the research. “Some patients will sail through a surgery, and others are severely affected by it.”

The study was published online in JAMA Surgery.

Given the growing number of older adults with breast cancer, understanding how age-related syndromes, such as frailty, may alter cancer outcomes and how cancer treatments change aging trajectories remains important.

To investigate, Dr. Minami and colleagues used Surveillance, Epidemiology, and End Results Medicare data to identify 31,084 women (mean age, 73) who had been diagnosed with ductal carcinoma in situ (DCIS) or stage I HR-positive, ERBB2-positive breast cancer and who underwent surgery (23% mastectomy, 77% lumpectomy) and radiation therapy.

Worsening frailty status was defined as a decline of 0.03 or greater in a validated frailty index from the time of diagnosis to 1 year. This level of change has been linked to greater mortality risk and greater cost of care.

Frailty status at diagnosis was “robust” in 56% of the women, prefrail in 40%, mildly frail in 4%, and moderately to severely frail in 0.3%.

According to the researchers, 21.4% of the women experienced clinically significant declines in their frailty status after treatment. These declines occurred in 25% of women who underwent mastectomy and 20% of those who underwent lumpectomy.

After adjusting for covariates, there was a higher likelihood of worsening frailty among women who were robustly frail at baseline, in comparison with those who were moderately to severely frail at baseline (odds ratio, 6.12), and in those who underwent mastectomy vs. lumpectomy (OR, 1.31).

Older age and race were also linked to worsening frailty status following treatment. Compared with younger women (aged 65-74 years), older women were more likely to experience worsening frailty (OR, 1.21 for women aged 75-79; OR, 1.53 for those aged 80-84; OR, 1.94 for those aged 85 and older). In addition, Black women were more likely than non-Hispanic White women to experience worsening frailty after treatment (OR, 1.12).

“Previous studies have documented lasting declines in functional status after surgery in older patients with breast cancer, but breast cancer treatment has not been implicated in worsening frailty to date,” Dr. Minami and colleagues explain. But “given the substantial proportion of women experiencing worsening frailty and the significant difference by breast surgery type, frailty status as a cancer therapy outcome should be further explored.” In addition, “tailoring locoregional therapy intensity in this population is important,” they write.

Dr. Cate explained that randomized clinical trials such as COMET and LORIS, which explore the monitoring of patients with DCIS in lieu of active treatment, “will likely make a big impact on this population, as we currently do not have randomized controlled data for observation of breast cancer.”

Dr. Cate added as well that assessing a patient’s ECOG [Eastern Cooperative Oncology Group] performance status is vital “to determine who can really tolerate a breast cancer surgery” and that opting for antiestrogens, such as aromatase inhibitors, which can keep cancer at bay for years, “may be preferable for many older patients.”

The study was funded by Brigham and Women’s Hospital’s Department of Surgery’s Beal Fellowship. Dr. Minami and Dr. Cate have disclosed no relevant financial relationships.
 

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

A substantial number of older women may experience worsening frailty after undergoing surgery and radiation therapy for early-stage breast cancer, according to a new study.

About 1 in 5 experienced clinically significant deterioration in frailty status after treatment, the study team found. Women at highest risk for declines in frailty following treatment had “robust” baseline frailty status at diagnosis and underwent more invasive mastectomy compared with lumpectomy.

The fact that “robust” older women were more likely to become frail after locoregional therapy suggests that “thoughtful treatment decisions should be undertaken in all older women, not simply those who have frailty at diagnosis,” said the investigators, led by Christina Minami, MD, of Dana-Farber/Brigham and Women’s Cancer Center in Boston.

The study findings emphasize that there is no one-size-fits-all approach to breast cancer treatment in the elderly, said Sarah P. Cate, MD, director, Breast Surgery Quality Program, Mount Sinai Health System, New York, who wasn’t involved in the research. “Some patients will sail through a surgery, and others are severely affected by it.”

The study was published online in JAMA Surgery.

Given the growing number of older adults with breast cancer, understanding how age-related syndromes, such as frailty, may alter cancer outcomes and how cancer treatments change aging trajectories remains important.

To investigate, Dr. Minami and colleagues used Surveillance, Epidemiology, and End Results Medicare data to identify 31,084 women (mean age, 73) who had been diagnosed with ductal carcinoma in situ (DCIS) or stage I HR-positive, ERBB2-positive breast cancer and who underwent surgery (23% mastectomy, 77% lumpectomy) and radiation therapy.

Worsening frailty status was defined as a decline of 0.03 or greater in a validated frailty index from the time of diagnosis to 1 year. This level of change has been linked to greater mortality risk and greater cost of care.

Frailty status at diagnosis was “robust” in 56% of the women, prefrail in 40%, mildly frail in 4%, and moderately to severely frail in 0.3%.

According to the researchers, 21.4% of the women experienced clinically significant declines in their frailty status after treatment. These declines occurred in 25% of women who underwent mastectomy and 20% of those who underwent lumpectomy.

After adjusting for covariates, there was a higher likelihood of worsening frailty among women who were robustly frail at baseline, in comparison with those who were moderately to severely frail at baseline (odds ratio, 6.12), and in those who underwent mastectomy vs. lumpectomy (OR, 1.31).

Older age and race were also linked to worsening frailty status following treatment. Compared with younger women (aged 65-74 years), older women were more likely to experience worsening frailty (OR, 1.21 for women aged 75-79; OR, 1.53 for those aged 80-84; OR, 1.94 for those aged 85 and older). In addition, Black women were more likely than non-Hispanic White women to experience worsening frailty after treatment (OR, 1.12).

“Previous studies have documented lasting declines in functional status after surgery in older patients with breast cancer, but breast cancer treatment has not been implicated in worsening frailty to date,” Dr. Minami and colleagues explain. But “given the substantial proportion of women experiencing worsening frailty and the significant difference by breast surgery type, frailty status as a cancer therapy outcome should be further explored.” In addition, “tailoring locoregional therapy intensity in this population is important,” they write.

Dr. Cate explained that randomized clinical trials such as COMET and LORIS, which explore the monitoring of patients with DCIS in lieu of active treatment, “will likely make a big impact on this population, as we currently do not have randomized controlled data for observation of breast cancer.”

Dr. Cate added as well that assessing a patient’s ECOG [Eastern Cooperative Oncology Group] performance status is vital “to determine who can really tolerate a breast cancer surgery” and that opting for antiestrogens, such as aromatase inhibitors, which can keep cancer at bay for years, “may be preferable for many older patients.”

The study was funded by Brigham and Women’s Hospital’s Department of Surgery’s Beal Fellowship. Dr. Minami and Dr. Cate have disclosed no relevant financial relationships.
 

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

A substantial number of older women may experience worsening frailty after undergoing surgery and radiation therapy for early-stage breast cancer, according to a new study.

About 1 in 5 experienced clinically significant deterioration in frailty status after treatment, the study team found. Women at highest risk for declines in frailty following treatment had “robust” baseline frailty status at diagnosis and underwent more invasive mastectomy compared with lumpectomy.

The fact that “robust” older women were more likely to become frail after locoregional therapy suggests that “thoughtful treatment decisions should be undertaken in all older women, not simply those who have frailty at diagnosis,” said the investigators, led by Christina Minami, MD, of Dana-Farber/Brigham and Women’s Cancer Center in Boston.

The study findings emphasize that there is no one-size-fits-all approach to breast cancer treatment in the elderly, said Sarah P. Cate, MD, director, Breast Surgery Quality Program, Mount Sinai Health System, New York, who wasn’t involved in the research. “Some patients will sail through a surgery, and others are severely affected by it.”

The study was published online in JAMA Surgery.

Given the growing number of older adults with breast cancer, understanding how age-related syndromes, such as frailty, may alter cancer outcomes and how cancer treatments change aging trajectories remains important.

To investigate, Dr. Minami and colleagues used Surveillance, Epidemiology, and End Results Medicare data to identify 31,084 women (mean age, 73) who had been diagnosed with ductal carcinoma in situ (DCIS) or stage I HR-positive, ERBB2-positive breast cancer and who underwent surgery (23% mastectomy, 77% lumpectomy) and radiation therapy.

Worsening frailty status was defined as a decline of 0.03 or greater in a validated frailty index from the time of diagnosis to 1 year. This level of change has been linked to greater mortality risk and greater cost of care.

Frailty status at diagnosis was “robust” in 56% of the women, prefrail in 40%, mildly frail in 4%, and moderately to severely frail in 0.3%.

According to the researchers, 21.4% of the women experienced clinically significant declines in their frailty status after treatment. These declines occurred in 25% of women who underwent mastectomy and 20% of those who underwent lumpectomy.

After adjusting for covariates, there was a higher likelihood of worsening frailty among women who were robustly frail at baseline, in comparison with those who were moderately to severely frail at baseline (odds ratio, 6.12), and in those who underwent mastectomy vs. lumpectomy (OR, 1.31).

Older age and race were also linked to worsening frailty status following treatment. Compared with younger women (aged 65-74 years), older women were more likely to experience worsening frailty (OR, 1.21 for women aged 75-79; OR, 1.53 for those aged 80-84; OR, 1.94 for those aged 85 and older). In addition, Black women were more likely than non-Hispanic White women to experience worsening frailty after treatment (OR, 1.12).

“Previous studies have documented lasting declines in functional status after surgery in older patients with breast cancer, but breast cancer treatment has not been implicated in worsening frailty to date,” Dr. Minami and colleagues explain. But “given the substantial proportion of women experiencing worsening frailty and the significant difference by breast surgery type, frailty status as a cancer therapy outcome should be further explored.” In addition, “tailoring locoregional therapy intensity in this population is important,” they write.

Dr. Cate explained that randomized clinical trials such as COMET and LORIS, which explore the monitoring of patients with DCIS in lieu of active treatment, “will likely make a big impact on this population, as we currently do not have randomized controlled data for observation of breast cancer.”

Dr. Cate added as well that assessing a patient’s ECOG [Eastern Cooperative Oncology Group] performance status is vital “to determine who can really tolerate a breast cancer surgery” and that opting for antiestrogens, such as aromatase inhibitors, which can keep cancer at bay for years, “may be preferable for many older patients.”

The study was funded by Brigham and Women’s Hospital’s Department of Surgery’s Beal Fellowship. Dr. Minami and Dr. Cate have disclosed no relevant financial relationships.
 

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

A radioligand treatment approved for certain men with metastatic castration-resistant prostate cancer is in short supply because of manufacturing and delivery issues, according to the Food and Drug Administration. 

The therapy lutetium Lu 177 vipivotide tetraxetan (Pluvicto), approved in March 2022, will remain in limited supply until the drug’s manufacturer, Novartis, can ramp up production of the drug over the next 12 months.

In a letter in February, Novartis said it is giving priority to patients who have already started the regimen so they can “appropriately complete their course of therapy.” The manufacturer will not be taking any orders for new patients over the next 4-6 months, as they work to increase supply.

“We are operating our production site at full capacity to treat as many patients as possible, as quickly as possible,” Novartis said. “However, with a nuclear medicine like Pluvicto, there is no backup supply that we can draw from when we experience a delay.”

Pluvicto is currently made in small batches in the company’s manufacturing facility in Italy. The drug only has a 5-day window to reach its intended patient, after which time it cannot be used. Any disruption in the production or shipping process can create a delay.

Novartis said the facility in Italy is currently operating at full capacity and the company is “working to increase production capacity and supply” of the drug over the next 12 months at two new manufacturing sites in the United States. 

The company also encountered supply problems with Pluvicto in 2022 after quality issues were discovered in the manufacturing process.

Currently, patients who are waiting for their first dose of Pluvicto will need to be rescheduled. The manufacturer will be reaching out to health care professionals with options for rescheduling.

Jonathan McConathy, MD, PhD, told The Wall Street Journal that “people will die from this shortage, for sure.”

Dr. McConathy, a radiologist at the University of Alabama at Birmingham who has consulted for Novartis, explained that some patients who would have benefited from the drug likely won’t receive it in time.

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

A radioligand treatment approved for certain men with metastatic castration-resistant prostate cancer is in short supply because of manufacturing and delivery issues, according to the Food and Drug Administration. 

The therapy lutetium Lu 177 vipivotide tetraxetan (Pluvicto), approved in March 2022, will remain in limited supply until the drug’s manufacturer, Novartis, can ramp up production of the drug over the next 12 months.

In a letter in February, Novartis said it is giving priority to patients who have already started the regimen so they can “appropriately complete their course of therapy.” The manufacturer will not be taking any orders for new patients over the next 4-6 months, as they work to increase supply.

“We are operating our production site at full capacity to treat as many patients as possible, as quickly as possible,” Novartis said. “However, with a nuclear medicine like Pluvicto, there is no backup supply that we can draw from when we experience a delay.”

Pluvicto is currently made in small batches in the company’s manufacturing facility in Italy. The drug only has a 5-day window to reach its intended patient, after which time it cannot be used. Any disruption in the production or shipping process can create a delay.

Novartis said the facility in Italy is currently operating at full capacity and the company is “working to increase production capacity and supply” of the drug over the next 12 months at two new manufacturing sites in the United States. 

The company also encountered supply problems with Pluvicto in 2022 after quality issues were discovered in the manufacturing process.

Currently, patients who are waiting for their first dose of Pluvicto will need to be rescheduled. The manufacturer will be reaching out to health care professionals with options for rescheduling.

Jonathan McConathy, MD, PhD, told The Wall Street Journal that “people will die from this shortage, for sure.”

Dr. McConathy, a radiologist at the University of Alabama at Birmingham who has consulted for Novartis, explained that some patients who would have benefited from the drug likely won’t receive it in time.

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

A radioligand treatment approved for certain men with metastatic castration-resistant prostate cancer is in short supply because of manufacturing and delivery issues, according to the Food and Drug Administration. 

The therapy lutetium Lu 177 vipivotide tetraxetan (Pluvicto), approved in March 2022, will remain in limited supply until the drug’s manufacturer, Novartis, can ramp up production of the drug over the next 12 months.

In a letter in February, Novartis said it is giving priority to patients who have already started the regimen so they can “appropriately complete their course of therapy.” The manufacturer will not be taking any orders for new patients over the next 4-6 months, as they work to increase supply.

“We are operating our production site at full capacity to treat as many patients as possible, as quickly as possible,” Novartis said. “However, with a nuclear medicine like Pluvicto, there is no backup supply that we can draw from when we experience a delay.”

Pluvicto is currently made in small batches in the company’s manufacturing facility in Italy. The drug only has a 5-day window to reach its intended patient, after which time it cannot be used. Any disruption in the production or shipping process can create a delay.

Novartis said the facility in Italy is currently operating at full capacity and the company is “working to increase production capacity and supply” of the drug over the next 12 months at two new manufacturing sites in the United States. 

The company also encountered supply problems with Pluvicto in 2022 after quality issues were discovered in the manufacturing process.

Currently, patients who are waiting for their first dose of Pluvicto will need to be rescheduled. The manufacturer will be reaching out to health care professionals with options for rescheduling.

Jonathan McConathy, MD, PhD, told The Wall Street Journal that “people will die from this shortage, for sure.”

Dr. McConathy, a radiologist at the University of Alabama at Birmingham who has consulted for Novartis, explained that some patients who would have benefited from the drug likely won’t receive it in time.

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

If a patient’s prostate-specific antigen (PSA) spikes 2 points in just 90 days, what is your first thought? This patient has a strong likelihood of aggressive prostate cancer, right? If that same patient also presents with severe, burning bone pain with no precipitating trauma to the area and rest and over-the-counter  painkillers are not helping, you’d think, “check for metastases,” right?

That patient was me in late January 2023.

As a research scientist member of the American Urological Association, I knew enough to know I had to consult my urologist ASAP.

With the above symptoms, I’ll admit I was scared. Fortunately, if that’s the right word, I was no stranger to a rapid, dramatic spike in PSA. In 2021 I was temporarily living in a new city, and I wanted to form a relationship with a good local urologist. The urologist that I was referred to gave me a thorough consultation, including a vigorous digital rectal exam (DRE) and sent me across the street for a blood draw.

To my shock, my PSA had spiked over 2 points, to 9.9 from 7.8 a few months earlier. I freaked. Had my 3-cm tumor burst out into an aggressive cancer? Research on PubMed provided an array of studies showing what could cause PSA to suddenly rise, including a DRE performed 72 hours before the blood draw.1 A week later, my PSA was back down to its normal 7.6. 

But in January 2023, I had none of those previously reported experiences that could suddenly trigger a spike in PSA, like a DRE or riding on a thin bicycle seat for a few hours before the lab visit. 
 

The COVID effect

I went back to PubMed and found a new circumstance that could cause a surge in PSA: COVID-19. A recent study² of 91 men with benign prostatic hypertrophy by researchers in Turkey found that PSA spiked from 0 to 5 points during the COVID infection period and up to 2 points higher 3 months after the infection had cleared. I had tested positive for COVID-19 in mid-December 2022, 4 weeks before my 9.9 PSA reading.

Using Google translate, I communicated with the team in Turkey and found out that the PSA spike can last up to 6 months.

That study helps explain why my PSA dropped over 1.5 points to 8.5 just 2 weeks after the 9.9 reading, with the expectation that it would return to its previous normal of 7.8 within 6 months of infection with SARS-CoV-2. To be safe, my urologist scheduled another PSA test in May, along with an updated multiparametric MRI, which may be followed by an in-bore MRI-guided biopsy of the 3-cm tumor if the mass has enlarged.
 

COVID-19 pain

What about my burning bone pain in my upper right humerus and right rotator cuff that was not precipitated by trauma or strain? A radiograph found no evidence of metastasis, thank goodness. And my research showed that several studies³ have found that COVID-19 can cause burning musculoskeletal pain, including enthesopathy, which is what I had per the radiology report. So my PSA spike and searing pain were likely consequences of the infection.

To avoid the risk for a gross misdiagnosis after a radical spike in PSA, the informed urologist should ask the patient if he has had COVID-19 in the previous 6 months. Overlooking that question could lead to the wrong diagnostic decisions about a rapid jump in PSA or unexplained bone pain.

References

1. Bossens MM et al. Eur J Cancer. 1995;31A:682-5.

2. Cinislioglu AE et al. Urology. 2022;159:16-21.

3. Ciaffi J et al. Joint Bone Spine. 2021;88:105158.

Dr. Keller is founder of the Keller Research Institute, Jacksonville, Fla. He reported serving as a research scientist for the American Urological Association, serving on the advisory board of Active Surveillance Patient’s International, and serving on the boards of numerous nonprofit organizations.

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

If a patient’s prostate-specific antigen (PSA) spikes 2 points in just 90 days, what is your first thought? This patient has a strong likelihood of aggressive prostate cancer, right? If that same patient also presents with severe, burning bone pain with no precipitating trauma to the area and rest and over-the-counter  painkillers are not helping, you’d think, “check for metastases,” right?

That patient was me in late January 2023.

As a research scientist member of the American Urological Association, I knew enough to know I had to consult my urologist ASAP.

With the above symptoms, I’ll admit I was scared. Fortunately, if that’s the right word, I was no stranger to a rapid, dramatic spike in PSA. In 2021 I was temporarily living in a new city, and I wanted to form a relationship with a good local urologist. The urologist that I was referred to gave me a thorough consultation, including a vigorous digital rectal exam (DRE) and sent me across the street for a blood draw.

To my shock, my PSA had spiked over 2 points, to 9.9 from 7.8 a few months earlier. I freaked. Had my 3-cm tumor burst out into an aggressive cancer? Research on PubMed provided an array of studies showing what could cause PSA to suddenly rise, including a DRE performed 72 hours before the blood draw.1 A week later, my PSA was back down to its normal 7.6. 

But in January 2023, I had none of those previously reported experiences that could suddenly trigger a spike in PSA, like a DRE or riding on a thin bicycle seat for a few hours before the lab visit. 
 

The COVID effect

I went back to PubMed and found a new circumstance that could cause a surge in PSA: COVID-19. A recent study² of 91 men with benign prostatic hypertrophy by researchers in Turkey found that PSA spiked from 0 to 5 points during the COVID infection period and up to 2 points higher 3 months after the infection had cleared. I had tested positive for COVID-19 in mid-December 2022, 4 weeks before my 9.9 PSA reading.

Using Google translate, I communicated with the team in Turkey and found out that the PSA spike can last up to 6 months.

That study helps explain why my PSA dropped over 1.5 points to 8.5 just 2 weeks after the 9.9 reading, with the expectation that it would return to its previous normal of 7.8 within 6 months of infection with SARS-CoV-2. To be safe, my urologist scheduled another PSA test in May, along with an updated multiparametric MRI, which may be followed by an in-bore MRI-guided biopsy of the 3-cm tumor if the mass has enlarged.
 

COVID-19 pain

What about my burning bone pain in my upper right humerus and right rotator cuff that was not precipitated by trauma or strain? A radiograph found no evidence of metastasis, thank goodness. And my research showed that several studies³ have found that COVID-19 can cause burning musculoskeletal pain, including enthesopathy, which is what I had per the radiology report. So my PSA spike and searing pain were likely consequences of the infection.

To avoid the risk for a gross misdiagnosis after a radical spike in PSA, the informed urologist should ask the patient if he has had COVID-19 in the previous 6 months. Overlooking that question could lead to the wrong diagnostic decisions about a rapid jump in PSA or unexplained bone pain.

References

1. Bossens MM et al. Eur J Cancer. 1995;31A:682-5.

2. Cinislioglu AE et al. Urology. 2022;159:16-21.

3. Ciaffi J et al. Joint Bone Spine. 2021;88:105158.

Dr. Keller is founder of the Keller Research Institute, Jacksonville, Fla. He reported serving as a research scientist for the American Urological Association, serving on the advisory board of Active Surveillance Patient’s International, and serving on the boards of numerous nonprofit organizations.

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

If a patient’s prostate-specific antigen (PSA) spikes 2 points in just 90 days, what is your first thought? This patient has a strong likelihood of aggressive prostate cancer, right? If that same patient also presents with severe, burning bone pain with no precipitating trauma to the area and rest and over-the-counter  painkillers are not helping, you’d think, “check for metastases,” right?

That patient was me in late January 2023.

As a research scientist member of the American Urological Association, I knew enough to know I had to consult my urologist ASAP.

With the above symptoms, I’ll admit I was scared. Fortunately, if that’s the right word, I was no stranger to a rapid, dramatic spike in PSA. In 2021 I was temporarily living in a new city, and I wanted to form a relationship with a good local urologist. The urologist that I was referred to gave me a thorough consultation, including a vigorous digital rectal exam (DRE) and sent me across the street for a blood draw.

To my shock, my PSA had spiked over 2 points, to 9.9 from 7.8 a few months earlier. I freaked. Had my 3-cm tumor burst out into an aggressive cancer? Research on PubMed provided an array of studies showing what could cause PSA to suddenly rise, including a DRE performed 72 hours before the blood draw.1 A week later, my PSA was back down to its normal 7.6. 

But in January 2023, I had none of those previously reported experiences that could suddenly trigger a spike in PSA, like a DRE or riding on a thin bicycle seat for a few hours before the lab visit. 
 

The COVID effect

I went back to PubMed and found a new circumstance that could cause a surge in PSA: COVID-19. A recent study² of 91 men with benign prostatic hypertrophy by researchers in Turkey found that PSA spiked from 0 to 5 points during the COVID infection period and up to 2 points higher 3 months after the infection had cleared. I had tested positive for COVID-19 in mid-December 2022, 4 weeks before my 9.9 PSA reading.

Using Google translate, I communicated with the team in Turkey and found out that the PSA spike can last up to 6 months.

That study helps explain why my PSA dropped over 1.5 points to 8.5 just 2 weeks after the 9.9 reading, with the expectation that it would return to its previous normal of 7.8 within 6 months of infection with SARS-CoV-2. To be safe, my urologist scheduled another PSA test in May, along with an updated multiparametric MRI, which may be followed by an in-bore MRI-guided biopsy of the 3-cm tumor if the mass has enlarged.
 

COVID-19 pain

What about my burning bone pain in my upper right humerus and right rotator cuff that was not precipitated by trauma or strain? A radiograph found no evidence of metastasis, thank goodness. And my research showed that several studies³ have found that COVID-19 can cause burning musculoskeletal pain, including enthesopathy, which is what I had per the radiology report. So my PSA spike and searing pain were likely consequences of the infection.

To avoid the risk for a gross misdiagnosis after a radical spike in PSA, the informed urologist should ask the patient if he has had COVID-19 in the previous 6 months. Overlooking that question could lead to the wrong diagnostic decisions about a rapid jump in PSA or unexplained bone pain.

References

1. Bossens MM et al. Eur J Cancer. 1995;31A:682-5.

2. Cinislioglu AE et al. Urology. 2022;159:16-21.

3. Ciaffi J et al. Joint Bone Spine. 2021;88:105158.

Dr. Keller is founder of the Keller Research Institute, Jacksonville, Fla. He reported serving as a research scientist for the American Urological Association, serving on the advisory board of Active Surveillance Patient’s International, and serving on the boards of numerous nonprofit organizations.

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

Patients who are already depressed before they receive a lung cancer diagnosis are more likely to have a worse overall survival (OS), and the driver for this may be inflammation, suggests a new study.

The findings underscore the importance of assessing and treating depression in patients with cancer, particularly given the high rate of depression among those with lung cancer versus other types of cancer, the investigators said.

The study involved 186 patients with newly diagnosed stage IV non–small cell lung cancer (NSCLC), of whom 35% had self-reported moderate to severe depressive symptoms.

Depression was reliably associated with lung-relevant systemic inflammation responses (SIRs), which included neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and Advanced Lung Cancer Inflammation Index (ALI) score.

These SIRs were prognostic for 2-year OS.

Overall mortality at 2 years was 61%. Higher NLRs and PLRs and lower ALI scores all predicted worse OS (hazard ratio, 1.91, 2.08, and 0.53, respectively).

The findings were published online in PLoS ONE (2023 Feb 24.

“These patients with high levels of depression are at much higher risk for poor outcomes,” but the key finding was that patients with the highest depression levels were driving the relationship, lead author Barbara Andersen, PhD, professor of psychology at Ohio State University, Columbus, stated in a press release.

“It was patients with high depression levels who had strikingly higher inflammation levels, and that is what really drove the correlation we saw,” she explained.

For example, 56% of patients with no depression symptoms or only mild depression symptoms had a PLR above the cutoff for dangerous levels of inflammation, compared with 42% whose PLR was below the cutoff. However, among those with high depression levels, 77% and 23% had a PLR above and below the cutoff, respectively.

“These highly depressed patients were 1.3-3 times more likely to have high inflammation levels, even after controlling for other factors related to inflammation biomarker levels, including demographics and smoking status,” Dr. Andersen noted.

“Depression levels may be as important or even more important than other factors that have been associated with how people fare with lung cancer,” she suggested.

In a previous study, the team controlled for baseline depression and found that “the trajectory of depression from diagnosis through 2 years (18 assessments) predicted NSCLC patients’ survival (HR, 1.09), above and beyond baseline depression, sociodemographics, smoking status, cell type, and receipt of targeted treatments and immunotherapies.”

“Taken together, data support psychological, behavioral, and biologic toxicities of depression capable of influencing treatment response and/or survival,” they wrote.

“The results may help explain why a substantial portion of lung cancer patients fail to respond to new immunotherapy and targeted treatments that have led to significantly longer survival for many people with the disease,” Dr. Andersen said.

The investigators concluded that “intensive study of depression among patients with NSCLC, combined with measures of cell biology, inflammation, and immunity, is needed to extend these findings and discover their mechanisms, with the long-term aim to improve patients’ quality of life, treatment responses, and longevity.”

This study was funded by the Ohio State University Comprehensive Cancer Center and Pelotonia through grants to individual authors. Dr. Andersen reported having no relevant disclosures.

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

Patients who are already depressed before they receive a lung cancer diagnosis are more likely to have a worse overall survival (OS), and the driver for this may be inflammation, suggests a new study.

The findings underscore the importance of assessing and treating depression in patients with cancer, particularly given the high rate of depression among those with lung cancer versus other types of cancer, the investigators said.

The study involved 186 patients with newly diagnosed stage IV non–small cell lung cancer (NSCLC), of whom 35% had self-reported moderate to severe depressive symptoms.

Depression was reliably associated with lung-relevant systemic inflammation responses (SIRs), which included neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and Advanced Lung Cancer Inflammation Index (ALI) score.

These SIRs were prognostic for 2-year OS.

Overall mortality at 2 years was 61%. Higher NLRs and PLRs and lower ALI scores all predicted worse OS (hazard ratio, 1.91, 2.08, and 0.53, respectively).

The findings were published online in PLoS ONE (2023 Feb 24.

“These patients with high levels of depression are at much higher risk for poor outcomes,” but the key finding was that patients with the highest depression levels were driving the relationship, lead author Barbara Andersen, PhD, professor of psychology at Ohio State University, Columbus, stated in a press release.

“It was patients with high depression levels who had strikingly higher inflammation levels, and that is what really drove the correlation we saw,” she explained.

For example, 56% of patients with no depression symptoms or only mild depression symptoms had a PLR above the cutoff for dangerous levels of inflammation, compared with 42% whose PLR was below the cutoff. However, among those with high depression levels, 77% and 23% had a PLR above and below the cutoff, respectively.

“These highly depressed patients were 1.3-3 times more likely to have high inflammation levels, even after controlling for other factors related to inflammation biomarker levels, including demographics and smoking status,” Dr. Andersen noted.

“Depression levels may be as important or even more important than other factors that have been associated with how people fare with lung cancer,” she suggested.

In a previous study, the team controlled for baseline depression and found that “the trajectory of depression from diagnosis through 2 years (18 assessments) predicted NSCLC patients’ survival (HR, 1.09), above and beyond baseline depression, sociodemographics, smoking status, cell type, and receipt of targeted treatments and immunotherapies.”

“Taken together, data support psychological, behavioral, and biologic toxicities of depression capable of influencing treatment response and/or survival,” they wrote.

“The results may help explain why a substantial portion of lung cancer patients fail to respond to new immunotherapy and targeted treatments that have led to significantly longer survival for many people with the disease,” Dr. Andersen said.

The investigators concluded that “intensive study of depression among patients with NSCLC, combined with measures of cell biology, inflammation, and immunity, is needed to extend these findings and discover their mechanisms, with the long-term aim to improve patients’ quality of life, treatment responses, and longevity.”

This study was funded by the Ohio State University Comprehensive Cancer Center and Pelotonia through grants to individual authors. Dr. Andersen reported having no relevant disclosures.

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

Patients who are already depressed before they receive a lung cancer diagnosis are more likely to have a worse overall survival (OS), and the driver for this may be inflammation, suggests a new study.

The findings underscore the importance of assessing and treating depression in patients with cancer, particularly given the high rate of depression among those with lung cancer versus other types of cancer, the investigators said.

The study involved 186 patients with newly diagnosed stage IV non–small cell lung cancer (NSCLC), of whom 35% had self-reported moderate to severe depressive symptoms.

Depression was reliably associated with lung-relevant systemic inflammation responses (SIRs), which included neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and Advanced Lung Cancer Inflammation Index (ALI) score.

These SIRs were prognostic for 2-year OS.

Overall mortality at 2 years was 61%. Higher NLRs and PLRs and lower ALI scores all predicted worse OS (hazard ratio, 1.91, 2.08, and 0.53, respectively).

The findings were published online in PLoS ONE (2023 Feb 24.

“These patients with high levels of depression are at much higher risk for poor outcomes,” but the key finding was that patients with the highest depression levels were driving the relationship, lead author Barbara Andersen, PhD, professor of psychology at Ohio State University, Columbus, stated in a press release.

“It was patients with high depression levels who had strikingly higher inflammation levels, and that is what really drove the correlation we saw,” she explained.

For example, 56% of patients with no depression symptoms or only mild depression symptoms had a PLR above the cutoff for dangerous levels of inflammation, compared with 42% whose PLR was below the cutoff. However, among those with high depression levels, 77% and 23% had a PLR above and below the cutoff, respectively.

“These highly depressed patients were 1.3-3 times more likely to have high inflammation levels, even after controlling for other factors related to inflammation biomarker levels, including demographics and smoking status,” Dr. Andersen noted.

“Depression levels may be as important or even more important than other factors that have been associated with how people fare with lung cancer,” she suggested.

In a previous study, the team controlled for baseline depression and found that “the trajectory of depression from diagnosis through 2 years (18 assessments) predicted NSCLC patients’ survival (HR, 1.09), above and beyond baseline depression, sociodemographics, smoking status, cell type, and receipt of targeted treatments and immunotherapies.”

“Taken together, data support psychological, behavioral, and biologic toxicities of depression capable of influencing treatment response and/or survival,” they wrote.

“The results may help explain why a substantial portion of lung cancer patients fail to respond to new immunotherapy and targeted treatments that have led to significantly longer survival for many people with the disease,” Dr. Andersen said.

The investigators concluded that “intensive study of depression among patients with NSCLC, combined with measures of cell biology, inflammation, and immunity, is needed to extend these findings and discover their mechanisms, with the long-term aim to improve patients’ quality of life, treatment responses, and longevity.”

This study was funded by the Ohio State University Comprehensive Cancer Center and Pelotonia through grants to individual authors. Dr. Andersen reported having no relevant disclosures.

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

Until just over a year ago, Pat Trueman, an 82-year-old in New Hampshire, had always been a “go-go-go” kind of person. Then she started feeling tired easily, even while doing basic housework.

“I had no stamina,” Ms. Trueman said. “I didn’t feel that bad, but I just couldn’t do anything.” She had also begun noticing black and blue bruises appearing on her body, so she met with her cardiologist. But when switching medications and getting a pacemaker didn’t rid Ms. Trueman of the symptoms, her doctor referred her to a hematologist oncologist.

A bone marrow biopsy eventually revealed that Ms. Trueman had myelodysplastic neoplasms, or MDS, a blood cancer affecting an estimated 60,000-170,000 people in the United States, mostly over age 60. MDS includes several bone marrow disorders in which the bone marrow does not produce enough healthy, normal blood cells. Cytopenias are therefore a key feature of MDS, whether it’s anemia (in Ms. Trueman’s case), neutropenia, or thrombocytopenia.

Jamie Koprivnikar, MD, a hematologist oncologist at Hackensack (N.J) University Medical Center, describes the condition to her patients using a factory metaphor: “Our bone marrow is the factory where the red blood cells, white blood cells, and platelets are made, and MDS is where the machinery of the factory is broken, so the factory is making defective parts and not enough parts.”

courtesy Chad Hunt

The paradox of MDS is that too many cells are in the bone marrow while too few are in the blood, since most in the marrow die before reaching the blood, explained Azra Raza, MD, a professor of medicine and director of the MDS Center at Columbia University Medical Center, New York, and author of The First Cell (New York: Basic Books, 2019).

Although MDS is not rare, the condition has seen remarkably few new therapies in recent years. Most are either improvements on an existing treatment – such as an oral formulation of an infused drug – or a drug borrowed from therapies for other blood cancers, particularly acute myeloid leukemia (AML).

“We’re looking at taking a lot of the therapies that we’ve used to treat AML and then trying to apply them to MDS,” Dr. Koprivnikar said. “With all the improvement that we’re seeing there with leukemia, we’re definitely expecting this trickle-down effect to also help our high-risk MDS patients.”
 

Workup begins with risk stratification

While different types of MDS exist, based on morphology of the blood cells, after diagnosis the most important determination to make is of the patient’s risk level, based on the International Prognostic Scoring System–Revised (IPSS-R), updated in 2022.

While there are six MDS risk levels, patients generally fall into the high-risk and low-risk categories. The risk-level workup includes “a bone marrow biopsy with morphology, looking at how many blasts they have, looking for dysplasia, cytogenetics, and a full spectrum myeloid mutation testing, or molecular testing,” according to Anna Halpern, MD, an assistant professor of hematology in the clinical research division at Fred Hutchinson Cancer Center, Seattle. ”I use that information and along with their age, in some cases to calculate an IPSS-M or IPPS-R score, and what goes into that risk stratification includes how low their blood counts are as well as any adverse risks features we might see in their marrow, like adverse risk genetics, adverse risk mutations or increased blasts.”

Treatment decisions then turn on whether a patient is high risk – about a third of MDS patients – or low risk, because those treatment goals differ.

“With low-risk, the goal is to improve quality of life,” Dr. Raza said. “For higher-risk MDS, the goal is to prolong survival and delay progression to acute leukemia” since nearly a third of MDS patients will eventually develop AML.

More specifically, the aim with low-risk MDS is “to foster transfusion independence, either to prevent transfusions or to decrease the need for transfusions in people already receiving them,” explained Ellen Ritchie, MD, an assistant professor of medicine and hematologist-oncologist at Weill Cornell Medicine, New York. “We’re not hoping so much to cure the myelofibrosis at that point, but rather to improve blood counts.”

Sometimes, Dr. Halpern said, such treatment means active surveillance monitoring of blood counts, and at other times, it means treating cytopenia – most often anemia. The erythropoiesis-stimulating agents used to treat anemia are epoetin alfa (Epogen/Procrit) or darbepoetin alfa (Aranesp).

Ms. Trueman, whose MDS is low risk, started taking Aranesp, but she didn’t feel well on the drug and didn’t think it was helping much. She was taken off that drug and now relies only on transfusions for treatment, when her blood counts fall too low.

A newer anemia medication, luspatercept (Reblozyl), was approved in 2020 but is reserved primarily for those who fail one of the other erythropoiesis-stimulating agents and have a subtype of MDS with ring sideroblasts. Although white blood cell and platelet growth factors exist for other cytopenias, they’re rarely used because they offer little survival benefit and carry risks, Dr. Halpern said. The only other medication typically used for low-risk MDS is lenalidomide (Revlimid), which is reserved only for those with 5q-deletion syndrome.

The goal of treating high-risk MDS, on the other hand, is to cure it – when possible.

“The only curative approach for MDS is an allogeneic stem cell transplant or bone marrow transplant,” Dr. Halpern said, but transplants carry high rates of morbidity and mortality and therefore require a base level of physical fitness for a patient to consider it.

Dr. Koprivnikar observed that “MDS is certainly a disease of the elderly, and with each increasing decade of life, incidence increases. So there are a lot of patients who do not qualify for transplant.”

Age is not the sole determining factor, however. Dr. Ritchie noted that transplants can be offered to patients up to age 75 and sometimes older, depending on their physical condition. “It all depends upon the patient, their fitness, how much caretaker support they have, and what their comorbid illnesses are.”

If a transplant isn’t an option, Dr. Halpern and Dr. Raza said, they steer patients toward clinical trial participation. Otherwise, the first-line treatment is chemotherapy with hypomethylating agents to hopefully put patients in remission, Dr. Ritchie said.

The main chemo agents for high-risk patients ineligible for transplant are azacitidine (Vidaza) or decitabine (Dacogen), offered indefinitely until patients stop responding or experience progression or intolerance, Dr. Koprivnikar said. The only recently approved drug in this space is Inqovi, which is not a new agent, but it provides decitabine and cedazuridine in an oral pill form, so that patients can avoid infusions.
 

Treatment gaps

Few treatments options currently exist for patients with MDS, beyond erythropoiesis-stimulating agents for low-risk MDS and chemotherapy or transplant for high-risk MDS, as well as lenalidomide and luspatercept for specific subpopulations. With few breakthroughs occurring, Dr. Halpern expects that progress will only happen gradually, with new treatments coming primarily in the form of AML therapies.

“The biggest gap in our MDS regimen is treatment that can successfully treat or alter the natural history of TP53-mutated disease,” said Dr. Halpern, referring to an adverse risk mutation that can occur spontaneously or as a result of exposure to chemotherapy or radiation. “TP53-mutated MDS is very challenging to treat, and we have not had any successful therapy, so that is the biggest area of need.”

The most promising possibility in that area is an anti-CD47 drug called magrolimab, a drug being tested in a trial of which Dr. Halpern is a principal investigator. Not yet approved, magrolimab has been showing promise for AML when given with azacitidine (Vidaza) and venetoclax (Venclexta).

Venetoclax, currently used for AML, is another drug that Dr. Halpern expects to be approved for MDS soon. A phase 1b trial presented at the 2021 annual meeting of the American Hematology Society found that more than three-quarters of patients with high-risk MDS responded to the combination of venetoclax and azacitidine.

Unlike so many other cancers, MDS has seen little success with immunotherapy, which tends to have too much toxicity for patients with MDS. While Dr. Halpern sees potential for more exploration in this realm, she doesn’t anticipate immunotherapy or chimeric antigen receptor T-cell therapy becoming treatments for MDS in the near future.

“What I do think is, hopefully, we will have better treatment for TP53-mutated disease,” she said, while adding that there are currently no standard options for patients who stopped responding or don’t respond to hypomethylating agents.

Similarly, few new treatments have emerged for low-risk MDS, but there a couple of possibilities on the horizon.

“For a while, low-risk, transfusion-dependent MDS was an area that was being overlooked, and we are starting to see more activity in that area as well, with more drugs being developed,” Dr. Koprivnikar said. Drugs showing promise include imetelstat – an investigative telomerase inhibitor – and IRAK inhibitors. A phase 3 trial of imetelstat recently met its primary endpoint of 8 weeks of transfusion independence in low-risk MDS patients who aren’t responding to or cannot take erythropoiesis-stimulating agents, like Ms. Trueman. If effective and approved, a drug like imetelstat may allow patients like Ms. Trueman to resume some activities that she misses now.

“I have so much energy in my head, and I want to do so much, but I can’t,” Ms. Trueman said. “Now I think I’m getting lazy and I don’t like it because I’m not that kind of person. It’s pretty hard.”

Dr. Raza disclosed relationships with Epizyme, Grail, Vor, Taiho, RareCells, and TFC Therapeutics. Dr Ritchie reported ties with Jazz Pharmaceuticals, Novartis, Takeda, Incyte, AbbVie, Astellas, and Imago Biosciences. Dr. Halpern disclosed relationships with AbbVie, Notable Labs, Imago, Bayer, Gilead, Jazz, Incyte, Karyopharm, and Disc Medicine.

Until just over a year ago, Pat Trueman, an 82-year-old in New Hampshire, had always been a “go-go-go” kind of person. Then she started feeling tired easily, even while doing basic housework.

“I had no stamina,” Ms. Trueman said. “I didn’t feel that bad, but I just couldn’t do anything.” She had also begun noticing black and blue bruises appearing on her body, so she met with her cardiologist. But when switching medications and getting a pacemaker didn’t rid Ms. Trueman of the symptoms, her doctor referred her to a hematologist oncologist.

A bone marrow biopsy eventually revealed that Ms. Trueman had myelodysplastic neoplasms, or MDS, a blood cancer affecting an estimated 60,000-170,000 people in the United States, mostly over age 60. MDS includes several bone marrow disorders in which the bone marrow does not produce enough healthy, normal blood cells. Cytopenias are therefore a key feature of MDS, whether it’s anemia (in Ms. Trueman’s case), neutropenia, or thrombocytopenia.

Jamie Koprivnikar, MD, a hematologist oncologist at Hackensack (N.J) University Medical Center, describes the condition to her patients using a factory metaphor: “Our bone marrow is the factory where the red blood cells, white blood cells, and platelets are made, and MDS is where the machinery of the factory is broken, so the factory is making defective parts and not enough parts.”

courtesy Chad Hunt

The paradox of MDS is that too many cells are in the bone marrow while too few are in the blood, since most in the marrow die before reaching the blood, explained Azra Raza, MD, a professor of medicine and director of the MDS Center at Columbia University Medical Center, New York, and author of The First Cell (New York: Basic Books, 2019).

Although MDS is not rare, the condition has seen remarkably few new therapies in recent years. Most are either improvements on an existing treatment – such as an oral formulation of an infused drug – or a drug borrowed from therapies for other blood cancers, particularly acute myeloid leukemia (AML).

“We’re looking at taking a lot of the therapies that we’ve used to treat AML and then trying to apply them to MDS,” Dr. Koprivnikar said. “With all the improvement that we’re seeing there with leukemia, we’re definitely expecting this trickle-down effect to also help our high-risk MDS patients.”
 

Workup begins with risk stratification

While different types of MDS exist, based on morphology of the blood cells, after diagnosis the most important determination to make is of the patient’s risk level, based on the International Prognostic Scoring System–Revised (IPSS-R), updated in 2022.

While there are six MDS risk levels, patients generally fall into the high-risk and low-risk categories. The risk-level workup includes “a bone marrow biopsy with morphology, looking at how many blasts they have, looking for dysplasia, cytogenetics, and a full spectrum myeloid mutation testing, or molecular testing,” according to Anna Halpern, MD, an assistant professor of hematology in the clinical research division at Fred Hutchinson Cancer Center, Seattle. ”I use that information and along with their age, in some cases to calculate an IPSS-M or IPPS-R score, and what goes into that risk stratification includes how low their blood counts are as well as any adverse risks features we might see in their marrow, like adverse risk genetics, adverse risk mutations or increased blasts.”

Treatment decisions then turn on whether a patient is high risk – about a third of MDS patients – or low risk, because those treatment goals differ.

“With low-risk, the goal is to improve quality of life,” Dr. Raza said. “For higher-risk MDS, the goal is to prolong survival and delay progression to acute leukemia” since nearly a third of MDS patients will eventually develop AML.

More specifically, the aim with low-risk MDS is “to foster transfusion independence, either to prevent transfusions or to decrease the need for transfusions in people already receiving them,” explained Ellen Ritchie, MD, an assistant professor of medicine and hematologist-oncologist at Weill Cornell Medicine, New York. “We’re not hoping so much to cure the myelofibrosis at that point, but rather to improve blood counts.”

Sometimes, Dr. Halpern said, such treatment means active surveillance monitoring of blood counts, and at other times, it means treating cytopenia – most often anemia. The erythropoiesis-stimulating agents used to treat anemia are epoetin alfa (Epogen/Procrit) or darbepoetin alfa (Aranesp).

Ms. Trueman, whose MDS is low risk, started taking Aranesp, but she didn’t feel well on the drug and didn’t think it was helping much. She was taken off that drug and now relies only on transfusions for treatment, when her blood counts fall too low.

A newer anemia medication, luspatercept (Reblozyl), was approved in 2020 but is reserved primarily for those who fail one of the other erythropoiesis-stimulating agents and have a subtype of MDS with ring sideroblasts. Although white blood cell and platelet growth factors exist for other cytopenias, they’re rarely used because they offer little survival benefit and carry risks, Dr. Halpern said. The only other medication typically used for low-risk MDS is lenalidomide (Revlimid), which is reserved only for those with 5q-deletion syndrome.

The goal of treating high-risk MDS, on the other hand, is to cure it – when possible.

“The only curative approach for MDS is an allogeneic stem cell transplant or bone marrow transplant,” Dr. Halpern said, but transplants carry high rates of morbidity and mortality and therefore require a base level of physical fitness for a patient to consider it.

Dr. Koprivnikar observed that “MDS is certainly a disease of the elderly, and with each increasing decade of life, incidence increases. So there are a lot of patients who do not qualify for transplant.”

Age is not the sole determining factor, however. Dr. Ritchie noted that transplants can be offered to patients up to age 75 and sometimes older, depending on their physical condition. “It all depends upon the patient, their fitness, how much caretaker support they have, and what their comorbid illnesses are.”

If a transplant isn’t an option, Dr. Halpern and Dr. Raza said, they steer patients toward clinical trial participation. Otherwise, the first-line treatment is chemotherapy with hypomethylating agents to hopefully put patients in remission, Dr. Ritchie said.

The main chemo agents for high-risk patients ineligible for transplant are azacitidine (Vidaza) or decitabine (Dacogen), offered indefinitely until patients stop responding or experience progression or intolerance, Dr. Koprivnikar said. The only recently approved drug in this space is Inqovi, which is not a new agent, but it provides decitabine and cedazuridine in an oral pill form, so that patients can avoid infusions.
 

Treatment gaps

Few treatments options currently exist for patients with MDS, beyond erythropoiesis-stimulating agents for low-risk MDS and chemotherapy or transplant for high-risk MDS, as well as lenalidomide and luspatercept for specific subpopulations. With few breakthroughs occurring, Dr. Halpern expects that progress will only happen gradually, with new treatments coming primarily in the form of AML therapies.

“The biggest gap in our MDS regimen is treatment that can successfully treat or alter the natural history of TP53-mutated disease,” said Dr. Halpern, referring to an adverse risk mutation that can occur spontaneously or as a result of exposure to chemotherapy or radiation. “TP53-mutated MDS is very challenging to treat, and we have not had any successful therapy, so that is the biggest area of need.”

The most promising possibility in that area is an anti-CD47 drug called magrolimab, a drug being tested in a trial of which Dr. Halpern is a principal investigator. Not yet approved, magrolimab has been showing promise for AML when given with azacitidine (Vidaza) and venetoclax (Venclexta).

Venetoclax, currently used for AML, is another drug that Dr. Halpern expects to be approved for MDS soon. A phase 1b trial presented at the 2021 annual meeting of the American Hematology Society found that more than three-quarters of patients with high-risk MDS responded to the combination of venetoclax and azacitidine.

Unlike so many other cancers, MDS has seen little success with immunotherapy, which tends to have too much toxicity for patients with MDS. While Dr. Halpern sees potential for more exploration in this realm, she doesn’t anticipate immunotherapy or chimeric antigen receptor T-cell therapy becoming treatments for MDS in the near future.

“What I do think is, hopefully, we will have better treatment for TP53-mutated disease,” she said, while adding that there are currently no standard options for patients who stopped responding or don’t respond to hypomethylating agents.

Similarly, few new treatments have emerged for low-risk MDS, but there a couple of possibilities on the horizon.

“For a while, low-risk, transfusion-dependent MDS was an area that was being overlooked, and we are starting to see more activity in that area as well, with more drugs being developed,” Dr. Koprivnikar said. Drugs showing promise include imetelstat – an investigative telomerase inhibitor – and IRAK inhibitors. A phase 3 trial of imetelstat recently met its primary endpoint of 8 weeks of transfusion independence in low-risk MDS patients who aren’t responding to or cannot take erythropoiesis-stimulating agents, like Ms. Trueman. If effective and approved, a drug like imetelstat may allow patients like Ms. Trueman to resume some activities that she misses now.

“I have so much energy in my head, and I want to do so much, but I can’t,” Ms. Trueman said. “Now I think I’m getting lazy and I don’t like it because I’m not that kind of person. It’s pretty hard.”

Dr. Raza disclosed relationships with Epizyme, Grail, Vor, Taiho, RareCells, and TFC Therapeutics. Dr Ritchie reported ties with Jazz Pharmaceuticals, Novartis, Takeda, Incyte, AbbVie, Astellas, and Imago Biosciences. Dr. Halpern disclosed relationships with AbbVie, Notable Labs, Imago, Bayer, Gilead, Jazz, Incyte, Karyopharm, and Disc Medicine.

Until just over a year ago, Pat Trueman, an 82-year-old in New Hampshire, had always been a “go-go-go” kind of person. Then she started feeling tired easily, even while doing basic housework.

“I had no stamina,” Ms. Trueman said. “I didn’t feel that bad, but I just couldn’t do anything.” She had also begun noticing black and blue bruises appearing on her body, so she met with her cardiologist. But when switching medications and getting a pacemaker didn’t rid Ms. Trueman of the symptoms, her doctor referred her to a hematologist oncologist.

A bone marrow biopsy eventually revealed that Ms. Trueman had myelodysplastic neoplasms, or MDS, a blood cancer affecting an estimated 60,000-170,000 people in the United States, mostly over age 60. MDS includes several bone marrow disorders in which the bone marrow does not produce enough healthy, normal blood cells. Cytopenias are therefore a key feature of MDS, whether it’s anemia (in Ms. Trueman’s case), neutropenia, or thrombocytopenia.

Jamie Koprivnikar, MD, a hematologist oncologist at Hackensack (N.J) University Medical Center, describes the condition to her patients using a factory metaphor: “Our bone marrow is the factory where the red blood cells, white blood cells, and platelets are made, and MDS is where the machinery of the factory is broken, so the factory is making defective parts and not enough parts.”

courtesy Chad Hunt

The paradox of MDS is that too many cells are in the bone marrow while too few are in the blood, since most in the marrow die before reaching the blood, explained Azra Raza, MD, a professor of medicine and director of the MDS Center at Columbia University Medical Center, New York, and author of The First Cell (New York: Basic Books, 2019).

Although MDS is not rare, the condition has seen remarkably few new therapies in recent years. Most are either improvements on an existing treatment – such as an oral formulation of an infused drug – or a drug borrowed from therapies for other blood cancers, particularly acute myeloid leukemia (AML).

“We’re looking at taking a lot of the therapies that we’ve used to treat AML and then trying to apply them to MDS,” Dr. Koprivnikar said. “With all the improvement that we’re seeing there with leukemia, we’re definitely expecting this trickle-down effect to also help our high-risk MDS patients.”
 

Workup begins with risk stratification

While different types of MDS exist, based on morphology of the blood cells, after diagnosis the most important determination to make is of the patient’s risk level, based on the International Prognostic Scoring System–Revised (IPSS-R), updated in 2022.

While there are six MDS risk levels, patients generally fall into the high-risk and low-risk categories. The risk-level workup includes “a bone marrow biopsy with morphology, looking at how many blasts they have, looking for dysplasia, cytogenetics, and a full spectrum myeloid mutation testing, or molecular testing,” according to Anna Halpern, MD, an assistant professor of hematology in the clinical research division at Fred Hutchinson Cancer Center, Seattle. ”I use that information and along with their age, in some cases to calculate an IPSS-M or IPPS-R score, and what goes into that risk stratification includes how low their blood counts are as well as any adverse risks features we might see in their marrow, like adverse risk genetics, adverse risk mutations or increased blasts.”

Treatment decisions then turn on whether a patient is high risk – about a third of MDS patients – or low risk, because those treatment goals differ.

“With low-risk, the goal is to improve quality of life,” Dr. Raza said. “For higher-risk MDS, the goal is to prolong survival and delay progression to acute leukemia” since nearly a third of MDS patients will eventually develop AML.

More specifically, the aim with low-risk MDS is “to foster transfusion independence, either to prevent transfusions or to decrease the need for transfusions in people already receiving them,” explained Ellen Ritchie, MD, an assistant professor of medicine and hematologist-oncologist at Weill Cornell Medicine, New York. “We’re not hoping so much to cure the myelofibrosis at that point, but rather to improve blood counts.”

Sometimes, Dr. Halpern said, such treatment means active surveillance monitoring of blood counts, and at other times, it means treating cytopenia – most often anemia. The erythropoiesis-stimulating agents used to treat anemia are epoetin alfa (Epogen/Procrit) or darbepoetin alfa (Aranesp).

Ms. Trueman, whose MDS is low risk, started taking Aranesp, but she didn’t feel well on the drug and didn’t think it was helping much. She was taken off that drug and now relies only on transfusions for treatment, when her blood counts fall too low.

A newer anemia medication, luspatercept (Reblozyl), was approved in 2020 but is reserved primarily for those who fail one of the other erythropoiesis-stimulating agents and have a subtype of MDS with ring sideroblasts. Although white blood cell and platelet growth factors exist for other cytopenias, they’re rarely used because they offer little survival benefit and carry risks, Dr. Halpern said. The only other medication typically used for low-risk MDS is lenalidomide (Revlimid), which is reserved only for those with 5q-deletion syndrome.

The goal of treating high-risk MDS, on the other hand, is to cure it – when possible.

“The only curative approach for MDS is an allogeneic stem cell transplant or bone marrow transplant,” Dr. Halpern said, but transplants carry high rates of morbidity and mortality and therefore require a base level of physical fitness for a patient to consider it.

Dr. Koprivnikar observed that “MDS is certainly a disease of the elderly, and with each increasing decade of life, incidence increases. So there are a lot of patients who do not qualify for transplant.”

Age is not the sole determining factor, however. Dr. Ritchie noted that transplants can be offered to patients up to age 75 and sometimes older, depending on their physical condition. “It all depends upon the patient, their fitness, how much caretaker support they have, and what their comorbid illnesses are.”

If a transplant isn’t an option, Dr. Halpern and Dr. Raza said, they steer patients toward clinical trial participation. Otherwise, the first-line treatment is chemotherapy with hypomethylating agents to hopefully put patients in remission, Dr. Ritchie said.

The main chemo agents for high-risk patients ineligible for transplant are azacitidine (Vidaza) or decitabine (Dacogen), offered indefinitely until patients stop responding or experience progression or intolerance, Dr. Koprivnikar said. The only recently approved drug in this space is Inqovi, which is not a new agent, but it provides decitabine and cedazuridine in an oral pill form, so that patients can avoid infusions.
 

Treatment gaps

Few treatments options currently exist for patients with MDS, beyond erythropoiesis-stimulating agents for low-risk MDS and chemotherapy or transplant for high-risk MDS, as well as lenalidomide and luspatercept for specific subpopulations. With few breakthroughs occurring, Dr. Halpern expects that progress will only happen gradually, with new treatments coming primarily in the form of AML therapies.

“The biggest gap in our MDS regimen is treatment that can successfully treat or alter the natural history of TP53-mutated disease,” said Dr. Halpern, referring to an adverse risk mutation that can occur spontaneously or as a result of exposure to chemotherapy or radiation. “TP53-mutated MDS is very challenging to treat, and we have not had any successful therapy, so that is the biggest area of need.”

The most promising possibility in that area is an anti-CD47 drug called magrolimab, a drug being tested in a trial of which Dr. Halpern is a principal investigator. Not yet approved, magrolimab has been showing promise for AML when given with azacitidine (Vidaza) and venetoclax (Venclexta).

Venetoclax, currently used for AML, is another drug that Dr. Halpern expects to be approved for MDS soon. A phase 1b trial presented at the 2021 annual meeting of the American Hematology Society found that more than three-quarters of patients with high-risk MDS responded to the combination of venetoclax and azacitidine.

Unlike so many other cancers, MDS has seen little success with immunotherapy, which tends to have too much toxicity for patients with MDS. While Dr. Halpern sees potential for more exploration in this realm, she doesn’t anticipate immunotherapy or chimeric antigen receptor T-cell therapy becoming treatments for MDS in the near future.

“What I do think is, hopefully, we will have better treatment for TP53-mutated disease,” she said, while adding that there are currently no standard options for patients who stopped responding or don’t respond to hypomethylating agents.

Similarly, few new treatments have emerged for low-risk MDS, but there a couple of possibilities on the horizon.

“For a while, low-risk, transfusion-dependent MDS was an area that was being overlooked, and we are starting to see more activity in that area as well, with more drugs being developed,” Dr. Koprivnikar said. Drugs showing promise include imetelstat – an investigative telomerase inhibitor – and IRAK inhibitors. A phase 3 trial of imetelstat recently met its primary endpoint of 8 weeks of transfusion independence in low-risk MDS patients who aren’t responding to or cannot take erythropoiesis-stimulating agents, like Ms. Trueman. If effective and approved, a drug like imetelstat may allow patients like Ms. Trueman to resume some activities that she misses now.

“I have so much energy in my head, and I want to do so much, but I can’t,” Ms. Trueman said. “Now I think I’m getting lazy and I don’t like it because I’m not that kind of person. It’s pretty hard.”

Dr. Raza disclosed relationships with Epizyme, Grail, Vor, Taiho, RareCells, and TFC Therapeutics. Dr Ritchie reported ties with Jazz Pharmaceuticals, Novartis, Takeda, Incyte, AbbVie, Astellas, and Imago Biosciences. Dr. Halpern disclosed relationships with AbbVie, Notable Labs, Imago, Bayer, Gilead, Jazz, Incyte, Karyopharm, and Disc Medicine.

Screening high-risk populations for lung cancer saves lives. The National Lung Screening Trial (NLST) demonstrated a 20% relative reduction in lung cancer mortality with annual screening over 3 years with low-dose CT as compared with x-rays. The NELSON trial found a higher benefit: Men at high risk for lung cancer had a 26% reduced risk of dying from lung cancer and women had a 61% reduced risk over 10 years. However, the 2022 American Lung Association State of Lung Cancer report shows that less than 6% of eligible people get screened. Why is this?

There are many reasons, but I submit that at least one hurdle is related to the difficulties associated with ordering the low-dose CT in the electronic medical record (EMR) and following the results. The rules and regulations around lung cancer screening are complex. First, the ordering provider must be able to determine if the patient is eligible for screening and has insurance coverage – a complicated procedure, which is constantly in flux, and is based on age, smoking history, smoke-free interval, and type of insurance coverage. Most EMRs do not have a way of flagging high-risk individuals, and clinic coordinators (for those practices that have one) are often put in charge of determining eligibility.

Secondly, the health care provider must order the scan. Unlike mammography, people must have a prescreening visit with a physician or other health care provider – a visit which is poorly compensated, and often must be supported by the institution. Many EMRs also do not have a smooth mechanism to make sure all the “boxes have been checked” before the scan can be ordered. Is there a complete smoking history? Has the patient had their prescreening visit? Has the patient been counseled regarding tobacco use? Has eligibility for insurance payment been confirmed?

Coordinating follow-up is cumbersome. Abnormal findings are common and usually nonmalignant, but must be followed up, and the follow-up recommendations are complicated and are based upon the appearance of the finding. This may be difficult for a general practitioner, so referrals to pulmonologists are often scheduled. Best practices state the patient be followed in a multidisciplinary pulmonary module clinic, but again, most multidisciplinary pulmonary module clinics are found in the academic setting.

All this involves a lot of back-and-forth for the patient: First to see their primary care physician, then to see a pulmonologist or other health care provider for the counseling regarding risks and benefits of screening and the importance of smoking cessation, and then a visit to a radiologist as well as a visit to a smoking cessation clinic, then a return follow-up visit. Academic medical centers and NCI-approved cancer centers often have these procedures worked out, but many private or smaller practices do not. Yes, the local IT folks can modify an EMR, but in a small practice, there are other “more important” problems that take precedence.

Would coupling lung cancer screening with breast cancer scanning help? One study followed 874 women who attended mammographic screening and found that over 11% were at high risk for lung cancer. This would appear to be an ideal “teaching moment” to educate the importance of lung cancer screening to women. It could also cut down on some of the logistical issues associated with lung cancer screening, particularly if a health care provider and coordinator were immediately available for counseling and eligibility determination at the time of the mammography visit. The radiology clinic staff could schedule a scan and return visit while the patient was still in the mammography suite.

Of course, the logistical hassle is just one of many associated with lung cancer screening. The internal stigma the patient may experience about their smoking history, the unconscious bias on the part of many health professionals, the many other screening and prevention regulations providers are now required to follow, the institution’s reluctance to support a screening program, the rushed pace in many clinics: These all certainly contribute to the problem. However, we have overcome all of these issues when it comes to mammography, such as work flow, stigma, logistical issues, seamless incorporation of ordering scans and referrals to specialists in the EMR, etc. We can and must do the same for our patients at high risk for lung cancer, and routine scheduling of mammograms and low-dose CTs may help.

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation. Ivy Elkins, cofounder of EGFR Resisters, a patient, survivor, and caregiver advocacy group, contributed to this article.

Screening high-risk populations for lung cancer saves lives. The National Lung Screening Trial (NLST) demonstrated a 20% relative reduction in lung cancer mortality with annual screening over 3 years with low-dose CT as compared with x-rays. The NELSON trial found a higher benefit: Men at high risk for lung cancer had a 26% reduced risk of dying from lung cancer and women had a 61% reduced risk over 10 years. However, the 2022 American Lung Association State of Lung Cancer report shows that less than 6% of eligible people get screened. Why is this?

There are many reasons, but I submit that at least one hurdle is related to the difficulties associated with ordering the low-dose CT in the electronic medical record (EMR) and following the results. The rules and regulations around lung cancer screening are complex. First, the ordering provider must be able to determine if the patient is eligible for screening and has insurance coverage – a complicated procedure, which is constantly in flux, and is based on age, smoking history, smoke-free interval, and type of insurance coverage. Most EMRs do not have a way of flagging high-risk individuals, and clinic coordinators (for those practices that have one) are often put in charge of determining eligibility.

Secondly, the health care provider must order the scan. Unlike mammography, people must have a prescreening visit with a physician or other health care provider – a visit which is poorly compensated, and often must be supported by the institution. Many EMRs also do not have a smooth mechanism to make sure all the “boxes have been checked” before the scan can be ordered. Is there a complete smoking history? Has the patient had their prescreening visit? Has the patient been counseled regarding tobacco use? Has eligibility for insurance payment been confirmed?

Coordinating follow-up is cumbersome. Abnormal findings are common and usually nonmalignant, but must be followed up, and the follow-up recommendations are complicated and are based upon the appearance of the finding. This may be difficult for a general practitioner, so referrals to pulmonologists are often scheduled. Best practices state the patient be followed in a multidisciplinary pulmonary module clinic, but again, most multidisciplinary pulmonary module clinics are found in the academic setting.

All this involves a lot of back-and-forth for the patient: First to see their primary care physician, then to see a pulmonologist or other health care provider for the counseling regarding risks and benefits of screening and the importance of smoking cessation, and then a visit to a radiologist as well as a visit to a smoking cessation clinic, then a return follow-up visit. Academic medical centers and NCI-approved cancer centers often have these procedures worked out, but many private or smaller practices do not. Yes, the local IT folks can modify an EMR, but in a small practice, there are other “more important” problems that take precedence.

Would coupling lung cancer screening with breast cancer scanning help? One study followed 874 women who attended mammographic screening and found that over 11% were at high risk for lung cancer. This would appear to be an ideal “teaching moment” to educate the importance of lung cancer screening to women. It could also cut down on some of the logistical issues associated with lung cancer screening, particularly if a health care provider and coordinator were immediately available for counseling and eligibility determination at the time of the mammography visit. The radiology clinic staff could schedule a scan and return visit while the patient was still in the mammography suite.

Of course, the logistical hassle is just one of many associated with lung cancer screening. The internal stigma the patient may experience about their smoking history, the unconscious bias on the part of many health professionals, the many other screening and prevention regulations providers are now required to follow, the institution’s reluctance to support a screening program, the rushed pace in many clinics: These all certainly contribute to the problem. However, we have overcome all of these issues when it comes to mammography, such as work flow, stigma, logistical issues, seamless incorporation of ordering scans and referrals to specialists in the EMR, etc. We can and must do the same for our patients at high risk for lung cancer, and routine scheduling of mammograms and low-dose CTs may help.

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation. Ivy Elkins, cofounder of EGFR Resisters, a patient, survivor, and caregiver advocacy group, contributed to this article.

Screening high-risk populations for lung cancer saves lives. The National Lung Screening Trial (NLST) demonstrated a 20% relative reduction in lung cancer mortality with annual screening over 3 years with low-dose CT as compared with x-rays. The NELSON trial found a higher benefit: Men at high risk for lung cancer had a 26% reduced risk of dying from lung cancer and women had a 61% reduced risk over 10 years. However, the 2022 American Lung Association State of Lung Cancer report shows that less than 6% of eligible people get screened. Why is this?

There are many reasons, but I submit that at least one hurdle is related to the difficulties associated with ordering the low-dose CT in the electronic medical record (EMR) and following the results. The rules and regulations around lung cancer screening are complex. First, the ordering provider must be able to determine if the patient is eligible for screening and has insurance coverage – a complicated procedure, which is constantly in flux, and is based on age, smoking history, smoke-free interval, and type of insurance coverage. Most EMRs do not have a way of flagging high-risk individuals, and clinic coordinators (for those practices that have one) are often put in charge of determining eligibility.

Secondly, the health care provider must order the scan. Unlike mammography, people must have a prescreening visit with a physician or other health care provider – a visit which is poorly compensated, and often must be supported by the institution. Many EMRs also do not have a smooth mechanism to make sure all the “boxes have been checked” before the scan can be ordered. Is there a complete smoking history? Has the patient had their prescreening visit? Has the patient been counseled regarding tobacco use? Has eligibility for insurance payment been confirmed?

Coordinating follow-up is cumbersome. Abnormal findings are common and usually nonmalignant, but must be followed up, and the follow-up recommendations are complicated and are based upon the appearance of the finding. This may be difficult for a general practitioner, so referrals to pulmonologists are often scheduled. Best practices state the patient be followed in a multidisciplinary pulmonary module clinic, but again, most multidisciplinary pulmonary module clinics are found in the academic setting.

All this involves a lot of back-and-forth for the patient: First to see their primary care physician, then to see a pulmonologist or other health care provider for the counseling regarding risks and benefits of screening and the importance of smoking cessation, and then a visit to a radiologist as well as a visit to a smoking cessation clinic, then a return follow-up visit. Academic medical centers and NCI-approved cancer centers often have these procedures worked out, but many private or smaller practices do not. Yes, the local IT folks can modify an EMR, but in a small practice, there are other “more important” problems that take precedence.

Would coupling lung cancer screening with breast cancer scanning help? One study followed 874 women who attended mammographic screening and found that over 11% were at high risk for lung cancer. This would appear to be an ideal “teaching moment” to educate the importance of lung cancer screening to women. It could also cut down on some of the logistical issues associated with lung cancer screening, particularly if a health care provider and coordinator were immediately available for counseling and eligibility determination at the time of the mammography visit. The radiology clinic staff could schedule a scan and return visit while the patient was still in the mammography suite.

Of course, the logistical hassle is just one of many associated with lung cancer screening. The internal stigma the patient may experience about their smoking history, the unconscious bias on the part of many health professionals, the many other screening and prevention regulations providers are now required to follow, the institution’s reluctance to support a screening program, the rushed pace in many clinics: These all certainly contribute to the problem. However, we have overcome all of these issues when it comes to mammography, such as work flow, stigma, logistical issues, seamless incorporation of ordering scans and referrals to specialists in the EMR, etc. We can and must do the same for our patients at high risk for lung cancer, and routine scheduling of mammograms and low-dose CTs may help.

Dr. Schiller is a medical oncologist and founding member of Oncologists United for Climate and Health. She is a former board member of the International Association for the Study of Lung Cancer and a current board member of the Lung Cancer Research Foundation. Ivy Elkins, cofounder of EGFR Resisters, a patient, survivor, and caregiver advocacy group, contributed to this article.

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

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

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

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

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

Analyzing detection rates

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Additional considerations

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Analyzing detection rates

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Additional considerations

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Analyzing detection rates

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Additional considerations

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Lower rates of cancer mortality

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

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

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

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

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

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

Further study underway

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

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

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

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

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

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

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

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

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

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

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

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

Lower rates of cancer mortality

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

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

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

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

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

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

Further study underway

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

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

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

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

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

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

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

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

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

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

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

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

Lower rates of cancer mortality

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

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

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

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

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

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

Further study underway

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

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

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

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

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

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

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

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

The consensus statement was published online in JAMA Dermatology.
 

The need for guidance

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The consensus statement was published online in JAMA Dermatology.
 

The need for guidance

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The consensus statement was published online in JAMA Dermatology.
 

The need for guidance

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

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

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

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

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

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

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

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

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

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

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

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

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

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