Oncology

Last year, Eric Singhi, MD, a thoracic medical oncologist at MD Anderson Cancer Center in Houston, noticed a shift in his team. The small band of four clinicians, once motivated and enthusiastic, were now withdrawn and distant.

“We had to take a break from clinic one day. We went out, got food and…acknowledged something was off,” Singhi recalled.

That something: Intense emotional exhaustion.

No thoracic oncology team has it easy. Lung cancer remains the leading cause of cancer deaths. But over the last 12 months Singhi’s team had taken on more and more cases in younger patients. Watching patients so close to their own age struggle and ultimately be consumed by this disease took its toll, Singhi said. And the toll was showing up in the lives of his colleagues.

Singhi’s team was suffering from compassion fatigue — the mental, physical, or emotional exhaustion brought on by prolonged exposure to the trauma of people in one’s care. Also referred to secondary trauma, compassion fatigue “leaves someone feeling numb, detached, or like they don’t have emotional resources to keep on giving,” Singhi said.

This fatigue is common among people who work in high-stress caretaking professions. Those involved in cancer care, who frequently find themselves navigating life and death conversations and experiences with patients, are particularly at risk, experts told this news organization.

“I think anyone in medical oncology or hematology who has practiced long enough will feel this,” said Alfred Lee, MD, PhD, burnout researcher and director of the hematology/oncology fellowship at Yale School of Medicine in New Haven, Connecticut. “It’s par for the course, even in training.”

Still, compassion fatigue can be hard to detect without help. Left unaddressed, compassion fatigue can undermine good patient care, even lead to burnout.

“I’ve absolutely treated people leaving the field who think they shouldn’t be a doctor anymore,” said Jennifer Bickel, MD, recently named MD Anderson’s inaugural vice president and chief wellness officer. Those are preventable losses the field can’t afford in a provider shortage, she said.

 

Recognizing the Signs

Compassion is an essential part of patient care as is empathy. Expressing compassion or feeling empathy toward patients can foster the doctor-patient bond and help both navigate challenging conversations and decisions.

“Compassion and being able to empathize are so important — it’s how you gain trust,” Singhi said. This is especially true for patients who may be underrepresented. “That’s how they become a partner in their care, how they agree to listen about a clinical trial or agree to adhere to their treatment plan,” Singhi noted.

But there’s a risk when clinicians start to give too much.

Overtime, repeated exposure to patients’ trauma can create a sense of heaviness and fatigue, and ultimately cause caregivers to detach, Lee said.

A case study of compassion fatigue, based on the experience of one oncologist, highlighted that the condition parallels posttraumatic stress disorder, aligning on three main symptoms: Feeling hyperarousal, notably hypervigilance or irritability, avoiding stressful situations, and reliving traumatic events.

The initial phases of compassion fatigue, however, can be subtle and easily dismissed. An oncologist may begin to feel a creeping sense of detachment — a divide slowly growing with their patients, a buzz of dissatisfaction on the job, unusual mood changes.

While it’s normal for healthcare workers to experience moments of irritability, dissatisfaction, exhaustion or avoidance, when these experiences become pervasive, compassion fatigue could be the culprit, according to Marra Ackerman, MD, a psychiatrist at NYU Langone Health in New York City.

Compassion fatigue is “a form of coping more than anything,” Ackerman explained. Most of the time, it’s not a conscious choice, she said. When a brain experiences repeated distressing inputs it can shift into self-protection mode. The tipping point is different for everyone, but eventually the brain tries to detach and distance itself from the stressor, Ackerman said. And, in oncology, that stressor is often very sick patients.

If not addressed, the emotional exhaustion can limit a doctor’s efficacy at work. Clinicians suffering from compassion fatigue may find themselves calling in sick more often, making more mistakes, avoiding very sick patients, or having panic attacks at work, said Ackerman.

Clinicians also might use food, drugs, or alcohol to feel better, or detach from their patients, Lee added. “We find if you detach, you can’t provide the care patients need,” he said.

When trying to identify the issue, it’s important to understand that compassion fatigue is not burnout. The two issues can look similar, sharing symptoms like emotional detachment or disillusionment, and may co-exist, but the phenomena stem from different root causes.

While compassion fatigue is rooted in emotions and isn’t necessarily tied to work, burnout is a product of work-related stress. It’s often caused by system-level problems that leave clinicians feeling their work has lost its meaning. Inefficient technology or excessive data entry, for instance, could be drivers of burnout for oncologists because these tasks can pull the doctor away from the meaningful work of treating patients.

 

What Can Be Done

Oncology comes with its own set of risks and traumas, but for a long time, doctors weren’t equipped or encouraged to see the constant life-or-death tension of the job as a risk factor to their well-being, said Bickel.

“It’s not something we are inherently taught to identify and it’s not something we can identify without time for self-reflection,” Bickel told this news organization. In fact, many people don’t see their own compassion fatigue until a colleague points it out or they’re already past it and have some distance.

Although common among oncology clinicians, compassion fatigue is not inevitable. Oncologists can learn strategies to help manage their exposures to suffering and stave off reverting to coping mechanisms that only perpetuate the problem.

The key, Bickel said, is creating environments where people can feel safe and share their vulnerabilities. Formal peer support check-ins are a good example because they normalize regular communication about day-to-day difficulties as they happen and create space to experience grief. In these groups, no one has to worry that they’re complaining, she said.

Formalized groups also serve as a training ground where staff can learn to be better listeners. Healthcare providers are more likely to reach out to peers because so few people outside their field can relate to the challenges, Bickel explained. That’s why Moffitt Cancer Center, where Bickel recently worked before moving to MD Anderson, offers trainings to help staff learn to listen more effectively. Thirty doctors, nurses and health professionals have received the training so far and serve as a point of contact for colleagues who might be struggling, Bickel said. They can offer their peers an empathic ear, without providing unsolicited advice or commentary.

NYU Langone has a similar offering, Ackerman said. Providers can reach out to fellow nurses or doctors who have more mental health training. The conversation isn’t recorded like an appointment with a therapist may be. It’s more like mentorship where doctors can be open about what they are facing and find some comradery from someone who understands, without fear of stigma.

Talking to colleagues or having debriefs with your care team is critical because it eliminates the isolation that allows compassion fatigue to fester, Lee said. “Reflecting on positive encounters can help inspire us to keep going. Reflecting on the negative can be therapeutic and help find that sense of balance that everyone needs to find.”

As for Singhi’s team, “lots has changed since we’ve become more open,” he said. The team talks about hard patients early and often. These discussions have helped team members keep the challenges at work from seeping into their home life.

Experts agree that the threshold for seeking out help and guidance should be low. Waiting for depression or more severe symptoms to set in is not the best point of intervention, Bickel said. As soon as an oncologist begins to acknowledge a shift in how they connect with patients and the job, that’s enough to reach out.

“It’s not about what you can handle, it’s about how can you thrive and find joy,” she said.

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

Last year, Eric Singhi, MD, a thoracic medical oncologist at MD Anderson Cancer Center in Houston, noticed a shift in his team. The small band of four clinicians, once motivated and enthusiastic, were now withdrawn and distant.

“We had to take a break from clinic one day. We went out, got food and…acknowledged something was off,” Singhi recalled.

That something: Intense emotional exhaustion.

No thoracic oncology team has it easy. Lung cancer remains the leading cause of cancer deaths. But over the last 12 months Singhi’s team had taken on more and more cases in younger patients. Watching patients so close to their own age struggle and ultimately be consumed by this disease took its toll, Singhi said. And the toll was showing up in the lives of his colleagues.

Singhi’s team was suffering from compassion fatigue — the mental, physical, or emotional exhaustion brought on by prolonged exposure to the trauma of people in one’s care. Also referred to secondary trauma, compassion fatigue “leaves someone feeling numb, detached, or like they don’t have emotional resources to keep on giving,” Singhi said.

This fatigue is common among people who work in high-stress caretaking professions. Those involved in cancer care, who frequently find themselves navigating life and death conversations and experiences with patients, are particularly at risk, experts told this news organization.

“I think anyone in medical oncology or hematology who has practiced long enough will feel this,” said Alfred Lee, MD, PhD, burnout researcher and director of the hematology/oncology fellowship at Yale School of Medicine in New Haven, Connecticut. “It’s par for the course, even in training.”

Still, compassion fatigue can be hard to detect without help. Left unaddressed, compassion fatigue can undermine good patient care, even lead to burnout.

“I’ve absolutely treated people leaving the field who think they shouldn’t be a doctor anymore,” said Jennifer Bickel, MD, recently named MD Anderson’s inaugural vice president and chief wellness officer. Those are preventable losses the field can’t afford in a provider shortage, she said.

 

Recognizing the Signs

Compassion is an essential part of patient care as is empathy. Expressing compassion or feeling empathy toward patients can foster the doctor-patient bond and help both navigate challenging conversations and decisions.

“Compassion and being able to empathize are so important — it’s how you gain trust,” Singhi said. This is especially true for patients who may be underrepresented. “That’s how they become a partner in their care, how they agree to listen about a clinical trial or agree to adhere to their treatment plan,” Singhi noted.

But there’s a risk when clinicians start to give too much.

Overtime, repeated exposure to patients’ trauma can create a sense of heaviness and fatigue, and ultimately cause caregivers to detach, Lee said.

A case study of compassion fatigue, based on the experience of one oncologist, highlighted that the condition parallels posttraumatic stress disorder, aligning on three main symptoms: Feeling hyperarousal, notably hypervigilance or irritability, avoiding stressful situations, and reliving traumatic events.

The initial phases of compassion fatigue, however, can be subtle and easily dismissed. An oncologist may begin to feel a creeping sense of detachment — a divide slowly growing with their patients, a buzz of dissatisfaction on the job, unusual mood changes.

While it’s normal for healthcare workers to experience moments of irritability, dissatisfaction, exhaustion or avoidance, when these experiences become pervasive, compassion fatigue could be the culprit, according to Marra Ackerman, MD, a psychiatrist at NYU Langone Health in New York City.

Compassion fatigue is “a form of coping more than anything,” Ackerman explained. Most of the time, it’s not a conscious choice, she said. When a brain experiences repeated distressing inputs it can shift into self-protection mode. The tipping point is different for everyone, but eventually the brain tries to detach and distance itself from the stressor, Ackerman said. And, in oncology, that stressor is often very sick patients.

If not addressed, the emotional exhaustion can limit a doctor’s efficacy at work. Clinicians suffering from compassion fatigue may find themselves calling in sick more often, making more mistakes, avoiding very sick patients, or having panic attacks at work, said Ackerman.

Clinicians also might use food, drugs, or alcohol to feel better, or detach from their patients, Lee added. “We find if you detach, you can’t provide the care patients need,” he said.

When trying to identify the issue, it’s important to understand that compassion fatigue is not burnout. The two issues can look similar, sharing symptoms like emotional detachment or disillusionment, and may co-exist, but the phenomena stem from different root causes.

While compassion fatigue is rooted in emotions and isn’t necessarily tied to work, burnout is a product of work-related stress. It’s often caused by system-level problems that leave clinicians feeling their work has lost its meaning. Inefficient technology or excessive data entry, for instance, could be drivers of burnout for oncologists because these tasks can pull the doctor away from the meaningful work of treating patients.

 

What Can Be Done

Oncology comes with its own set of risks and traumas, but for a long time, doctors weren’t equipped or encouraged to see the constant life-or-death tension of the job as a risk factor to their well-being, said Bickel.

“It’s not something we are inherently taught to identify and it’s not something we can identify without time for self-reflection,” Bickel told this news organization. In fact, many people don’t see their own compassion fatigue until a colleague points it out or they’re already past it and have some distance.

Although common among oncology clinicians, compassion fatigue is not inevitable. Oncologists can learn strategies to help manage their exposures to suffering and stave off reverting to coping mechanisms that only perpetuate the problem.

The key, Bickel said, is creating environments where people can feel safe and share their vulnerabilities. Formal peer support check-ins are a good example because they normalize regular communication about day-to-day difficulties as they happen and create space to experience grief. In these groups, no one has to worry that they’re complaining, she said.

Formalized groups also serve as a training ground where staff can learn to be better listeners. Healthcare providers are more likely to reach out to peers because so few people outside their field can relate to the challenges, Bickel explained. That’s why Moffitt Cancer Center, where Bickel recently worked before moving to MD Anderson, offers trainings to help staff learn to listen more effectively. Thirty doctors, nurses and health professionals have received the training so far and serve as a point of contact for colleagues who might be struggling, Bickel said. They can offer their peers an empathic ear, without providing unsolicited advice or commentary.

NYU Langone has a similar offering, Ackerman said. Providers can reach out to fellow nurses or doctors who have more mental health training. The conversation isn’t recorded like an appointment with a therapist may be. It’s more like mentorship where doctors can be open about what they are facing and find some comradery from someone who understands, without fear of stigma.

Talking to colleagues or having debriefs with your care team is critical because it eliminates the isolation that allows compassion fatigue to fester, Lee said. “Reflecting on positive encounters can help inspire us to keep going. Reflecting on the negative can be therapeutic and help find that sense of balance that everyone needs to find.”

As for Singhi’s team, “lots has changed since we’ve become more open,” he said. The team talks about hard patients early and often. These discussions have helped team members keep the challenges at work from seeping into their home life.

Experts agree that the threshold for seeking out help and guidance should be low. Waiting for depression or more severe symptoms to set in is not the best point of intervention, Bickel said. As soon as an oncologist begins to acknowledge a shift in how they connect with patients and the job, that’s enough to reach out.

“It’s not about what you can handle, it’s about how can you thrive and find joy,” she said.

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

Last year, Eric Singhi, MD, a thoracic medical oncologist at MD Anderson Cancer Center in Houston, noticed a shift in his team. The small band of four clinicians, once motivated and enthusiastic, were now withdrawn and distant.

“We had to take a break from clinic one day. We went out, got food and…acknowledged something was off,” Singhi recalled.

That something: Intense emotional exhaustion.

No thoracic oncology team has it easy. Lung cancer remains the leading cause of cancer deaths. But over the last 12 months Singhi’s team had taken on more and more cases in younger patients. Watching patients so close to their own age struggle and ultimately be consumed by this disease took its toll, Singhi said. And the toll was showing up in the lives of his colleagues.

Singhi’s team was suffering from compassion fatigue — the mental, physical, or emotional exhaustion brought on by prolonged exposure to the trauma of people in one’s care. Also referred to secondary trauma, compassion fatigue “leaves someone feeling numb, detached, or like they don’t have emotional resources to keep on giving,” Singhi said.

This fatigue is common among people who work in high-stress caretaking professions. Those involved in cancer care, who frequently find themselves navigating life and death conversations and experiences with patients, are particularly at risk, experts told this news organization.

“I think anyone in medical oncology or hematology who has practiced long enough will feel this,” said Alfred Lee, MD, PhD, burnout researcher and director of the hematology/oncology fellowship at Yale School of Medicine in New Haven, Connecticut. “It’s par for the course, even in training.”

Still, compassion fatigue can be hard to detect without help. Left unaddressed, compassion fatigue can undermine good patient care, even lead to burnout.

“I’ve absolutely treated people leaving the field who think they shouldn’t be a doctor anymore,” said Jennifer Bickel, MD, recently named MD Anderson’s inaugural vice president and chief wellness officer. Those are preventable losses the field can’t afford in a provider shortage, she said.

 

Recognizing the Signs

Compassion is an essential part of patient care as is empathy. Expressing compassion or feeling empathy toward patients can foster the doctor-patient bond and help both navigate challenging conversations and decisions.

“Compassion and being able to empathize are so important — it’s how you gain trust,” Singhi said. This is especially true for patients who may be underrepresented. “That’s how they become a partner in their care, how they agree to listen about a clinical trial or agree to adhere to their treatment plan,” Singhi noted.

But there’s a risk when clinicians start to give too much.

Overtime, repeated exposure to patients’ trauma can create a sense of heaviness and fatigue, and ultimately cause caregivers to detach, Lee said.

A case study of compassion fatigue, based on the experience of one oncologist, highlighted that the condition parallels posttraumatic stress disorder, aligning on three main symptoms: Feeling hyperarousal, notably hypervigilance or irritability, avoiding stressful situations, and reliving traumatic events.

The initial phases of compassion fatigue, however, can be subtle and easily dismissed. An oncologist may begin to feel a creeping sense of detachment — a divide slowly growing with their patients, a buzz of dissatisfaction on the job, unusual mood changes.

While it’s normal for healthcare workers to experience moments of irritability, dissatisfaction, exhaustion or avoidance, when these experiences become pervasive, compassion fatigue could be the culprit, according to Marra Ackerman, MD, a psychiatrist at NYU Langone Health in New York City.

Compassion fatigue is “a form of coping more than anything,” Ackerman explained. Most of the time, it’s not a conscious choice, she said. When a brain experiences repeated distressing inputs it can shift into self-protection mode. The tipping point is different for everyone, but eventually the brain tries to detach and distance itself from the stressor, Ackerman said. And, in oncology, that stressor is often very sick patients.

If not addressed, the emotional exhaustion can limit a doctor’s efficacy at work. Clinicians suffering from compassion fatigue may find themselves calling in sick more often, making more mistakes, avoiding very sick patients, or having panic attacks at work, said Ackerman.

Clinicians also might use food, drugs, or alcohol to feel better, or detach from their patients, Lee added. “We find if you detach, you can’t provide the care patients need,” he said.

When trying to identify the issue, it’s important to understand that compassion fatigue is not burnout. The two issues can look similar, sharing symptoms like emotional detachment or disillusionment, and may co-exist, but the phenomena stem from different root causes.

While compassion fatigue is rooted in emotions and isn’t necessarily tied to work, burnout is a product of work-related stress. It’s often caused by system-level problems that leave clinicians feeling their work has lost its meaning. Inefficient technology or excessive data entry, for instance, could be drivers of burnout for oncologists because these tasks can pull the doctor away from the meaningful work of treating patients.

 

What Can Be Done

Oncology comes with its own set of risks and traumas, but for a long time, doctors weren’t equipped or encouraged to see the constant life-or-death tension of the job as a risk factor to their well-being, said Bickel.

“It’s not something we are inherently taught to identify and it’s not something we can identify without time for self-reflection,” Bickel told this news organization. In fact, many people don’t see their own compassion fatigue until a colleague points it out or they’re already past it and have some distance.

Although common among oncology clinicians, compassion fatigue is not inevitable. Oncologists can learn strategies to help manage their exposures to suffering and stave off reverting to coping mechanisms that only perpetuate the problem.

The key, Bickel said, is creating environments where people can feel safe and share their vulnerabilities. Formal peer support check-ins are a good example because they normalize regular communication about day-to-day difficulties as they happen and create space to experience grief. In these groups, no one has to worry that they’re complaining, she said.

Formalized groups also serve as a training ground where staff can learn to be better listeners. Healthcare providers are more likely to reach out to peers because so few people outside their field can relate to the challenges, Bickel explained. That’s why Moffitt Cancer Center, where Bickel recently worked before moving to MD Anderson, offers trainings to help staff learn to listen more effectively. Thirty doctors, nurses and health professionals have received the training so far and serve as a point of contact for colleagues who might be struggling, Bickel said. They can offer their peers an empathic ear, without providing unsolicited advice or commentary.

NYU Langone has a similar offering, Ackerman said. Providers can reach out to fellow nurses or doctors who have more mental health training. The conversation isn’t recorded like an appointment with a therapist may be. It’s more like mentorship where doctors can be open about what they are facing and find some comradery from someone who understands, without fear of stigma.

Talking to colleagues or having debriefs with your care team is critical because it eliminates the isolation that allows compassion fatigue to fester, Lee said. “Reflecting on positive encounters can help inspire us to keep going. Reflecting on the negative can be therapeutic and help find that sense of balance that everyone needs to find.”

As for Singhi’s team, “lots has changed since we’ve become more open,” he said. The team talks about hard patients early and often. These discussions have helped team members keep the challenges at work from seeping into their home life.

Experts agree that the threshold for seeking out help and guidance should be low. Waiting for depression or more severe symptoms to set in is not the best point of intervention, Bickel said. As soon as an oncologist begins to acknowledge a shift in how they connect with patients and the job, that’s enough to reach out.

“It’s not about what you can handle, it’s about how can you thrive and find joy,” she said.

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

Overtreatment of men with prostate cancer and limited life expectancy (LE) has persisted in the era of active surveillance and worsened in some instances, according to a new study of nearly 250,000 veterans.

“Overtreatment of men with limited longevity for intermediate- and high-risk tumors has not only failed to improve but has actually worsened over the last 20 years,” Timothy Daskivich, MD, MSHPM, with Cedars-Sinai Medical Center, Los Angeles, said in an interview.

“Many doctors assume that the increase in uptake of active surveillance for low-risk prostate cancers has solved the problem of overtreatment, but this trend has not affected overtreatment of men with low likelihood of living long enough to benefit from treatment who have higher-risk tumors,” Daskivich said.

The study was published online on November 11 in JAMA Internal Medicine.

‘Concerning’ Real-World Data

For men with low- and intermediate-risk prostate cancer expected to live fewer than 10 years, prostate cancer screening and aggressive treatment are not recommended.

Daskivich and colleagues analyzed data on 243,928 men (mean age, 66 years) in the Veterans Affairs (VA) Health System with clinically localized prostate cancer diagnosed between 2000 and 2019.

About 21% had LE < 10 years, and about 4% had LE < 5 years, according to the validated age-adjusted Prostate Cancer Comorbidity Index.

Overtreatment was defined as aggressive treatment (surgery or radiation) in those with LE < 10 years and low- to intermediate-risk disease and in those with LE < 5 years and high-risk disease, in line with current guidelines.

Among men with LE < 10 years, the proportion of men overtreated with surgery or radiotherapy for low-risk disease decreased 22% but increased 22% for intermediate-risk disease during the study period.

Among men with LE < 5 years, the proportion of men treated with definitive treatment for high-risk disease increased 29%.

“While lower-risk tumors are treated less aggressively across the board, including in men with limited longevity, it seems that we are more indiscriminately treating men with higher-risk disease without considering their expected longevity,” Daskivich said, in an interview.

Is This Happening in the General US Population?

Daskivich noted that the sample included a large sample of men diagnosed with localized prostate cancer in the VA Health System.

“Rates of overtreatment are likely to be lower in the VA [Health System], so the problem may be worse in the community setting. The VA [Health System] has been exemplary in its uptake of active surveillance for low-risk cancers, leading the effort to reduce overtreatment of men with low-risk cancers. However, the problem of overtreatment of men with limited longevity persists in the VA [Health System], underscoring the pervasiveness of this problem,” he explained.

“We don’t have a perfect head-to-head comparison of overtreatment in the VA setting vs in the community. [However, one study shows] that this is not a VA-specific phenomenon and that there is an increase in overtreatment of men with limited longevity in a Medicare population as well,” Daskivich noted.

Is Overtreatment All Bad?

Overtreatment of prostate cancer, especially in cases where the cancer is unlikely to progress or cause symptoms, can lead to significant physical, psychological, and financial harms, Christopher Anderson, MD, urologist with Columbia University Irving Medical Center in New York City, who wasn’t involved in the study, noted in an interview.

In the study by Daskivich and colleagues, over three quarters of the overtreatment was radiation therapy, which carries the risk for urinary, bowel, and sexual issues.

“Overscreening, which can lead to overtreatment, is a core issue,” Anderson said. It’s easy to order a “simple” prostate-specific antigen blood test, but in an older man with limited LE, that can lead to a host of further testing, he commented.

Stopping the pipeline of overscreening that then feeds into the cascade of overtreatment is the first step in addressing the problem of prostate cancer overtreatment, Nancy Li Schoenborn, MD, MHS, with Johns Hopkins University School of Medicine, Baltimore, and Louise C. Walter, MD, with University of California San Francisco, wrote in an editorial in JAMA Internal Medicine.

Considering LE during screening decision-making is “fundamental to reducing harms of prostate cancer overdiagnosis and overtreatment” because limited LE increases the likelihood of experiencing “harms all along the diagnostic and treatment cascade following screening,” the editorial writers said.

The time spent diagnosing, monitoring, and treating asymptomatic prostate cancer in men with limited LE distracts from monitoring and treating chronic symptomatic life-limiting illnesses, they noted.

Tough to Talk About?

Anderson noted that, in general, doctors are not great at estimating and counseling patients on LE. “It’s sometimes difficult to have that conversation,” he said.

Daskivich said physicians may fail to include average LE when advising patients on treatments because they believe that the patients do not want to discuss this topic. “Yet, in interviews with patients, we found that prostate cancer patients reported they wanted this information,” he continued, in an interview.

Solving the problem of overscreening and overtreatment will require a “multifaceted approach, including improving access to life expectancy data at the point of care for providers, educating providers on how to communicate this information, and improving data sources to predict longevity,” Daskivich said.

He said it’s equally important to note that some men with prostate cancer may choose treatment even if they have a limited longevity.

“Not all patients will choose conservative management, even if it is recommended by guidelines. However, they need to be given the opportunity to make a good decision for themselves with the best possible data,” Daskivich said.

This work was supported in part by a US Department of VA Merit Review. Daskivich reported receiving personal fees from the Medical Education Speakers Network, EDAP, and RAND; research support from Lantheus and Janssen; and a patent pending for a system for healthcare visit quality assessment outside the submitted work. Schoenborn, Walter, and Anderson had no relevant disclosures.

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

Overtreatment of men with prostate cancer and limited life expectancy (LE) has persisted in the era of active surveillance and worsened in some instances, according to a new study of nearly 250,000 veterans.

“Overtreatment of men with limited longevity for intermediate- and high-risk tumors has not only failed to improve but has actually worsened over the last 20 years,” Timothy Daskivich, MD, MSHPM, with Cedars-Sinai Medical Center, Los Angeles, said in an interview.

“Many doctors assume that the increase in uptake of active surveillance for low-risk prostate cancers has solved the problem of overtreatment, but this trend has not affected overtreatment of men with low likelihood of living long enough to benefit from treatment who have higher-risk tumors,” Daskivich said.

The study was published online on November 11 in JAMA Internal Medicine.

‘Concerning’ Real-World Data

For men with low- and intermediate-risk prostate cancer expected to live fewer than 10 years, prostate cancer screening and aggressive treatment are not recommended.

Daskivich and colleagues analyzed data on 243,928 men (mean age, 66 years) in the Veterans Affairs (VA) Health System with clinically localized prostate cancer diagnosed between 2000 and 2019.

About 21% had LE < 10 years, and about 4% had LE < 5 years, according to the validated age-adjusted Prostate Cancer Comorbidity Index.

Overtreatment was defined as aggressive treatment (surgery or radiation) in those with LE < 10 years and low- to intermediate-risk disease and in those with LE < 5 years and high-risk disease, in line with current guidelines.

Among men with LE < 10 years, the proportion of men overtreated with surgery or radiotherapy for low-risk disease decreased 22% but increased 22% for intermediate-risk disease during the study period.

Among men with LE < 5 years, the proportion of men treated with definitive treatment for high-risk disease increased 29%.

“While lower-risk tumors are treated less aggressively across the board, including in men with limited longevity, it seems that we are more indiscriminately treating men with higher-risk disease without considering their expected longevity,” Daskivich said, in an interview.

Is This Happening in the General US Population?

Daskivich noted that the sample included a large sample of men diagnosed with localized prostate cancer in the VA Health System.

“Rates of overtreatment are likely to be lower in the VA [Health System], so the problem may be worse in the community setting. The VA [Health System] has been exemplary in its uptake of active surveillance for low-risk cancers, leading the effort to reduce overtreatment of men with low-risk cancers. However, the problem of overtreatment of men with limited longevity persists in the VA [Health System], underscoring the pervasiveness of this problem,” he explained.

“We don’t have a perfect head-to-head comparison of overtreatment in the VA setting vs in the community. [However, one study shows] that this is not a VA-specific phenomenon and that there is an increase in overtreatment of men with limited longevity in a Medicare population as well,” Daskivich noted.

Is Overtreatment All Bad?

Overtreatment of prostate cancer, especially in cases where the cancer is unlikely to progress or cause symptoms, can lead to significant physical, psychological, and financial harms, Christopher Anderson, MD, urologist with Columbia University Irving Medical Center in New York City, who wasn’t involved in the study, noted in an interview.

In the study by Daskivich and colleagues, over three quarters of the overtreatment was radiation therapy, which carries the risk for urinary, bowel, and sexual issues.

“Overscreening, which can lead to overtreatment, is a core issue,” Anderson said. It’s easy to order a “simple” prostate-specific antigen blood test, but in an older man with limited LE, that can lead to a host of further testing, he commented.

Stopping the pipeline of overscreening that then feeds into the cascade of overtreatment is the first step in addressing the problem of prostate cancer overtreatment, Nancy Li Schoenborn, MD, MHS, with Johns Hopkins University School of Medicine, Baltimore, and Louise C. Walter, MD, with University of California San Francisco, wrote in an editorial in JAMA Internal Medicine.

Considering LE during screening decision-making is “fundamental to reducing harms of prostate cancer overdiagnosis and overtreatment” because limited LE increases the likelihood of experiencing “harms all along the diagnostic and treatment cascade following screening,” the editorial writers said.

The time spent diagnosing, monitoring, and treating asymptomatic prostate cancer in men with limited LE distracts from monitoring and treating chronic symptomatic life-limiting illnesses, they noted.

Tough to Talk About?

Anderson noted that, in general, doctors are not great at estimating and counseling patients on LE. “It’s sometimes difficult to have that conversation,” he said.

Daskivich said physicians may fail to include average LE when advising patients on treatments because they believe that the patients do not want to discuss this topic. “Yet, in interviews with patients, we found that prostate cancer patients reported they wanted this information,” he continued, in an interview.

Solving the problem of overscreening and overtreatment will require a “multifaceted approach, including improving access to life expectancy data at the point of care for providers, educating providers on how to communicate this information, and improving data sources to predict longevity,” Daskivich said.

He said it’s equally important to note that some men with prostate cancer may choose treatment even if they have a limited longevity.

“Not all patients will choose conservative management, even if it is recommended by guidelines. However, they need to be given the opportunity to make a good decision for themselves with the best possible data,” Daskivich said.

This work was supported in part by a US Department of VA Merit Review. Daskivich reported receiving personal fees from the Medical Education Speakers Network, EDAP, and RAND; research support from Lantheus and Janssen; and a patent pending for a system for healthcare visit quality assessment outside the submitted work. Schoenborn, Walter, and Anderson had no relevant disclosures.

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

Overtreatment of men with prostate cancer and limited life expectancy (LE) has persisted in the era of active surveillance and worsened in some instances, according to a new study of nearly 250,000 veterans.

“Overtreatment of men with limited longevity for intermediate- and high-risk tumors has not only failed to improve but has actually worsened over the last 20 years,” Timothy Daskivich, MD, MSHPM, with Cedars-Sinai Medical Center, Los Angeles, said in an interview.

“Many doctors assume that the increase in uptake of active surveillance for low-risk prostate cancers has solved the problem of overtreatment, but this trend has not affected overtreatment of men with low likelihood of living long enough to benefit from treatment who have higher-risk tumors,” Daskivich said.

The study was published online on November 11 in JAMA Internal Medicine.

‘Concerning’ Real-World Data

For men with low- and intermediate-risk prostate cancer expected to live fewer than 10 years, prostate cancer screening and aggressive treatment are not recommended.

Daskivich and colleagues analyzed data on 243,928 men (mean age, 66 years) in the Veterans Affairs (VA) Health System with clinically localized prostate cancer diagnosed between 2000 and 2019.

About 21% had LE < 10 years, and about 4% had LE < 5 years, according to the validated age-adjusted Prostate Cancer Comorbidity Index.

Overtreatment was defined as aggressive treatment (surgery or radiation) in those with LE < 10 years and low- to intermediate-risk disease and in those with LE < 5 years and high-risk disease, in line with current guidelines.

Among men with LE < 10 years, the proportion of men overtreated with surgery or radiotherapy for low-risk disease decreased 22% but increased 22% for intermediate-risk disease during the study period.

Among men with LE < 5 years, the proportion of men treated with definitive treatment for high-risk disease increased 29%.

“While lower-risk tumors are treated less aggressively across the board, including in men with limited longevity, it seems that we are more indiscriminately treating men with higher-risk disease without considering their expected longevity,” Daskivich said, in an interview.

Is This Happening in the General US Population?

Daskivich noted that the sample included a large sample of men diagnosed with localized prostate cancer in the VA Health System.

“Rates of overtreatment are likely to be lower in the VA [Health System], so the problem may be worse in the community setting. The VA [Health System] has been exemplary in its uptake of active surveillance for low-risk cancers, leading the effort to reduce overtreatment of men with low-risk cancers. However, the problem of overtreatment of men with limited longevity persists in the VA [Health System], underscoring the pervasiveness of this problem,” he explained.

“We don’t have a perfect head-to-head comparison of overtreatment in the VA setting vs in the community. [However, one study shows] that this is not a VA-specific phenomenon and that there is an increase in overtreatment of men with limited longevity in a Medicare population as well,” Daskivich noted.

Is Overtreatment All Bad?

Overtreatment of prostate cancer, especially in cases where the cancer is unlikely to progress or cause symptoms, can lead to significant physical, psychological, and financial harms, Christopher Anderson, MD, urologist with Columbia University Irving Medical Center in New York City, who wasn’t involved in the study, noted in an interview.

In the study by Daskivich and colleagues, over three quarters of the overtreatment was radiation therapy, which carries the risk for urinary, bowel, and sexual issues.

“Overscreening, which can lead to overtreatment, is a core issue,” Anderson said. It’s easy to order a “simple” prostate-specific antigen blood test, but in an older man with limited LE, that can lead to a host of further testing, he commented.

Stopping the pipeline of overscreening that then feeds into the cascade of overtreatment is the first step in addressing the problem of prostate cancer overtreatment, Nancy Li Schoenborn, MD, MHS, with Johns Hopkins University School of Medicine, Baltimore, and Louise C. Walter, MD, with University of California San Francisco, wrote in an editorial in JAMA Internal Medicine.

Considering LE during screening decision-making is “fundamental to reducing harms of prostate cancer overdiagnosis and overtreatment” because limited LE increases the likelihood of experiencing “harms all along the diagnostic and treatment cascade following screening,” the editorial writers said.

The time spent diagnosing, monitoring, and treating asymptomatic prostate cancer in men with limited LE distracts from monitoring and treating chronic symptomatic life-limiting illnesses, they noted.

Tough to Talk About?

Anderson noted that, in general, doctors are not great at estimating and counseling patients on LE. “It’s sometimes difficult to have that conversation,” he said.

Daskivich said physicians may fail to include average LE when advising patients on treatments because they believe that the patients do not want to discuss this topic. “Yet, in interviews with patients, we found that prostate cancer patients reported they wanted this information,” he continued, in an interview.

Solving the problem of overscreening and overtreatment will require a “multifaceted approach, including improving access to life expectancy data at the point of care for providers, educating providers on how to communicate this information, and improving data sources to predict longevity,” Daskivich said.

He said it’s equally important to note that some men with prostate cancer may choose treatment even if they have a limited longevity.

“Not all patients will choose conservative management, even if it is recommended by guidelines. However, they need to be given the opportunity to make a good decision for themselves with the best possible data,” Daskivich said.

This work was supported in part by a US Department of VA Merit Review. Daskivich reported receiving personal fees from the Medical Education Speakers Network, EDAP, and RAND; research support from Lantheus and Janssen; and a patent pending for a system for healthcare visit quality assessment outside the submitted work. Schoenborn, Walter, and Anderson had no relevant disclosures.

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

The use of surrogate endpoints to predict overall survival in oncology trials has been vigorously debated in the oncology community. 

In multiple studies, we have shown that the correlation of surrogate endpoints with overall survival has been weak and, in most cases, inadequate. However, others have made arguments against using overall survival as the gold standard endpoint for cancer drug trials. These arguments include claims that overall survival is not a feasible endpoint for pivotal cancer drug trials and that negative overall survival results may be unreliable.

In this column, we counter some of these arguments from the perspective of an oncologist who treats cancer and is engaged in oncology research and a patient advocate with lived experience of cancer.

Argument: Overall survival is not the only meaningful clinical endpoint. Response rates and progression-free survival also are important clinical endpoints because patients feel good when their tumor shrinks or they have more time without disease progression. Both situations can improve patients’ quality of life. 

Response: On the face of it, this argument sounds reasonable, but it treats response rates and progression-free survival as clinical endpoints rather than surrogate endpoints that need to be validated. A patient would surely welcome news that treatment has reduced the size of their tumor and would feel dismayed if the tumor is growing. However, these reactions rest on the belief that these changes signal recovery in the case of a shrinking tumor, or worsening symptoms in the case of a growing tumor, neither of which may be true. 

“Disease progression” and “progression-free survival” were developed as technical terms to signify whether a therapy in a phase 2 clinical trial was sufficiently promising to advance to phase 3. The terms were not intended to inform clinical practice or establish whether a new therapy provides clinically meaningful benefits for patients. In clinical trials, a progression event is defined as an increase in the sum of tumor diameters by more than 20%, or the appearance of a new lesion. These are both arbitrary benchmarks that in no way imply that a patient’s subjective experience of symptoms or their survival time would differ widely between a tumor growth of 19% vs 21%, or if a new, tiny lesion develops.

Of course, disease progression sometimes does affect a patient’s quality of life, but trials treat all progression events equally. An event in the brain that affects the patient’s ability to walk and an asymptomatic tumor growth in the lung from 1 cm to 1.3 cm are both considered disease progression in trials.

Patients care about progression-free survival because they mistakenly believe that an improvement will probably lead to improved overall survival or quality of life. But overall survival and quality of life can actually be affected detrimentally, despite progression-free survival gains, because the patient may experience treatment-related physical and financial toxicity without clinical benefit. Conversely, it is possible to have better overall survival and quality of life without any improvement in progression-free survival.

With response rates, the relationships to overall survival and quality of life are even weaker. Because progression-free survival and response rates do not represent clinical benefit, they cannot be considered clinical endpoints. They are surrogate endpoints that need to be validated.

A patient will reasonably welcome a treatment-related change that improves the prospect of living a longer life or enduring less suffering but should not be misled when these outcomes have not been demonstrated as being clinically beneficial.

Argument: It is not ethical to wait for overall survival when there is an unmet need.

Response: The phrase “unmet need” is used to represent the lack of effective treatment options for a particular condition. Regulators may expedite approval of a new drug that is intended to fulfil the need because waiting for overall survival may not seem ethical in these settings. 

In reality, however, the term is used inconsistently, both when the need is either questionable (the indication is indolent) or the need is real but one or more treatment options already exist. 

When the need for a drug with clinical benefit is genuinely unmet, presenting patients with just any drug is unethical; their need will continue to exist despite drug approvals if survival is not improved. In fact, approving ineffective drugs can impede the development of drugs that work.

Argument: Overall survival is not a practical endpoint for drug trials for rare cancers. 

Response: This argument has some practical validity because the low prevalence of a rare cancer may limit study recruitment opportunities. From an equity perspective, however, patients with rare cancers are no less deserving of treatments based on meaningful evidence of safety and efficacy than are patients with common cancers. Like any other patient with cancer, they should know those treatments have shown the potential for an overall survival or quality of life benefit before undergoing potentially toxic treatments. 

Several trials, such as FIRM-ACT, VIT-0910, AEWS0031, and rEECur, have shown that international collaboration makes randomized clinical trials with an endpoint of overall survival possible for most rare cancers. We support offering early access via accelerated approval when scientific evidence suggests a drug has potential benefit for patients, but the trial should be followed to confirm an overall survival benefit and the drug should be withdrawn if an overall survival benefit is lacking. 

Argument: The point of measuring overall survival is to ensure that the treatment does not worsen overall survival. 

Response: This argument is frequently made, even by regulators. However, unless a drug is tested in a justified noninferiority design trial where the aim is to determine whether it provides compensatory benefits — easier administration, lower cost, or fewer side effects than the alternative — the goal of new cancer drugs is to improve survival. Merely “not worsening survival” is incongruent with medicine’s fundamental goal of benevolence. All drugs have toxicities, some of which can be fatal. Recommending a treatment with toxicities because it did not worsen survival would harm patients and go against the Hippocratic Oath.

Argument: Overall survival in this trial was negative, but this was probably a false-negative finding. We expect future trials will be positive. 

Response: When a drug fails to improve overall survival, some experts will argue that it was a false-negative result and a future trial will be positive. For instance, to explain the negative overall survival findings in a 2020 confirmatory trial, the researchers cited a subgroup analysis in which the drug received accelerated approval based on early exploratory results. However, the subgroup analysis violated the statistical plan and raised the likelihood that the early trial’s favorable outcome was false-positive.

A second trend that increases the likelihood of false-positives is when the same anticancer medications are studied across multiple trials. If we run dozens of trials of the same drug, some of them will eventually be positive by chance alone. 

Dismissing a negative overall survival finding as a statistical artifact puts patients at risk because oncologists may continue to use the drug, despite it providing no discernable clinical benefit to patients. 

Argument: The overall survival was negative because of crossover so that patients in the control arm received the therapy at progression. 

Response: Highly effective drugs will continue to show overall survival gains despite crossover — that is, when patients in the control arm receive the experimental drug at the time of progression.

For example, a trial evaluating the addition of pertuzumab in first-line HER2-positive metastatic breast cancer allowed crossover and still showed a significant overall survival benefit. Another trial evaluating sunitinib vs placebo in advanced gastrointestinal stromal tumors showed a significant overall survival improvement despite 80% of patients in the placebo arm crossing over to sunitinib at progression.

However, in the SONIA trial, receiving cyclin-dependent kinase 4/6 inhibitors as first-line treatment of metastatic hormone receptor–positive breast cancer did not improve survival and added toxicities compared with receipt of the same agents as second-line treatment.

If crossover negates an overall survival benefit, this implies that patients in the experimental arm who received the drug upfront and patients in control arm who get the drug only at progression have no difference in survival times. If the survival outcomes in the groups are similar, that is evidence that the new drug should be given only to those who need treatment at the time of progression and not to everyone upfront. 

Giving patients the drug at the time of progression would spare patients toxicities, preserve efficacy, and save health systems costs.

Argument: Although overall survival is negative in the confirmatory trial, the clinical practice guidelines recommend using the drug, and the guidelines should be followed.

Response: We cannot ignore results of a confirmatory trial just because the drug is already in the guidelines. Guidelines should be updated on the basis of the latest evidence, rather than clinical practice being dictated by outdated guidelines. When a drug given accelerated approval appears in the guidelines, the confidence level of the evidence should be rated low until confirmatory results are available. If a confirmatory trial shows that overall survival does not improve, the guidelines should be quickly updated. However, even if they are not, physicians should not just blindly follow the guidelines.

Furthermore, practitioners should be aware that members of oncology guidelines committees often have financial conflicts of interest with pharmaceutical companies, which the literature shows can bias guideline recommendations.

 

The Bottom Line

We believe that despite arguments put forward against relying on or measuring overall survival, it continues to be the most patient-centric marker of clinical benefit. Patients deserve to know that the cancer drugs their oncologists recommend will contribute to a longer or better life.

Bishal Gyawali, Associate Professor, Department of Oncology and Department of Public Health Sciences; Scientist, Division of Cancer Care and Epidemiology, Queen’s University, Kingston, Ontario, Canada; Affiliated Faculty at the Program on Regulation, Therapeutics, and Law, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, has disclosed the financial relationship by receiving consulting fees from Vivio Health. Sharon Batt, Cancer survivor and patient advocate; Adjunct professor, Department of Bioethics and Department of Political Science, Dalhousie University, Halifax, Nova Scotia, Canada, has disclosed no relevant financial relationships.

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

The use of surrogate endpoints to predict overall survival in oncology trials has been vigorously debated in the oncology community. 

In multiple studies, we have shown that the correlation of surrogate endpoints with overall survival has been weak and, in most cases, inadequate. However, others have made arguments against using overall survival as the gold standard endpoint for cancer drug trials. These arguments include claims that overall survival is not a feasible endpoint for pivotal cancer drug trials and that negative overall survival results may be unreliable.

In this column, we counter some of these arguments from the perspective of an oncologist who treats cancer and is engaged in oncology research and a patient advocate with lived experience of cancer.

Argument: Overall survival is not the only meaningful clinical endpoint. Response rates and progression-free survival also are important clinical endpoints because patients feel good when their tumor shrinks or they have more time without disease progression. Both situations can improve patients’ quality of life. 

Response: On the face of it, this argument sounds reasonable, but it treats response rates and progression-free survival as clinical endpoints rather than surrogate endpoints that need to be validated. A patient would surely welcome news that treatment has reduced the size of their tumor and would feel dismayed if the tumor is growing. However, these reactions rest on the belief that these changes signal recovery in the case of a shrinking tumor, or worsening symptoms in the case of a growing tumor, neither of which may be true. 

“Disease progression” and “progression-free survival” were developed as technical terms to signify whether a therapy in a phase 2 clinical trial was sufficiently promising to advance to phase 3. The terms were not intended to inform clinical practice or establish whether a new therapy provides clinically meaningful benefits for patients. In clinical trials, a progression event is defined as an increase in the sum of tumor diameters by more than 20%, or the appearance of a new lesion. These are both arbitrary benchmarks that in no way imply that a patient’s subjective experience of symptoms or their survival time would differ widely between a tumor growth of 19% vs 21%, or if a new, tiny lesion develops.

Of course, disease progression sometimes does affect a patient’s quality of life, but trials treat all progression events equally. An event in the brain that affects the patient’s ability to walk and an asymptomatic tumor growth in the lung from 1 cm to 1.3 cm are both considered disease progression in trials.

Patients care about progression-free survival because they mistakenly believe that an improvement will probably lead to improved overall survival or quality of life. But overall survival and quality of life can actually be affected detrimentally, despite progression-free survival gains, because the patient may experience treatment-related physical and financial toxicity without clinical benefit. Conversely, it is possible to have better overall survival and quality of life without any improvement in progression-free survival.

With response rates, the relationships to overall survival and quality of life are even weaker. Because progression-free survival and response rates do not represent clinical benefit, they cannot be considered clinical endpoints. They are surrogate endpoints that need to be validated.

A patient will reasonably welcome a treatment-related change that improves the prospect of living a longer life or enduring less suffering but should not be misled when these outcomes have not been demonstrated as being clinically beneficial.

Argument: It is not ethical to wait for overall survival when there is an unmet need.

Response: The phrase “unmet need” is used to represent the lack of effective treatment options for a particular condition. Regulators may expedite approval of a new drug that is intended to fulfil the need because waiting for overall survival may not seem ethical in these settings. 

In reality, however, the term is used inconsistently, both when the need is either questionable (the indication is indolent) or the need is real but one or more treatment options already exist. 

When the need for a drug with clinical benefit is genuinely unmet, presenting patients with just any drug is unethical; their need will continue to exist despite drug approvals if survival is not improved. In fact, approving ineffective drugs can impede the development of drugs that work.

Argument: Overall survival is not a practical endpoint for drug trials for rare cancers. 

Response: This argument has some practical validity because the low prevalence of a rare cancer may limit study recruitment opportunities. From an equity perspective, however, patients with rare cancers are no less deserving of treatments based on meaningful evidence of safety and efficacy than are patients with common cancers. Like any other patient with cancer, they should know those treatments have shown the potential for an overall survival or quality of life benefit before undergoing potentially toxic treatments. 

Several trials, such as FIRM-ACT, VIT-0910, AEWS0031, and rEECur, have shown that international collaboration makes randomized clinical trials with an endpoint of overall survival possible for most rare cancers. We support offering early access via accelerated approval when scientific evidence suggests a drug has potential benefit for patients, but the trial should be followed to confirm an overall survival benefit and the drug should be withdrawn if an overall survival benefit is lacking. 

Argument: The point of measuring overall survival is to ensure that the treatment does not worsen overall survival. 

Response: This argument is frequently made, even by regulators. However, unless a drug is tested in a justified noninferiority design trial where the aim is to determine whether it provides compensatory benefits — easier administration, lower cost, or fewer side effects than the alternative — the goal of new cancer drugs is to improve survival. Merely “not worsening survival” is incongruent with medicine’s fundamental goal of benevolence. All drugs have toxicities, some of which can be fatal. Recommending a treatment with toxicities because it did not worsen survival would harm patients and go against the Hippocratic Oath.

Argument: Overall survival in this trial was negative, but this was probably a false-negative finding. We expect future trials will be positive. 

Response: When a drug fails to improve overall survival, some experts will argue that it was a false-negative result and a future trial will be positive. For instance, to explain the negative overall survival findings in a 2020 confirmatory trial, the researchers cited a subgroup analysis in which the drug received accelerated approval based on early exploratory results. However, the subgroup analysis violated the statistical plan and raised the likelihood that the early trial’s favorable outcome was false-positive.

A second trend that increases the likelihood of false-positives is when the same anticancer medications are studied across multiple trials. If we run dozens of trials of the same drug, some of them will eventually be positive by chance alone. 

Dismissing a negative overall survival finding as a statistical artifact puts patients at risk because oncologists may continue to use the drug, despite it providing no discernable clinical benefit to patients. 

Argument: The overall survival was negative because of crossover so that patients in the control arm received the therapy at progression. 

Response: Highly effective drugs will continue to show overall survival gains despite crossover — that is, when patients in the control arm receive the experimental drug at the time of progression.

For example, a trial evaluating the addition of pertuzumab in first-line HER2-positive metastatic breast cancer allowed crossover and still showed a significant overall survival benefit. Another trial evaluating sunitinib vs placebo in advanced gastrointestinal stromal tumors showed a significant overall survival improvement despite 80% of patients in the placebo arm crossing over to sunitinib at progression.

However, in the SONIA trial, receiving cyclin-dependent kinase 4/6 inhibitors as first-line treatment of metastatic hormone receptor–positive breast cancer did not improve survival and added toxicities compared with receipt of the same agents as second-line treatment.

If crossover negates an overall survival benefit, this implies that patients in the experimental arm who received the drug upfront and patients in control arm who get the drug only at progression have no difference in survival times. If the survival outcomes in the groups are similar, that is evidence that the new drug should be given only to those who need treatment at the time of progression and not to everyone upfront. 

Giving patients the drug at the time of progression would spare patients toxicities, preserve efficacy, and save health systems costs.

Argument: Although overall survival is negative in the confirmatory trial, the clinical practice guidelines recommend using the drug, and the guidelines should be followed.

Response: We cannot ignore results of a confirmatory trial just because the drug is already in the guidelines. Guidelines should be updated on the basis of the latest evidence, rather than clinical practice being dictated by outdated guidelines. When a drug given accelerated approval appears in the guidelines, the confidence level of the evidence should be rated low until confirmatory results are available. If a confirmatory trial shows that overall survival does not improve, the guidelines should be quickly updated. However, even if they are not, physicians should not just blindly follow the guidelines.

Furthermore, practitioners should be aware that members of oncology guidelines committees often have financial conflicts of interest with pharmaceutical companies, which the literature shows can bias guideline recommendations.

 

The Bottom Line

We believe that despite arguments put forward against relying on or measuring overall survival, it continues to be the most patient-centric marker of clinical benefit. Patients deserve to know that the cancer drugs their oncologists recommend will contribute to a longer or better life.

Bishal Gyawali, Associate Professor, Department of Oncology and Department of Public Health Sciences; Scientist, Division of Cancer Care and Epidemiology, Queen’s University, Kingston, Ontario, Canada; Affiliated Faculty at the Program on Regulation, Therapeutics, and Law, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, has disclosed the financial relationship by receiving consulting fees from Vivio Health. Sharon Batt, Cancer survivor and patient advocate; Adjunct professor, Department of Bioethics and Department of Political Science, Dalhousie University, Halifax, Nova Scotia, Canada, has disclosed no relevant financial relationships.

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

The use of surrogate endpoints to predict overall survival in oncology trials has been vigorously debated in the oncology community. 

In multiple studies, we have shown that the correlation of surrogate endpoints with overall survival has been weak and, in most cases, inadequate. However, others have made arguments against using overall survival as the gold standard endpoint for cancer drug trials. These arguments include claims that overall survival is not a feasible endpoint for pivotal cancer drug trials and that negative overall survival results may be unreliable.

In this column, we counter some of these arguments from the perspective of an oncologist who treats cancer and is engaged in oncology research and a patient advocate with lived experience of cancer.

Argument: Overall survival is not the only meaningful clinical endpoint. Response rates and progression-free survival also are important clinical endpoints because patients feel good when their tumor shrinks or they have more time without disease progression. Both situations can improve patients’ quality of life. 

Response: On the face of it, this argument sounds reasonable, but it treats response rates and progression-free survival as clinical endpoints rather than surrogate endpoints that need to be validated. A patient would surely welcome news that treatment has reduced the size of their tumor and would feel dismayed if the tumor is growing. However, these reactions rest on the belief that these changes signal recovery in the case of a shrinking tumor, or worsening symptoms in the case of a growing tumor, neither of which may be true. 

“Disease progression” and “progression-free survival” were developed as technical terms to signify whether a therapy in a phase 2 clinical trial was sufficiently promising to advance to phase 3. The terms were not intended to inform clinical practice or establish whether a new therapy provides clinically meaningful benefits for patients. In clinical trials, a progression event is defined as an increase in the sum of tumor diameters by more than 20%, or the appearance of a new lesion. These are both arbitrary benchmarks that in no way imply that a patient’s subjective experience of symptoms or their survival time would differ widely between a tumor growth of 19% vs 21%, or if a new, tiny lesion develops.

Of course, disease progression sometimes does affect a patient’s quality of life, but trials treat all progression events equally. An event in the brain that affects the patient’s ability to walk and an asymptomatic tumor growth in the lung from 1 cm to 1.3 cm are both considered disease progression in trials.

Patients care about progression-free survival because they mistakenly believe that an improvement will probably lead to improved overall survival or quality of life. But overall survival and quality of life can actually be affected detrimentally, despite progression-free survival gains, because the patient may experience treatment-related physical and financial toxicity without clinical benefit. Conversely, it is possible to have better overall survival and quality of life without any improvement in progression-free survival.

With response rates, the relationships to overall survival and quality of life are even weaker. Because progression-free survival and response rates do not represent clinical benefit, they cannot be considered clinical endpoints. They are surrogate endpoints that need to be validated.

A patient will reasonably welcome a treatment-related change that improves the prospect of living a longer life or enduring less suffering but should not be misled when these outcomes have not been demonstrated as being clinically beneficial.

Argument: It is not ethical to wait for overall survival when there is an unmet need.

Response: The phrase “unmet need” is used to represent the lack of effective treatment options for a particular condition. Regulators may expedite approval of a new drug that is intended to fulfil the need because waiting for overall survival may not seem ethical in these settings. 

In reality, however, the term is used inconsistently, both when the need is either questionable (the indication is indolent) or the need is real but one or more treatment options already exist. 

When the need for a drug with clinical benefit is genuinely unmet, presenting patients with just any drug is unethical; their need will continue to exist despite drug approvals if survival is not improved. In fact, approving ineffective drugs can impede the development of drugs that work.

Argument: Overall survival is not a practical endpoint for drug trials for rare cancers. 

Response: This argument has some practical validity because the low prevalence of a rare cancer may limit study recruitment opportunities. From an equity perspective, however, patients with rare cancers are no less deserving of treatments based on meaningful evidence of safety and efficacy than are patients with common cancers. Like any other patient with cancer, they should know those treatments have shown the potential for an overall survival or quality of life benefit before undergoing potentially toxic treatments. 

Several trials, such as FIRM-ACT, VIT-0910, AEWS0031, and rEECur, have shown that international collaboration makes randomized clinical trials with an endpoint of overall survival possible for most rare cancers. We support offering early access via accelerated approval when scientific evidence suggests a drug has potential benefit for patients, but the trial should be followed to confirm an overall survival benefit and the drug should be withdrawn if an overall survival benefit is lacking. 

Argument: The point of measuring overall survival is to ensure that the treatment does not worsen overall survival. 

Response: This argument is frequently made, even by regulators. However, unless a drug is tested in a justified noninferiority design trial where the aim is to determine whether it provides compensatory benefits — easier administration, lower cost, or fewer side effects than the alternative — the goal of new cancer drugs is to improve survival. Merely “not worsening survival” is incongruent with medicine’s fundamental goal of benevolence. All drugs have toxicities, some of which can be fatal. Recommending a treatment with toxicities because it did not worsen survival would harm patients and go against the Hippocratic Oath.

Argument: Overall survival in this trial was negative, but this was probably a false-negative finding. We expect future trials will be positive. 

Response: When a drug fails to improve overall survival, some experts will argue that it was a false-negative result and a future trial will be positive. For instance, to explain the negative overall survival findings in a 2020 confirmatory trial, the researchers cited a subgroup analysis in which the drug received accelerated approval based on early exploratory results. However, the subgroup analysis violated the statistical plan and raised the likelihood that the early trial’s favorable outcome was false-positive.

A second trend that increases the likelihood of false-positives is when the same anticancer medications are studied across multiple trials. If we run dozens of trials of the same drug, some of them will eventually be positive by chance alone. 

Dismissing a negative overall survival finding as a statistical artifact puts patients at risk because oncologists may continue to use the drug, despite it providing no discernable clinical benefit to patients. 

Argument: The overall survival was negative because of crossover so that patients in the control arm received the therapy at progression. 

Response: Highly effective drugs will continue to show overall survival gains despite crossover — that is, when patients in the control arm receive the experimental drug at the time of progression.

For example, a trial evaluating the addition of pertuzumab in first-line HER2-positive metastatic breast cancer allowed crossover and still showed a significant overall survival benefit. Another trial evaluating sunitinib vs placebo in advanced gastrointestinal stromal tumors showed a significant overall survival improvement despite 80% of patients in the placebo arm crossing over to sunitinib at progression.

However, in the SONIA trial, receiving cyclin-dependent kinase 4/6 inhibitors as first-line treatment of metastatic hormone receptor–positive breast cancer did not improve survival and added toxicities compared with receipt of the same agents as second-line treatment.

If crossover negates an overall survival benefit, this implies that patients in the experimental arm who received the drug upfront and patients in control arm who get the drug only at progression have no difference in survival times. If the survival outcomes in the groups are similar, that is evidence that the new drug should be given only to those who need treatment at the time of progression and not to everyone upfront. 

Giving patients the drug at the time of progression would spare patients toxicities, preserve efficacy, and save health systems costs.

Argument: Although overall survival is negative in the confirmatory trial, the clinical practice guidelines recommend using the drug, and the guidelines should be followed.

Response: We cannot ignore results of a confirmatory trial just because the drug is already in the guidelines. Guidelines should be updated on the basis of the latest evidence, rather than clinical practice being dictated by outdated guidelines. When a drug given accelerated approval appears in the guidelines, the confidence level of the evidence should be rated low until confirmatory results are available. If a confirmatory trial shows that overall survival does not improve, the guidelines should be quickly updated. However, even if they are not, physicians should not just blindly follow the guidelines.

Furthermore, practitioners should be aware that members of oncology guidelines committees often have financial conflicts of interest with pharmaceutical companies, which the literature shows can bias guideline recommendations.

 

The Bottom Line

We believe that despite arguments put forward against relying on or measuring overall survival, it continues to be the most patient-centric marker of clinical benefit. Patients deserve to know that the cancer drugs their oncologists recommend will contribute to a longer or better life.

Bishal Gyawali, Associate Professor, Department of Oncology and Department of Public Health Sciences; Scientist, Division of Cancer Care and Epidemiology, Queen’s University, Kingston, Ontario, Canada; Affiliated Faculty at the Program on Regulation, Therapeutics, and Law, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, has disclosed the financial relationship by receiving consulting fees from Vivio Health. Sharon Batt, Cancer survivor and patient advocate; Adjunct professor, Department of Bioethics and Department of Political Science, Dalhousie University, Halifax, Nova Scotia, Canada, has disclosed no relevant financial relationships.

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

TOPLINE:

Dysbiosis of the oral microbiome is associated with various upper gastrointestinal (UGI) disorders and precancerous lesions, with specific microbial signatures varying by disease and oral site, research shows.

METHODOLOGY:

• Emerging evidence suggests that the oral microbiota may contribute to the development of gastrointestinal malignancies, leading to efforts to identify biomarkers for early detection and progress of disease.
• In this population-based cross-sectional study, researchers studied the association between the microbiome of saliva, subgingival, and buccal mucosa and UGI disorders, particularly precancerous lesions.
• Participants included 388 adults who underwent upper endoscopy with biopsies for histopathologic analysis.
• UGI symptoms were evaluated using a validated tool, and 16S ribosomal RNA sequencing was used to characterize microbial diversity and composition of 380 saliva, 200 subgingival, and 267 buccal mucosa samples.

TAKEAWAY:

• Saliva dysbiosis was associated with several UGI disorders, including gastroesophageal reflux symptoms alone, symptomatic esophagitis, combined esophagitis and Barrett’s esophagus (BE), Helicobacter pylori–positive histology, chemical reactive gastritis, atrophic H pylori gastritis, and intestinal metaplasia.
• In contrast, dysbiosis in subgingival and buccal mucosa was more specifically associated with BE and atrophic H pylori gastritis.
• Among several identified genera, Prevotella and Fusobacterium in saliva were associated with gastric atrophy and intestinal metaplasia, and in subgingival samples, there was a notable link between Fretibacterium in BE and Fusobacterium in gastric atrophy and intestinal metaplasia.

IN PRACTICE:

“Our study for the first time suggests that microbiota in the subgingival and buccal regions may serve as more specific biomarkers for detecting precancerous lesions in asymptomatic patients, particularly for Barrett’s esophagus,” the authors wrote. “Saliva might be more appropriate for monitoring any UGI disorders at the population level.”

SOURCE:

The study, with first author Fatemeh Sadeghi, PhD, with Karolinska Institutet, Stockholm, Sweden, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The study used bacterial DNA, which cannot distinguish metabolically active bacteria. Data on diet and probiotic use were not collected. The cross-sectional design precludes conclusions about causality.

DISCLOSURES:

The authors declared no conflicts of interest. The study was funded by the Swedish Cancer Society and the Swedish Research Council.

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

TOPLINE:

Dysbiosis of the oral microbiome is associated with various upper gastrointestinal (UGI) disorders and precancerous lesions, with specific microbial signatures varying by disease and oral site, research shows.

METHODOLOGY:

• Emerging evidence suggests that the oral microbiota may contribute to the development of gastrointestinal malignancies, leading to efforts to identify biomarkers for early detection and progress of disease.
• In this population-based cross-sectional study, researchers studied the association between the microbiome of saliva, subgingival, and buccal mucosa and UGI disorders, particularly precancerous lesions.
• Participants included 388 adults who underwent upper endoscopy with biopsies for histopathologic analysis.
• UGI symptoms were evaluated using a validated tool, and 16S ribosomal RNA sequencing was used to characterize microbial diversity and composition of 380 saliva, 200 subgingival, and 267 buccal mucosa samples.

TAKEAWAY:

• Saliva dysbiosis was associated with several UGI disorders, including gastroesophageal reflux symptoms alone, symptomatic esophagitis, combined esophagitis and Barrett’s esophagus (BE), Helicobacter pylori–positive histology, chemical reactive gastritis, atrophic H pylori gastritis, and intestinal metaplasia.
• In contrast, dysbiosis in subgingival and buccal mucosa was more specifically associated with BE and atrophic H pylori gastritis.
• Among several identified genera, Prevotella and Fusobacterium in saliva were associated with gastric atrophy and intestinal metaplasia, and in subgingival samples, there was a notable link between Fretibacterium in BE and Fusobacterium in gastric atrophy and intestinal metaplasia.

IN PRACTICE:

“Our study for the first time suggests that microbiota in the subgingival and buccal regions may serve as more specific biomarkers for detecting precancerous lesions in asymptomatic patients, particularly for Barrett’s esophagus,” the authors wrote. “Saliva might be more appropriate for monitoring any UGI disorders at the population level.”

SOURCE:

The study, with first author Fatemeh Sadeghi, PhD, with Karolinska Institutet, Stockholm, Sweden, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The study used bacterial DNA, which cannot distinguish metabolically active bacteria. Data on diet and probiotic use were not collected. The cross-sectional design precludes conclusions about causality.

DISCLOSURES:

The authors declared no conflicts of interest. The study was funded by the Swedish Cancer Society and the Swedish Research Council.

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

TOPLINE:

Dysbiosis of the oral microbiome is associated with various upper gastrointestinal (UGI) disorders and precancerous lesions, with specific microbial signatures varying by disease and oral site, research shows.

METHODOLOGY:

• Emerging evidence suggests that the oral microbiota may contribute to the development of gastrointestinal malignancies, leading to efforts to identify biomarkers for early detection and progress of disease.
• In this population-based cross-sectional study, researchers studied the association between the microbiome of saliva, subgingival, and buccal mucosa and UGI disorders, particularly precancerous lesions.
• Participants included 388 adults who underwent upper endoscopy with biopsies for histopathologic analysis.
• UGI symptoms were evaluated using a validated tool, and 16S ribosomal RNA sequencing was used to characterize microbial diversity and composition of 380 saliva, 200 subgingival, and 267 buccal mucosa samples.

TAKEAWAY:

• Saliva dysbiosis was associated with several UGI disorders, including gastroesophageal reflux symptoms alone, symptomatic esophagitis, combined esophagitis and Barrett’s esophagus (BE), Helicobacter pylori–positive histology, chemical reactive gastritis, atrophic H pylori gastritis, and intestinal metaplasia.
• In contrast, dysbiosis in subgingival and buccal mucosa was more specifically associated with BE and atrophic H pylori gastritis.
• Among several identified genera, Prevotella and Fusobacterium in saliva were associated with gastric atrophy and intestinal metaplasia, and in subgingival samples, there was a notable link between Fretibacterium in BE and Fusobacterium in gastric atrophy and intestinal metaplasia.

IN PRACTICE:

“Our study for the first time suggests that microbiota in the subgingival and buccal regions may serve as more specific biomarkers for detecting precancerous lesions in asymptomatic patients, particularly for Barrett’s esophagus,” the authors wrote. “Saliva might be more appropriate for monitoring any UGI disorders at the population level.”

SOURCE:

The study, with first author Fatemeh Sadeghi, PhD, with Karolinska Institutet, Stockholm, Sweden, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The study used bacterial DNA, which cannot distinguish metabolically active bacteria. Data on diet and probiotic use were not collected. The cross-sectional design precludes conclusions about causality.

DISCLOSURES:

The authors declared no conflicts of interest. The study was funded by the Swedish Cancer Society and the Swedish Research Council.

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

TOPLINE: More than 28% of US Department of Veterans Affairs (VA) patients with colorectal cancer were diagnosed through emergency presentations, which were associated with a higher mortality risk. Emergency presentations increased during COVID-19 from prepandemic rates.

METHODOLOGY:

•       A retrospective cohort study analyzed 9096 incident colorectal cancer cancer cases diagnosed in the Veterans Health Administration from 2017 to 2021.
•       Researchers applied a validated algorithm to identify emergency presentations, defined as cancer diagnoses within 30 days following emergency care episodes or unplanned hospital admissions.
•       Analysis utilized multivariable logistic regression and Cox proportional hazards models to examine associations between emergency presentations and cancer stage, treatment, and mortality.

TAKEAWAY:

•      Patients with emergency presentations were more likely to have advanced stage disease (odds ratio [OR], 1.70; 95% CI, 1.53-1.88) compared to those without emergency presentations.
•      Emergency presentations were associated with lower likelihood of receiving cancer treatment (OR, 0.65; 95% CI, 0.56-0.75) and higher mortality risk (hazard ratio [HR], 1.70; 95% CI, 1.56-1.84).
•      The proportion of emergency presentations increased from 26.4% in 2017-2019 to 31.4% during the COVID-19 pandemic years 2020-2021 (P < .0001).

IN PRACTICE: " Our findings from one of the largest studies within a US population to examine emergency presentations among patients with colorectal cancer show that emergency presentations are common and an important negative predictor of cancer outcomes…Our study findings highlight the need for continued research and implementation efforts focused on measurement and mitigation of emergency presentations among patients with colorectal cancer.”

SOURCE: The study was led by the Center for Innovations in Quality, Effectiveness and Safety at Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston. It was published online on December 11 in Digestive Diseases and Sciences.

LIMITATIONS: The study's findings are limited by the predominantly male veteran population with lower socioeconomic status, which may affect generalizability. The equal access health care model used by the VA and its and strong screening programs may result in emergency presentation rates that differ from the private sector.

TOPLINE: More than 28% of US Department of Veterans Affairs (VA) patients with colorectal cancer were diagnosed through emergency presentations, which were associated with a higher mortality risk. Emergency presentations increased during COVID-19 from prepandemic rates.

METHODOLOGY:

•       A retrospective cohort study analyzed 9096 incident colorectal cancer cancer cases diagnosed in the Veterans Health Administration from 2017 to 2021.
•       Researchers applied a validated algorithm to identify emergency presentations, defined as cancer diagnoses within 30 days following emergency care episodes or unplanned hospital admissions.
•       Analysis utilized multivariable logistic regression and Cox proportional hazards models to examine associations between emergency presentations and cancer stage, treatment, and mortality.

TAKEAWAY:

•      Patients with emergency presentations were more likely to have advanced stage disease (odds ratio [OR], 1.70; 95% CI, 1.53-1.88) compared to those without emergency presentations.
•      Emergency presentations were associated with lower likelihood of receiving cancer treatment (OR, 0.65; 95% CI, 0.56-0.75) and higher mortality risk (hazard ratio [HR], 1.70; 95% CI, 1.56-1.84).
•      The proportion of emergency presentations increased from 26.4% in 2017-2019 to 31.4% during the COVID-19 pandemic years 2020-2021 (P < .0001).

IN PRACTICE: " Our findings from one of the largest studies within a US population to examine emergency presentations among patients with colorectal cancer show that emergency presentations are common and an important negative predictor of cancer outcomes…Our study findings highlight the need for continued research and implementation efforts focused on measurement and mitigation of emergency presentations among patients with colorectal cancer.”

SOURCE: The study was led by the Center for Innovations in Quality, Effectiveness and Safety at Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston. It was published online on December 11 in Digestive Diseases and Sciences.

LIMITATIONS: The study's findings are limited by the predominantly male veteran population with lower socioeconomic status, which may affect generalizability. The equal access health care model used by the VA and its and strong screening programs may result in emergency presentation rates that differ from the private sector.

TOPLINE: More than 28% of US Department of Veterans Affairs (VA) patients with colorectal cancer were diagnosed through emergency presentations, which were associated with a higher mortality risk. Emergency presentations increased during COVID-19 from prepandemic rates.

METHODOLOGY:

•       A retrospective cohort study analyzed 9096 incident colorectal cancer cancer cases diagnosed in the Veterans Health Administration from 2017 to 2021.
•       Researchers applied a validated algorithm to identify emergency presentations, defined as cancer diagnoses within 30 days following emergency care episodes or unplanned hospital admissions.
•       Analysis utilized multivariable logistic regression and Cox proportional hazards models to examine associations between emergency presentations and cancer stage, treatment, and mortality.

TAKEAWAY:

•      Patients with emergency presentations were more likely to have advanced stage disease (odds ratio [OR], 1.70; 95% CI, 1.53-1.88) compared to those without emergency presentations.
•      Emergency presentations were associated with lower likelihood of receiving cancer treatment (OR, 0.65; 95% CI, 0.56-0.75) and higher mortality risk (hazard ratio [HR], 1.70; 95% CI, 1.56-1.84).
•      The proportion of emergency presentations increased from 26.4% in 2017-2019 to 31.4% during the COVID-19 pandemic years 2020-2021 (P < .0001).

IN PRACTICE: " Our findings from one of the largest studies within a US population to examine emergency presentations among patients with colorectal cancer show that emergency presentations are common and an important negative predictor of cancer outcomes…Our study findings highlight the need for continued research and implementation efforts focused on measurement and mitigation of emergency presentations among patients with colorectal cancer.”

SOURCE: The study was led by the Center for Innovations in Quality, Effectiveness and Safety at Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston. It was published online on December 11 in Digestive Diseases and Sciences.

LIMITATIONS: The study's findings are limited by the predominantly male veteran population with lower socioeconomic status, which may affect generalizability. The equal access health care model used by the VA and its and strong screening programs may result in emergency presentation rates that differ from the private sector.

TOPLINE:

Physical activity before stage I cancer diagnosis is associated with reduced risk for disease progression and mortality. Members engaging in at least 60 minutes of weekly physical activity showed a 27% lower risk for progression and 47% lower risk for mortality compared with inactive individuals.

METHODOLOGY:

• Physical activity plays a significant role in reducing cancer mortality with high levels having been associated with an 18% reduction in cancer-specific mortality compared with lower levels in patients with pre- and/or post-diagnosed cancer.
• The new analysis included 28,248 members with stage I cancers enrolled in an oncology programme in South Africa, with physical activity recorded through fitness devices, logged gym sessions, and participation in organized events.
• Participants were categorized into three groups: No physical activity (0 min/wk), low physical activity (< 60 min/wk), and moderate to high physical activity (≥ 60 min/wk) based on activity levels 12 months before diagnosis.
• Researchers measured outcomes including time to progression, time to death, and all-cause mortality, with a follow-up period ranging from 1-154 months.
• Analysis adjusted for covariates including age, sex, socioeconomic status, and patient complexity measured by Johns Hopkins Adjusted Clinical Groups Systems software.

TAKEAWAY:

• Members with low physical activity showed a hazard ratio (HR) of 0.84 (95% CI, 0.79-0.89) for progression or death compared with those with no activity, whereas those with moderate to high activity showed an HR of 0.73 (95% CI, 0.70-0.77).
• For all-cause mortality, low physical activity members demonstrated an HR of 0.67 (95% CI, 0.61-0.74), whereas moderate to high activity members showed an HR of 0.53 (95% CI, 0.50-0.58) compared with inactive members.
• At 24 months post-diagnosis, individuals with moderate to high physical activity showed 80% probability of nonprogression compared with 74% for inactive individuals.
• Survival probability at 24 months was 95% for moderate to high activity members vs 91% for those with no physical activity.

IN PRACTICE:

“Physical activity may be considered to confer substantial benefits in terms of progression and overall mortality to those diagnosed with cancer. In a world where cancer continues to be a significant public health burden, the promotion of physical activity can yield important benefits regarding the progression of cancer as well as its prevention and management,” the authors of the study wrote.

SOURCE:

This study was led by Ntokozo Mabena of Discovery Vitality in Sandton, South Africa. It was published online in British Journal of Sports Medicine.

LIMITATIONS:

According to the authors, potential biases exist from not adjusting for confounding factors such as smoking status and alcohol consumption, along with incomplete body mass index data. The study assumed members without recorded physical activity points were inactive, which may not be accurate for all individuals. The findings may not be generalizable to the broader South African population as the study cohort had access to private medical insurance.

DISCLOSURES:

Authors Mabena, Sandra Lehmann, Deepak Patel, and Mosima Mabunda are employed by Discovery. Other authors Mike Greyling and Jon S. Patricios serve as a consultant for Discovery and an editor of British Journal of Sports Medicine, respectively.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Physical activity before stage I cancer diagnosis is associated with reduced risk for disease progression and mortality. Members engaging in at least 60 minutes of weekly physical activity showed a 27% lower risk for progression and 47% lower risk for mortality compared with inactive individuals.

METHODOLOGY:

• Physical activity plays a significant role in reducing cancer mortality with high levels having been associated with an 18% reduction in cancer-specific mortality compared with lower levels in patients with pre- and/or post-diagnosed cancer.
• The new analysis included 28,248 members with stage I cancers enrolled in an oncology programme in South Africa, with physical activity recorded through fitness devices, logged gym sessions, and participation in organized events.
• Participants were categorized into three groups: No physical activity (0 min/wk), low physical activity (< 60 min/wk), and moderate to high physical activity (≥ 60 min/wk) based on activity levels 12 months before diagnosis.
• Researchers measured outcomes including time to progression, time to death, and all-cause mortality, with a follow-up period ranging from 1-154 months.
• Analysis adjusted for covariates including age, sex, socioeconomic status, and patient complexity measured by Johns Hopkins Adjusted Clinical Groups Systems software.

TAKEAWAY:

• Members with low physical activity showed a hazard ratio (HR) of 0.84 (95% CI, 0.79-0.89) for progression or death compared with those with no activity, whereas those with moderate to high activity showed an HR of 0.73 (95% CI, 0.70-0.77).
• For all-cause mortality, low physical activity members demonstrated an HR of 0.67 (95% CI, 0.61-0.74), whereas moderate to high activity members showed an HR of 0.53 (95% CI, 0.50-0.58) compared with inactive members.
• At 24 months post-diagnosis, individuals with moderate to high physical activity showed 80% probability of nonprogression compared with 74% for inactive individuals.
• Survival probability at 24 months was 95% for moderate to high activity members vs 91% for those with no physical activity.

IN PRACTICE:

“Physical activity may be considered to confer substantial benefits in terms of progression and overall mortality to those diagnosed with cancer. In a world where cancer continues to be a significant public health burden, the promotion of physical activity can yield important benefits regarding the progression of cancer as well as its prevention and management,” the authors of the study wrote.

SOURCE:

This study was led by Ntokozo Mabena of Discovery Vitality in Sandton, South Africa. It was published online in British Journal of Sports Medicine.

LIMITATIONS:

According to the authors, potential biases exist from not adjusting for confounding factors such as smoking status and alcohol consumption, along with incomplete body mass index data. The study assumed members without recorded physical activity points were inactive, which may not be accurate for all individuals. The findings may not be generalizable to the broader South African population as the study cohort had access to private medical insurance.

DISCLOSURES:

Authors Mabena, Sandra Lehmann, Deepak Patel, and Mosima Mabunda are employed by Discovery. Other authors Mike Greyling and Jon S. Patricios serve as a consultant for Discovery and an editor of British Journal of Sports Medicine, respectively.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Physical activity before stage I cancer diagnosis is associated with reduced risk for disease progression and mortality. Members engaging in at least 60 minutes of weekly physical activity showed a 27% lower risk for progression and 47% lower risk for mortality compared with inactive individuals.

METHODOLOGY:

• Physical activity plays a significant role in reducing cancer mortality with high levels having been associated with an 18% reduction in cancer-specific mortality compared with lower levels in patients with pre- and/or post-diagnosed cancer.
• The new analysis included 28,248 members with stage I cancers enrolled in an oncology programme in South Africa, with physical activity recorded through fitness devices, logged gym sessions, and participation in organized events.
• Participants were categorized into three groups: No physical activity (0 min/wk), low physical activity (< 60 min/wk), and moderate to high physical activity (≥ 60 min/wk) based on activity levels 12 months before diagnosis.
• Researchers measured outcomes including time to progression, time to death, and all-cause mortality, with a follow-up period ranging from 1-154 months.
• Analysis adjusted for covariates including age, sex, socioeconomic status, and patient complexity measured by Johns Hopkins Adjusted Clinical Groups Systems software.

TAKEAWAY:

• Members with low physical activity showed a hazard ratio (HR) of 0.84 (95% CI, 0.79-0.89) for progression or death compared with those with no activity, whereas those with moderate to high activity showed an HR of 0.73 (95% CI, 0.70-0.77).
• For all-cause mortality, low physical activity members demonstrated an HR of 0.67 (95% CI, 0.61-0.74), whereas moderate to high activity members showed an HR of 0.53 (95% CI, 0.50-0.58) compared with inactive members.
• At 24 months post-diagnosis, individuals with moderate to high physical activity showed 80% probability of nonprogression compared with 74% for inactive individuals.
• Survival probability at 24 months was 95% for moderate to high activity members vs 91% for those with no physical activity.

IN PRACTICE:

“Physical activity may be considered to confer substantial benefits in terms of progression and overall mortality to those diagnosed with cancer. In a world where cancer continues to be a significant public health burden, the promotion of physical activity can yield important benefits regarding the progression of cancer as well as its prevention and management,” the authors of the study wrote.

SOURCE:

This study was led by Ntokozo Mabena of Discovery Vitality in Sandton, South Africa. It was published online in British Journal of Sports Medicine.

LIMITATIONS:

According to the authors, potential biases exist from not adjusting for confounding factors such as smoking status and alcohol consumption, along with incomplete body mass index data. The study assumed members without recorded physical activity points were inactive, which may not be accurate for all individuals. The findings may not be generalizable to the broader South African population as the study cohort had access to private medical insurance.

DISCLOSURES:

Authors Mabena, Sandra Lehmann, Deepak Patel, and Mosima Mabunda are employed by Discovery. Other authors Mike Greyling and Jon S. Patricios serve as a consultant for Discovery and an editor of British Journal of Sports Medicine, respectively.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

This transcript has been edited for clarity. 

Hello. I’m Dr. Maurie Markman from City of Hope. I wanted to briefly discuss a very important paper. This is one that probably didn’t get as much attention as I believe it should. It looks at a very important clinically relevant question, and one that might very much say, can we do more such studies but only do them faster?

This was a trial reported in the Journal of Clinical Oncology earlier this year titled, “Radiation Therapy With or Without Cisplatin for Local Recurrences of Endometrial Cancer: Results From an NRG Oncology/GOG Prospective Randomized Multicenter Clinical Study.” 

Fortunately, most patients with endometrial cancer have low-grade cancers and are cured with standard surgery, plus or minus radiation. However, a small percentage of patients, even with low-grade endometrial cancer, will recur.

There are several questions that come up. What is the optimal therapy? What is the outcome for such patients? Should we perhaps give chemotherapy along with the radiation as we do, for example, standardly in cervical cancer?

This study attempted to address that question. There was a total of 165 patients randomized in this trial that went on for 12 years, looking at local radiation vs radiation plus cisplatin — which is, again, standardly given as chemoradiation in cervical cancer.

What were the results? When this paper was reported 16 years after the study was initiated, the results showed the addition of chemotherapy did not add to the benefits of the radiation and in fact increased toxicity. Very importantly, the local control and overall control of the disease was excellent. In fact, at 3 years, 73% of the patients treated with radiation alone were disease-free.

It’s very important to know this, the value of radiation, and that adding chemotherapy with radiation doesn’t make a difference.

One might ask, if this is an important clinical question, is there a way or would there be a way in the future to take a question like this and significantly expand the population of individuals and the population of oncologists that might participate in community-based studies, where you’re asking a very simple question? 

You irradiate vs something else; you have a standard of care; you’re looking at progression-free survival, which is a very valid endpoint, or overall survival, and you don’t anticipate significant differences in toxicity because you might use this therapy otherwise. 

Would it be possible to answer the question not in 12 years, but in half that time or maybe 20% of that time? The results are important for patients being treated today and their doctors who are advising on optimal therapy.

For those of you who are interested in the question of the management of endometrial cancer, this type of pragmatic trial, I would encourage you to read this important paper. Thank you for your attention.

Maurie Markman, Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix, has disclosed the following relevant financial relationships: Received income in an amount equal to or greater than $250 from GlaxoSmithKline and AstraZeneca.

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

This transcript has been edited for clarity. 

Hello. I’m Dr. Maurie Markman from City of Hope. I wanted to briefly discuss a very important paper. This is one that probably didn’t get as much attention as I believe it should. It looks at a very important clinically relevant question, and one that might very much say, can we do more such studies but only do them faster?

This was a trial reported in the Journal of Clinical Oncology earlier this year titled, “Radiation Therapy With or Without Cisplatin for Local Recurrences of Endometrial Cancer: Results From an NRG Oncology/GOG Prospective Randomized Multicenter Clinical Study.” 

Fortunately, most patients with endometrial cancer have low-grade cancers and are cured with standard surgery, plus or minus radiation. However, a small percentage of patients, even with low-grade endometrial cancer, will recur.

There are several questions that come up. What is the optimal therapy? What is the outcome for such patients? Should we perhaps give chemotherapy along with the radiation as we do, for example, standardly in cervical cancer?

This study attempted to address that question. There was a total of 165 patients randomized in this trial that went on for 12 years, looking at local radiation vs radiation plus cisplatin — which is, again, standardly given as chemoradiation in cervical cancer.

What were the results? When this paper was reported 16 years after the study was initiated, the results showed the addition of chemotherapy did not add to the benefits of the radiation and in fact increased toxicity. Very importantly, the local control and overall control of the disease was excellent. In fact, at 3 years, 73% of the patients treated with radiation alone were disease-free.

It’s very important to know this, the value of radiation, and that adding chemotherapy with radiation doesn’t make a difference.

One might ask, if this is an important clinical question, is there a way or would there be a way in the future to take a question like this and significantly expand the population of individuals and the population of oncologists that might participate in community-based studies, where you’re asking a very simple question? 

You irradiate vs something else; you have a standard of care; you’re looking at progression-free survival, which is a very valid endpoint, or overall survival, and you don’t anticipate significant differences in toxicity because you might use this therapy otherwise. 

Would it be possible to answer the question not in 12 years, but in half that time or maybe 20% of that time? The results are important for patients being treated today and their doctors who are advising on optimal therapy.

For those of you who are interested in the question of the management of endometrial cancer, this type of pragmatic trial, I would encourage you to read this important paper. Thank you for your attention.

Maurie Markman, Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix, has disclosed the following relevant financial relationships: Received income in an amount equal to or greater than $250 from GlaxoSmithKline and AstraZeneca.

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

This transcript has been edited for clarity. 

Hello. I’m Dr. Maurie Markman from City of Hope. I wanted to briefly discuss a very important paper. This is one that probably didn’t get as much attention as I believe it should. It looks at a very important clinically relevant question, and one that might very much say, can we do more such studies but only do them faster?

This was a trial reported in the Journal of Clinical Oncology earlier this year titled, “Radiation Therapy With or Without Cisplatin for Local Recurrences of Endometrial Cancer: Results From an NRG Oncology/GOG Prospective Randomized Multicenter Clinical Study.” 

Fortunately, most patients with endometrial cancer have low-grade cancers and are cured with standard surgery, plus or minus radiation. However, a small percentage of patients, even with low-grade endometrial cancer, will recur.

There are several questions that come up. What is the optimal therapy? What is the outcome for such patients? Should we perhaps give chemotherapy along with the radiation as we do, for example, standardly in cervical cancer?

This study attempted to address that question. There was a total of 165 patients randomized in this trial that went on for 12 years, looking at local radiation vs radiation plus cisplatin — which is, again, standardly given as chemoradiation in cervical cancer.

What were the results? When this paper was reported 16 years after the study was initiated, the results showed the addition of chemotherapy did not add to the benefits of the radiation and in fact increased toxicity. Very importantly, the local control and overall control of the disease was excellent. In fact, at 3 years, 73% of the patients treated with radiation alone were disease-free.

It’s very important to know this, the value of radiation, and that adding chemotherapy with radiation doesn’t make a difference.

One might ask, if this is an important clinical question, is there a way or would there be a way in the future to take a question like this and significantly expand the population of individuals and the population of oncologists that might participate in community-based studies, where you’re asking a very simple question? 

You irradiate vs something else; you have a standard of care; you’re looking at progression-free survival, which is a very valid endpoint, or overall survival, and you don’t anticipate significant differences in toxicity because you might use this therapy otherwise. 

Would it be possible to answer the question not in 12 years, but in half that time or maybe 20% of that time? The results are important for patients being treated today and their doctors who are advising on optimal therapy.

For those of you who are interested in the question of the management of endometrial cancer, this type of pragmatic trial, I would encourage you to read this important paper. Thank you for your attention.

Maurie Markman, Professor of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center; President, Medicine & Science, City of Hope Atlanta, Chicago, Phoenix, has disclosed the following relevant financial relationships: Received income in an amount equal to or greater than $250 from GlaxoSmithKline and AstraZeneca.

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

Exposure to Agent Orange and depleted urology are associated with increased risk of bladder cancer, according to a recent Urology meta-analysis. About 3200 US veterans are diagnosed with bladder cancer each year, which is the fourth most diagnosed cancer among veterans. “Identifying veterans exposed to these risk factors is crucial for implementing screening protocols and connecting them with preventive healthcare measures when possible,” the authors said. 

A meta-analysis using narrative synthesis to incorporate diverse studies examined the impact of exposure to Agent Orange, depleted uranium exposure, contaminated drinking water, and other environmental contaminants. The researchers found 7 studies of Agent Orange exposure that in total showed a statistically significant increase in bladder cancer risk (hazard ratio [HR], 1.17; 95% confidence interval [CI], 1.01-1.36; P < .001) among 2,705,283 veterans. Six studies revealed that depleted uranium exposure caused a statistically significant association with bladder cancer as well (HR, 2.13; 95% CI, 1.31-3.48; P = .002) among 28,899 patients. Exposure to contaminated drinking water exposure in 4 studies also suggested an increased bladder cancer risk (HR, 1.25; 95% CI, 0.97-1.61; P = .08) among 370,408 veterans. 

The authors identified other factors that also contributed to increased bladder cancer risk, including smoking, occupational exposures to substances like asbestos and diesel fumes, and exposure to ionizing radiation from nuclear tests. “These findings emphasize the urgent need for enhanced clinical management strategies and preventive measures for veterans exposed to these carcinogenic agents,” the authors asserted. 

The authors report no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

Exposure to Agent Orange and depleted urology are associated with increased risk of bladder cancer, according to a recent Urology meta-analysis. About 3200 US veterans are diagnosed with bladder cancer each year, which is the fourth most diagnosed cancer among veterans. “Identifying veterans exposed to these risk factors is crucial for implementing screening protocols and connecting them with preventive healthcare measures when possible,” the authors said. 

A meta-analysis using narrative synthesis to incorporate diverse studies examined the impact of exposure to Agent Orange, depleted uranium exposure, contaminated drinking water, and other environmental contaminants. The researchers found 7 studies of Agent Orange exposure that in total showed a statistically significant increase in bladder cancer risk (hazard ratio [HR], 1.17; 95% confidence interval [CI], 1.01-1.36; P < .001) among 2,705,283 veterans. Six studies revealed that depleted uranium exposure caused a statistically significant association with bladder cancer as well (HR, 2.13; 95% CI, 1.31-3.48; P = .002) among 28,899 patients. Exposure to contaminated drinking water exposure in 4 studies also suggested an increased bladder cancer risk (HR, 1.25; 95% CI, 0.97-1.61; P = .08) among 370,408 veterans. 

The authors identified other factors that also contributed to increased bladder cancer risk, including smoking, occupational exposures to substances like asbestos and diesel fumes, and exposure to ionizing radiation from nuclear tests. “These findings emphasize the urgent need for enhanced clinical management strategies and preventive measures for veterans exposed to these carcinogenic agents,” the authors asserted. 

The authors report no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

Exposure to Agent Orange and depleted urology are associated with increased risk of bladder cancer, according to a recent Urology meta-analysis. About 3200 US veterans are diagnosed with bladder cancer each year, which is the fourth most diagnosed cancer among veterans. “Identifying veterans exposed to these risk factors is crucial for implementing screening protocols and connecting them with preventive healthcare measures when possible,” the authors said. 

A meta-analysis using narrative synthesis to incorporate diverse studies examined the impact of exposure to Agent Orange, depleted uranium exposure, contaminated drinking water, and other environmental contaminants. The researchers found 7 studies of Agent Orange exposure that in total showed a statistically significant increase in bladder cancer risk (hazard ratio [HR], 1.17; 95% confidence interval [CI], 1.01-1.36; P < .001) among 2,705,283 veterans. Six studies revealed that depleted uranium exposure caused a statistically significant association with bladder cancer as well (HR, 2.13; 95% CI, 1.31-3.48; P = .002) among 28,899 patients. Exposure to contaminated drinking water exposure in 4 studies also suggested an increased bladder cancer risk (HR, 1.25; 95% CI, 0.97-1.61; P = .08) among 370,408 veterans. 

The authors identified other factors that also contributed to increased bladder cancer risk, including smoking, occupational exposures to substances like asbestos and diesel fumes, and exposure to ionizing radiation from nuclear tests. “These findings emphasize the urgent need for enhanced clinical management strategies and preventive measures for veterans exposed to these carcinogenic agents,” the authors asserted. 

The authors report no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

TOPLINE:

Merkel cell carcinoma (MCC) is less common and is associated with higher mortality rates than melanoma, according to a study that also reported that male gender, older age, and exposure to ultraviolet radiation (UVR) are significant risk factors.

METHODOLOGY:

• Researchers identified 19,444 MCC cases and 646,619 melanoma cases diagnosed between 2000 and 2021 using data from the Surveillance, Epidemiology, and End Results (SEER) Program.
• Ambient UVR exposure data were obtained from the National Aeronautics and Space Administration’s total ozone mapping spectrometer database.
• Risk factors and cancer-specific mortality rates were evaluated for both cancers.

TAKEAWAY:

• Incidence rates per 100,000 person-years of MCC and melanoma were 0.8 and 27.3, respectively.
• Men (adjusted incidence rate ratio [IRR], 1.72 for MCC and 1.23 for melanoma), older age groups (IRR: 2.69 for MCC and 1.62 for melanoma among those 70-79 years; and 5.68 for MCC and 2.26 for melanoma among those 80 years or older) showed higher incidences of MCC and melanoma. Non-Hispanic White individuals were at higher risk for MCC and melanoma than other racial/ethnic groups.
• Exposure to UVR was associated with higher incidences of melanoma (IRR, 1.24-1.49) and MCC (IRR, 1.15-1.20) in non-Hispanic White individuals, particularly on the head and neck. These associations were unclear among racial/ethnic groups.
• Individuals with MCC had a higher risk for cancer-specific mortality than those with melanoma (adjusted hazard ratio [HR], 2.33; 95% CI, 2.26-2.42). Cancer-specific survival for both cancers improved for cases diagnosed during 2012-2021 vs 2004-2011 (MCC: HR, 0.83; 95% CI, 0.78-0.89; melanoma: HR, 0.75; 95% CI, 0.74-0.76).

IN PRACTICE:

“MCC and melanoma are aggressive skin cancers with similar risk factors including male sex, older age, and UV radiation exposure. Clinicians should be alert to diagnosis of these cancers to allow for prompt treatment,” the authors wrote, adding: “It is encouraging that survival for both cancers has increased in recent years, with the largest gains in survival seen in distant stage melanoma, coinciding with the approval of BRAF and PD-1 inhibitors used for distant stage disease,” although mortality for advanced stage tumors “continues to be very high.”

SOURCE:

The study was led by Jacob T. Tribble, BA, National Cancer Institute, Rockville, Maryland. It was published online on January 5 in the Journal of Investigative Dermatology.

LIMITATIONS:

The study relied on SEER’s general staging system rather than the American Joint Committee on Cancer standard, and UVR exposure estimates did not account for individual sun protection behaviors or prior residential history. Race and ethnicity served as a proxy for UVR sensitivity, which may introduce misclassification bias.

DISCLOSURES:

The research was supported by the Intramural Research Program of the National Cancer Institute, the National Institutes of Health, the American Association for Dental Research, and the Colgate-Palmolive Company. The authors reported no conflict of interests.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Merkel cell carcinoma (MCC) is less common and is associated with higher mortality rates than melanoma, according to a study that also reported that male gender, older age, and exposure to ultraviolet radiation (UVR) are significant risk factors.

METHODOLOGY:

• Researchers identified 19,444 MCC cases and 646,619 melanoma cases diagnosed between 2000 and 2021 using data from the Surveillance, Epidemiology, and End Results (SEER) Program.
• Ambient UVR exposure data were obtained from the National Aeronautics and Space Administration’s total ozone mapping spectrometer database.
• Risk factors and cancer-specific mortality rates were evaluated for both cancers.

TAKEAWAY:

• Incidence rates per 100,000 person-years of MCC and melanoma were 0.8 and 27.3, respectively.
• Men (adjusted incidence rate ratio [IRR], 1.72 for MCC and 1.23 for melanoma), older age groups (IRR: 2.69 for MCC and 1.62 for melanoma among those 70-79 years; and 5.68 for MCC and 2.26 for melanoma among those 80 years or older) showed higher incidences of MCC and melanoma. Non-Hispanic White individuals were at higher risk for MCC and melanoma than other racial/ethnic groups.
• Exposure to UVR was associated with higher incidences of melanoma (IRR, 1.24-1.49) and MCC (IRR, 1.15-1.20) in non-Hispanic White individuals, particularly on the head and neck. These associations were unclear among racial/ethnic groups.
• Individuals with MCC had a higher risk for cancer-specific mortality than those with melanoma (adjusted hazard ratio [HR], 2.33; 95% CI, 2.26-2.42). Cancer-specific survival for both cancers improved for cases diagnosed during 2012-2021 vs 2004-2011 (MCC: HR, 0.83; 95% CI, 0.78-0.89; melanoma: HR, 0.75; 95% CI, 0.74-0.76).

IN PRACTICE:

“MCC and melanoma are aggressive skin cancers with similar risk factors including male sex, older age, and UV radiation exposure. Clinicians should be alert to diagnosis of these cancers to allow for prompt treatment,” the authors wrote, adding: “It is encouraging that survival for both cancers has increased in recent years, with the largest gains in survival seen in distant stage melanoma, coinciding with the approval of BRAF and PD-1 inhibitors used for distant stage disease,” although mortality for advanced stage tumors “continues to be very high.”

SOURCE:

The study was led by Jacob T. Tribble, BA, National Cancer Institute, Rockville, Maryland. It was published online on January 5 in the Journal of Investigative Dermatology.

LIMITATIONS:

The study relied on SEER’s general staging system rather than the American Joint Committee on Cancer standard, and UVR exposure estimates did not account for individual sun protection behaviors or prior residential history. Race and ethnicity served as a proxy for UVR sensitivity, which may introduce misclassification bias.

DISCLOSURES:

The research was supported by the Intramural Research Program of the National Cancer Institute, the National Institutes of Health, the American Association for Dental Research, and the Colgate-Palmolive Company. The authors reported no conflict of interests.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Merkel cell carcinoma (MCC) is less common and is associated with higher mortality rates than melanoma, according to a study that also reported that male gender, older age, and exposure to ultraviolet radiation (UVR) are significant risk factors.

METHODOLOGY:

• Researchers identified 19,444 MCC cases and 646,619 melanoma cases diagnosed between 2000 and 2021 using data from the Surveillance, Epidemiology, and End Results (SEER) Program.
• Ambient UVR exposure data were obtained from the National Aeronautics and Space Administration’s total ozone mapping spectrometer database.
• Risk factors and cancer-specific mortality rates were evaluated for both cancers.

TAKEAWAY:

• Incidence rates per 100,000 person-years of MCC and melanoma were 0.8 and 27.3, respectively.
• Men (adjusted incidence rate ratio [IRR], 1.72 for MCC and 1.23 for melanoma), older age groups (IRR: 2.69 for MCC and 1.62 for melanoma among those 70-79 years; and 5.68 for MCC and 2.26 for melanoma among those 80 years or older) showed higher incidences of MCC and melanoma. Non-Hispanic White individuals were at higher risk for MCC and melanoma than other racial/ethnic groups.
• Exposure to UVR was associated with higher incidences of melanoma (IRR, 1.24-1.49) and MCC (IRR, 1.15-1.20) in non-Hispanic White individuals, particularly on the head and neck. These associations were unclear among racial/ethnic groups.
• Individuals with MCC had a higher risk for cancer-specific mortality than those with melanoma (adjusted hazard ratio [HR], 2.33; 95% CI, 2.26-2.42). Cancer-specific survival for both cancers improved for cases diagnosed during 2012-2021 vs 2004-2011 (MCC: HR, 0.83; 95% CI, 0.78-0.89; melanoma: HR, 0.75; 95% CI, 0.74-0.76).

IN PRACTICE:

“MCC and melanoma are aggressive skin cancers with similar risk factors including male sex, older age, and UV radiation exposure. Clinicians should be alert to diagnosis of these cancers to allow for prompt treatment,” the authors wrote, adding: “It is encouraging that survival for both cancers has increased in recent years, with the largest gains in survival seen in distant stage melanoma, coinciding with the approval of BRAF and PD-1 inhibitors used for distant stage disease,” although mortality for advanced stage tumors “continues to be very high.”

SOURCE:

The study was led by Jacob T. Tribble, BA, National Cancer Institute, Rockville, Maryland. It was published online on January 5 in the Journal of Investigative Dermatology.

LIMITATIONS:

The study relied on SEER’s general staging system rather than the American Joint Committee on Cancer standard, and UVR exposure estimates did not account for individual sun protection behaviors or prior residential history. Race and ethnicity served as a proxy for UVR sensitivity, which may introduce misclassification bias.

DISCLOSURES:

The research was supported by the Intramural Research Program of the National Cancer Institute, the National Institutes of Health, the American Association for Dental Research, and the Colgate-Palmolive Company. The authors reported no conflict of interests.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.