Cancer

Offering adjuvant therapy to patients with stage III melanoma offers no melanoma-specific or overall survival benefit, reveals extended follow-up from the first population-based national study to estimate the impact of the treatment.

Hildur Helgadottir, MD, PhD, presented the new findings at the 22nd European Association of Dermato-Oncology (EADO) Congress 2026 on April 24 and described the lead-up to the latest update on the study.

To investigate the impact of adjuvant treatment in patients with stage III melanoma, researchers initially conducted a study in which they used the Swedish Melanoma Registry (SweMR) to identify a precohort of those treated before the introduction of adjuvant therapy in 2018 and a postcohort of those treated subsequently, following both groups out to 2023, she explained.

The analysis revealed no significant difference in melanoma-specific survival between the two groups, at a hazard ratio of 0.92, nor in overall survival, at a hazard ratio of 0.93 (P = .60 for both). However, median follow-up differed between the groups, at 69 months vs 39 months for the precohort vs the postcohort.

Helgadottir, who is a senior research specialist at the Karolinska Comprehensive Cancer Center in Stockholm, Sweden, said that when the earlier results were presented at the European Society for Medical Oncology 2024, there was some criticism that the follow-up was not long enough and that there was no information on the actual adjuvant treatment received in the postcohort patients.

The researchers therefore extended their study out to 2024 to increase the median follow-up to 60 months vs 92 months in the postcohort group vs the precohort group.

They also focused patient selection on patients aged less than 75 years because exposure to adjuvant therapy in older patients was low and restricted the analysis to sentinel lymph node-positive stage IIIB-D cutaneous melanoma diagnosed between 2016 and 2020. This was because adjuvant exposure in stage IIIA disease was low, and patients with clinically detected stage III melanoma started to receive neoadjuvant therapy from 2022 onward.

The current analysis, which was recently published in the European Journal of Cancer, involved 287 patients in the precohort and 349 in the postcohort, who had a median age of 60.0 years and 61.0 years, respectively, and of whom 62.0% and 60.5%, respectively, were male. The groups were well balanced in terms of baseline disease characteristics.

Helgadottir explained that 73% of patients in the postcohort received some form of adjuvant treatment, with the majority treated with PD-1 inhibitors, and a smaller proportion given B-Raf serine-threonine kinase inhibitors. The main reasons for not giving adjuvant therapy were favorable tumor characteristics and the presence of comorbidities.

Five-year melanoma-specific survival rates in the precohorts and postcohorts were 71.4% vs 73.2%, at a hazard ratio adjusted for age, sex, and American Joint Committee on Cancer stage of 1.01 (P = .931). Five-year overall survival rates were 67.3% vs 70.1%, at an adjusted hazard ratio of 0.96 (P = .791).

Helgadottir showed that there were also no significant survival differences in any of the prespecified subgroups for neither melanoma-specific nor overall survival.

There were, again, no significant differences in survival outcomes between the two patient groups, she reported.

The latest results are similar to those from another study conducted in Netherlands and a Danish analysis, Helgadottir said.

Taken together, and “considering the side effects and the costs, it is possible that we will go back to closely following up our patients and treating only at relapse,” she said, “and optimally, of course, that will be already in the neoadjuvant setting.”

“And of course we will need biomarkers because there could be some patients that really need adjuvant treatment, but we need to identify these patients,” continued Helgadottir. Overall survival results from KEYNOTE-054, which compares pembrolizumab with placebo after resection of high-risk stage III melanoma, are awaited, she continued.

Helgadottir explained that adjuvant treatment for stage III melanoma was approved in Sweden in 2018, with treatments freely available to all Swedish residents.

The SweMR is a population-based national register that has near-complete and detailed data on primary cutaneous melanomas, including nodal status and satellite and in-transit disease, and is linked to the national Cause of Death Registry. Helgadottir noted, however, that the SweMR does not contain any information on relapses or the nature of the oncologic treatment received by patients with melanoma.

Following her presentation, she was challenged by an audience member as to whether, on the basis of her findings, she would go back to following up with patients and treating at relapses.

“Maybe we should do that and believe in our own data, and we do. But still, the gold standard must always be the randomized clinical trial,” Helgadottir responded. “So I think, although that we believe in this data, we also want to see the results of the randomized studies.”

The audience member commented that she can see in the data from her own institution that they treat fewer and fewer patients with melanoma with adjuvant therapy by discussing it more thoroughly and being stricter on who should receive it.

Helgadottir agreed, adding that “based on this experience, we did not introduce it to stage II patients because it’s always harder to go back” once a group of patients has started to receive a treatment.

The research was supported by Regional Cancer Centres in Sweden and with grants from the Swedish Cancer Society, Region Stockholm, and the Cancer Research Funds of Radiumhemmet. Helgadottir declared having relationships with Bristol Myers Squibb, Merck Sharp & Dohme, Pierre Fabre, and Novartis.

The trial was supported by SkinVision. The researchers declared having no relevant financial relationships.

This article was previously published by Medscape.

Offering adjuvant therapy to patients with stage III melanoma offers no melanoma-specific or overall survival benefit, reveals extended follow-up from the first population-based national study to estimate the impact of the treatment.

Hildur Helgadottir, MD, PhD, presented the new findings at the 22nd European Association of Dermato-Oncology (EADO) Congress 2026 on April 24 and described the lead-up to the latest update on the study.

To investigate the impact of adjuvant treatment in patients with stage III melanoma, researchers initially conducted a study in which they used the Swedish Melanoma Registry (SweMR) to identify a precohort of those treated before the introduction of adjuvant therapy in 2018 and a postcohort of those treated subsequently, following both groups out to 2023, she explained.

The analysis revealed no significant difference in melanoma-specific survival between the two groups, at a hazard ratio of 0.92, nor in overall survival, at a hazard ratio of 0.93 (P = .60 for both). However, median follow-up differed between the groups, at 69 months vs 39 months for the precohort vs the postcohort.

Helgadottir, who is a senior research specialist at the Karolinska Comprehensive Cancer Center in Stockholm, Sweden, said that when the earlier results were presented at the European Society for Medical Oncology 2024, there was some criticism that the follow-up was not long enough and that there was no information on the actual adjuvant treatment received in the postcohort patients.

The researchers therefore extended their study out to 2024 to increase the median follow-up to 60 months vs 92 months in the postcohort group vs the precohort group.

They also focused patient selection on patients aged less than 75 years because exposure to adjuvant therapy in older patients was low and restricted the analysis to sentinel lymph node-positive stage IIIB-D cutaneous melanoma diagnosed between 2016 and 2020. This was because adjuvant exposure in stage IIIA disease was low, and patients with clinically detected stage III melanoma started to receive neoadjuvant therapy from 2022 onward.

The current analysis, which was recently published in the European Journal of Cancer, involved 287 patients in the precohort and 349 in the postcohort, who had a median age of 60.0 years and 61.0 years, respectively, and of whom 62.0% and 60.5%, respectively, were male. The groups were well balanced in terms of baseline disease characteristics.

Helgadottir explained that 73% of patients in the postcohort received some form of adjuvant treatment, with the majority treated with PD-1 inhibitors, and a smaller proportion given B-Raf serine-threonine kinase inhibitors. The main reasons for not giving adjuvant therapy were favorable tumor characteristics and the presence of comorbidities.

Five-year melanoma-specific survival rates in the precohorts and postcohorts were 71.4% vs 73.2%, at a hazard ratio adjusted for age, sex, and American Joint Committee on Cancer stage of 1.01 (P = .931). Five-year overall survival rates were 67.3% vs 70.1%, at an adjusted hazard ratio of 0.96 (P = .791).

Helgadottir showed that there were also no significant survival differences in any of the prespecified subgroups for neither melanoma-specific nor overall survival.

There were, again, no significant differences in survival outcomes between the two patient groups, she reported.

The latest results are similar to those from another study conducted in Netherlands and a Danish analysis, Helgadottir said.

Taken together, and “considering the side effects and the costs, it is possible that we will go back to closely following up our patients and treating only at relapse,” she said, “and optimally, of course, that will be already in the neoadjuvant setting.”

“And of course we will need biomarkers because there could be some patients that really need adjuvant treatment, but we need to identify these patients,” continued Helgadottir. Overall survival results from KEYNOTE-054, which compares pembrolizumab with placebo after resection of high-risk stage III melanoma, are awaited, she continued.

Helgadottir explained that adjuvant treatment for stage III melanoma was approved in Sweden in 2018, with treatments freely available to all Swedish residents.

The SweMR is a population-based national register that has near-complete and detailed data on primary cutaneous melanomas, including nodal status and satellite and in-transit disease, and is linked to the national Cause of Death Registry. Helgadottir noted, however, that the SweMR does not contain any information on relapses or the nature of the oncologic treatment received by patients with melanoma.

Following her presentation, she was challenged by an audience member as to whether, on the basis of her findings, she would go back to following up with patients and treating at relapses.

“Maybe we should do that and believe in our own data, and we do. But still, the gold standard must always be the randomized clinical trial,” Helgadottir responded. “So I think, although that we believe in this data, we also want to see the results of the randomized studies.”

The audience member commented that she can see in the data from her own institution that they treat fewer and fewer patients with melanoma with adjuvant therapy by discussing it more thoroughly and being stricter on who should receive it.

Helgadottir agreed, adding that “based on this experience, we did not introduce it to stage II patients because it’s always harder to go back” once a group of patients has started to receive a treatment.

The research was supported by Regional Cancer Centres in Sweden and with grants from the Swedish Cancer Society, Region Stockholm, and the Cancer Research Funds of Radiumhemmet. Helgadottir declared having relationships with Bristol Myers Squibb, Merck Sharp & Dohme, Pierre Fabre, and Novartis.

The trial was supported by SkinVision. The researchers declared having no relevant financial relationships.

This article was previously published by Medscape.

Offering adjuvant therapy to patients with stage III melanoma offers no melanoma-specific or overall survival benefit, reveals extended follow-up from the first population-based national study to estimate the impact of the treatment.

Hildur Helgadottir, MD, PhD, presented the new findings at the 22nd European Association of Dermato-Oncology (EADO) Congress 2026 on April 24 and described the lead-up to the latest update on the study.

To investigate the impact of adjuvant treatment in patients with stage III melanoma, researchers initially conducted a study in which they used the Swedish Melanoma Registry (SweMR) to identify a precohort of those treated before the introduction of adjuvant therapy in 2018 and a postcohort of those treated subsequently, following both groups out to 2023, she explained.

The analysis revealed no significant difference in melanoma-specific survival between the two groups, at a hazard ratio of 0.92, nor in overall survival, at a hazard ratio of 0.93 (P = .60 for both). However, median follow-up differed between the groups, at 69 months vs 39 months for the precohort vs the postcohort.

Helgadottir, who is a senior research specialist at the Karolinska Comprehensive Cancer Center in Stockholm, Sweden, said that when the earlier results were presented at the European Society for Medical Oncology 2024, there was some criticism that the follow-up was not long enough and that there was no information on the actual adjuvant treatment received in the postcohort patients.

The researchers therefore extended their study out to 2024 to increase the median follow-up to 60 months vs 92 months in the postcohort group vs the precohort group.

They also focused patient selection on patients aged less than 75 years because exposure to adjuvant therapy in older patients was low and restricted the analysis to sentinel lymph node-positive stage IIIB-D cutaneous melanoma diagnosed between 2016 and 2020. This was because adjuvant exposure in stage IIIA disease was low, and patients with clinically detected stage III melanoma started to receive neoadjuvant therapy from 2022 onward.

The current analysis, which was recently published in the European Journal of Cancer, involved 287 patients in the precohort and 349 in the postcohort, who had a median age of 60.0 years and 61.0 years, respectively, and of whom 62.0% and 60.5%, respectively, were male. The groups were well balanced in terms of baseline disease characteristics.

Helgadottir explained that 73% of patients in the postcohort received some form of adjuvant treatment, with the majority treated with PD-1 inhibitors, and a smaller proportion given B-Raf serine-threonine kinase inhibitors. The main reasons for not giving adjuvant therapy were favorable tumor characteristics and the presence of comorbidities.

Five-year melanoma-specific survival rates in the precohorts and postcohorts were 71.4% vs 73.2%, at a hazard ratio adjusted for age, sex, and American Joint Committee on Cancer stage of 1.01 (P = .931). Five-year overall survival rates were 67.3% vs 70.1%, at an adjusted hazard ratio of 0.96 (P = .791).

Helgadottir showed that there were also no significant survival differences in any of the prespecified subgroups for neither melanoma-specific nor overall survival.

There were, again, no significant differences in survival outcomes between the two patient groups, she reported.

The latest results are similar to those from another study conducted in Netherlands and a Danish analysis, Helgadottir said.

Taken together, and “considering the side effects and the costs, it is possible that we will go back to closely following up our patients and treating only at relapse,” she said, “and optimally, of course, that will be already in the neoadjuvant setting.”

“And of course we will need biomarkers because there could be some patients that really need adjuvant treatment, but we need to identify these patients,” continued Helgadottir. Overall survival results from KEYNOTE-054, which compares pembrolizumab with placebo after resection of high-risk stage III melanoma, are awaited, she continued.

Helgadottir explained that adjuvant treatment for stage III melanoma was approved in Sweden in 2018, with treatments freely available to all Swedish residents.

The SweMR is a population-based national register that has near-complete and detailed data on primary cutaneous melanomas, including nodal status and satellite and in-transit disease, and is linked to the national Cause of Death Registry. Helgadottir noted, however, that the SweMR does not contain any information on relapses or the nature of the oncologic treatment received by patients with melanoma.

Following her presentation, she was challenged by an audience member as to whether, on the basis of her findings, she would go back to following up with patients and treating at relapses.

“Maybe we should do that and believe in our own data, and we do. But still, the gold standard must always be the randomized clinical trial,” Helgadottir responded. “So I think, although that we believe in this data, we also want to see the results of the randomized studies.”

The audience member commented that she can see in the data from her own institution that they treat fewer and fewer patients with melanoma with adjuvant therapy by discussing it more thoroughly and being stricter on who should receive it.

Helgadottir agreed, adding that “based on this experience, we did not introduce it to stage II patients because it’s always harder to go back” once a group of patients has started to receive a treatment.

The research was supported by Regional Cancer Centres in Sweden and with grants from the Swedish Cancer Society, Region Stockholm, and the Cancer Research Funds of Radiumhemmet. Helgadottir declared having relationships with Bristol Myers Squibb, Merck Sharp & Dohme, Pierre Fabre, and Novartis.

The trial was supported by SkinVision. The researchers declared having no relevant financial relationships.

This article was previously published by Medscape.

Wildfire smoke exposure may be associated with increased risks for multiple types of cancer, suggests an analysis of prospective cohort data from over 90,000 individuals.

To determine how this widespread pollution might be affecting cancer risk, senior author Shuguang Leng, MBBS, PhD, and colleagues analyzed data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. That prospective national study enrolled approximately 154,000 participants between 1993 and 2001 and tracked cancer incidence through 2018. Of these, 91,460 participants had wildfire smoke exposure data and were included in the analysis.

During the 2006-2018 exposure period, the investigators identified incident cases of 242 ovarian, 800 colorectal, 896 bladder, 1696 hematopoietic, 1739 breast, and 1758 lung cancers, as well as 1127 melanoma cases. The median 36-month moving average for wildfire smoke PM_2.5 (fine particulate matter) across the cohort was 0.37 µg/m³.

Wildfire smoke exposure was significantly associated with increased risks for lung, colorectal, breast, bladder, and hematopoietic cancer, according to the results of the study presented by Leng at American Association for Cancer Research (AACR) Annual Meeting 2026.

Each 1 µg/m³ increase in the 36-month moving average of wildfire smoke PM_2.5 was associated with a 63% higher risk for hematopoietic cancer (HR, 1.63; 95% CI, 1.02-2.60), a nearly twofold higher risk for lung cancer (hazard ratio [HR], 1.92; 95% CI, 1.18-3.15), more than twofold higher risks for breast cancer (HR, 2.09; 95% CI, 1.34-3.26) and colorectal cancer (HR, 2.31; 95% CI, 1.11-4.81), and a more than threefold higher risk for bladder cancer (HR, 3.49; 95% CI, 1.66-7.34). No significant associations were observed for ovarian cancer or melanoma.

The investigators quantified wildfire smoke exposure at each participant’s residence on a monthly basis using three measures: near-ground wildfire smoke PM_2.5, wildfire smoke black carbon, and satellite-derived wildfire smoke plume-day counts, with measurements available from 2006 until first cancer diagnosis or last contact.

Given evidence that 3 years of air pollution exposure can influence the development of epidermal growth factor receptor-positive lung adenocarcinoma, the team modeled exposure as a time-varying variable using 36-month moving averages preceding each month. HRs were estimated using Cox proportional hazards models stratified by study center, with restricted cubic splines applied to evaluate dose-response relationships. Models were adjusted for age, sex, race and ethnicity, education, smoking history, BMI, and trial arm.

All five cancer types linked with wildfire smoke exposure showed linear dose-response relationships, Leng noted, “which means the higher the exposure, the higher the cancer risk.”

Results based on wildfire smoke plume-day counts were generally consistent with those for PM_2.5, while associations for black carbon exposure were observed only for breast and bladder cancers.

With wildfires on the rise, these findings suggest that the resulting smoke may become a “major driver for cancer burden in the US in the coming decades,” said Leng, of the University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico.

“Wildfire smoke has become a major source of air pollution in the United States,” he continued. Large fires in the US are three times more common than they were 50 years ago, and the “tons of toxicants and particles” released by these fires “can travel hundreds of miles to affect communities far away.”

The investigators also conducted histology-specific analyses, finding that adenocarcinoma showed the strongest association with wildfire smoke among lung cancer subtypes. Among colorectal cancers, proximal tumors appeared more sensitive to wildfire smoke exposure, while among bladder cancers, the association was strongest for muscle-invasive disease.

Wildfire Smoke Exposure Expected to Rise

Under even the most conservative climate projections, wildfire smoke exposure in the US is expected to rise over the next 20-30 years, Leng said.

Annual average wildfire smoke PM_2.5 levels, currently estimated at around 0.5 µg/m³, could rise to 1 µg/m³. Based on the study’s dose-response data, this would correspond to substantially greater cancer risk.

There will be “a much larger area” of the US exposed “at a much higher dose,” Leng predicted.

Mitigating the Risks of Wildfire Smoke

This is a “strong hypothesis-generating study,” Jun Wu, PhD, professor of environmental and occupational health at the UC Irvine Program in Public Health, Irvine, California, told Medscape Medical News.

“This is one of the first large, prospective US cohort studies to examine wildfire smoke specifically in relation to cancer risk, especially cancer sites beyond the lung,” Wu said. “A major strength is that the PLCO platform has around 91,000 participants with longitudinal follow-up and detailed covariate data, including smoking history, which is often a weak point in previous air pollution-cancer studies.”

According to Wu, who was not involved in the analysis but recently published data linking wildfire smoke exposure to preterm birth, the reported risks for colorectal, breast, bladder, and hematopoietic cancers represent novel contributions to the literature. However, she cautioned against viewing the specific HRs as a precise estimates of risk due to wide confidence intervals.

The findings should encourage individuals, public health officials, and clinicians to mitigate the risks of wildfire smoke, Wu said.

Specifically, she suggested that public health assessments expand beyond acute outcomes like emergency department visits to include long-term endpoints such as cancer, while community clean-air shelters need to be made more widely available.

She advised clinicians to incorporate wildfire exposure into routine patient histories and to provide vulnerable patients — such as those with asthma, chronic obstructive pulmonary disease, heart failure, or pregnancy — with smoke-season action plans.

Risk mitigation begins with awareness, according to Wu, who advised individuals check their local air quality index on AirNow.gov or PurpleAir.

On smoky days, she suggested prioritizing indoor air quality by keeping windows closed and running air purifiers. If going outside on such days is necessary, she suggested an N95 or KN95 mask, as these offer “meaningful protection,” while cloth and surgical masks do not.

These preventive steps may have once been out of the ordinary, Wu said, but the risk for wildfire smoke exposure is becoming a part of everyday life.

“The common thread is a shift in framing,” Wu said. “Wildfire smoke has traditionally been treated as an acute event, but the emerging evidence points to a chronic environmental exposure. Both our clinical and public health systems have room to grow into that reality.”

The analysis was funded by the National Institutes of Health. The investigators and Wu reported having no conflicts of interest.

This article was previously published on Medscape.

Wildfire smoke exposure may be associated with increased risks for multiple types of cancer, suggests an analysis of prospective cohort data from over 90,000 individuals.

To determine how this widespread pollution might be affecting cancer risk, senior author Shuguang Leng, MBBS, PhD, and colleagues analyzed data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. That prospective national study enrolled approximately 154,000 participants between 1993 and 2001 and tracked cancer incidence through 2018. Of these, 91,460 participants had wildfire smoke exposure data and were included in the analysis.

During the 2006-2018 exposure period, the investigators identified incident cases of 242 ovarian, 800 colorectal, 896 bladder, 1696 hematopoietic, 1739 breast, and 1758 lung cancers, as well as 1127 melanoma cases. The median 36-month moving average for wildfire smoke PM_2.5 (fine particulate matter) across the cohort was 0.37 µg/m³.

Wildfire smoke exposure was significantly associated with increased risks for lung, colorectal, breast, bladder, and hematopoietic cancer, according to the results of the study presented by Leng at American Association for Cancer Research (AACR) Annual Meeting 2026.

Each 1 µg/m³ increase in the 36-month moving average of wildfire smoke PM_2.5 was associated with a 63% higher risk for hematopoietic cancer (HR, 1.63; 95% CI, 1.02-2.60), a nearly twofold higher risk for lung cancer (hazard ratio [HR], 1.92; 95% CI, 1.18-3.15), more than twofold higher risks for breast cancer (HR, 2.09; 95% CI, 1.34-3.26) and colorectal cancer (HR, 2.31; 95% CI, 1.11-4.81), and a more than threefold higher risk for bladder cancer (HR, 3.49; 95% CI, 1.66-7.34). No significant associations were observed for ovarian cancer or melanoma.

The investigators quantified wildfire smoke exposure at each participant’s residence on a monthly basis using three measures: near-ground wildfire smoke PM_2.5, wildfire smoke black carbon, and satellite-derived wildfire smoke plume-day counts, with measurements available from 2006 until first cancer diagnosis or last contact.

Given evidence that 3 years of air pollution exposure can influence the development of epidermal growth factor receptor-positive lung adenocarcinoma, the team modeled exposure as a time-varying variable using 36-month moving averages preceding each month. HRs were estimated using Cox proportional hazards models stratified by study center, with restricted cubic splines applied to evaluate dose-response relationships. Models were adjusted for age, sex, race and ethnicity, education, smoking history, BMI, and trial arm.

All five cancer types linked with wildfire smoke exposure showed linear dose-response relationships, Leng noted, “which means the higher the exposure, the higher the cancer risk.”

Results based on wildfire smoke plume-day counts were generally consistent with those for PM_2.5, while associations for black carbon exposure were observed only for breast and bladder cancers.

With wildfires on the rise, these findings suggest that the resulting smoke may become a “major driver for cancer burden in the US in the coming decades,” said Leng, of the University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico.

“Wildfire smoke has become a major source of air pollution in the United States,” he continued. Large fires in the US are three times more common than they were 50 years ago, and the “tons of toxicants and particles” released by these fires “can travel hundreds of miles to affect communities far away.”

The investigators also conducted histology-specific analyses, finding that adenocarcinoma showed the strongest association with wildfire smoke among lung cancer subtypes. Among colorectal cancers, proximal tumors appeared more sensitive to wildfire smoke exposure, while among bladder cancers, the association was strongest for muscle-invasive disease.

Wildfire Smoke Exposure Expected to Rise

Under even the most conservative climate projections, wildfire smoke exposure in the US is expected to rise over the next 20-30 years, Leng said.

Annual average wildfire smoke PM_2.5 levels, currently estimated at around 0.5 µg/m³, could rise to 1 µg/m³. Based on the study’s dose-response data, this would correspond to substantially greater cancer risk.

There will be “a much larger area” of the US exposed “at a much higher dose,” Leng predicted.

Mitigating the Risks of Wildfire Smoke

This is a “strong hypothesis-generating study,” Jun Wu, PhD, professor of environmental and occupational health at the UC Irvine Program in Public Health, Irvine, California, told Medscape Medical News.

“This is one of the first large, prospective US cohort studies to examine wildfire smoke specifically in relation to cancer risk, especially cancer sites beyond the lung,” Wu said. “A major strength is that the PLCO platform has around 91,000 participants with longitudinal follow-up and detailed covariate data, including smoking history, which is often a weak point in previous air pollution-cancer studies.”

According to Wu, who was not involved in the analysis but recently published data linking wildfire smoke exposure to preterm birth, the reported risks for colorectal, breast, bladder, and hematopoietic cancers represent novel contributions to the literature. However, she cautioned against viewing the specific HRs as a precise estimates of risk due to wide confidence intervals.

The findings should encourage individuals, public health officials, and clinicians to mitigate the risks of wildfire smoke, Wu said.

Specifically, she suggested that public health assessments expand beyond acute outcomes like emergency department visits to include long-term endpoints such as cancer, while community clean-air shelters need to be made more widely available.

She advised clinicians to incorporate wildfire exposure into routine patient histories and to provide vulnerable patients — such as those with asthma, chronic obstructive pulmonary disease, heart failure, or pregnancy — with smoke-season action plans.

Risk mitigation begins with awareness, according to Wu, who advised individuals check their local air quality index on AirNow.gov or PurpleAir.

On smoky days, she suggested prioritizing indoor air quality by keeping windows closed and running air purifiers. If going outside on such days is necessary, she suggested an N95 or KN95 mask, as these offer “meaningful protection,” while cloth and surgical masks do not.

These preventive steps may have once been out of the ordinary, Wu said, but the risk for wildfire smoke exposure is becoming a part of everyday life.

“The common thread is a shift in framing,” Wu said. “Wildfire smoke has traditionally been treated as an acute event, but the emerging evidence points to a chronic environmental exposure. Both our clinical and public health systems have room to grow into that reality.”

The analysis was funded by the National Institutes of Health. The investigators and Wu reported having no conflicts of interest.

This article was previously published on Medscape.

Wildfire smoke exposure may be associated with increased risks for multiple types of cancer, suggests an analysis of prospective cohort data from over 90,000 individuals.

To determine how this widespread pollution might be affecting cancer risk, senior author Shuguang Leng, MBBS, PhD, and colleagues analyzed data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. That prospective national study enrolled approximately 154,000 participants between 1993 and 2001 and tracked cancer incidence through 2018. Of these, 91,460 participants had wildfire smoke exposure data and were included in the analysis.

During the 2006-2018 exposure period, the investigators identified incident cases of 242 ovarian, 800 colorectal, 896 bladder, 1696 hematopoietic, 1739 breast, and 1758 lung cancers, as well as 1127 melanoma cases. The median 36-month moving average for wildfire smoke PM_2.5 (fine particulate matter) across the cohort was 0.37 µg/m³.

Wildfire smoke exposure was significantly associated with increased risks for lung, colorectal, breast, bladder, and hematopoietic cancer, according to the results of the study presented by Leng at American Association for Cancer Research (AACR) Annual Meeting 2026.

Each 1 µg/m³ increase in the 36-month moving average of wildfire smoke PM_2.5 was associated with a 63% higher risk for hematopoietic cancer (HR, 1.63; 95% CI, 1.02-2.60), a nearly twofold higher risk for lung cancer (hazard ratio [HR], 1.92; 95% CI, 1.18-3.15), more than twofold higher risks for breast cancer (HR, 2.09; 95% CI, 1.34-3.26) and colorectal cancer (HR, 2.31; 95% CI, 1.11-4.81), and a more than threefold higher risk for bladder cancer (HR, 3.49; 95% CI, 1.66-7.34). No significant associations were observed for ovarian cancer or melanoma.

The investigators quantified wildfire smoke exposure at each participant’s residence on a monthly basis using three measures: near-ground wildfire smoke PM_2.5, wildfire smoke black carbon, and satellite-derived wildfire smoke plume-day counts, with measurements available from 2006 until first cancer diagnosis or last contact.

Given evidence that 3 years of air pollution exposure can influence the development of epidermal growth factor receptor-positive lung adenocarcinoma, the team modeled exposure as a time-varying variable using 36-month moving averages preceding each month. HRs were estimated using Cox proportional hazards models stratified by study center, with restricted cubic splines applied to evaluate dose-response relationships. Models were adjusted for age, sex, race and ethnicity, education, smoking history, BMI, and trial arm.

All five cancer types linked with wildfire smoke exposure showed linear dose-response relationships, Leng noted, “which means the higher the exposure, the higher the cancer risk.”

Results based on wildfire smoke plume-day counts were generally consistent with those for PM_2.5, while associations for black carbon exposure were observed only for breast and bladder cancers.

With wildfires on the rise, these findings suggest that the resulting smoke may become a “major driver for cancer burden in the US in the coming decades,” said Leng, of the University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico.

“Wildfire smoke has become a major source of air pollution in the United States,” he continued. Large fires in the US are three times more common than they were 50 years ago, and the “tons of toxicants and particles” released by these fires “can travel hundreds of miles to affect communities far away.”

The investigators also conducted histology-specific analyses, finding that adenocarcinoma showed the strongest association with wildfire smoke among lung cancer subtypes. Among colorectal cancers, proximal tumors appeared more sensitive to wildfire smoke exposure, while among bladder cancers, the association was strongest for muscle-invasive disease.

Wildfire Smoke Exposure Expected to Rise

Under even the most conservative climate projections, wildfire smoke exposure in the US is expected to rise over the next 20-30 years, Leng said.

Annual average wildfire smoke PM_2.5 levels, currently estimated at around 0.5 µg/m³, could rise to 1 µg/m³. Based on the study’s dose-response data, this would correspond to substantially greater cancer risk.

There will be “a much larger area” of the US exposed “at a much higher dose,” Leng predicted.

Mitigating the Risks of Wildfire Smoke

This is a “strong hypothesis-generating study,” Jun Wu, PhD, professor of environmental and occupational health at the UC Irvine Program in Public Health, Irvine, California, told Medscape Medical News.

“This is one of the first large, prospective US cohort studies to examine wildfire smoke specifically in relation to cancer risk, especially cancer sites beyond the lung,” Wu said. “A major strength is that the PLCO platform has around 91,000 participants with longitudinal follow-up and detailed covariate data, including smoking history, which is often a weak point in previous air pollution-cancer studies.”

According to Wu, who was not involved in the analysis but recently published data linking wildfire smoke exposure to preterm birth, the reported risks for colorectal, breast, bladder, and hematopoietic cancers represent novel contributions to the literature. However, she cautioned against viewing the specific HRs as a precise estimates of risk due to wide confidence intervals.

The findings should encourage individuals, public health officials, and clinicians to mitigate the risks of wildfire smoke, Wu said.

Specifically, she suggested that public health assessments expand beyond acute outcomes like emergency department visits to include long-term endpoints such as cancer, while community clean-air shelters need to be made more widely available.

She advised clinicians to incorporate wildfire exposure into routine patient histories and to provide vulnerable patients — such as those with asthma, chronic obstructive pulmonary disease, heart failure, or pregnancy — with smoke-season action plans.

Risk mitigation begins with awareness, according to Wu, who advised individuals check their local air quality index on AirNow.gov or PurpleAir.

On smoky days, she suggested prioritizing indoor air quality by keeping windows closed and running air purifiers. If going outside on such days is necessary, she suggested an N95 or KN95 mask, as these offer “meaningful protection,” while cloth and surgical masks do not.

These preventive steps may have once been out of the ordinary, Wu said, but the risk for wildfire smoke exposure is becoming a part of everyday life.

“The common thread is a shift in framing,” Wu said. “Wildfire smoke has traditionally been treated as an acute event, but the emerging evidence points to a chronic environmental exposure. Both our clinical and public health systems have room to grow into that reality.”

The analysis was funded by the National Institutes of Health. The investigators and Wu reported having no conflicts of interest.

This article was previously published on Medscape.

TOPLINE: In 75,453 veterans with head and neck squamous cell carcinoma (HNSCC), 36.4% live in rural or highly rural areas and 32.0% have a national area deprivation index (ADI) ≥ 75. The average drive time to the nearest tertiary or complex US Department of Veterans Affairs (VA) facility is 94 minutes, highlighting potential access and equity barriers related to rurality, deprivation, and distance.

METHODOLOGY:

• A retrospective descriptive study using nationwide VA data from fiscal years 2012 to 2022 identified 75,453 veterans with head and neck squamous cell carcinoma (HNSCC) by International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes.

• Patients were grouped into 5 primary tumor subsites: oral cavity, oropharynx, hypopharynx, larynx, and nasopharynx.

• Rurality was classified using Rural-Urban Commuting Area-derived urban, rural, and highly rural scores; socioeconomic disadvantage was measured with national ADI scores.

• Travel burden was assessed using time and distance to the nearest primary, secondary, and tertiary VA facilities.

TAKEAWAY:

• Oropharyngeal cancer (OPC) cases among veterans increased from 26.3% in 2012 to 46.0% in 2022, while laryngeal cancers decreased from 41.2% to 29.3%.

• HNSCCs locations included 35.6% in the larynx, 34.4% in the oropharynx, 22.6% in the oral cavity 3.7% in the hypopharynx, and 3.7% in the nasopharynx.

• Veterans with OPC were younger than non-OPC patients and more likely to be White; > 70% were current or former smokers.

IN PRACTICE: “Understanding the geographic and socioeconomic landscape of veterans with HNSCC will allow us to tease out the factors associated with poor outcomes and ultimately design interventions that target high-risk veteran populations to improve overall health outcomes,” the authors argued.

SOURCE: The study was led by researchers at the Veterans Affairs Pittsburgh Healthcare System. It was published online in Head & Neck.

LIMITATIONS: The inability to extract accurate data from a large dataset, challenges in obtaining tumor stage information due to varying documentation practices across physicians and treatment courses, and the inability to assess HPV or p16 data for the cohort represents significant limitations that may have impacted interpretation of results. Clinical outcome measures and cause of death assessment were limited in this national database, affecting the ability to draw conclusions regarding the impact of rurality, area deprivation, and travel time on outcomes.

DISCLOSURES: Chad Brenner reported holding several patents related to the development and use of circulating tumor DNA tests in patients with HNSCC. Jose P. Zevallos disclosed being the founder, equity shareholder, and board member of Droplet Biosciences and Echogenesis Therapeutics, serving as chief scientific advisor and shareholder of Vine Medical, and acting as a consultant for Merck and Johnson & Johnson. Matthew E. Spector reported serving as a consultant for Hologic. Kristen L. Zayan, Jennifer L. McCoy, Monique Y. Boudreaux-Kelly, Zachary Hahn, John Hotchkiss, and Jessica H. Maxwell declared no 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: In 75,453 veterans with head and neck squamous cell carcinoma (HNSCC), 36.4% live in rural or highly rural areas and 32.0% have a national area deprivation index (ADI) ≥ 75. The average drive time to the nearest tertiary or complex US Department of Veterans Affairs (VA) facility is 94 minutes, highlighting potential access and equity barriers related to rurality, deprivation, and distance.

METHODOLOGY:

• A retrospective descriptive study using nationwide VA data from fiscal years 2012 to 2022 identified 75,453 veterans with head and neck squamous cell carcinoma (HNSCC) by International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes.

• Patients were grouped into 5 primary tumor subsites: oral cavity, oropharynx, hypopharynx, larynx, and nasopharynx.

• Rurality was classified using Rural-Urban Commuting Area-derived urban, rural, and highly rural scores; socioeconomic disadvantage was measured with national ADI scores.

• Travel burden was assessed using time and distance to the nearest primary, secondary, and tertiary VA facilities.

TAKEAWAY:

• Oropharyngeal cancer (OPC) cases among veterans increased from 26.3% in 2012 to 46.0% in 2022, while laryngeal cancers decreased from 41.2% to 29.3%.

• HNSCCs locations included 35.6% in the larynx, 34.4% in the oropharynx, 22.6% in the oral cavity 3.7% in the hypopharynx, and 3.7% in the nasopharynx.

• Veterans with OPC were younger than non-OPC patients and more likely to be White; > 70% were current or former smokers.

IN PRACTICE: “Understanding the geographic and socioeconomic landscape of veterans with HNSCC will allow us to tease out the factors associated with poor outcomes and ultimately design interventions that target high-risk veteran populations to improve overall health outcomes,” the authors argued.

SOURCE: The study was led by researchers at the Veterans Affairs Pittsburgh Healthcare System. It was published online in Head & Neck.

LIMITATIONS: The inability to extract accurate data from a large dataset, challenges in obtaining tumor stage information due to varying documentation practices across physicians and treatment courses, and the inability to assess HPV or p16 data for the cohort represents significant limitations that may have impacted interpretation of results. Clinical outcome measures and cause of death assessment were limited in this national database, affecting the ability to draw conclusions regarding the impact of rurality, area deprivation, and travel time on outcomes.

DISCLOSURES: Chad Brenner reported holding several patents related to the development and use of circulating tumor DNA tests in patients with HNSCC. Jose P. Zevallos disclosed being the founder, equity shareholder, and board member of Droplet Biosciences and Echogenesis Therapeutics, serving as chief scientific advisor and shareholder of Vine Medical, and acting as a consultant for Merck and Johnson & Johnson. Matthew E. Spector reported serving as a consultant for Hologic. Kristen L. Zayan, Jennifer L. McCoy, Monique Y. Boudreaux-Kelly, Zachary Hahn, John Hotchkiss, and Jessica H. Maxwell declared no 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: In 75,453 veterans with head and neck squamous cell carcinoma (HNSCC), 36.4% live in rural or highly rural areas and 32.0% have a national area deprivation index (ADI) ≥ 75. The average drive time to the nearest tertiary or complex US Department of Veterans Affairs (VA) facility is 94 minutes, highlighting potential access and equity barriers related to rurality, deprivation, and distance.

METHODOLOGY:

• A retrospective descriptive study using nationwide VA data from fiscal years 2012 to 2022 identified 75,453 veterans with head and neck squamous cell carcinoma (HNSCC) by International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes.

• Patients were grouped into 5 primary tumor subsites: oral cavity, oropharynx, hypopharynx, larynx, and nasopharynx.

• Rurality was classified using Rural-Urban Commuting Area-derived urban, rural, and highly rural scores; socioeconomic disadvantage was measured with national ADI scores.

• Travel burden was assessed using time and distance to the nearest primary, secondary, and tertiary VA facilities.

TAKEAWAY:

• Oropharyngeal cancer (OPC) cases among veterans increased from 26.3% in 2012 to 46.0% in 2022, while laryngeal cancers decreased from 41.2% to 29.3%.

• HNSCCs locations included 35.6% in the larynx, 34.4% in the oropharynx, 22.6% in the oral cavity 3.7% in the hypopharynx, and 3.7% in the nasopharynx.

• Veterans with OPC were younger than non-OPC patients and more likely to be White; > 70% were current or former smokers.

IN PRACTICE: “Understanding the geographic and socioeconomic landscape of veterans with HNSCC will allow us to tease out the factors associated with poor outcomes and ultimately design interventions that target high-risk veteran populations to improve overall health outcomes,” the authors argued.

SOURCE: The study was led by researchers at the Veterans Affairs Pittsburgh Healthcare System. It was published online in Head & Neck.

LIMITATIONS: The inability to extract accurate data from a large dataset, challenges in obtaining tumor stage information due to varying documentation practices across physicians and treatment courses, and the inability to assess HPV or p16 data for the cohort represents significant limitations that may have impacted interpretation of results. Clinical outcome measures and cause of death assessment were limited in this national database, affecting the ability to draw conclusions regarding the impact of rurality, area deprivation, and travel time on outcomes.

DISCLOSURES: Chad Brenner reported holding several patents related to the development and use of circulating tumor DNA tests in patients with HNSCC. Jose P. Zevallos disclosed being the founder, equity shareholder, and board member of Droplet Biosciences and Echogenesis Therapeutics, serving as chief scientific advisor and shareholder of Vine Medical, and acting as a consultant for Merck and Johnson & Johnson. Matthew E. Spector reported serving as a consultant for Hologic. Kristen L. Zayan, Jennifer L. McCoy, Monique Y. Boudreaux-Kelly, Zachary Hahn, John Hotchkiss, and Jessica H. Maxwell declared no 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.

Adults who have never been married had a higher cancer risk than their married or previously married peers, with patterns observed across many major cancer types and particularly strong for cancers linked to infections, smoking, and reproductive factors, new data suggest.

The findings are based on a large, population-based cancer registry analysis of more than 4 million cases, making it the largest study of its kind in the US.

First author Paulo Pinheiro, PhD, cautioned, however, that the study does not suggest that marriage itself is protective.

"As with any observational study, we cannot establish causation, and unmeasured factors may contribute to the associations,” said Pinheiro, with Sylvester Comprehensive Cancer Center, University of Miami Health System, in Miami.

Marital status may, however, help identify groups with different patterns of cancer risk, which likely reflect social and lifestyle behaviors rather than a direct causal effect, Pinheiro explained.

Married individuals, for instance, are less likely to smoke — a known cancer risk factor — and more likely to have children and undergo cancer screening, which can influence cancer incidence through reproductive effects and screening, including earlier detection and removal of precancerous lesions.

"Marital status is therefore best understood as a marker of those accumulated factors," Pinheiro said.

The study was published online on April 8 in Cancer Research Communications.

Filling a Data Gap

Marriage has consistently been associated with earlier cancer diagnosis and improved survival among those with cancer, but its relationship to cancer incidence remains less clear.

To address that gap, researchers analyzed data from 12 US states that included demographic and cancer information for more than 4.2 million cancer cases diagnosed between 2015 and 2022.

The analysis included more than 500 million person-years at risk in adults 30 years or older, representing an annual population of more than 62 million. The never-married group comprised about 19% of the total population — 22% were men and 17% were women.

Compared with ever-married individuals, never-married men and women had higher cancer incidence across many major cancer types, racial and ethnic groups, and age groups.

Overall, cancer rates were about 68% higher in never-married men and 85% higher in never-married women compared with their ever-married counterparts (incidence rate ratios [IRRs], 1.68 and 1.85, respectively).

Never-married Black men had the highest overall cancer rates (1600 per 100,000), whereas married Black men had significantly lower rates than married White men (752.6 vs 836.2 per 100,000), suggesting complex interactions between marital status and structural factors, the researchers noted.

Site-specific patterns revealed clues to potential mechanisms linking marital status and cancer.

Compared with ever-married individuals, never-married people had the highest excess risks for human papillomavirus-related cancers — about five times higher for anal cancer in men (IRR, 5.04) and approaching three times higher for cervical cancer in women (IRR, 2.64).

Other strong associations between never-married individuals and cancer risk were observed for smoking-related cancers, including lung (IRR, 2.1 for both men and women) and esophageal cancers (IRR, 2.4 in men and 2.7 in women), and malignancies including liver (IRR, 2.3 for both men and women), bladder (IRR, 2.3 women only), and colorectal (IRR, 2.1 women only) cancers.

Among women, the higher incidence of ovarian and uterine cancers (IRR, 2.4 for both) among the never-married group supports the influence of reproductive mechanisms, such as giving birth, on cancer risk.

The association between marital status and cancer risk was weaker for breast, prostate, and thyroid cancers (with IRRs < 2), suggesting potentially less modifiable etiologies.

Overall, “methodologically, it is quite robust, particularly in its clear framing of ever- vs never-married individuals and the use of standardized incidence rates and regression modeling,” Pinheiro said.

The analysis did not adjust for individual-level risk factors such as smoking, diet, physical activity, or alcohol use — factors that may partly explain the observed associations.

Adjusting for these lifestyle and health behavior factors at the individual level would require detailed information on these behaviors, and “data at that level simply do not exist at a national scale,” Pinheiro said. It would also “obscure the real-world pattern we are trying to measure.”

Gilbert Welch, MD, noted that adjusting for these individual-level cancer risk factors “would certainly attenuate the associations.”

“That said, it wouldn’t be crazy to suggest marriage drives some of these risk factors,” said Welch, general internist and senior investigator at the Center for Surgery and Public Health, Brigham and Women’s Hospital, Boston. Married couples benefit from combined incomes and shared expenses, and “may well help support individuals in making healthy choices (like not smoking).”

But, he added, “it would be crazy to suggest that the reason to get married is to lower cancer risk.”

The authors flagged a study limitation — the fact that ever-married status lumps together people who are currently married, divorced, and widowed, and these groups may have different risk profiles. Additionally, “individuals in strained or abusive marriages may not experience protective social benefits,” while those in long-term cohabiting relationships classified as never-married may experience high levels of support, the authors wrote.

Overall, though, Pinheiro clarified that the main finding is “not about marriage as a causal agent, but about identifying a large population group, the never-married, with a consistently higher cancer burden that has been largely overlooked in public health practice and cancer prevention efforts.”

Linda Waite, professor, Department of Sociology, University of Chicago, who wasn’t involved in the study, wasn’t surprised by the findings. For men, not having a spouse may “disadvantage” them in ways that might increase cancer risk.

Unmarried men are more likely to drink and smoke heavily, which increase cancer risk, she said. A spouse may also influence health awareness and decisions, such as noticing suspicious symptoms, pushing their partner to see a doctor, or helping manage their partner’s care.

Plus, “for both men and women, having a spouse may improve medical care by giving each partner a companion for medical appointments and another person to help manage risks of disease,” Waite said.

The study had no commercial funding. Pinheiro and Waite had no relevant disclosures.

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

Adults who have never been married had a higher cancer risk than their married or previously married peers, with patterns observed across many major cancer types and particularly strong for cancers linked to infections, smoking, and reproductive factors, new data suggest.

The findings are based on a large, population-based cancer registry analysis of more than 4 million cases, making it the largest study of its kind in the US.

First author Paulo Pinheiro, PhD, cautioned, however, that the study does not suggest that marriage itself is protective.

"As with any observational study, we cannot establish causation, and unmeasured factors may contribute to the associations,” said Pinheiro, with Sylvester Comprehensive Cancer Center, University of Miami Health System, in Miami.

Marital status may, however, help identify groups with different patterns of cancer risk, which likely reflect social and lifestyle behaviors rather than a direct causal effect, Pinheiro explained.

Married individuals, for instance, are less likely to smoke — a known cancer risk factor — and more likely to have children and undergo cancer screening, which can influence cancer incidence through reproductive effects and screening, including earlier detection and removal of precancerous lesions.

"Marital status is therefore best understood as a marker of those accumulated factors," Pinheiro said.

The study was published online on April 8 in Cancer Research Communications.

Filling a Data Gap

Marriage has consistently been associated with earlier cancer diagnosis and improved survival among those with cancer, but its relationship to cancer incidence remains less clear.

To address that gap, researchers analyzed data from 12 US states that included demographic and cancer information for more than 4.2 million cancer cases diagnosed between 2015 and 2022.

The analysis included more than 500 million person-years at risk in adults 30 years or older, representing an annual population of more than 62 million. The never-married group comprised about 19% of the total population — 22% were men and 17% were women.

Compared with ever-married individuals, never-married men and women had higher cancer incidence across many major cancer types, racial and ethnic groups, and age groups.

Overall, cancer rates were about 68% higher in never-married men and 85% higher in never-married women compared with their ever-married counterparts (incidence rate ratios [IRRs], 1.68 and 1.85, respectively).

Never-married Black men had the highest overall cancer rates (1600 per 100,000), whereas married Black men had significantly lower rates than married White men (752.6 vs 836.2 per 100,000), suggesting complex interactions between marital status and structural factors, the researchers noted.

Site-specific patterns revealed clues to potential mechanisms linking marital status and cancer.

Compared with ever-married individuals, never-married people had the highest excess risks for human papillomavirus-related cancers — about five times higher for anal cancer in men (IRR, 5.04) and approaching three times higher for cervical cancer in women (IRR, 2.64).

Other strong associations between never-married individuals and cancer risk were observed for smoking-related cancers, including lung (IRR, 2.1 for both men and women) and esophageal cancers (IRR, 2.4 in men and 2.7 in women), and malignancies including liver (IRR, 2.3 for both men and women), bladder (IRR, 2.3 women only), and colorectal (IRR, 2.1 women only) cancers.

Among women, the higher incidence of ovarian and uterine cancers (IRR, 2.4 for both) among the never-married group supports the influence of reproductive mechanisms, such as giving birth, on cancer risk.

The association between marital status and cancer risk was weaker for breast, prostate, and thyroid cancers (with IRRs < 2), suggesting potentially less modifiable etiologies.

Overall, “methodologically, it is quite robust, particularly in its clear framing of ever- vs never-married individuals and the use of standardized incidence rates and regression modeling,” Pinheiro said.

The analysis did not adjust for individual-level risk factors such as smoking, diet, physical activity, or alcohol use — factors that may partly explain the observed associations.

Adjusting for these lifestyle and health behavior factors at the individual level would require detailed information on these behaviors, and “data at that level simply do not exist at a national scale,” Pinheiro said. It would also “obscure the real-world pattern we are trying to measure.”

Gilbert Welch, MD, noted that adjusting for these individual-level cancer risk factors “would certainly attenuate the associations.”

“That said, it wouldn’t be crazy to suggest marriage drives some of these risk factors,” said Welch, general internist and senior investigator at the Center for Surgery and Public Health, Brigham and Women’s Hospital, Boston. Married couples benefit from combined incomes and shared expenses, and “may well help support individuals in making healthy choices (like not smoking).”

But, he added, “it would be crazy to suggest that the reason to get married is to lower cancer risk.”

The authors flagged a study limitation — the fact that ever-married status lumps together people who are currently married, divorced, and widowed, and these groups may have different risk profiles. Additionally, “individuals in strained or abusive marriages may not experience protective social benefits,” while those in long-term cohabiting relationships classified as never-married may experience high levels of support, the authors wrote.

Overall, though, Pinheiro clarified that the main finding is “not about marriage as a causal agent, but about identifying a large population group, the never-married, with a consistently higher cancer burden that has been largely overlooked in public health practice and cancer prevention efforts.”

Linda Waite, professor, Department of Sociology, University of Chicago, who wasn’t involved in the study, wasn’t surprised by the findings. For men, not having a spouse may “disadvantage” them in ways that might increase cancer risk.

Unmarried men are more likely to drink and smoke heavily, which increase cancer risk, she said. A spouse may also influence health awareness and decisions, such as noticing suspicious symptoms, pushing their partner to see a doctor, or helping manage their partner’s care.

Plus, “for both men and women, having a spouse may improve medical care by giving each partner a companion for medical appointments and another person to help manage risks of disease,” Waite said.

The study had no commercial funding. Pinheiro and Waite had no relevant disclosures.

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

Adults who have never been married had a higher cancer risk than their married or previously married peers, with patterns observed across many major cancer types and particularly strong for cancers linked to infections, smoking, and reproductive factors, new data suggest.

The findings are based on a large, population-based cancer registry analysis of more than 4 million cases, making it the largest study of its kind in the US.

First author Paulo Pinheiro, PhD, cautioned, however, that the study does not suggest that marriage itself is protective.

"As with any observational study, we cannot establish causation, and unmeasured factors may contribute to the associations,” said Pinheiro, with Sylvester Comprehensive Cancer Center, University of Miami Health System, in Miami.

Marital status may, however, help identify groups with different patterns of cancer risk, which likely reflect social and lifestyle behaviors rather than a direct causal effect, Pinheiro explained.

Married individuals, for instance, are less likely to smoke — a known cancer risk factor — and more likely to have children and undergo cancer screening, which can influence cancer incidence through reproductive effects and screening, including earlier detection and removal of precancerous lesions.

"Marital status is therefore best understood as a marker of those accumulated factors," Pinheiro said.

The study was published online on April 8 in Cancer Research Communications.

Filling a Data Gap

Marriage has consistently been associated with earlier cancer diagnosis and improved survival among those with cancer, but its relationship to cancer incidence remains less clear.

To address that gap, researchers analyzed data from 12 US states that included demographic and cancer information for more than 4.2 million cancer cases diagnosed between 2015 and 2022.

The analysis included more than 500 million person-years at risk in adults 30 years or older, representing an annual population of more than 62 million. The never-married group comprised about 19% of the total population — 22% were men and 17% were women.

Compared with ever-married individuals, never-married men and women had higher cancer incidence across many major cancer types, racial and ethnic groups, and age groups.

Overall, cancer rates were about 68% higher in never-married men and 85% higher in never-married women compared with their ever-married counterparts (incidence rate ratios [IRRs], 1.68 and 1.85, respectively).

Never-married Black men had the highest overall cancer rates (1600 per 100,000), whereas married Black men had significantly lower rates than married White men (752.6 vs 836.2 per 100,000), suggesting complex interactions between marital status and structural factors, the researchers noted.

Site-specific patterns revealed clues to potential mechanisms linking marital status and cancer.

Compared with ever-married individuals, never-married people had the highest excess risks for human papillomavirus-related cancers — about five times higher for anal cancer in men (IRR, 5.04) and approaching three times higher for cervical cancer in women (IRR, 2.64).

Other strong associations between never-married individuals and cancer risk were observed for smoking-related cancers, including lung (IRR, 2.1 for both men and women) and esophageal cancers (IRR, 2.4 in men and 2.7 in women), and malignancies including liver (IRR, 2.3 for both men and women), bladder (IRR, 2.3 women only), and colorectal (IRR, 2.1 women only) cancers.

Among women, the higher incidence of ovarian and uterine cancers (IRR, 2.4 for both) among the never-married group supports the influence of reproductive mechanisms, such as giving birth, on cancer risk.

The association between marital status and cancer risk was weaker for breast, prostate, and thyroid cancers (with IRRs < 2), suggesting potentially less modifiable etiologies.

Overall, “methodologically, it is quite robust, particularly in its clear framing of ever- vs never-married individuals and the use of standardized incidence rates and regression modeling,” Pinheiro said.

The analysis did not adjust for individual-level risk factors such as smoking, diet, physical activity, or alcohol use — factors that may partly explain the observed associations.

Adjusting for these lifestyle and health behavior factors at the individual level would require detailed information on these behaviors, and “data at that level simply do not exist at a national scale,” Pinheiro said. It would also “obscure the real-world pattern we are trying to measure.”

Gilbert Welch, MD, noted that adjusting for these individual-level cancer risk factors “would certainly attenuate the associations.”

“That said, it wouldn’t be crazy to suggest marriage drives some of these risk factors,” said Welch, general internist and senior investigator at the Center for Surgery and Public Health, Brigham and Women’s Hospital, Boston. Married couples benefit from combined incomes and shared expenses, and “may well help support individuals in making healthy choices (like not smoking).”

But, he added, “it would be crazy to suggest that the reason to get married is to lower cancer risk.”

The authors flagged a study limitation — the fact that ever-married status lumps together people who are currently married, divorced, and widowed, and these groups may have different risk profiles. Additionally, “individuals in strained or abusive marriages may not experience protective social benefits,” while those in long-term cohabiting relationships classified as never-married may experience high levels of support, the authors wrote.

Overall, though, Pinheiro clarified that the main finding is “not about marriage as a causal agent, but about identifying a large population group, the never-married, with a consistently higher cancer burden that has been largely overlooked in public health practice and cancer prevention efforts.”

Linda Waite, professor, Department of Sociology, University of Chicago, who wasn’t involved in the study, wasn’t surprised by the findings. For men, not having a spouse may “disadvantage” them in ways that might increase cancer risk.

Unmarried men are more likely to drink and smoke heavily, which increase cancer risk, she said. A spouse may also influence health awareness and decisions, such as noticing suspicious symptoms, pushing their partner to see a doctor, or helping manage their partner’s care.

Plus, “for both men and women, having a spouse may improve medical care by giving each partner a companion for medical appointments and another person to help manage risks of disease,” Waite said.

The study had no commercial funding. Pinheiro and Waite had no relevant disclosures.

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

SAN FRANCISCO – The treatment of early-stage diffuse large B-cell lymphoma (DLBCL) is evolving after decades of failed attempts to improve on the standard treatment of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), a hematologist-oncologist said at the Association of Veterans Affairs (VA) Hematology/Oncology regional meeting on lymphoma on March 21.

A combination therapy known as pola-R-CHP is now the preferred option for many patients but has limited additional benefit, said Solomon A. Graf, MD, of the University of Washington and VA Puget Sound Health Care System. Pola-R-CHP is a modified regimen of R-CHOP that replaced vincristine in R-CHOP with polatuzumab vedotin.

The keys to treatment, Graf said, include consideration of disease variations that can affect therapy efficacy and understanding the special needs of older patients.

Understanding DLBCL

DLBCL is the most common non-Hodgkin lymphoma in the US with about 30,000 new cases per year; the median age at diagnosis is 67 years, Graf said.

“The overall incidence of DLBCL has been relatively stable over the last decades,” he said. “But gratifyingly, the rate of death from this disease has steadily been declining since about the turn of the century.”

Pola-R-CHP: A New Standard, Significant Limitations

From 2002-2022, “many attempts to improve on first-line DLBCL therapy did not pan out,” Graf said, as more than a dozen large phase 3 trials failed to dethrone R-CHOP as the standard. Most of the trials attempted to add an agent to R-CHOP but showed no additional benefit.

Then, in 2021, the landmark POLARIX study was published. The double-blind, randomized trial on the new regime showed a progression-free survival benefit (PFS) vs R-CHOP (76.7% vs 70.2% at 2 years, respectively). Safety profiles were similar between the 2 combination therapies.

However, overall survival (OS) did not differ.

"Pola-R-CHP is now considered a preferred standard, despite no overall survival benefit and despite increased upfront cost,” Graf said. (A 2023 analysis found that pola-R-CHP is more cost-effective than R-CHOP in DLBCL.)

Pola-R-CHP or Not Pola-R-CHP?

Pola-R-CHP is not for all patients with DLBCL. In advanced cases, Graf said, genomic analyses provide important information that helps clinicians understand whether patients will fare better with R-CHOP. Cell-of-origin classifications include germinal center B-cell like (GCB), activated B-cell like (ABC), and unclassifiable.

“If it’s GCB type, there's no clear benefit for Pola-R-CHP,” Graf said. “On the other hand, the ABC subtype does much better when treated with Pola-R-CHP.”

Graf highlighted the recently updated VA Oncology Clinical Pathway for DLBCL, which recommends cell-of-origin testing by the Hans algorithm for certain advanced-stage patients. The guidelines suggest R-CHOP for GCB-type patients and Pola-R-CHP for non–GCB-type patients. However, he cautioned that the Hans algorithm comes with an increased risk of misclassification.

Early-Stage Disease: Radiation or No Radiation?

About 25% to 30% of patients have stage I or II disease, and the landmark 1998 SWOG trial initially suggested that 3 cycles of CHOP plus radiation had superior PFS and OS compared with 8 cycles of CHOP alone, Graf said. This trial was conducted prior to the R-CHOP era. However, follow-up revealed that the benefit vanished over time and the risk of secondary cancers grew. “Both strategies are perfectly viable, but there isn’t as much of a preference anymore,” Graf said.

A pair of recent trials – a 2019 European study and a 2020 US study – support eliminating radiation and lowering the number of cycles of therapy in certain patients, he said.

Managing Older Patients

Patients with DLBCL tend to be older, Graf said, and many have comorbidities and other limitations. A standard course of 6 cycles of therapy may be too much for them, he said. Graf highlighted the Elderly Prognostic Index, a tool created by an Italian group that allows clinicians to predict outcomes based on patient fitness levels.

Graf offered additional guidance for this population:

• Consider corticosteroids in the prephase setting, which can be “very valuable” and improve a patient’s ECOG performance status, “giving you better confidence about proceeding with more standard therapy.”
• Include anthracycline-based therapies such as R-CHOP if appropriate, such as in patients who are focused on living longer, since they “are really crucial to achieving cure in patients with DLBCL.” Graf noted that he has “a low threshold to involve cardiology if there’s anthracycline use and some underlying cardiac comorbidity.”
• Adjust dosage as appropriate: “You can adjust in the middle, be rather flexible and creative about these doses and dosing levels as you get going with your patient and see just what they can tolerate,” he said. “Sometimes you can ramp it up over the course, and sometimes you have to ramp it down to respond to toxicities.”
• Be aware that older patients are at much higher risk of suffering from toxicities due to the vincristine component of R-CHOP. These include neurotoxicities and constipation.

Graf highlighted the phase 3 Polar Bear study, which may offer more insight into therapy options in patients aged ≥ 75 years who are frail or those aged ≥ 80 years. The trial is scheduled to end in early 2027.

Graf discloses relationships with Janssen, TG Therapeutics, BeOne, AstraZeneca, Genentech, Incyte, Eli Lilly, and Pfizer.

SAN FRANCISCO – The treatment of early-stage diffuse large B-cell lymphoma (DLBCL) is evolving after decades of failed attempts to improve on the standard treatment of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), a hematologist-oncologist said at the Association of Veterans Affairs (VA) Hematology/Oncology regional meeting on lymphoma on March 21.

A combination therapy known as pola-R-CHP is now the preferred option for many patients but has limited additional benefit, said Solomon A. Graf, MD, of the University of Washington and VA Puget Sound Health Care System. Pola-R-CHP is a modified regimen of R-CHOP that replaced vincristine in R-CHOP with polatuzumab vedotin.

The keys to treatment, Graf said, include consideration of disease variations that can affect therapy efficacy and understanding the special needs of older patients.

Understanding DLBCL

DLBCL is the most common non-Hodgkin lymphoma in the US with about 30,000 new cases per year; the median age at diagnosis is 67 years, Graf said.

“The overall incidence of DLBCL has been relatively stable over the last decades,” he said. “But gratifyingly, the rate of death from this disease has steadily been declining since about the turn of the century.”

Pola-R-CHP: A New Standard, Significant Limitations

From 2002-2022, “many attempts to improve on first-line DLBCL therapy did not pan out,” Graf said, as more than a dozen large phase 3 trials failed to dethrone R-CHOP as the standard. Most of the trials attempted to add an agent to R-CHOP but showed no additional benefit.

Then, in 2021, the landmark POLARIX study was published. The double-blind, randomized trial on the new regime showed a progression-free survival benefit (PFS) vs R-CHOP (76.7% vs 70.2% at 2 years, respectively). Safety profiles were similar between the 2 combination therapies.

However, overall survival (OS) did not differ.

"Pola-R-CHP is now considered a preferred standard, despite no overall survival benefit and despite increased upfront cost,” Graf said. (A 2023 analysis found that pola-R-CHP is more cost-effective than R-CHOP in DLBCL.)

Pola-R-CHP or Not Pola-R-CHP?

Pola-R-CHP is not for all patients with DLBCL. In advanced cases, Graf said, genomic analyses provide important information that helps clinicians understand whether patients will fare better with R-CHOP. Cell-of-origin classifications include germinal center B-cell like (GCB), activated B-cell like (ABC), and unclassifiable.

“If it’s GCB type, there's no clear benefit for Pola-R-CHP,” Graf said. “On the other hand, the ABC subtype does much better when treated with Pola-R-CHP.”

Graf highlighted the recently updated VA Oncology Clinical Pathway for DLBCL, which recommends cell-of-origin testing by the Hans algorithm for certain advanced-stage patients. The guidelines suggest R-CHOP for GCB-type patients and Pola-R-CHP for non–GCB-type patients. However, he cautioned that the Hans algorithm comes with an increased risk of misclassification.

Early-Stage Disease: Radiation or No Radiation?

About 25% to 30% of patients have stage I or II disease, and the landmark 1998 SWOG trial initially suggested that 3 cycles of CHOP plus radiation had superior PFS and OS compared with 8 cycles of CHOP alone, Graf said. This trial was conducted prior to the R-CHOP era. However, follow-up revealed that the benefit vanished over time and the risk of secondary cancers grew. “Both strategies are perfectly viable, but there isn’t as much of a preference anymore,” Graf said.

A pair of recent trials – a 2019 European study and a 2020 US study – support eliminating radiation and lowering the number of cycles of therapy in certain patients, he said.

Managing Older Patients

Patients with DLBCL tend to be older, Graf said, and many have comorbidities and other limitations. A standard course of 6 cycles of therapy may be too much for them, he said. Graf highlighted the Elderly Prognostic Index, a tool created by an Italian group that allows clinicians to predict outcomes based on patient fitness levels.

Graf offered additional guidance for this population:

• Consider corticosteroids in the prephase setting, which can be “very valuable” and improve a patient’s ECOG performance status, “giving you better confidence about proceeding with more standard therapy.”
• Include anthracycline-based therapies such as R-CHOP if appropriate, such as in patients who are focused on living longer, since they “are really crucial to achieving cure in patients with DLBCL.” Graf noted that he has “a low threshold to involve cardiology if there’s anthracycline use and some underlying cardiac comorbidity.”
• Adjust dosage as appropriate: “You can adjust in the middle, be rather flexible and creative about these doses and dosing levels as you get going with your patient and see just what they can tolerate,” he said. “Sometimes you can ramp it up over the course, and sometimes you have to ramp it down to respond to toxicities.”
• Be aware that older patients are at much higher risk of suffering from toxicities due to the vincristine component of R-CHOP. These include neurotoxicities and constipation.

Graf highlighted the phase 3 Polar Bear study, which may offer more insight into therapy options in patients aged ≥ 75 years who are frail or those aged ≥ 80 years. The trial is scheduled to end in early 2027.

Graf discloses relationships with Janssen, TG Therapeutics, BeOne, AstraZeneca, Genentech, Incyte, Eli Lilly, and Pfizer.

SAN FRANCISCO – The treatment of early-stage diffuse large B-cell lymphoma (DLBCL) is evolving after decades of failed attempts to improve on the standard treatment of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), a hematologist-oncologist said at the Association of Veterans Affairs (VA) Hematology/Oncology regional meeting on lymphoma on March 21.

A combination therapy known as pola-R-CHP is now the preferred option for many patients but has limited additional benefit, said Solomon A. Graf, MD, of the University of Washington and VA Puget Sound Health Care System. Pola-R-CHP is a modified regimen of R-CHOP that replaced vincristine in R-CHOP with polatuzumab vedotin.

The keys to treatment, Graf said, include consideration of disease variations that can affect therapy efficacy and understanding the special needs of older patients.

Understanding DLBCL

DLBCL is the most common non-Hodgkin lymphoma in the US with about 30,000 new cases per year; the median age at diagnosis is 67 years, Graf said.

“The overall incidence of DLBCL has been relatively stable over the last decades,” he said. “But gratifyingly, the rate of death from this disease has steadily been declining since about the turn of the century.”

Pola-R-CHP: A New Standard, Significant Limitations

From 2002-2022, “many attempts to improve on first-line DLBCL therapy did not pan out,” Graf said, as more than a dozen large phase 3 trials failed to dethrone R-CHOP as the standard. Most of the trials attempted to add an agent to R-CHOP but showed no additional benefit.

Then, in 2021, the landmark POLARIX study was published. The double-blind, randomized trial on the new regime showed a progression-free survival benefit (PFS) vs R-CHOP (76.7% vs 70.2% at 2 years, respectively). Safety profiles were similar between the 2 combination therapies.

However, overall survival (OS) did not differ.

"Pola-R-CHP is now considered a preferred standard, despite no overall survival benefit and despite increased upfront cost,” Graf said. (A 2023 analysis found that pola-R-CHP is more cost-effective than R-CHOP in DLBCL.)

Pola-R-CHP or Not Pola-R-CHP?

Pola-R-CHP is not for all patients with DLBCL. In advanced cases, Graf said, genomic analyses provide important information that helps clinicians understand whether patients will fare better with R-CHOP. Cell-of-origin classifications include germinal center B-cell like (GCB), activated B-cell like (ABC), and unclassifiable.

“If it’s GCB type, there's no clear benefit for Pola-R-CHP,” Graf said. “On the other hand, the ABC subtype does much better when treated with Pola-R-CHP.”

Graf highlighted the recently updated VA Oncology Clinical Pathway for DLBCL, which recommends cell-of-origin testing by the Hans algorithm for certain advanced-stage patients. The guidelines suggest R-CHOP for GCB-type patients and Pola-R-CHP for non–GCB-type patients. However, he cautioned that the Hans algorithm comes with an increased risk of misclassification.

Early-Stage Disease: Radiation or No Radiation?

About 25% to 30% of patients have stage I or II disease, and the landmark 1998 SWOG trial initially suggested that 3 cycles of CHOP plus radiation had superior PFS and OS compared with 8 cycles of CHOP alone, Graf said. This trial was conducted prior to the R-CHOP era. However, follow-up revealed that the benefit vanished over time and the risk of secondary cancers grew. “Both strategies are perfectly viable, but there isn’t as much of a preference anymore,” Graf said.

A pair of recent trials – a 2019 European study and a 2020 US study – support eliminating radiation and lowering the number of cycles of therapy in certain patients, he said.

Managing Older Patients

Patients with DLBCL tend to be older, Graf said, and many have comorbidities and other limitations. A standard course of 6 cycles of therapy may be too much for them, he said. Graf highlighted the Elderly Prognostic Index, a tool created by an Italian group that allows clinicians to predict outcomes based on patient fitness levels.

Graf offered additional guidance for this population:

• Consider corticosteroids in the prephase setting, which can be “very valuable” and improve a patient’s ECOG performance status, “giving you better confidence about proceeding with more standard therapy.”
• Include anthracycline-based therapies such as R-CHOP if appropriate, such as in patients who are focused on living longer, since they “are really crucial to achieving cure in patients with DLBCL.” Graf noted that he has “a low threshold to involve cardiology if there’s anthracycline use and some underlying cardiac comorbidity.”
• Adjust dosage as appropriate: “You can adjust in the middle, be rather flexible and creative about these doses and dosing levels as you get going with your patient and see just what they can tolerate,” he said. “Sometimes you can ramp it up over the course, and sometimes you have to ramp it down to respond to toxicities.”
• Be aware that older patients are at much higher risk of suffering from toxicities due to the vincristine component of R-CHOP. These include neurotoxicities and constipation.

Graf highlighted the phase 3 Polar Bear study, which may offer more insight into therapy options in patients aged ≥ 75 years who are frail or those aged ≥ 80 years. The trial is scheduled to end in early 2027.

Graf discloses relationships with Janssen, TG Therapeutics, BeOne, AstraZeneca, Genentech, Incyte, Eli Lilly, and Pfizer.

TOPLINE:

Among 1.3 million male veterans treated for prostate cancer, 11,327 (0.86%) developed breast cancer an average of 5.4 years after initial diagnosis. Younger age at prostate cancer diagnosis, metastatic disease, androgen deprivation therapy (ADT), radiation treatment, and prolonged use of certain cardiovascular disease (CVD) medications were associated with increased risk for breast cancer.

METHODOLOGY:

• Researchers used a retrospective cohort design in Veterans Health Administration (VHA) care, pulling data from the Veterans Affairs (VA) Prostate Cancer Data Core at the VA Corporate Data Warehouse.
• Participants included 1,314,492 male veterans with prostate cancer treated at VHA facilities from January 1, 2000, to March 12, 2024.
• Exposure definitions included prostate cancer treatments (ADT, anti-androgen treatment, radiation-brachytherapy, and platinum chemotherapy) and CVD medications (furosemide, spironolactone, digoxin) captured via inpatient/outpatient/fee-based pharmacy and Current Procedural Terminology codes.
• Analysis measured time from prostate cancer diagnosis to breast cancer diagnosis, death, or March 12, 2024, applying Cox proportional hazards and Fine-Gray competing risk methods, with a sensitivity analysis adding body mass index (BMI) after excluding 71,718 missing values.

TAKEAWAY:

• Metastatic prostate cancer at diagnosis more than doubled the risk for breast cancer compared to nonmetastatic disease (hazard ratio [HR], 2.03; 95% CI, 1.90-2.17; P < .0001; subdistribution hazard ratio [SHR], 1.68; 95% CI, 1.57-1.81; P < .0001).
• Younger age at prostate cancer diagnosis was associated with increased risk for breast cancer (HR, 0.97; 95% CI, 0.97-0.98; P < .0001; SHR, 0.957; 95% CI, 0.955-0.959; P < .0001), indicating that for each additional year of age at diagnosis, the risk decreased.
• Continuation of CVD medications after prostate cancer diagnosis was associated with increased risk for breast cancer: furosemide (HR, 1.51; 95% CI, 1.39-1.63; P < .0001; SHR, 1.21; 95% CI, 1.12-1.31; P < .0001), spironolactone (HR, 1.36; 95% CI, 1.15-1.61; P = .0004; SHR, 1.23; 95% CI, 1.04-1.47; P = .0174), and digoxin (HR, 1.49; 95% CI, 1.29-1.72; P < .0001; SHR, 1.26; 95% CI, 1.10-1.46; P = .0015).
• Radiation therapy and ADT were associated with increased risk for breast cancer (radiation: HR, 1.06; 95% CI, 1.02-1.11; P = .0088; SHR, 1.10; 95% CI, 1.05-1.15; P < .0001; ADT: HR, 1.24; 95% CI, 1.17-1.32; P < .0001; SHR, 1.28; 95% CI, 1.20-1.37; P < .0001), while abiraterone was associated with decreased risk (HR, 0.36; 95% CI, 0.31-0.42; P < .0001; SHR, 0.39; 95% CI, 0.34-0.45; P < .0001).

IN PRACTICE:

"While there is a lack of data, male veterans with previous prostate cancer are at an elevated risk of breast cancer (0.87%), than their civilian counterparts (0.14%),” the authors wrote. “To address the current gap in knowledge and data, this study leveraged an existing large cohort of male veterans with prostate cancer and examined factors associated with increased risk of male breast cancer."

SOURCE:

The study was led by Erum Z. Whyne, VA North Texas Health Care System in Dallas, and Haekyung Jeon-Slaughter, University of Texas Southwestern Medical Center in Dallas. It was published online in The Prostate.

LIMITATIONS:

Though the study findings are based on large, representative data from male veterans with previously diagnosed prostate cancer, the results might not be generalizable to the overall male breast cancer population. As a retrospective cohort study, results may be biased and causality is difficult to establish. The study did not examine other known risk factors for male breast cancer incidence, such as family history, BRCA2 mutations, and military environmental exposure due to lack of data. BMI had missingness of 5.46% (n = 71,718) and was not included as a covariate in the final model, though sensitivity analysis showed it was not significantly associated with increased risk for male breast cancer.

DISCLOSURES:

The research was supported using resources and facilities of the VA Informatics and Computing Infrastructure (VINCI), VA HSR RES 13-457. The VA North Texas Health Care System Institutional Review Board approved the study and waived informed consent. No conflicts of interest were disclosed by the authors.

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

TOPLINE:

Among 1.3 million male veterans treated for prostate cancer, 11,327 (0.86%) developed breast cancer an average of 5.4 years after initial diagnosis. Younger age at prostate cancer diagnosis, metastatic disease, androgen deprivation therapy (ADT), radiation treatment, and prolonged use of certain cardiovascular disease (CVD) medications were associated with increased risk for breast cancer.

METHODOLOGY:

• Researchers used a retrospective cohort design in Veterans Health Administration (VHA) care, pulling data from the Veterans Affairs (VA) Prostate Cancer Data Core at the VA Corporate Data Warehouse.
• Participants included 1,314,492 male veterans with prostate cancer treated at VHA facilities from January 1, 2000, to March 12, 2024.
• Exposure definitions included prostate cancer treatments (ADT, anti-androgen treatment, radiation-brachytherapy, and platinum chemotherapy) and CVD medications (furosemide, spironolactone, digoxin) captured via inpatient/outpatient/fee-based pharmacy and Current Procedural Terminology codes.
• Analysis measured time from prostate cancer diagnosis to breast cancer diagnosis, death, or March 12, 2024, applying Cox proportional hazards and Fine-Gray competing risk methods, with a sensitivity analysis adding body mass index (BMI) after excluding 71,718 missing values.

TAKEAWAY:

• Metastatic prostate cancer at diagnosis more than doubled the risk for breast cancer compared to nonmetastatic disease (hazard ratio [HR], 2.03; 95% CI, 1.90-2.17; P < .0001; subdistribution hazard ratio [SHR], 1.68; 95% CI, 1.57-1.81; P < .0001).
• Younger age at prostate cancer diagnosis was associated with increased risk for breast cancer (HR, 0.97; 95% CI, 0.97-0.98; P < .0001; SHR, 0.957; 95% CI, 0.955-0.959; P < .0001), indicating that for each additional year of age at diagnosis, the risk decreased.
• Continuation of CVD medications after prostate cancer diagnosis was associated with increased risk for breast cancer: furosemide (HR, 1.51; 95% CI, 1.39-1.63; P < .0001; SHR, 1.21; 95% CI, 1.12-1.31; P < .0001), spironolactone (HR, 1.36; 95% CI, 1.15-1.61; P = .0004; SHR, 1.23; 95% CI, 1.04-1.47; P = .0174), and digoxin (HR, 1.49; 95% CI, 1.29-1.72; P < .0001; SHR, 1.26; 95% CI, 1.10-1.46; P = .0015).
• Radiation therapy and ADT were associated with increased risk for breast cancer (radiation: HR, 1.06; 95% CI, 1.02-1.11; P = .0088; SHR, 1.10; 95% CI, 1.05-1.15; P < .0001; ADT: HR, 1.24; 95% CI, 1.17-1.32; P < .0001; SHR, 1.28; 95% CI, 1.20-1.37; P < .0001), while abiraterone was associated with decreased risk (HR, 0.36; 95% CI, 0.31-0.42; P < .0001; SHR, 0.39; 95% CI, 0.34-0.45; P < .0001).

IN PRACTICE:

"While there is a lack of data, male veterans with previous prostate cancer are at an elevated risk of breast cancer (0.87%), than their civilian counterparts (0.14%),” the authors wrote. “To address the current gap in knowledge and data, this study leveraged an existing large cohort of male veterans with prostate cancer and examined factors associated with increased risk of male breast cancer."

SOURCE:

The study was led by Erum Z. Whyne, VA North Texas Health Care System in Dallas, and Haekyung Jeon-Slaughter, University of Texas Southwestern Medical Center in Dallas. It was published online in The Prostate.

LIMITATIONS:

Though the study findings are based on large, representative data from male veterans with previously diagnosed prostate cancer, the results might not be generalizable to the overall male breast cancer population. As a retrospective cohort study, results may be biased and causality is difficult to establish. The study did not examine other known risk factors for male breast cancer incidence, such as family history, BRCA2 mutations, and military environmental exposure due to lack of data. BMI had missingness of 5.46% (n = 71,718) and was not included as a covariate in the final model, though sensitivity analysis showed it was not significantly associated with increased risk for male breast cancer.

DISCLOSURES:

The research was supported using resources and facilities of the VA Informatics and Computing Infrastructure (VINCI), VA HSR RES 13-457. The VA North Texas Health Care System Institutional Review Board approved the study and waived informed consent. No conflicts of interest were disclosed by the authors.

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

TOPLINE:

Among 1.3 million male veterans treated for prostate cancer, 11,327 (0.86%) developed breast cancer an average of 5.4 years after initial diagnosis. Younger age at prostate cancer diagnosis, metastatic disease, androgen deprivation therapy (ADT), radiation treatment, and prolonged use of certain cardiovascular disease (CVD) medications were associated with increased risk for breast cancer.

METHODOLOGY:

• Researchers used a retrospective cohort design in Veterans Health Administration (VHA) care, pulling data from the Veterans Affairs (VA) Prostate Cancer Data Core at the VA Corporate Data Warehouse.
• Participants included 1,314,492 male veterans with prostate cancer treated at VHA facilities from January 1, 2000, to March 12, 2024.
• Exposure definitions included prostate cancer treatments (ADT, anti-androgen treatment, radiation-brachytherapy, and platinum chemotherapy) and CVD medications (furosemide, spironolactone, digoxin) captured via inpatient/outpatient/fee-based pharmacy and Current Procedural Terminology codes.
• Analysis measured time from prostate cancer diagnosis to breast cancer diagnosis, death, or March 12, 2024, applying Cox proportional hazards and Fine-Gray competing risk methods, with a sensitivity analysis adding body mass index (BMI) after excluding 71,718 missing values.

TAKEAWAY:

• Metastatic prostate cancer at diagnosis more than doubled the risk for breast cancer compared to nonmetastatic disease (hazard ratio [HR], 2.03; 95% CI, 1.90-2.17; P < .0001; subdistribution hazard ratio [SHR], 1.68; 95% CI, 1.57-1.81; P < .0001).
• Younger age at prostate cancer diagnosis was associated with increased risk for breast cancer (HR, 0.97; 95% CI, 0.97-0.98; P < .0001; SHR, 0.957; 95% CI, 0.955-0.959; P < .0001), indicating that for each additional year of age at diagnosis, the risk decreased.
• Continuation of CVD medications after prostate cancer diagnosis was associated with increased risk for breast cancer: furosemide (HR, 1.51; 95% CI, 1.39-1.63; P < .0001; SHR, 1.21; 95% CI, 1.12-1.31; P < .0001), spironolactone (HR, 1.36; 95% CI, 1.15-1.61; P = .0004; SHR, 1.23; 95% CI, 1.04-1.47; P = .0174), and digoxin (HR, 1.49; 95% CI, 1.29-1.72; P < .0001; SHR, 1.26; 95% CI, 1.10-1.46; P = .0015).
• Radiation therapy and ADT were associated with increased risk for breast cancer (radiation: HR, 1.06; 95% CI, 1.02-1.11; P = .0088; SHR, 1.10; 95% CI, 1.05-1.15; P < .0001; ADT: HR, 1.24; 95% CI, 1.17-1.32; P < .0001; SHR, 1.28; 95% CI, 1.20-1.37; P < .0001), while abiraterone was associated with decreased risk (HR, 0.36; 95% CI, 0.31-0.42; P < .0001; SHR, 0.39; 95% CI, 0.34-0.45; P < .0001).

IN PRACTICE:

"While there is a lack of data, male veterans with previous prostate cancer are at an elevated risk of breast cancer (0.87%), than their civilian counterparts (0.14%),” the authors wrote. “To address the current gap in knowledge and data, this study leveraged an existing large cohort of male veterans with prostate cancer and examined factors associated with increased risk of male breast cancer."

SOURCE:

The study was led by Erum Z. Whyne, VA North Texas Health Care System in Dallas, and Haekyung Jeon-Slaughter, University of Texas Southwestern Medical Center in Dallas. It was published online in The Prostate.

LIMITATIONS:

Though the study findings are based on large, representative data from male veterans with previously diagnosed prostate cancer, the results might not be generalizable to the overall male breast cancer population. As a retrospective cohort study, results may be biased and causality is difficult to establish. The study did not examine other known risk factors for male breast cancer incidence, such as family history, BRCA2 mutations, and military environmental exposure due to lack of data. BMI had missingness of 5.46% (n = 71,718) and was not included as a covariate in the final model, though sensitivity analysis showed it was not significantly associated with increased risk for male breast cancer.

DISCLOSURES:

The research was supported using resources and facilities of the VA Informatics and Computing Infrastructure (VINCI), VA HSR RES 13-457. The VA North Texas Health Care System Institutional Review Board approved the study and waived informed consent. No conflicts of interest were disclosed by the authors.

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

TOPLINE:

Among adults with obesity, nonsurgical weight loss was significantly associated with reduced odds for developing obesity-related and other cancers at 3 and 5 years, a study of real-world data found.

METHODOLOGY:

• Although weight loss after bariatric surgery is linked to a reduced risk for cancer, the effect of nonsurgical weight loss on cancer risk remains unclear.
• Researchers conducted a retrospective observational study using electronic health record data from a US health system to assess the association between nonsurgical weight loss and the risk for cancer among adults with obesity.
• The inclusion criteria were age of ≥ 20 years, BMI > 30, and at least seven health system visits over 3 years. Patients with a history of alcohol or substance abuse, amputations, HIV infection, organ transplant, thyroid problems, or those who underwent bariatric surgery were excluded.
• The 143,630 patients who met inclusion criteria (7703 cancer cases and 135,927 controls) were divided into 3 cohorts based on weight change over time intervals of 3 years (115,942 patients), 5 years (105,472 patients), and 10 years (59,112 patients).
• Primary endpoints included obesity-related cancers (esophageal cancer, liver cancer, gallbladder cancer, pancreatic cancer, colorectal cancer, renal cell carcinoma, endometrial cancer, multiple myeloma, and postmenopausal breast cancer), and secondary endpoints included all malignant neoplasms.

TAKEAWAY:

• Each 1% reduction in BMI was associated with reduced odds of obesity-related cancers at 3 years and 5 years (odds ratio [OR], 0.99 and 0.989, respectively; P < .001 for both). These results translate to 5% weight loss corresponding to 4.9% and 5.4% reductions in obesity-related cancer odds at 3 and 5 years, respectively.
• Weight loss was associated with reduced odds of endometrial cancer at 3, 5, and 10 years (OR, 0.978; P < .05), of renal cell carcinoma at 3 and 5 years (OR, 0.983; P < .05), and of multiple myeloma at 10 years (OR, 0.969; P = .004).
• Weight loss was also associated with reduced odds of developing any malignancy at 3 years (OR, 0.992), 5 years (OR, 0.994), and 10 years (OR, 0.991; P = .001 for all). These results translate into a 5% weight loss corresponding to 3.9%, 3%, and 4.4% lower odds of any malignancy at 3, 5, and 10 years, respectively.

IN PRACTICE:

"Real-world weight loss was associated with a decreased risk of developing obesity-related cancers and all other cancers. Our study serves as a call for action and a strong public health message to healthcare stakeholders to intensify efforts and resources to treat obesity as a chronic disease to help reduce the risk of developing cancer," the author wrote.

SOURCE:

This study, led by endocrinologist Kenda Alkwatli, MD, Starling Physicians, Wethersfield, Connecticut, was published online in Obesity.

LIMITATIONS:

The study included only individuals with sufficient longitudinal health records, which may have introduced selection bias. It could not distinguish between intentional and unintentional weight loss or differentiate between fat and lean mass. Due to its observational nature, the study could not assess whether weight loss preceding cancer diagnosis was related to delay in diagnosis.

DISCLOSURES:

The study was funded in part by the Cleveland Clinic Center for Quantitative Metabolic Research. Three authors reported receiving research funding, consulting fees, honoraria, grants, or research support and holding patent applications, license agreements, leadership roles, or equity in healthcare and biotechnology companies.

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:

Among adults with obesity, nonsurgical weight loss was significantly associated with reduced odds for developing obesity-related and other cancers at 3 and 5 years, a study of real-world data found.

METHODOLOGY:

• Although weight loss after bariatric surgery is linked to a reduced risk for cancer, the effect of nonsurgical weight loss on cancer risk remains unclear.
• Researchers conducted a retrospective observational study using electronic health record data from a US health system to assess the association between nonsurgical weight loss and the risk for cancer among adults with obesity.
• The inclusion criteria were age of ≥ 20 years, BMI > 30, and at least seven health system visits over 3 years. Patients with a history of alcohol or substance abuse, amputations, HIV infection, organ transplant, thyroid problems, or those who underwent bariatric surgery were excluded.
• The 143,630 patients who met inclusion criteria (7703 cancer cases and 135,927 controls) were divided into 3 cohorts based on weight change over time intervals of 3 years (115,942 patients), 5 years (105,472 patients), and 10 years (59,112 patients).
• Primary endpoints included obesity-related cancers (esophageal cancer, liver cancer, gallbladder cancer, pancreatic cancer, colorectal cancer, renal cell carcinoma, endometrial cancer, multiple myeloma, and postmenopausal breast cancer), and secondary endpoints included all malignant neoplasms.

TAKEAWAY:

• Each 1% reduction in BMI was associated with reduced odds of obesity-related cancers at 3 years and 5 years (odds ratio [OR], 0.99 and 0.989, respectively; P < .001 for both). These results translate to 5% weight loss corresponding to 4.9% and 5.4% reductions in obesity-related cancer odds at 3 and 5 years, respectively.
• Weight loss was associated with reduced odds of endometrial cancer at 3, 5, and 10 years (OR, 0.978; P < .05), of renal cell carcinoma at 3 and 5 years (OR, 0.983; P < .05), and of multiple myeloma at 10 years (OR, 0.969; P = .004).
• Weight loss was also associated with reduced odds of developing any malignancy at 3 years (OR, 0.992), 5 years (OR, 0.994), and 10 years (OR, 0.991; P = .001 for all). These results translate into a 5% weight loss corresponding to 3.9%, 3%, and 4.4% lower odds of any malignancy at 3, 5, and 10 years, respectively.

IN PRACTICE:

"Real-world weight loss was associated with a decreased risk of developing obesity-related cancers and all other cancers. Our study serves as a call for action and a strong public health message to healthcare stakeholders to intensify efforts and resources to treat obesity as a chronic disease to help reduce the risk of developing cancer," the author wrote.

SOURCE:

This study, led by endocrinologist Kenda Alkwatli, MD, Starling Physicians, Wethersfield, Connecticut, was published online in Obesity.

LIMITATIONS:

The study included only individuals with sufficient longitudinal health records, which may have introduced selection bias. It could not distinguish between intentional and unintentional weight loss or differentiate between fat and lean mass. Due to its observational nature, the study could not assess whether weight loss preceding cancer diagnosis was related to delay in diagnosis.

DISCLOSURES:

The study was funded in part by the Cleveland Clinic Center for Quantitative Metabolic Research. Three authors reported receiving research funding, consulting fees, honoraria, grants, or research support and holding patent applications, license agreements, leadership roles, or equity in healthcare and biotechnology companies.

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:

Among adults with obesity, nonsurgical weight loss was significantly associated with reduced odds for developing obesity-related and other cancers at 3 and 5 years, a study of real-world data found.

METHODOLOGY:

• Although weight loss after bariatric surgery is linked to a reduced risk for cancer, the effect of nonsurgical weight loss on cancer risk remains unclear.
• Researchers conducted a retrospective observational study using electronic health record data from a US health system to assess the association between nonsurgical weight loss and the risk for cancer among adults with obesity.
• The inclusion criteria were age of ≥ 20 years, BMI > 30, and at least seven health system visits over 3 years. Patients with a history of alcohol or substance abuse, amputations, HIV infection, organ transplant, thyroid problems, or those who underwent bariatric surgery were excluded.
• The 143,630 patients who met inclusion criteria (7703 cancer cases and 135,927 controls) were divided into 3 cohorts based on weight change over time intervals of 3 years (115,942 patients), 5 years (105,472 patients), and 10 years (59,112 patients).
• Primary endpoints included obesity-related cancers (esophageal cancer, liver cancer, gallbladder cancer, pancreatic cancer, colorectal cancer, renal cell carcinoma, endometrial cancer, multiple myeloma, and postmenopausal breast cancer), and secondary endpoints included all malignant neoplasms.

TAKEAWAY:

• Each 1% reduction in BMI was associated with reduced odds of obesity-related cancers at 3 years and 5 years (odds ratio [OR], 0.99 and 0.989, respectively; P < .001 for both). These results translate to 5% weight loss corresponding to 4.9% and 5.4% reductions in obesity-related cancer odds at 3 and 5 years, respectively.
• Weight loss was associated with reduced odds of endometrial cancer at 3, 5, and 10 years (OR, 0.978; P < .05), of renal cell carcinoma at 3 and 5 years (OR, 0.983; P < .05), and of multiple myeloma at 10 years (OR, 0.969; P = .004).
• Weight loss was also associated with reduced odds of developing any malignancy at 3 years (OR, 0.992), 5 years (OR, 0.994), and 10 years (OR, 0.991; P = .001 for all). These results translate into a 5% weight loss corresponding to 3.9%, 3%, and 4.4% lower odds of any malignancy at 3, 5, and 10 years, respectively.

IN PRACTICE:

"Real-world weight loss was associated with a decreased risk of developing obesity-related cancers and all other cancers. Our study serves as a call for action and a strong public health message to healthcare stakeholders to intensify efforts and resources to treat obesity as a chronic disease to help reduce the risk of developing cancer," the author wrote.

SOURCE:

This study, led by endocrinologist Kenda Alkwatli, MD, Starling Physicians, Wethersfield, Connecticut, was published online in Obesity.

LIMITATIONS:

The study included only individuals with sufficient longitudinal health records, which may have introduced selection bias. It could not distinguish between intentional and unintentional weight loss or differentiate between fat and lean mass. Due to its observational nature, the study could not assess whether weight loss preceding cancer diagnosis was related to delay in diagnosis.

DISCLOSURES:

The study was funded in part by the Cleveland Clinic Center for Quantitative Metabolic Research. Three authors reported receiving research funding, consulting fees, honoraria, grants, or research support and holding patent applications, license agreements, leadership roles, or equity in healthcare and biotechnology companies.

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:

More than 1 in 8 colorectal cancer (CRC) cases among veterans occur outside the standard screening age of 50-75 years or those with high-risk personal or family history. High-risk patients face > 6 times the risk for CRC compared with average-risk patients aged 50-75 years who are up to date with screening, while Black patients have > 50% higher risk compared with White patients.

METHODOLOGY:

• Researchers conducted a case-control analysis using Veterans Health Administration (VHA) Corporate Data Warehouse data from 2012-2018 at 2 sites: Veterans Affairs (VA) New York Harbor Health Care System and VA Puget Sound Health Care System.

• Participants included 3714 cases among veterans with CRC matched to 14,856 controls (4:1), with matching on age (± 3 years), sex, and facility site; each control was used once.

• Screening categories included 5 groups by age (50-75 years vs < 50 years or > 75 years), screening up-to-date status, and high-risk status (inflammatory bowel disease, hereditary cancer syndromes, or family history).

• CRC screening was considered up to date if US Preventive Services Task Force-recommended tests were completed on time (colonoscopy ≤ 10 years; guaiac-based fecal occult blood test or fecal immunochemical test ≤ 1 year).

TAKEAWAY:

• Compared with category 1 (age 50-75 years and up-to-date with screening), CRC was associated with category 4 (age < 50 years or > 75 years and not up to date) (odds ratio [OR], 1.40; 95% CI, 1.11-1.78), and category 5 (high risk) (OR, 6.23; 95% CI, 5.06-7.66).

• Race and comorbidity associations included higher CRC risk for Black vs White patients (OR, 1.54; 95% CI, 1.37-1.73), and higher CRC risk with diabetes (OR, 1.65; 95% CI, 1.51-1.81) and alcohol use disorder (OR, 1.53; 95% CI, 1.35-1.73).

• Among 3714 CRC cases, 71.1% occurred in individuals aged 50-75 years not up to date with screening.

• A total of 12.5% of CRC cases occurred in people outside age 50-75 or with high-risk personal or family history, suggesting that conventional screening-adherence metrics may miss a clinically relevant minority.

IN PRACTICE:

“The conventional measure of CRC screening, focused on average-risk individuals aged 50 to 75, does not reflect screening status in an important minority of CRC patients," the authors wrote.

SOURCE:

The study was led by researchers at NYU Grossman School of Medicine and Veterans Affairs New York Harbor Health Care System, and published online July 9, 2026 in Medicine.

LIMITATIONS:

The study population consisted predominantly of male veterans (97.1%), who tend to be older and have more comorbidities compared with the US population, which may limit the generalizability of findings to other populations. Researchers defined screening status cross-sectionally relative to a single point in time rather than assessing longitudinal screening adherence, which may not fully capture the consistency of screening over time that is likely important for defining CRC risk. Veterans may receive screening at non-VA medical facilities, potentially leading to incomplete documentation of screening status and important covariates such as race, ethnicity, and comorbidities. The possibility of residual confounding cannot be excluded despite adjustment for multiple risk factors in the analysis.

DISCLOSURES:

This study received support from NIH grant K08 CA230162 and the AGA Caroline Craig Augustyn & Damian Augustyn Award in Digestive Cancer, both awarded to Peter S. Liang. Liang disclosed receiving research support from Freenome and serving on the advisory boards for Guardant Health and Natera. The remaining authors reported no funding or conflicts of interest to disclose.

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

TOPLINE:

More than 1 in 8 colorectal cancer (CRC) cases among veterans occur outside the standard screening age of 50-75 years or those with high-risk personal or family history. High-risk patients face > 6 times the risk for CRC compared with average-risk patients aged 50-75 years who are up to date with screening, while Black patients have > 50% higher risk compared with White patients.

METHODOLOGY:

• Researchers conducted a case-control analysis using Veterans Health Administration (VHA) Corporate Data Warehouse data from 2012-2018 at 2 sites: Veterans Affairs (VA) New York Harbor Health Care System and VA Puget Sound Health Care System.

• Participants included 3714 cases among veterans with CRC matched to 14,856 controls (4:1), with matching on age (± 3 years), sex, and facility site; each control was used once.

• Screening categories included 5 groups by age (50-75 years vs < 50 years or > 75 years), screening up-to-date status, and high-risk status (inflammatory bowel disease, hereditary cancer syndromes, or family history).

• CRC screening was considered up to date if US Preventive Services Task Force-recommended tests were completed on time (colonoscopy ≤ 10 years; guaiac-based fecal occult blood test or fecal immunochemical test ≤ 1 year).

TAKEAWAY:

• Compared with category 1 (age 50-75 years and up-to-date with screening), CRC was associated with category 4 (age < 50 years or > 75 years and not up to date) (odds ratio [OR], 1.40; 95% CI, 1.11-1.78), and category 5 (high risk) (OR, 6.23; 95% CI, 5.06-7.66).

• Race and comorbidity associations included higher CRC risk for Black vs White patients (OR, 1.54; 95% CI, 1.37-1.73), and higher CRC risk with diabetes (OR, 1.65; 95% CI, 1.51-1.81) and alcohol use disorder (OR, 1.53; 95% CI, 1.35-1.73).

• Among 3714 CRC cases, 71.1% occurred in individuals aged 50-75 years not up to date with screening.

• A total of 12.5% of CRC cases occurred in people outside age 50-75 or with high-risk personal or family history, suggesting that conventional screening-adherence metrics may miss a clinically relevant minority.

IN PRACTICE:

“The conventional measure of CRC screening, focused on average-risk individuals aged 50 to 75, does not reflect screening status in an important minority of CRC patients," the authors wrote.

SOURCE:

The study was led by researchers at NYU Grossman School of Medicine and Veterans Affairs New York Harbor Health Care System, and published online July 9, 2026 in Medicine.

LIMITATIONS:

The study population consisted predominantly of male veterans (97.1%), who tend to be older and have more comorbidities compared with the US population, which may limit the generalizability of findings to other populations. Researchers defined screening status cross-sectionally relative to a single point in time rather than assessing longitudinal screening adherence, which may not fully capture the consistency of screening over time that is likely important for defining CRC risk. Veterans may receive screening at non-VA medical facilities, potentially leading to incomplete documentation of screening status and important covariates such as race, ethnicity, and comorbidities. The possibility of residual confounding cannot be excluded despite adjustment for multiple risk factors in the analysis.

DISCLOSURES:

This study received support from NIH grant K08 CA230162 and the AGA Caroline Craig Augustyn & Damian Augustyn Award in Digestive Cancer, both awarded to Peter S. Liang. Liang disclosed receiving research support from Freenome and serving on the advisory boards for Guardant Health and Natera. The remaining authors reported no funding or conflicts of interest to disclose.

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

TOPLINE:

More than 1 in 8 colorectal cancer (CRC) cases among veterans occur outside the standard screening age of 50-75 years or those with high-risk personal or family history. High-risk patients face > 6 times the risk for CRC compared with average-risk patients aged 50-75 years who are up to date with screening, while Black patients have > 50% higher risk compared with White patients.

METHODOLOGY:

• Researchers conducted a case-control analysis using Veterans Health Administration (VHA) Corporate Data Warehouse data from 2012-2018 at 2 sites: Veterans Affairs (VA) New York Harbor Health Care System and VA Puget Sound Health Care System.

• Participants included 3714 cases among veterans with CRC matched to 14,856 controls (4:1), with matching on age (± 3 years), sex, and facility site; each control was used once.

• Screening categories included 5 groups by age (50-75 years vs < 50 years or > 75 years), screening up-to-date status, and high-risk status (inflammatory bowel disease, hereditary cancer syndromes, or family history).

• CRC screening was considered up to date if US Preventive Services Task Force-recommended tests were completed on time (colonoscopy ≤ 10 years; guaiac-based fecal occult blood test or fecal immunochemical test ≤ 1 year).

TAKEAWAY:

• Compared with category 1 (age 50-75 years and up-to-date with screening), CRC was associated with category 4 (age < 50 years or > 75 years and not up to date) (odds ratio [OR], 1.40; 95% CI, 1.11-1.78), and category 5 (high risk) (OR, 6.23; 95% CI, 5.06-7.66).

• Race and comorbidity associations included higher CRC risk for Black vs White patients (OR, 1.54; 95% CI, 1.37-1.73), and higher CRC risk with diabetes (OR, 1.65; 95% CI, 1.51-1.81) and alcohol use disorder (OR, 1.53; 95% CI, 1.35-1.73).

• Among 3714 CRC cases, 71.1% occurred in individuals aged 50-75 years not up to date with screening.

• A total of 12.5% of CRC cases occurred in people outside age 50-75 or with high-risk personal or family history, suggesting that conventional screening-adherence metrics may miss a clinically relevant minority.

IN PRACTICE:

“The conventional measure of CRC screening, focused on average-risk individuals aged 50 to 75, does not reflect screening status in an important minority of CRC patients," the authors wrote.

SOURCE:

The study was led by researchers at NYU Grossman School of Medicine and Veterans Affairs New York Harbor Health Care System, and published online July 9, 2026 in Medicine.

LIMITATIONS:

The study population consisted predominantly of male veterans (97.1%), who tend to be older and have more comorbidities compared with the US population, which may limit the generalizability of findings to other populations. Researchers defined screening status cross-sectionally relative to a single point in time rather than assessing longitudinal screening adherence, which may not fully capture the consistency of screening over time that is likely important for defining CRC risk. Veterans may receive screening at non-VA medical facilities, potentially leading to incomplete documentation of screening status and important covariates such as race, ethnicity, and comorbidities. The possibility of residual confounding cannot be excluded despite adjustment for multiple risk factors in the analysis.

DISCLOSURES:

This study received support from NIH grant K08 CA230162 and the AGA Caroline Craig Augustyn & Damian Augustyn Award in Digestive Cancer, both awarded to Peter S. Liang. Liang disclosed receiving research support from Freenome and serving on the advisory boards for Guardant Health and Natera. The remaining authors reported no funding or conflicts of interest to disclose.

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

Simple exercises performed during chemotherapy may significantly reduce treatment-related cognitive impairment, according to findings from a phase 3 randomized controlled trial.

Among patients with cancer receiving 2-week cycles of chemotherapy, a structured and individualized exercise “prescription” combining walking and resistance band training significantly reduced cognitive impairment and mental fatigue compared with usual care.

The results are “practice-changing,” colead author Karen Mustian, PhD, MPH, with the Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York, told Medscape Medical News. “Cancer care providers should consider incorporating structured, home-based exercise programs, such as walking and resistance band exercises, into routine chemotherapy care.”

The findings, published online in the Journal of the National Comprehensive Cancer Network (NCCN), reinforce recommendations by the NCCN that survivors with cancer-related cognitive dysfunction engage in routine physical activity.

“Many patients who need chemotherapy worry that they’ll experience ‘chemo brain,’” Lindsay L. Peterson, MD, medical oncologist at Washington University School of Medicine in St. Louis, who was not involved in this research, added in a statement.

This study offers “encouraging news” — exercise may be something patients can do to reduce their risk for cognitive impairment during chemotherapy, Peterson said.

Less Brain Fog, Mental Fatigue

Up to three-fourth of patients experience cancer-related cognitive impairment during treatment, which often occurs alongside mental fatigue. Research assessing the effects of exercise on cancer-related cognitive impairment during treatment is limited. To investigate, Mustian and colleagues enrolled 687 chemotherapy-naive adults with various cancers as well as Karnofsky performance status scores of at least 70 and no physical limitations, who were scheduled to start chemotherapy with cycles of 2, 3, or 4 weeks. Participants were randomly assigned to either the Exercise for Cancer Patients (EXCAP) intervention or usual care while undergoing chemotherapy. Developed by Mustian and colleagues, EXCAP is a 6-week, home-based, individually tailored walking and resistance band exercise program, introduced during a single in-person training session and reinforced through follow-up calls.

Before chemotherapy began, participants in both groups averaged roughly 2 miles of walking daily. After 6 weeks, patients in the EXCAP group largely maintained their activity levels, while those receiving usual care reduced their daily steps by about half. The exercise group also added resistance-band training three times per week for about 25 minutes per session, while the usual care group did no resistance exercises.

Cognitive function was measured using the Functional Assessment of Cancer Therapy-Cognitive Function questionnaire, and mental fatigue was assessed using the Multidimensional Fatigue Symptom Inventory. Blood samples were collected to measure key inflammatory markers.

Overall, across the study population, cognitive function declined and mental fatigue worsened during chemotherapy, but outcomes differed by treatment group and chemotherapy schedule.

Patients assigned to EXCAP and receiving chemotherapy on 2-week cycles fared best. More specifically, compared with usual care, EXCAP participants undergoing 2-week chemotherapy cycles reported less overall cognitive impairment (mean difference, 7.0; P = .04) and lower perceived cognitive impairment (mean difference, 4.1; P = .05). The exercisers also received fewer perceived comments from others about cognitive difficulties (mean difference, 0.6; P = .02) and reported less mental fatigue (-1.6; P < .01).

These benefits, however, were not observed in patients receiving 3- and 4-week chemotherapy cycles. In the 3-week cohort, there were no significant differences between groups in cognitive impairment (mean difference, 0.5; P = .85) or mental fatigue (mean difference, -0.2; P = .60).

“This was surprising,” Mustian said. “We really don’t know why the patients receiving chemo every 2 weeks were the ones to benefit the most. We do not have the capacity in our current data to answer that question for sure.”

However, Mustian speculated that it’s possible patients who receive their chemotherapy on differing weekly schedules receive different chemotherapy agents that have different toxicity and adverse-effect profiles.

For instance, chemotherapy among patients on a 2-week cycle may come with less severe acute adverse effects, which in turn may allow patients to remain more active throughout their treatments. On the other hand, chemotherapy among patients on a 3-week cycle may come with more severe acute adverse effects, which prevent them from staying as active.

“Once a person starts to lower their activity levels, it is more difficult to get back to their baseline levels and maintain them, and definitely harder to add anything additional to their activity routines,” Mustian said.

Immune Benefits?

Mustian and her team also assessed ties between exercise, cognitive impairment, and inflammation during chemotherapy. Previous work from the team showed that patients who received the EXCAP intervention exhibited higher immunocompetence.

In the current study, the researchers observed that a “healthy inflammatory response” — reflecting balanced increases in both proinflammatory and anti-inflammatory cytokines — was associated with better cognitive outcomes, suggesting that immune regulation may play a role in chemotherapy-related cognitive symptoms.

While chemotherapy may contribute to cognitive impairment by disrupting the body’s inflammatory and immune responses, “exercise may help keep these body systems working more normally, which could explain why patients who exercised had better thinking and less mental fatigue,” Mustian said.

Role for Exercise Oncology

Mustian suggested that oncologists consider referring patients receiving chemotherapy to exercise oncology specialists who can tailor programs for individual capabilities.

There are now > 2000 exercise oncology programs across the US. “Many of them provide both in-person and remote online opportunities for patients to access highly qualified exercise oncology professionals,” Mustian said.

Taking time to learn about community resources, developing a referral method of referral, or even providing patients with simple handouts on credible exercise programs and NCCN guidelines can help, Mustian added.

Peterson noted that, for many patients, maintaining the ability to think clearly, remember details, and stay mentally engaged during treatment is essential to preserving independence, continuing to work and care for their families, and sustaining overall quality of life.

“Interventions that are accessible and low cost, such as structured physical activity, give us a powerful opportunity not only to support long-term survivorship, but to help patients remain as cognitively sharp and mentally resilient as possible throughout treatment,” Peterson said in a statement.

This study was supported by the National Cancer Institute. Mustian and Peterson reported having no relevant disclosures.

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

Simple exercises performed during chemotherapy may significantly reduce treatment-related cognitive impairment, according to findings from a phase 3 randomized controlled trial.

Among patients with cancer receiving 2-week cycles of chemotherapy, a structured and individualized exercise “prescription” combining walking and resistance band training significantly reduced cognitive impairment and mental fatigue compared with usual care.

The results are “practice-changing,” colead author Karen Mustian, PhD, MPH, with the Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York, told Medscape Medical News. “Cancer care providers should consider incorporating structured, home-based exercise programs, such as walking and resistance band exercises, into routine chemotherapy care.”

The findings, published online in the Journal of the National Comprehensive Cancer Network (NCCN), reinforce recommendations by the NCCN that survivors with cancer-related cognitive dysfunction engage in routine physical activity.

“Many patients who need chemotherapy worry that they’ll experience ‘chemo brain,’” Lindsay L. Peterson, MD, medical oncologist at Washington University School of Medicine in St. Louis, who was not involved in this research, added in a statement.

This study offers “encouraging news” — exercise may be something patients can do to reduce their risk for cognitive impairment during chemotherapy, Peterson said.

Less Brain Fog, Mental Fatigue

Up to three-fourth of patients experience cancer-related cognitive impairment during treatment, which often occurs alongside mental fatigue. Research assessing the effects of exercise on cancer-related cognitive impairment during treatment is limited. To investigate, Mustian and colleagues enrolled 687 chemotherapy-naive adults with various cancers as well as Karnofsky performance status scores of at least 70 and no physical limitations, who were scheduled to start chemotherapy with cycles of 2, 3, or 4 weeks. Participants were randomly assigned to either the Exercise for Cancer Patients (EXCAP) intervention or usual care while undergoing chemotherapy. Developed by Mustian and colleagues, EXCAP is a 6-week, home-based, individually tailored walking and resistance band exercise program, introduced during a single in-person training session and reinforced through follow-up calls.

Before chemotherapy began, participants in both groups averaged roughly 2 miles of walking daily. After 6 weeks, patients in the EXCAP group largely maintained their activity levels, while those receiving usual care reduced their daily steps by about half. The exercise group also added resistance-band training three times per week for about 25 minutes per session, while the usual care group did no resistance exercises.

Cognitive function was measured using the Functional Assessment of Cancer Therapy-Cognitive Function questionnaire, and mental fatigue was assessed using the Multidimensional Fatigue Symptom Inventory. Blood samples were collected to measure key inflammatory markers.

Overall, across the study population, cognitive function declined and mental fatigue worsened during chemotherapy, but outcomes differed by treatment group and chemotherapy schedule.

Patients assigned to EXCAP and receiving chemotherapy on 2-week cycles fared best. More specifically, compared with usual care, EXCAP participants undergoing 2-week chemotherapy cycles reported less overall cognitive impairment (mean difference, 7.0; P = .04) and lower perceived cognitive impairment (mean difference, 4.1; P = .05). The exercisers also received fewer perceived comments from others about cognitive difficulties (mean difference, 0.6; P = .02) and reported less mental fatigue (-1.6; P < .01).

These benefits, however, were not observed in patients receiving 3- and 4-week chemotherapy cycles. In the 3-week cohort, there were no significant differences between groups in cognitive impairment (mean difference, 0.5; P = .85) or mental fatigue (mean difference, -0.2; P = .60).

“This was surprising,” Mustian said. “We really don’t know why the patients receiving chemo every 2 weeks were the ones to benefit the most. We do not have the capacity in our current data to answer that question for sure.”

However, Mustian speculated that it’s possible patients who receive their chemotherapy on differing weekly schedules receive different chemotherapy agents that have different toxicity and adverse-effect profiles.

For instance, chemotherapy among patients on a 2-week cycle may come with less severe acute adverse effects, which in turn may allow patients to remain more active throughout their treatments. On the other hand, chemotherapy among patients on a 3-week cycle may come with more severe acute adverse effects, which prevent them from staying as active.

“Once a person starts to lower their activity levels, it is more difficult to get back to their baseline levels and maintain them, and definitely harder to add anything additional to their activity routines,” Mustian said.

Immune Benefits?

Mustian and her team also assessed ties between exercise, cognitive impairment, and inflammation during chemotherapy. Previous work from the team showed that patients who received the EXCAP intervention exhibited higher immunocompetence.

In the current study, the researchers observed that a “healthy inflammatory response” — reflecting balanced increases in both proinflammatory and anti-inflammatory cytokines — was associated with better cognitive outcomes, suggesting that immune regulation may play a role in chemotherapy-related cognitive symptoms.

While chemotherapy may contribute to cognitive impairment by disrupting the body’s inflammatory and immune responses, “exercise may help keep these body systems working more normally, which could explain why patients who exercised had better thinking and less mental fatigue,” Mustian said.

Role for Exercise Oncology

Mustian suggested that oncologists consider referring patients receiving chemotherapy to exercise oncology specialists who can tailor programs for individual capabilities.

There are now > 2000 exercise oncology programs across the US. “Many of them provide both in-person and remote online opportunities for patients to access highly qualified exercise oncology professionals,” Mustian said.

Taking time to learn about community resources, developing a referral method of referral, or even providing patients with simple handouts on credible exercise programs and NCCN guidelines can help, Mustian added.

Peterson noted that, for many patients, maintaining the ability to think clearly, remember details, and stay mentally engaged during treatment is essential to preserving independence, continuing to work and care for their families, and sustaining overall quality of life.

“Interventions that are accessible and low cost, such as structured physical activity, give us a powerful opportunity not only to support long-term survivorship, but to help patients remain as cognitively sharp and mentally resilient as possible throughout treatment,” Peterson said in a statement.

This study was supported by the National Cancer Institute. Mustian and Peterson reported having no relevant disclosures.

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

Simple exercises performed during chemotherapy may significantly reduce treatment-related cognitive impairment, according to findings from a phase 3 randomized controlled trial.

Among patients with cancer receiving 2-week cycles of chemotherapy, a structured and individualized exercise “prescription” combining walking and resistance band training significantly reduced cognitive impairment and mental fatigue compared with usual care.

The results are “practice-changing,” colead author Karen Mustian, PhD, MPH, with the Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York, told Medscape Medical News. “Cancer care providers should consider incorporating structured, home-based exercise programs, such as walking and resistance band exercises, into routine chemotherapy care.”

The findings, published online in the Journal of the National Comprehensive Cancer Network (NCCN), reinforce recommendations by the NCCN that survivors with cancer-related cognitive dysfunction engage in routine physical activity.

“Many patients who need chemotherapy worry that they’ll experience ‘chemo brain,’” Lindsay L. Peterson, MD, medical oncologist at Washington University School of Medicine in St. Louis, who was not involved in this research, added in a statement.

This study offers “encouraging news” — exercise may be something patients can do to reduce their risk for cognitive impairment during chemotherapy, Peterson said.

Less Brain Fog, Mental Fatigue

Up to three-fourth of patients experience cancer-related cognitive impairment during treatment, which often occurs alongside mental fatigue. Research assessing the effects of exercise on cancer-related cognitive impairment during treatment is limited. To investigate, Mustian and colleagues enrolled 687 chemotherapy-naive adults with various cancers as well as Karnofsky performance status scores of at least 70 and no physical limitations, who were scheduled to start chemotherapy with cycles of 2, 3, or 4 weeks. Participants were randomly assigned to either the Exercise for Cancer Patients (EXCAP) intervention or usual care while undergoing chemotherapy. Developed by Mustian and colleagues, EXCAP is a 6-week, home-based, individually tailored walking and resistance band exercise program, introduced during a single in-person training session and reinforced through follow-up calls.

Before chemotherapy began, participants in both groups averaged roughly 2 miles of walking daily. After 6 weeks, patients in the EXCAP group largely maintained their activity levels, while those receiving usual care reduced their daily steps by about half. The exercise group also added resistance-band training three times per week for about 25 minutes per session, while the usual care group did no resistance exercises.

Cognitive function was measured using the Functional Assessment of Cancer Therapy-Cognitive Function questionnaire, and mental fatigue was assessed using the Multidimensional Fatigue Symptom Inventory. Blood samples were collected to measure key inflammatory markers.

Overall, across the study population, cognitive function declined and mental fatigue worsened during chemotherapy, but outcomes differed by treatment group and chemotherapy schedule.

Patients assigned to EXCAP and receiving chemotherapy on 2-week cycles fared best. More specifically, compared with usual care, EXCAP participants undergoing 2-week chemotherapy cycles reported less overall cognitive impairment (mean difference, 7.0; P = .04) and lower perceived cognitive impairment (mean difference, 4.1; P = .05). The exercisers also received fewer perceived comments from others about cognitive difficulties (mean difference, 0.6; P = .02) and reported less mental fatigue (-1.6; P < .01).

These benefits, however, were not observed in patients receiving 3- and 4-week chemotherapy cycles. In the 3-week cohort, there were no significant differences between groups in cognitive impairment (mean difference, 0.5; P = .85) or mental fatigue (mean difference, -0.2; P = .60).

“This was surprising,” Mustian said. “We really don’t know why the patients receiving chemo every 2 weeks were the ones to benefit the most. We do not have the capacity in our current data to answer that question for sure.”

However, Mustian speculated that it’s possible patients who receive their chemotherapy on differing weekly schedules receive different chemotherapy agents that have different toxicity and adverse-effect profiles.

For instance, chemotherapy among patients on a 2-week cycle may come with less severe acute adverse effects, which in turn may allow patients to remain more active throughout their treatments. On the other hand, chemotherapy among patients on a 3-week cycle may come with more severe acute adverse effects, which prevent them from staying as active.

“Once a person starts to lower their activity levels, it is more difficult to get back to their baseline levels and maintain them, and definitely harder to add anything additional to their activity routines,” Mustian said.

Immune Benefits?

Mustian and her team also assessed ties between exercise, cognitive impairment, and inflammation during chemotherapy. Previous work from the team showed that patients who received the EXCAP intervention exhibited higher immunocompetence.

In the current study, the researchers observed that a “healthy inflammatory response” — reflecting balanced increases in both proinflammatory and anti-inflammatory cytokines — was associated with better cognitive outcomes, suggesting that immune regulation may play a role in chemotherapy-related cognitive symptoms.

While chemotherapy may contribute to cognitive impairment by disrupting the body’s inflammatory and immune responses, “exercise may help keep these body systems working more normally, which could explain why patients who exercised had better thinking and less mental fatigue,” Mustian said.

Role for Exercise Oncology

Mustian suggested that oncologists consider referring patients receiving chemotherapy to exercise oncology specialists who can tailor programs for individual capabilities.

There are now > 2000 exercise oncology programs across the US. “Many of them provide both in-person and remote online opportunities for patients to access highly qualified exercise oncology professionals,” Mustian said.

Taking time to learn about community resources, developing a referral method of referral, or even providing patients with simple handouts on credible exercise programs and NCCN guidelines can help, Mustian added.

Peterson noted that, for many patients, maintaining the ability to think clearly, remember details, and stay mentally engaged during treatment is essential to preserving independence, continuing to work and care for their families, and sustaining overall quality of life.

“Interventions that are accessible and low cost, such as structured physical activity, give us a powerful opportunity not only to support long-term survivorship, but to help patients remain as cognitively sharp and mentally resilient as possible throughout treatment,” Peterson said in a statement.

This study was supported by the National Cancer Institute. Mustian and Peterson reported having no relevant disclosures.

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