AVAHO

Treatment with a GLP-1 receptor agonist (RA) may offer a survival advantage in patients with colon cancer and obesity.

In a real-world analysis of nearly 7000 patients with colon cancer, those taking a GLP-1 RA were less than half as likely to die within 5 years compared with those who weren’t on a GLP-1 drug.

The association between GLP-1 exposure and lower 5–year mortality in colon cancer was “robust” and appeared to be concentrated in patients with severe obesity (BMI ≥ 35), lead investigator Raphael E. Cuomo, PhD, with University of California San Diego, told this news organization.

The apparent protective effect “persisted after controlling for differences in disease severity and demographics, as well as differences in circulating carcinoembryonic antigen, a biomarker of disease aggressiveness,” Cuomo said.

The study was published online in Cancer Investigation.
 

Effects Beyond Glucose-Lowering

Colon cancer remains a major global cause of cancer-related deaths, and obesity is both a risk factor and a driver of worse outcomes.

Beyond regulating blood sugar, GLP-1 drugs reduce systemic inflammation, improve insulin sensitivity, and promote weight loss. Prior preclinical work has also suggested they may prevent cancer cell growth, trigger cancer cell death, and reshape the tumor microenvironment.

To investigate further, Cuomo analyzed electronic health records of 6871 patients diagnosed with primary colon cancer before 2019 — of which 103 had at least 1 documented prescription for a GLP-1 drug within 5 years of diagnosis.

Five–year mortality was significantly lower in GLP-1 RA users than in nonusers (15.5% vs 37.1%; P < .001). A significant reduction in 5–year mortality among GLP-1 RA users was evident in an unadjusted model (odds ratio [OR], 0.38; P < .001) and persisted in fully adjusted models (OR, 0.28; P < .001).

When stratified by BMI, the odds of 5-year mortality with GLP-1 use was reduced only in patients with Class II obesity (BMI ≥ 35: fully adjusted hazard ratio [HR], 0.051; P = .004). In this group, fully adjusted hazard ratios suggested markedly lower risk for death (HR, 0.07; P = .009).

Beyond mortality, GLP-1 users also experienced fewer late cardiovascular events and had fewer markers of advanced colon cancer progression in the final months of follow-up, “which suggests that GLP-1 drugs exert benefits through both oncologic and cardiometabolic pathways,” Cuomo told this news organization.
 

Intriguing and Promising — but Further Studies Needed

“To further study the potential of GLP-1 therapy as an adjunct to standard care in colon cancer, randomized trials should be conducted with stratification by BMI, diabetes status, and disease severity, with endpoints spanning overall and cancerspecific survival and major cardiovascular events,” Cuomo said.

“We also need prospective translational studies integrating dosing/timing, adherence, tumor genomics, and serial biomarkers (including ctDNA and metabolic panels) to elucidate mechanisms, assess the role of adiposity and insulin resistance, and identify the patient subgroups most likely to benefit,” he noted.

For now, GLP1 medications are an option in “eligible colon cancer patients with severe obesity or diabetes who meet standard metabolic indications,” Cuomo told this news organization.

Commenting on this study for this news organization, David Greenwald, MD, director of Clinical Gastroenterology and Endoscopy at Icahn School of Medicine at Mount Sinai Hospital in New York City, noted “other studies have showed a lower risk of developing colorectal cancer in the first place and then improved survival.”

Greenwald cited a recent study that found people with diabetes who took GLP-1 RAs had a 44% lower risk of developing colorectal cancer than those who took insulin, and a 25% lower risk than those who took metformin.

The effects of GLP-1s in colon cancer are “very intriguing and very promising but more research is needed to confirm whether this is really true and the mechanisms behind it,” said Greenwald.

In terms of the lowering risk of developing colorectal cancer, “probably first and foremost is that the drugs are really effective in promoting weight loss. And if you can reduce obesity in the population, you do all sorts of good things — reduce diabetes, reduce heart disease, and maybe reduce colorectal cancer,” Greenwald said.

This study had no specific funding. Cuomo and Greenwald had no relevant disclosures.

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

Treatment with a GLP-1 receptor agonist (RA) may offer a survival advantage in patients with colon cancer and obesity.

In a real-world analysis of nearly 7000 patients with colon cancer, those taking a GLP-1 RA were less than half as likely to die within 5 years compared with those who weren’t on a GLP-1 drug.

The association between GLP-1 exposure and lower 5–year mortality in colon cancer was “robust” and appeared to be concentrated in patients with severe obesity (BMI ≥ 35), lead investigator Raphael E. Cuomo, PhD, with University of California San Diego, told this news organization.

The apparent protective effect “persisted after controlling for differences in disease severity and demographics, as well as differences in circulating carcinoembryonic antigen, a biomarker of disease aggressiveness,” Cuomo said.

The study was published online in Cancer Investigation.
 

Effects Beyond Glucose-Lowering

Colon cancer remains a major global cause of cancer-related deaths, and obesity is both a risk factor and a driver of worse outcomes.

Beyond regulating blood sugar, GLP-1 drugs reduce systemic inflammation, improve insulin sensitivity, and promote weight loss. Prior preclinical work has also suggested they may prevent cancer cell growth, trigger cancer cell death, and reshape the tumor microenvironment.

To investigate further, Cuomo analyzed electronic health records of 6871 patients diagnosed with primary colon cancer before 2019 — of which 103 had at least 1 documented prescription for a GLP-1 drug within 5 years of diagnosis.

Five–year mortality was significantly lower in GLP-1 RA users than in nonusers (15.5% vs 37.1%; P < .001). A significant reduction in 5–year mortality among GLP-1 RA users was evident in an unadjusted model (odds ratio [OR], 0.38; P < .001) and persisted in fully adjusted models (OR, 0.28; P < .001).

When stratified by BMI, the odds of 5-year mortality with GLP-1 use was reduced only in patients with Class II obesity (BMI ≥ 35: fully adjusted hazard ratio [HR], 0.051; P = .004). In this group, fully adjusted hazard ratios suggested markedly lower risk for death (HR, 0.07; P = .009).

Beyond mortality, GLP-1 users also experienced fewer late cardiovascular events and had fewer markers of advanced colon cancer progression in the final months of follow-up, “which suggests that GLP-1 drugs exert benefits through both oncologic and cardiometabolic pathways,” Cuomo told this news organization.
 

Intriguing and Promising — but Further Studies Needed

“To further study the potential of GLP-1 therapy as an adjunct to standard care in colon cancer, randomized trials should be conducted with stratification by BMI, diabetes status, and disease severity, with endpoints spanning overall and cancerspecific survival and major cardiovascular events,” Cuomo said.

“We also need prospective translational studies integrating dosing/timing, adherence, tumor genomics, and serial biomarkers (including ctDNA and metabolic panels) to elucidate mechanisms, assess the role of adiposity and insulin resistance, and identify the patient subgroups most likely to benefit,” he noted.

For now, GLP1 medications are an option in “eligible colon cancer patients with severe obesity or diabetes who meet standard metabolic indications,” Cuomo told this news organization.

Commenting on this study for this news organization, David Greenwald, MD, director of Clinical Gastroenterology and Endoscopy at Icahn School of Medicine at Mount Sinai Hospital in New York City, noted “other studies have showed a lower risk of developing colorectal cancer in the first place and then improved survival.”

Greenwald cited a recent study that found people with diabetes who took GLP-1 RAs had a 44% lower risk of developing colorectal cancer than those who took insulin, and a 25% lower risk than those who took metformin.

The effects of GLP-1s in colon cancer are “very intriguing and very promising but more research is needed to confirm whether this is really true and the mechanisms behind it,” said Greenwald.

In terms of the lowering risk of developing colorectal cancer, “probably first and foremost is that the drugs are really effective in promoting weight loss. And if you can reduce obesity in the population, you do all sorts of good things — reduce diabetes, reduce heart disease, and maybe reduce colorectal cancer,” Greenwald said.

This study had no specific funding. Cuomo and Greenwald had no relevant disclosures.

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

Treatment with a GLP-1 receptor agonist (RA) may offer a survival advantage in patients with colon cancer and obesity.

In a real-world analysis of nearly 7000 patients with colon cancer, those taking a GLP-1 RA were less than half as likely to die within 5 years compared with those who weren’t on a GLP-1 drug.

The association between GLP-1 exposure and lower 5–year mortality in colon cancer was “robust” and appeared to be concentrated in patients with severe obesity (BMI ≥ 35), lead investigator Raphael E. Cuomo, PhD, with University of California San Diego, told this news organization.

The apparent protective effect “persisted after controlling for differences in disease severity and demographics, as well as differences in circulating carcinoembryonic antigen, a biomarker of disease aggressiveness,” Cuomo said.

The study was published online in Cancer Investigation.
 

Effects Beyond Glucose-Lowering

Colon cancer remains a major global cause of cancer-related deaths, and obesity is both a risk factor and a driver of worse outcomes.

Beyond regulating blood sugar, GLP-1 drugs reduce systemic inflammation, improve insulin sensitivity, and promote weight loss. Prior preclinical work has also suggested they may prevent cancer cell growth, trigger cancer cell death, and reshape the tumor microenvironment.

To investigate further, Cuomo analyzed electronic health records of 6871 patients diagnosed with primary colon cancer before 2019 — of which 103 had at least 1 documented prescription for a GLP-1 drug within 5 years of diagnosis.

Five–year mortality was significantly lower in GLP-1 RA users than in nonusers (15.5% vs 37.1%; P < .001). A significant reduction in 5–year mortality among GLP-1 RA users was evident in an unadjusted model (odds ratio [OR], 0.38; P < .001) and persisted in fully adjusted models (OR, 0.28; P < .001).

When stratified by BMI, the odds of 5-year mortality with GLP-1 use was reduced only in patients with Class II obesity (BMI ≥ 35: fully adjusted hazard ratio [HR], 0.051; P = .004). In this group, fully adjusted hazard ratios suggested markedly lower risk for death (HR, 0.07; P = .009).

Beyond mortality, GLP-1 users also experienced fewer late cardiovascular events and had fewer markers of advanced colon cancer progression in the final months of follow-up, “which suggests that GLP-1 drugs exert benefits through both oncologic and cardiometabolic pathways,” Cuomo told this news organization.
 

Intriguing and Promising — but Further Studies Needed

“To further study the potential of GLP-1 therapy as an adjunct to standard care in colon cancer, randomized trials should be conducted with stratification by BMI, diabetes status, and disease severity, with endpoints spanning overall and cancerspecific survival and major cardiovascular events,” Cuomo said.

“We also need prospective translational studies integrating dosing/timing, adherence, tumor genomics, and serial biomarkers (including ctDNA and metabolic panels) to elucidate mechanisms, assess the role of adiposity and insulin resistance, and identify the patient subgroups most likely to benefit,” he noted.

For now, GLP1 medications are an option in “eligible colon cancer patients with severe obesity or diabetes who meet standard metabolic indications,” Cuomo told this news organization.

Commenting on this study for this news organization, David Greenwald, MD, director of Clinical Gastroenterology and Endoscopy at Icahn School of Medicine at Mount Sinai Hospital in New York City, noted “other studies have showed a lower risk of developing colorectal cancer in the first place and then improved survival.”

Greenwald cited a recent study that found people with diabetes who took GLP-1 RAs had a 44% lower risk of developing colorectal cancer than those who took insulin, and a 25% lower risk than those who took metformin.

The effects of GLP-1s in colon cancer are “very intriguing and very promising but more research is needed to confirm whether this is really true and the mechanisms behind it,” said Greenwald.

In terms of the lowering risk of developing colorectal cancer, “probably first and foremost is that the drugs are really effective in promoting weight loss. And if you can reduce obesity in the population, you do all sorts of good things — reduce diabetes, reduce heart disease, and maybe reduce colorectal cancer,” Greenwald said.

This study had no specific funding. Cuomo and Greenwald had no relevant disclosures.

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

Recent studies have cited an alarming increase in early-onset colorectal cancer (CRC) rates, raising concern among gastroenterologists, public health experts, and patients alike. Approximately 10% of CRC cases now occur in those under age 50, and that proportion continues to grow. Between 2000 and 2016, colon cancer rose by 13% and rectal cancer by 16% among those aged 40–49.

According to recently published data from the Surveillance, Epidemiology and End Results Program, between 2019 and 2022, CRC incidence among patients aged 45–49 rose by approximately 12% per year. 
 

A Potential Bacterial Connection

What accounts for this disturbing spike? A research group from the University of California, San Diego, may have uncovered part of the answer.

In their study of 981 CRC genomes, most carried mutations suggestive of prior exposure to colibactin, a toxin produced by certain Escherichia coli (E coli) strains. Patients with extremely early-onset CRC (aged < 40 years) were 3 times more likely to have colibactin-suggestive mutations than patients older than 70. Crucially, colonic exposure to colibactin was linked to an adenomatous polyposis coli driver mutation. 

These findings suggest that colibactin-induced injury in the gut microbiome may accelerate cancer development in some individuals. Environmental factors may contribute to the rise in early-onset CRC as well, such as consuming red meats, carcinogens from grilling, and processed meats and other highly processed foods; low fiber intake; lack of fruits and vegetables; drinking alcohol; lack of exercise; obesity; and colibactin exposure. 

In this video, we will take a closer look at how E coli and colibactin may increase CRC risk.
 

Bacteria’s Cancer-Causing Properties

The idea that bacteria has cancer-causing properties isn’t new. In the 1970s, researchers linked Streptococcus bovis type 1 (now called Streptococcus gallolyticus) to CRC in a subset of patients with bacterial endocarditis stemming from right-sided colon cancer. Similarly, Helicobacter pylori infection has long been associated with increased gastric cancer risk. 

Today, E coli infection is emerging as another possible contributor to CRC, especially via certain pathogenic strains containing the polyketide synthase (pks) genomic island, which encodes the colibactin and is sometimes present in the colon mucosa of patients with CRC.
 

Colibactin and DNA Damage

Colibactin-producing pks+ E coli strains can cause DNA double-strand breaks, one pathway to carcinogenesis. In animal studies, pks+ E coli strains have been linked to both increased risk for CRC and CRC progression.

In an important study published in Nature, Pleguezuelos-Manzano and colleagues repeatedly exposed intestinal organoids to pks+ E coli over 5 months and then performed whole genome sequencing. The result was a concerning potential for short insertions and deletions and single–base substitutions. 

The authors concluded that their “study describes the distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island.”

Other E coli virulence factors may also contribute. For example, alpha-hemolysin may downregulate DNA mismatch repair proteins. In other words, E coli is probably just a contributing factor for the development of CRC, not the sole cause. 
 

Biofilms and Inflammation

Previous studies have associated dense bacterial biofilms, particularly antibiotic-resistant strains, with CRC. This raises the possibility that widespread antibiotic overuse could predispose certain individuals to CRC development.

Biofilms normally separate the colon mucosal epithelium from bacteria and are essential for protecting against inflammation. In a 2018 study in Science, Dejea and colleagues concluded that “tumor-prone mice colonized with E coli (expressing colibactin), and enterotoxigenic B fragilis showed increased interleukin-17 in the colon and DNA damage in colonic epithelium with faster tumor onset and greater mortality, compared to mice with either bacteria strain alone. These data suggest an unexpected link between early neoplasia of the colon and tumorigenic bacteria.” 

Additional research revealed that E coli can create a pro-carcinogenic environment by stimulating mucosal inflammation, hindering DNA and mismatch repair mechanisms, and altering immune responses.
 

Dysbiosis and Diet

Colibactin can also drive dysbiosis and imbalance in bacteria in the colon, which fuels inflammation and disrupts mucosal barrier integrity. This creates a vicious cycle in which chronic inflammation can further drive additional mucus deterioration and dysbiosis.

In mouse models where the colon mucosal barrier is damaged with dextrin sulfate sodium (DSS), pks+ E coli gains better access to colon epithelium, causes injury, and can even lead to chronic colitis. Colibactin can also hinder epithelial recovery after DSS treatment. 

Diet plays a central role in this process. Low fiber consumption can disrupt the barrier between the colon mucus layer and the colon’s exterior layer where bacteria live. A traditional Western diet may bolster bacteria that degrade the mucus layer when the bacteria consume the glycosylated portion as an energy source.

Fortunately, diet is modifiable. High–fiber diets (ideally 25-30 g/d) boost short–chain fatty acids in the colon. This is important because short-chain fatty acids can decrease intercellular pH and impede Enterobacteriaceae replication, yet another reason why we should encourage patients to eat a diet high in vegetables, fruits, and [green] salads. 
 

Two Types of Bacterial Drivers 

There appear to be two broad types of bacteria associated with CRC development. It’s been hypothesized that there are “driver” bacteria that might initiate the development of CRC, possibly by creating oxidative stress and causing DNA breaks. Several potential pathogenic bacteria have been identified, including E coli, Enterococcus faecalis, and Bacteroides fragilis. Unfortunately, there are also bacteria such as Fusobacterium species and Streptococcus gallolyticus with the potential to alter intestinal permeability, resulting in downstream effects that can allow colon cancers to expand. Fusobacterium species and Streptococcus gallolyticus have the potential to cause DNA double–strand breaks in the intestine, which can produce chromosomal precariousness. 

These secondary bacteria can also lead to DNA epigenetic changes and gene mutations. However, it should be emphasized that “the direct causation of imprinted DNA changes resulting from a direct interaction between bacteria and host cells is not so far established.”

E coli produces compounds called cyclomodulins, which can cause DNA breaks and potentially trigger cell cycle arrest and even cell death through activation of the DNA damage checkpoint pathway. The DNA damage checkpoint pathway is a cellular signaling network that helps detect DNA lesions and allows for genetic stability by stopping growth to allow for repair and simulating cell survival or apoptosis. A key cyclomodulin that E coli makes is colibactin, produced by the pks locus. Other cyclomodulins include cytolethal distending toxin, cytotoxic necrotizing factor, and cycle-inhibiting factor. 

Previous research has shown that E coli is the only culturable bacteria found near CRC. A groundbreaking 1998 study employing PCR technology found E coli in 60% of colon polyp adenomas and an alarming 77% of CRC biopsies. 

E coli’s capability to downregulate essential DNA mismatch repair proteins has been implicated in colorectal carcinogenesis. Interestingly, when the genetic region responsible for producing colibactin is deleted in animals, the bacteria aren’t able to promote cancer.

Mechanistically, colibactin causes double-stranded DNA breaks, eukaryotic cell cycle arrest, and chromosome abnormalities. It also alkylates DNA. This occurs when the cyclopropane ring of colibactin interacts with the N3 position of adenine in DNA, forming a covalent bond and creating a DNA adduct. DNA adducts occur when a chemical moiety from an environmental or dietary source binds to DNA base. Colibactin can cause DNA interstrand cross-links to form via alkalization of adenine residues on opposing DNA strands, a crucial step in DNA damage. DNA adducts can occur through carcinogens in N-nitroso compounds, such as in processed meats and in polycyclic aromatic hydrocarbons found in cigarette smoke. Colibactin-induced damage may also stimulate the senescence–associated secretory phenotype pathway, increasing proinflammatory cytokines.
 

E coli and Inflammatory Bowel Disease 

E coli, the primary colibactin producer in the human intestinal microbiome, is found at higher bacterial percentages in the microbiomes of patients with inflammatory bowel disease (IBD). In a study by Dubinsky and colleagues, “the medium relative levels of colibactin–encoding E. coli were about threefold higher in IBD.”

Researchers have also postulated that antibiotics and microbiome dysbiosis may create conditions that allow colibactin–producing bacteria to overpopulate.
 

Future Directions

Not every patient with CRC carries a colorectal mutational signature, but these findings underscore the need for continued vigilance and prevention. 

From a public health standpoint, our advice remains consistent: Promote high-fiber diets with more vegetables and less red meat; avoid highly processed foods; avoid alcohol; encourage exercise; and address overweight and obesity. Our goal is to create the best possible colon environment to prevent DNA damage from bacterial and environmental carcinogens.

In the future, we need more research to clarify exactly how E coli and colibactin increase early–onset CRC risk and whether antibiotics and dysbiosis facilitate their ability to damage the DNA of colon mucosa. It’s still unclear why younger patients are at greater risk. In time, we may be able to screen for colibactin–producing bacteria such as E coli and manipulate the fecal microbiome to prevent damage. 

A recent mouse study in Nature by Jans and colleagues suggests it might be possible to block bacterial adhesion and hopefully mitigate damage caused by colibactin. With continued work, colibactin–targeted strategies could become a part of CRC prevention.

Benjamin H. Levy III, MD, is a gastroenterologist at the University of Chicago. In 2017, Levy, a previous Fulbright Fellow in France, also started a gastroenterology clinic for refugees resettling in Chicago. His clinical projects focus on the development of colorectal cancer screening campaigns. Levy, who gave a TEDx Talk about building health education campaigns using music and concerts, organizes "Tune It Up: A Concert To Raise Colorectal Cancer Awareness" with the American College of Gastroenterology (ACG). He frequently publishes on a variety of gastroenterology topics and serves on ACG’s Public Relations Committee and FDA-Related Matters Committee.

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

Recent studies have cited an alarming increase in early-onset colorectal cancer (CRC) rates, raising concern among gastroenterologists, public health experts, and patients alike. Approximately 10% of CRC cases now occur in those under age 50, and that proportion continues to grow. Between 2000 and 2016, colon cancer rose by 13% and rectal cancer by 16% among those aged 40–49.

According to recently published data from the Surveillance, Epidemiology and End Results Program, between 2019 and 2022, CRC incidence among patients aged 45–49 rose by approximately 12% per year. 
 

A Potential Bacterial Connection

What accounts for this disturbing spike? A research group from the University of California, San Diego, may have uncovered part of the answer.

In their study of 981 CRC genomes, most carried mutations suggestive of prior exposure to colibactin, a toxin produced by certain Escherichia coli (E coli) strains. Patients with extremely early-onset CRC (aged < 40 years) were 3 times more likely to have colibactin-suggestive mutations than patients older than 70. Crucially, colonic exposure to colibactin was linked to an adenomatous polyposis coli driver mutation. 

These findings suggest that colibactin-induced injury in the gut microbiome may accelerate cancer development in some individuals. Environmental factors may contribute to the rise in early-onset CRC as well, such as consuming red meats, carcinogens from grilling, and processed meats and other highly processed foods; low fiber intake; lack of fruits and vegetables; drinking alcohol; lack of exercise; obesity; and colibactin exposure. 

In this video, we will take a closer look at how E coli and colibactin may increase CRC risk.
 

Bacteria’s Cancer-Causing Properties

The idea that bacteria has cancer-causing properties isn’t new. In the 1970s, researchers linked Streptococcus bovis type 1 (now called Streptococcus gallolyticus) to CRC in a subset of patients with bacterial endocarditis stemming from right-sided colon cancer. Similarly, Helicobacter pylori infection has long been associated with increased gastric cancer risk. 

Today, E coli infection is emerging as another possible contributor to CRC, especially via certain pathogenic strains containing the polyketide synthase (pks) genomic island, which encodes the colibactin and is sometimes present in the colon mucosa of patients with CRC.
 

Colibactin and DNA Damage

Colibactin-producing pks+ E coli strains can cause DNA double-strand breaks, one pathway to carcinogenesis. In animal studies, pks+ E coli strains have been linked to both increased risk for CRC and CRC progression.

In an important study published in Nature, Pleguezuelos-Manzano and colleagues repeatedly exposed intestinal organoids to pks+ E coli over 5 months and then performed whole genome sequencing. The result was a concerning potential for short insertions and deletions and single–base substitutions. 

The authors concluded that their “study describes the distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island.”

Other E coli virulence factors may also contribute. For example, alpha-hemolysin may downregulate DNA mismatch repair proteins. In other words, E coli is probably just a contributing factor for the development of CRC, not the sole cause. 
 

Biofilms and Inflammation

Previous studies have associated dense bacterial biofilms, particularly antibiotic-resistant strains, with CRC. This raises the possibility that widespread antibiotic overuse could predispose certain individuals to CRC development.

Biofilms normally separate the colon mucosal epithelium from bacteria and are essential for protecting against inflammation. In a 2018 study in Science, Dejea and colleagues concluded that “tumor-prone mice colonized with E coli (expressing colibactin), and enterotoxigenic B fragilis showed increased interleukin-17 in the colon and DNA damage in colonic epithelium with faster tumor onset and greater mortality, compared to mice with either bacteria strain alone. These data suggest an unexpected link between early neoplasia of the colon and tumorigenic bacteria.” 

Additional research revealed that E coli can create a pro-carcinogenic environment by stimulating mucosal inflammation, hindering DNA and mismatch repair mechanisms, and altering immune responses.
 

Dysbiosis and Diet

Colibactin can also drive dysbiosis and imbalance in bacteria in the colon, which fuels inflammation and disrupts mucosal barrier integrity. This creates a vicious cycle in which chronic inflammation can further drive additional mucus deterioration and dysbiosis.

In mouse models where the colon mucosal barrier is damaged with dextrin sulfate sodium (DSS), pks+ E coli gains better access to colon epithelium, causes injury, and can even lead to chronic colitis. Colibactin can also hinder epithelial recovery after DSS treatment. 

Diet plays a central role in this process. Low fiber consumption can disrupt the barrier between the colon mucus layer and the colon’s exterior layer where bacteria live. A traditional Western diet may bolster bacteria that degrade the mucus layer when the bacteria consume the glycosylated portion as an energy source.

Fortunately, diet is modifiable. High–fiber diets (ideally 25-30 g/d) boost short–chain fatty acids in the colon. This is important because short-chain fatty acids can decrease intercellular pH and impede Enterobacteriaceae replication, yet another reason why we should encourage patients to eat a diet high in vegetables, fruits, and [green] salads. 
 

Two Types of Bacterial Drivers 

There appear to be two broad types of bacteria associated with CRC development. It’s been hypothesized that there are “driver” bacteria that might initiate the development of CRC, possibly by creating oxidative stress and causing DNA breaks. Several potential pathogenic bacteria have been identified, including E coli, Enterococcus faecalis, and Bacteroides fragilis. Unfortunately, there are also bacteria such as Fusobacterium species and Streptococcus gallolyticus with the potential to alter intestinal permeability, resulting in downstream effects that can allow colon cancers to expand. Fusobacterium species and Streptococcus gallolyticus have the potential to cause DNA double–strand breaks in the intestine, which can produce chromosomal precariousness. 

These secondary bacteria can also lead to DNA epigenetic changes and gene mutations. However, it should be emphasized that “the direct causation of imprinted DNA changes resulting from a direct interaction between bacteria and host cells is not so far established.”

E coli produces compounds called cyclomodulins, which can cause DNA breaks and potentially trigger cell cycle arrest and even cell death through activation of the DNA damage checkpoint pathway. The DNA damage checkpoint pathway is a cellular signaling network that helps detect DNA lesions and allows for genetic stability by stopping growth to allow for repair and simulating cell survival or apoptosis. A key cyclomodulin that E coli makes is colibactin, produced by the pks locus. Other cyclomodulins include cytolethal distending toxin, cytotoxic necrotizing factor, and cycle-inhibiting factor. 

Previous research has shown that E coli is the only culturable bacteria found near CRC. A groundbreaking 1998 study employing PCR technology found E coli in 60% of colon polyp adenomas and an alarming 77% of CRC biopsies. 

E coli’s capability to downregulate essential DNA mismatch repair proteins has been implicated in colorectal carcinogenesis. Interestingly, when the genetic region responsible for producing colibactin is deleted in animals, the bacteria aren’t able to promote cancer.

Mechanistically, colibactin causes double-stranded DNA breaks, eukaryotic cell cycle arrest, and chromosome abnormalities. It also alkylates DNA. This occurs when the cyclopropane ring of colibactin interacts with the N3 position of adenine in DNA, forming a covalent bond and creating a DNA adduct. DNA adducts occur when a chemical moiety from an environmental or dietary source binds to DNA base. Colibactin can cause DNA interstrand cross-links to form via alkalization of adenine residues on opposing DNA strands, a crucial step in DNA damage. DNA adducts can occur through carcinogens in N-nitroso compounds, such as in processed meats and in polycyclic aromatic hydrocarbons found in cigarette smoke. Colibactin-induced damage may also stimulate the senescence–associated secretory phenotype pathway, increasing proinflammatory cytokines.
 

E coli and Inflammatory Bowel Disease 

E coli, the primary colibactin producer in the human intestinal microbiome, is found at higher bacterial percentages in the microbiomes of patients with inflammatory bowel disease (IBD). In a study by Dubinsky and colleagues, “the medium relative levels of colibactin–encoding E. coli were about threefold higher in IBD.”

Researchers have also postulated that antibiotics and microbiome dysbiosis may create conditions that allow colibactin–producing bacteria to overpopulate.
 

Future Directions

Not every patient with CRC carries a colorectal mutational signature, but these findings underscore the need for continued vigilance and prevention. 

From a public health standpoint, our advice remains consistent: Promote high-fiber diets with more vegetables and less red meat; avoid highly processed foods; avoid alcohol; encourage exercise; and address overweight and obesity. Our goal is to create the best possible colon environment to prevent DNA damage from bacterial and environmental carcinogens.

In the future, we need more research to clarify exactly how E coli and colibactin increase early–onset CRC risk and whether antibiotics and dysbiosis facilitate their ability to damage the DNA of colon mucosa. It’s still unclear why younger patients are at greater risk. In time, we may be able to screen for colibactin–producing bacteria such as E coli and manipulate the fecal microbiome to prevent damage. 

A recent mouse study in Nature by Jans and colleagues suggests it might be possible to block bacterial adhesion and hopefully mitigate damage caused by colibactin. With continued work, colibactin–targeted strategies could become a part of CRC prevention.

Benjamin H. Levy III, MD, is a gastroenterologist at the University of Chicago. In 2017, Levy, a previous Fulbright Fellow in France, also started a gastroenterology clinic for refugees resettling in Chicago. His clinical projects focus on the development of colorectal cancer screening campaigns. Levy, who gave a TEDx Talk about building health education campaigns using music and concerts, organizes "Tune It Up: A Concert To Raise Colorectal Cancer Awareness" with the American College of Gastroenterology (ACG). He frequently publishes on a variety of gastroenterology topics and serves on ACG’s Public Relations Committee and FDA-Related Matters Committee.

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

Recent studies have cited an alarming increase in early-onset colorectal cancer (CRC) rates, raising concern among gastroenterologists, public health experts, and patients alike. Approximately 10% of CRC cases now occur in those under age 50, and that proportion continues to grow. Between 2000 and 2016, colon cancer rose by 13% and rectal cancer by 16% among those aged 40–49.

According to recently published data from the Surveillance, Epidemiology and End Results Program, between 2019 and 2022, CRC incidence among patients aged 45–49 rose by approximately 12% per year. 
 

A Potential Bacterial Connection

What accounts for this disturbing spike? A research group from the University of California, San Diego, may have uncovered part of the answer.

In their study of 981 CRC genomes, most carried mutations suggestive of prior exposure to colibactin, a toxin produced by certain Escherichia coli (E coli) strains. Patients with extremely early-onset CRC (aged < 40 years) were 3 times more likely to have colibactin-suggestive mutations than patients older than 70. Crucially, colonic exposure to colibactin was linked to an adenomatous polyposis coli driver mutation. 

These findings suggest that colibactin-induced injury in the gut microbiome may accelerate cancer development in some individuals. Environmental factors may contribute to the rise in early-onset CRC as well, such as consuming red meats, carcinogens from grilling, and processed meats and other highly processed foods; low fiber intake; lack of fruits and vegetables; drinking alcohol; lack of exercise; obesity; and colibactin exposure. 

In this video, we will take a closer look at how E coli and colibactin may increase CRC risk.
 

Bacteria’s Cancer-Causing Properties

The idea that bacteria has cancer-causing properties isn’t new. In the 1970s, researchers linked Streptococcus bovis type 1 (now called Streptococcus gallolyticus) to CRC in a subset of patients with bacterial endocarditis stemming from right-sided colon cancer. Similarly, Helicobacter pylori infection has long been associated with increased gastric cancer risk. 

Today, E coli infection is emerging as another possible contributor to CRC, especially via certain pathogenic strains containing the polyketide synthase (pks) genomic island, which encodes the colibactin and is sometimes present in the colon mucosa of patients with CRC.
 

Colibactin and DNA Damage

Colibactin-producing pks+ E coli strains can cause DNA double-strand breaks, one pathway to carcinogenesis. In animal studies, pks+ E coli strains have been linked to both increased risk for CRC and CRC progression.

In an important study published in Nature, Pleguezuelos-Manzano and colleagues repeatedly exposed intestinal organoids to pks+ E coli over 5 months and then performed whole genome sequencing. The result was a concerning potential for short insertions and deletions and single–base substitutions. 

The authors concluded that their “study describes the distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island.”

Other E coli virulence factors may also contribute. For example, alpha-hemolysin may downregulate DNA mismatch repair proteins. In other words, E coli is probably just a contributing factor for the development of CRC, not the sole cause. 
 

Biofilms and Inflammation

Previous studies have associated dense bacterial biofilms, particularly antibiotic-resistant strains, with CRC. This raises the possibility that widespread antibiotic overuse could predispose certain individuals to CRC development.

Biofilms normally separate the colon mucosal epithelium from bacteria and are essential for protecting against inflammation. In a 2018 study in Science, Dejea and colleagues concluded that “tumor-prone mice colonized with E coli (expressing colibactin), and enterotoxigenic B fragilis showed increased interleukin-17 in the colon and DNA damage in colonic epithelium with faster tumor onset and greater mortality, compared to mice with either bacteria strain alone. These data suggest an unexpected link between early neoplasia of the colon and tumorigenic bacteria.” 

Additional research revealed that E coli can create a pro-carcinogenic environment by stimulating mucosal inflammation, hindering DNA and mismatch repair mechanisms, and altering immune responses.
 

Dysbiosis and Diet

Colibactin can also drive dysbiosis and imbalance in bacteria in the colon, which fuels inflammation and disrupts mucosal barrier integrity. This creates a vicious cycle in which chronic inflammation can further drive additional mucus deterioration and dysbiosis.

In mouse models where the colon mucosal barrier is damaged with dextrin sulfate sodium (DSS), pks+ E coli gains better access to colon epithelium, causes injury, and can even lead to chronic colitis. Colibactin can also hinder epithelial recovery after DSS treatment. 

Diet plays a central role in this process. Low fiber consumption can disrupt the barrier between the colon mucus layer and the colon’s exterior layer where bacteria live. A traditional Western diet may bolster bacteria that degrade the mucus layer when the bacteria consume the glycosylated portion as an energy source.

Fortunately, diet is modifiable. High–fiber diets (ideally 25-30 g/d) boost short–chain fatty acids in the colon. This is important because short-chain fatty acids can decrease intercellular pH and impede Enterobacteriaceae replication, yet another reason why we should encourage patients to eat a diet high in vegetables, fruits, and [green] salads. 
 

Two Types of Bacterial Drivers 

There appear to be two broad types of bacteria associated with CRC development. It’s been hypothesized that there are “driver” bacteria that might initiate the development of CRC, possibly by creating oxidative stress and causing DNA breaks. Several potential pathogenic bacteria have been identified, including E coli, Enterococcus faecalis, and Bacteroides fragilis. Unfortunately, there are also bacteria such as Fusobacterium species and Streptococcus gallolyticus with the potential to alter intestinal permeability, resulting in downstream effects that can allow colon cancers to expand. Fusobacterium species and Streptococcus gallolyticus have the potential to cause DNA double–strand breaks in the intestine, which can produce chromosomal precariousness. 

These secondary bacteria can also lead to DNA epigenetic changes and gene mutations. However, it should be emphasized that “the direct causation of imprinted DNA changes resulting from a direct interaction between bacteria and host cells is not so far established.”

E coli produces compounds called cyclomodulins, which can cause DNA breaks and potentially trigger cell cycle arrest and even cell death through activation of the DNA damage checkpoint pathway. The DNA damage checkpoint pathway is a cellular signaling network that helps detect DNA lesions and allows for genetic stability by stopping growth to allow for repair and simulating cell survival or apoptosis. A key cyclomodulin that E coli makes is colibactin, produced by the pks locus. Other cyclomodulins include cytolethal distending toxin, cytotoxic necrotizing factor, and cycle-inhibiting factor. 

Previous research has shown that E coli is the only culturable bacteria found near CRC. A groundbreaking 1998 study employing PCR technology found E coli in 60% of colon polyp adenomas and an alarming 77% of CRC biopsies. 

E coli’s capability to downregulate essential DNA mismatch repair proteins has been implicated in colorectal carcinogenesis. Interestingly, when the genetic region responsible for producing colibactin is deleted in animals, the bacteria aren’t able to promote cancer.

Mechanistically, colibactin causes double-stranded DNA breaks, eukaryotic cell cycle arrest, and chromosome abnormalities. It also alkylates DNA. This occurs when the cyclopropane ring of colibactin interacts with the N3 position of adenine in DNA, forming a covalent bond and creating a DNA adduct. DNA adducts occur when a chemical moiety from an environmental or dietary source binds to DNA base. Colibactin can cause DNA interstrand cross-links to form via alkalization of adenine residues on opposing DNA strands, a crucial step in DNA damage. DNA adducts can occur through carcinogens in N-nitroso compounds, such as in processed meats and in polycyclic aromatic hydrocarbons found in cigarette smoke. Colibactin-induced damage may also stimulate the senescence–associated secretory phenotype pathway, increasing proinflammatory cytokines.
 

E coli and Inflammatory Bowel Disease 

E coli, the primary colibactin producer in the human intestinal microbiome, is found at higher bacterial percentages in the microbiomes of patients with inflammatory bowel disease (IBD). In a study by Dubinsky and colleagues, “the medium relative levels of colibactin–encoding E. coli were about threefold higher in IBD.”

Researchers have also postulated that antibiotics and microbiome dysbiosis may create conditions that allow colibactin–producing bacteria to overpopulate.
 

Future Directions

Not every patient with CRC carries a colorectal mutational signature, but these findings underscore the need for continued vigilance and prevention. 

From a public health standpoint, our advice remains consistent: Promote high-fiber diets with more vegetables and less red meat; avoid highly processed foods; avoid alcohol; encourage exercise; and address overweight and obesity. Our goal is to create the best possible colon environment to prevent DNA damage from bacterial and environmental carcinogens.

In the future, we need more research to clarify exactly how E coli and colibactin increase early–onset CRC risk and whether antibiotics and dysbiosis facilitate their ability to damage the DNA of colon mucosa. It’s still unclear why younger patients are at greater risk. In time, we may be able to screen for colibactin–producing bacteria such as E coli and manipulate the fecal microbiome to prevent damage. 

A recent mouse study in Nature by Jans and colleagues suggests it might be possible to block bacterial adhesion and hopefully mitigate damage caused by colibactin. With continued work, colibactin–targeted strategies could become a part of CRC prevention.

Benjamin H. Levy III, MD, is a gastroenterologist at the University of Chicago. In 2017, Levy, a previous Fulbright Fellow in France, also started a gastroenterology clinic for refugees resettling in Chicago. His clinical projects focus on the development of colorectal cancer screening campaigns. Levy, who gave a TEDx Talk about building health education campaigns using music and concerts, organizes "Tune It Up: A Concert To Raise Colorectal Cancer Awareness" with the American College of Gastroenterology (ACG). He frequently publishes on a variety of gastroenterology topics and serves on ACG’s Public Relations Committee and FDA-Related Matters Committee.

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

TOPLINE: 

Electronic health records patient portal signup rates were lower among vulnerable oncology patients at 64%, compared with 87% in nonvulnerable patients. Once adopted, both groups showed comparable meaningful use patterns. Non-English language emerged as a significant barrier to initial portal signup.

METHODOLOGY:

• Portal usage disparities persist across age, race, ethnicity, and health literacy groups, particularly at the initial signup stage.
• Oral anticancer medications represent a new frontier in cancer therapy, offering convenience but requiring high medication adherence and vigilant self-monitoring of symptoms.
• Researchers conducted a retrospective analysis of 280 patients who had recently started taking an oral anticancer medication at Tufts Medical Center, Boston, between October 2022 and March 2024.
• Vulnerability criteria included having an age ≥ 75 years, a non-English language preference, or subsidized insurance (Medicaid only or Medicare with Medicaid as secondary insurance).
• Analysis defined active portal use as having at least one message, while meaningful use was characterized by patient-provider bidirectional messaging.
• Portal messaging proxy use was determined through message content screening, particularly when non-English speaking patients sent messages in English or when message content indicated proxy use.

TAKEAWAY:

• Among the study population, 56% met vulnerability criteria, with 20% aged at least 75 years, 26% having a non-English language, and 30% having subsidized insurance.
• Non-English language was associated with lower portal signup rates (odds ratio [OR], 0.27; 95% CI, 0.15-0.49; P < .0001), whereas age and insurance status showed no significant association.
• Proxy messaging was utilized by 17% of vulnerable patients who signed up for the portal compared to 2.8% of nonvulnerable patients.
• Among patients who signed up for the portal, 31% used it specifically for communication about oral anticancer medications.

IN PRACTICE:

“Although patient portal signup was lower among vulnerable patients, once adopted, vulnerable patients demonstrated comparable meaningful use and greater proxy engagement. Fostering patient portal adoption requires a targeted approach with patient navigation and patient proxy engagement,” wrote the authors of the study.

SOURCE:

The study was led by Yenong Cao, MD, PhD, Boston Medical Center, Boston. It was published online on November 19 in JCO Oncology Practice.

LIMITATIONS:

The study was limited by its retrospective single-center design at Tufts Medical Center, which serves a large number of non-English, Chinese-speaking patients, potentially affecting the generalizability of findings. Additionally, formal proxy login identification was lacking in the Epic documentation during the study period, which may have led to underestimation of proxy portal use.

DISCLOSURES:

Cao reported being employed at Tufts Medical Center. Johnson Ching, PharmD, CSP, disclosed being employed at Duke University Hospital and SpeciaRx, LLC. Additional disclosures are noted in the original article. 

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: 

Electronic health records patient portal signup rates were lower among vulnerable oncology patients at 64%, compared with 87% in nonvulnerable patients. Once adopted, both groups showed comparable meaningful use patterns. Non-English language emerged as a significant barrier to initial portal signup.

METHODOLOGY:

• Portal usage disparities persist across age, race, ethnicity, and health literacy groups, particularly at the initial signup stage.
• Oral anticancer medications represent a new frontier in cancer therapy, offering convenience but requiring high medication adherence and vigilant self-monitoring of symptoms.
• Researchers conducted a retrospective analysis of 280 patients who had recently started taking an oral anticancer medication at Tufts Medical Center, Boston, between October 2022 and March 2024.
• Vulnerability criteria included having an age ≥ 75 years, a non-English language preference, or subsidized insurance (Medicaid only or Medicare with Medicaid as secondary insurance).
• Analysis defined active portal use as having at least one message, while meaningful use was characterized by patient-provider bidirectional messaging.
• Portal messaging proxy use was determined through message content screening, particularly when non-English speaking patients sent messages in English or when message content indicated proxy use.

TAKEAWAY:

• Among the study population, 56% met vulnerability criteria, with 20% aged at least 75 years, 26% having a non-English language, and 30% having subsidized insurance.
• Non-English language was associated with lower portal signup rates (odds ratio [OR], 0.27; 95% CI, 0.15-0.49; P < .0001), whereas age and insurance status showed no significant association.
• Proxy messaging was utilized by 17% of vulnerable patients who signed up for the portal compared to 2.8% of nonvulnerable patients.
• Among patients who signed up for the portal, 31% used it specifically for communication about oral anticancer medications.

IN PRACTICE:

“Although patient portal signup was lower among vulnerable patients, once adopted, vulnerable patients demonstrated comparable meaningful use and greater proxy engagement. Fostering patient portal adoption requires a targeted approach with patient navigation and patient proxy engagement,” wrote the authors of the study.

SOURCE:

The study was led by Yenong Cao, MD, PhD, Boston Medical Center, Boston. It was published online on November 19 in JCO Oncology Practice.

LIMITATIONS:

The study was limited by its retrospective single-center design at Tufts Medical Center, which serves a large number of non-English, Chinese-speaking patients, potentially affecting the generalizability of findings. Additionally, formal proxy login identification was lacking in the Epic documentation during the study period, which may have led to underestimation of proxy portal use.

DISCLOSURES:

Cao reported being employed at Tufts Medical Center. Johnson Ching, PharmD, CSP, disclosed being employed at Duke University Hospital and SpeciaRx, LLC. Additional disclosures are noted in the original article. 

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: 

Electronic health records patient portal signup rates were lower among vulnerable oncology patients at 64%, compared with 87% in nonvulnerable patients. Once adopted, both groups showed comparable meaningful use patterns. Non-English language emerged as a significant barrier to initial portal signup.

METHODOLOGY:

• Portal usage disparities persist across age, race, ethnicity, and health literacy groups, particularly at the initial signup stage.
• Oral anticancer medications represent a new frontier in cancer therapy, offering convenience but requiring high medication adherence and vigilant self-monitoring of symptoms.
• Researchers conducted a retrospective analysis of 280 patients who had recently started taking an oral anticancer medication at Tufts Medical Center, Boston, between October 2022 and March 2024.
• Vulnerability criteria included having an age ≥ 75 years, a non-English language preference, or subsidized insurance (Medicaid only or Medicare with Medicaid as secondary insurance).
• Analysis defined active portal use as having at least one message, while meaningful use was characterized by patient-provider bidirectional messaging.
• Portal messaging proxy use was determined through message content screening, particularly when non-English speaking patients sent messages in English or when message content indicated proxy use.

TAKEAWAY:

• Among the study population, 56% met vulnerability criteria, with 20% aged at least 75 years, 26% having a non-English language, and 30% having subsidized insurance.
• Non-English language was associated with lower portal signup rates (odds ratio [OR], 0.27; 95% CI, 0.15-0.49; P < .0001), whereas age and insurance status showed no significant association.
• Proxy messaging was utilized by 17% of vulnerable patients who signed up for the portal compared to 2.8% of nonvulnerable patients.
• Among patients who signed up for the portal, 31% used it specifically for communication about oral anticancer medications.

IN PRACTICE:

“Although patient portal signup was lower among vulnerable patients, once adopted, vulnerable patients demonstrated comparable meaningful use and greater proxy engagement. Fostering patient portal adoption requires a targeted approach with patient navigation and patient proxy engagement,” wrote the authors of the study.

SOURCE:

The study was led by Yenong Cao, MD, PhD, Boston Medical Center, Boston. It was published online on November 19 in JCO Oncology Practice.

LIMITATIONS:

The study was limited by its retrospective single-center design at Tufts Medical Center, which serves a large number of non-English, Chinese-speaking patients, potentially affecting the generalizability of findings. Additionally, formal proxy login identification was lacking in the Epic documentation during the study period, which may have led to underestimation of proxy portal use.

DISCLOSURES:

Cao reported being employed at Tufts Medical Center. Johnson Ching, PharmD, CSP, disclosed being employed at Duke University Hospital and SpeciaRx, LLC. Additional disclosures are noted in the original article. 

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.

Jerome Winegarden, MD, had bad news to deliver. A patient’s cancer was progressing, and the patient would need to stop his oral cancer medication. 

That would normally mean tossing a 30-day supply of pills, said Winegarden, an oncologist with Trinity Health, a statewide health system in Michigan.

But not in this case. 

Winegarden pointed to a sign on his exam room wall from YesRx, a nonprofit cancer drug repository program, that read: “Thank you, Michiganders! Donating cancer medication and supportive medication helps patients in Michigan.”

When Winegarden suggested donating the pills to YesRx, the patient was grateful. Turning a bad situation into hope for somebody else is “very powerful for patients,” Winegarden said. “We were going to be able to do something with [the medication], not just destroy it.”

In just 2 years of operation, YesRx has accepted donations and provided oral cancer or supportive care medications worth millions of dollars to nearly 1200 patients, at no cost to them, according to a recent analysis assessing the Michigan-based program. These patients couldn’t afford their prescribed medications or required immediate access and couldn’t wait for insurance approval, the researchers reported. The donated unopened or unused medications would otherwise have been wasted.

“This program is exactly what patients need: a safe way of recycling their unused prescriptions that actually benefits others with cancer,” said Fumiko Chino, MD, associate professor at MD Anderson Cancer Center, Houston, Texas, in a statement on YesRx.
 

Filling a Need

A growing body of research shows that patients with cancer face an increased risk for financial toxicity, given the high costs of oral cancer drugs as well as changes to insurance coverage that may require greater cost sharing by the patient. The financial burden on patients can be significant, with more than half reporting trouble affording their medications, an issue that can lead to persistent medical debt as well as gaps or delays in care that may impact patient outcomes. 

Alongside the affordability problem is one of waste. A 2023 analysis found that the mean cost of drug waste associated with dose reductions or discontinuations of oral anticancer drugs came to $4290 per patient. 

The YesRx program, however, turns that negative into a positive.

If YesRx has a relevant drug in stock, “we can get the medication into the patient’s hands within 24-to-48 hours,” said Maja Gibbons, PharmD, an oncology pharmacy specialist with Corewell Health in Grand Rapids, Michigan.

Facilitating quick access is one key goal of the program, said YesRx co-founder and chief medical officer Emily Mackler, PharmD, who led the recent analysis. “All the things we’re trying to do are to make sure that the patient doesn’t experience those gaps that can really be critical for their outcomes,” Mackler this news organization. 

The drug repository concept has been around for decades. While there is no federal program, 29 states have general drug repository programs, according to the National Conference of State Legislatures. 

One of the oldest repositories, Iowa’s SafeNetRx, which started in 2001, reports that it has given free medications worth $155 million to almost 161,000 patients. SafeNetRx also began a partnership with state cancer centers to boost oral anticancer drug donations. From 2016 to 2022, the repository donated 84,000 chemotherapy doses worth $15 million to patients in need, reported Natalie K. Heater and colleagues at Northwestern University in Health Affairs Scholar.

In addition to Iowa, four other states have cancer drug repositories: Florida, Montana, Nebraska, and Michigan.

Michigan enacted a drug repository law in 2006, but YesRx did not start until 2023. The Michigan Oncology Quality Consortium, Blue Cross Blue Shield of Michigan, Trinity Health, and the Michigan Society of Hematology and Oncology provided funding to get YesRx off the ground. YesRx, which grew from nine sites in 2023 to 105 in July 2025, helps new sites get certified as a repository by the state. 

The program accepts donations of any room-temperature oral cancer or supportive care medication that is in its original, sealed manufacturer packaging and has at least 6 months before it expires. Controlled substances are not eligible, but medications such as anticoagulants and antiemetics are. Donations are sent by overnight delivery to Trinity Pharmacy at Reichert Health. Trinity receives and inspects donations, and redispenses medications for all YesRx participants. 

Nearly 1600 people have donated oral cancer medications, valued at $28.6 million, according to the 2-year look at the program. “I am blown away by how many donations come in,” Mackler this news organization.

In the first 24 months, 1171 patients received, on average, a 1-month supply of a medication worth $18.4 million, at no cost. Slightly more than half (53%) were age 65 or older. The most common diagnoses among recipients were breast cancer (28%), leukemia (18%), lung cancer (12%), and prostate cancer (9%). 

A survey about the program revealed that recipients spanned about 90% of Michigan counties, with around 40% living in rural areas. Survey respondents highlighted the value of YesRx, with most saying it was easy to use and that they could not have provided this assistance without support from the program. 

“YesRx can kind of swoop in,” said Winegarden. When a new prescription presents an issue for a patient, Winegarden checks if YesRx has a 30-day supply of the drug. If it does, patients “can get started on their treatment while we figure out the financial piece of it.”

Gibbons connects with patients in need through oncologists and financial navigators, as well as education sessions she runs for patients starting treatment. The Corewell location in Grand Rapids also holds “YesRx Donation Days,” when patients and caregivers can drop off medications. 

In just over a year, Corewell has provided “more than half a million dollars’ worth of medication to our cancer patients,” she said. “It’s just a large relief for patients to know that this is going to be able to help someone else out,” said Gibbons. 

Many of the cancer drugs “can be challenging for patients to get rid of,” Gibbons said. YesRx “is helping make sure that these medications don’t end up in things like landfills and water systems where they should not be.”

Mackler says she has big plans for expanding access. Next on the agenda is to enlist more practices in rural areas, especially in Michigan’s Upper Peninsula.

“We want to be accessible to anyone in the state with cancer,” said Mackler. “We would love to be able to help other states get to this point as well.”

Winegarden and Gibbons have reported no relevant financial relationships.

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

Jerome Winegarden, MD, had bad news to deliver. A patient’s cancer was progressing, and the patient would need to stop his oral cancer medication. 

That would normally mean tossing a 30-day supply of pills, said Winegarden, an oncologist with Trinity Health, a statewide health system in Michigan.

But not in this case. 

Winegarden pointed to a sign on his exam room wall from YesRx, a nonprofit cancer drug repository program, that read: “Thank you, Michiganders! Donating cancer medication and supportive medication helps patients in Michigan.”

When Winegarden suggested donating the pills to YesRx, the patient was grateful. Turning a bad situation into hope for somebody else is “very powerful for patients,” Winegarden said. “We were going to be able to do something with [the medication], not just destroy it.”

In just 2 years of operation, YesRx has accepted donations and provided oral cancer or supportive care medications worth millions of dollars to nearly 1200 patients, at no cost to them, according to a recent analysis assessing the Michigan-based program. These patients couldn’t afford their prescribed medications or required immediate access and couldn’t wait for insurance approval, the researchers reported. The donated unopened or unused medications would otherwise have been wasted.

“This program is exactly what patients need: a safe way of recycling their unused prescriptions that actually benefits others with cancer,” said Fumiko Chino, MD, associate professor at MD Anderson Cancer Center, Houston, Texas, in a statement on YesRx.
 

Filling a Need

A growing body of research shows that patients with cancer face an increased risk for financial toxicity, given the high costs of oral cancer drugs as well as changes to insurance coverage that may require greater cost sharing by the patient. The financial burden on patients can be significant, with more than half reporting trouble affording their medications, an issue that can lead to persistent medical debt as well as gaps or delays in care that may impact patient outcomes. 

Alongside the affordability problem is one of waste. A 2023 analysis found that the mean cost of drug waste associated with dose reductions or discontinuations of oral anticancer drugs came to $4290 per patient. 

The YesRx program, however, turns that negative into a positive.

If YesRx has a relevant drug in stock, “we can get the medication into the patient’s hands within 24-to-48 hours,” said Maja Gibbons, PharmD, an oncology pharmacy specialist with Corewell Health in Grand Rapids, Michigan.

Facilitating quick access is one key goal of the program, said YesRx co-founder and chief medical officer Emily Mackler, PharmD, who led the recent analysis. “All the things we’re trying to do are to make sure that the patient doesn’t experience those gaps that can really be critical for their outcomes,” Mackler this news organization. 

The drug repository concept has been around for decades. While there is no federal program, 29 states have general drug repository programs, according to the National Conference of State Legislatures. 

One of the oldest repositories, Iowa’s SafeNetRx, which started in 2001, reports that it has given free medications worth $155 million to almost 161,000 patients. SafeNetRx also began a partnership with state cancer centers to boost oral anticancer drug donations. From 2016 to 2022, the repository donated 84,000 chemotherapy doses worth $15 million to patients in need, reported Natalie K. Heater and colleagues at Northwestern University in Health Affairs Scholar.

In addition to Iowa, four other states have cancer drug repositories: Florida, Montana, Nebraska, and Michigan.

Michigan enacted a drug repository law in 2006, but YesRx did not start until 2023. The Michigan Oncology Quality Consortium, Blue Cross Blue Shield of Michigan, Trinity Health, and the Michigan Society of Hematology and Oncology provided funding to get YesRx off the ground. YesRx, which grew from nine sites in 2023 to 105 in July 2025, helps new sites get certified as a repository by the state. 

The program accepts donations of any room-temperature oral cancer or supportive care medication that is in its original, sealed manufacturer packaging and has at least 6 months before it expires. Controlled substances are not eligible, but medications such as anticoagulants and antiemetics are. Donations are sent by overnight delivery to Trinity Pharmacy at Reichert Health. Trinity receives and inspects donations, and redispenses medications for all YesRx participants. 

Nearly 1600 people have donated oral cancer medications, valued at $28.6 million, according to the 2-year look at the program. “I am blown away by how many donations come in,” Mackler this news organization.

In the first 24 months, 1171 patients received, on average, a 1-month supply of a medication worth $18.4 million, at no cost. Slightly more than half (53%) were age 65 or older. The most common diagnoses among recipients were breast cancer (28%), leukemia (18%), lung cancer (12%), and prostate cancer (9%). 

A survey about the program revealed that recipients spanned about 90% of Michigan counties, with around 40% living in rural areas. Survey respondents highlighted the value of YesRx, with most saying it was easy to use and that they could not have provided this assistance without support from the program. 

“YesRx can kind of swoop in,” said Winegarden. When a new prescription presents an issue for a patient, Winegarden checks if YesRx has a 30-day supply of the drug. If it does, patients “can get started on their treatment while we figure out the financial piece of it.”

Gibbons connects with patients in need through oncologists and financial navigators, as well as education sessions she runs for patients starting treatment. The Corewell location in Grand Rapids also holds “YesRx Donation Days,” when patients and caregivers can drop off medications. 

In just over a year, Corewell has provided “more than half a million dollars’ worth of medication to our cancer patients,” she said. “It’s just a large relief for patients to know that this is going to be able to help someone else out,” said Gibbons. 

Many of the cancer drugs “can be challenging for patients to get rid of,” Gibbons said. YesRx “is helping make sure that these medications don’t end up in things like landfills and water systems where they should not be.”

Mackler says she has big plans for expanding access. Next on the agenda is to enlist more practices in rural areas, especially in Michigan’s Upper Peninsula.

“We want to be accessible to anyone in the state with cancer,” said Mackler. “We would love to be able to help other states get to this point as well.”

Winegarden and Gibbons have reported no relevant financial relationships.

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

Jerome Winegarden, MD, had bad news to deliver. A patient’s cancer was progressing, and the patient would need to stop his oral cancer medication. 

That would normally mean tossing a 30-day supply of pills, said Winegarden, an oncologist with Trinity Health, a statewide health system in Michigan.

But not in this case. 

Winegarden pointed to a sign on his exam room wall from YesRx, a nonprofit cancer drug repository program, that read: “Thank you, Michiganders! Donating cancer medication and supportive medication helps patients in Michigan.”

When Winegarden suggested donating the pills to YesRx, the patient was grateful. Turning a bad situation into hope for somebody else is “very powerful for patients,” Winegarden said. “We were going to be able to do something with [the medication], not just destroy it.”

In just 2 years of operation, YesRx has accepted donations and provided oral cancer or supportive care medications worth millions of dollars to nearly 1200 patients, at no cost to them, according to a recent analysis assessing the Michigan-based program. These patients couldn’t afford their prescribed medications or required immediate access and couldn’t wait for insurance approval, the researchers reported. The donated unopened or unused medications would otherwise have been wasted.

“This program is exactly what patients need: a safe way of recycling their unused prescriptions that actually benefits others with cancer,” said Fumiko Chino, MD, associate professor at MD Anderson Cancer Center, Houston, Texas, in a statement on YesRx.
 

Filling a Need

A growing body of research shows that patients with cancer face an increased risk for financial toxicity, given the high costs of oral cancer drugs as well as changes to insurance coverage that may require greater cost sharing by the patient. The financial burden on patients can be significant, with more than half reporting trouble affording their medications, an issue that can lead to persistent medical debt as well as gaps or delays in care that may impact patient outcomes. 

Alongside the affordability problem is one of waste. A 2023 analysis found that the mean cost of drug waste associated with dose reductions or discontinuations of oral anticancer drugs came to $4290 per patient. 

The YesRx program, however, turns that negative into a positive.

If YesRx has a relevant drug in stock, “we can get the medication into the patient’s hands within 24-to-48 hours,” said Maja Gibbons, PharmD, an oncology pharmacy specialist with Corewell Health in Grand Rapids, Michigan.

Facilitating quick access is one key goal of the program, said YesRx co-founder and chief medical officer Emily Mackler, PharmD, who led the recent analysis. “All the things we’re trying to do are to make sure that the patient doesn’t experience those gaps that can really be critical for their outcomes,” Mackler this news organization. 

The drug repository concept has been around for decades. While there is no federal program, 29 states have general drug repository programs, according to the National Conference of State Legislatures. 

One of the oldest repositories, Iowa’s SafeNetRx, which started in 2001, reports that it has given free medications worth $155 million to almost 161,000 patients. SafeNetRx also began a partnership with state cancer centers to boost oral anticancer drug donations. From 2016 to 2022, the repository donated 84,000 chemotherapy doses worth $15 million to patients in need, reported Natalie K. Heater and colleagues at Northwestern University in Health Affairs Scholar.

In addition to Iowa, four other states have cancer drug repositories: Florida, Montana, Nebraska, and Michigan.

Michigan enacted a drug repository law in 2006, but YesRx did not start until 2023. The Michigan Oncology Quality Consortium, Blue Cross Blue Shield of Michigan, Trinity Health, and the Michigan Society of Hematology and Oncology provided funding to get YesRx off the ground. YesRx, which grew from nine sites in 2023 to 105 in July 2025, helps new sites get certified as a repository by the state. 

The program accepts donations of any room-temperature oral cancer or supportive care medication that is in its original, sealed manufacturer packaging and has at least 6 months before it expires. Controlled substances are not eligible, but medications such as anticoagulants and antiemetics are. Donations are sent by overnight delivery to Trinity Pharmacy at Reichert Health. Trinity receives and inspects donations, and redispenses medications for all YesRx participants. 

Nearly 1600 people have donated oral cancer medications, valued at $28.6 million, according to the 2-year look at the program. “I am blown away by how many donations come in,” Mackler this news organization.

In the first 24 months, 1171 patients received, on average, a 1-month supply of a medication worth $18.4 million, at no cost. Slightly more than half (53%) were age 65 or older. The most common diagnoses among recipients were breast cancer (28%), leukemia (18%), lung cancer (12%), and prostate cancer (9%). 

A survey about the program revealed that recipients spanned about 90% of Michigan counties, with around 40% living in rural areas. Survey respondents highlighted the value of YesRx, with most saying it was easy to use and that they could not have provided this assistance without support from the program. 

“YesRx can kind of swoop in,” said Winegarden. When a new prescription presents an issue for a patient, Winegarden checks if YesRx has a 30-day supply of the drug. If it does, patients “can get started on their treatment while we figure out the financial piece of it.”

Gibbons connects with patients in need through oncologists and financial navigators, as well as education sessions she runs for patients starting treatment. The Corewell location in Grand Rapids also holds “YesRx Donation Days,” when patients and caregivers can drop off medications. 

In just over a year, Corewell has provided “more than half a million dollars’ worth of medication to our cancer patients,” she said. “It’s just a large relief for patients to know that this is going to be able to help someone else out,” said Gibbons. 

Many of the cancer drugs “can be challenging for patients to get rid of,” Gibbons said. YesRx “is helping make sure that these medications don’t end up in things like landfills and water systems where they should not be.”

Mackler says she has big plans for expanding access. Next on the agenda is to enlist more practices in rural areas, especially in Michigan’s Upper Peninsula.

“We want to be accessible to anyone in the state with cancer,” said Mackler. “We would love to be able to help other states get to this point as well.”

Winegarden and Gibbons have reported no relevant financial relationships.

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

The War on Cancer, declared by President Richard Nixon some 50 years ago, has been canceled during the second Trump administration in 2025 — so saith The New York Times Sunday magazine cover story on September 14, 2025. This war seems now to be best described as "The War on Cancer Research."

To our horror and disbelief, we've witnessed the slow but persistent drift of much of the United States citizenry away from science and the sudden and severe movement of the US government to crush much medical research. But it is not as if we were not warned.

In August 2024, on these pages and without political bias, I urged Medscape readers to pay attention to Project 2025. A great deal of what we as a population are now experiencing was laid out as a carefully constructed plan.

What is surprising is the cruel ruthlessness of the "move fast and break things" approach, taken with little apparent concern about the resultant human tragedies (workforce and patients) and no clear care about the resulting fallout. As we've now learned, destroying something as grand as our cancer research enterprise can be accomplished very quickly. Rebuilding it is certain to be slow and difficult and perhaps can never be accomplished.

In this new anti-science, anti-research, and anti-researcher reality, what can we now do?

First and foremost, we must recognize that the war on cancer is not over. Cancer is not canceled, even if much of the US government's research effort/funding has been. Those of us in medicine and public health often speak in quantification of causes of death of our populations. As such, I'll remind Medscape readers that cancer afflicts some 20 million humans worldwide each year, killing nearly 10 million. Although two-thirds of Americans diagnosed with a potentially lethal malignancy are cured, cancer still kills roughly 600,000 Americans each year. Cancer has been the second most frequent cause of death of Americans for 75 years.

Being inevitable and immutable, death itself is not the enemy. We all die. Disease, disability, pain, and human suffering are the real enemies of us all. Cancer maims, pains, diabetes, and torments some 20 million humans worldwide each year. That is a huge humanitarian problem that should be recognized by individuals of all creeds and backgrounds.

With this depletion of our domestic government basic and applied cancer research program, what can we do?

1. Think globally and look to the international scientific research enterprises — relying on them, much as they have relied on us.
2. Defend the universal importance of reliable and available literature on medical science.
3. Continue to translate and apply the vast amount of available published research in clinical practice and publish the results.
4. Urge private industries to expand their research budgets into areas of study that may not produce quickly tangible positive bottom-line results.
5. Remind the Secretary of the Department of Health and Human Services (for whom chronic diseases seem paramount) that cancer is the second leading American chronic disease by morbidity.
6. Redouble efforts of cancer prevention, especially urging the FDA to ban combustible tobacco and strive more diligently to decrease obesity.
7. Appeal to our vast philanthropic universe to increase its funding of nonprofit organizations active in the cancer investigation, diagnosis, and management space.

One such 501c3 organization is California-based Cancer Commons. (Disclosure: I named it in 2010 and serve as its editor in chief).

A commons is a space shared by a community to use for the common interest. As we originally envisioned it, a cancer commons is an open access internet location where individuals and organizations (eg, corporations, universities, government agencies, philanthropies) will voluntarily share their data to work together to defeat the common enemy of humans: cancer.

On September 8, 2025, Cancer Commons was the 15th annual Lundberg Institute Lecturer at the Commonwealth Club of California in San Francisco. At the lecture, Cancer Commons founder (and long-term survivor of metastatic malignant melanoma), Jay Martin "Martin" Tenenbaum, PhD, spoke of the need for a cancer commons and the founder's vision. Emma Shtivelman, PhD, the long-time compassionate chief scientist, described some of the thousands of patients with advanced cancer that she has helped — all free of charge. And newly named CEO Clifford Reid, MBA, PhD, used his entrepreneurial prowess to envision an ambitious future.

Cancer Commons has always focused on patients with cancer who are beyond standards of curative care. As Cancer Commons evolves, it anticipates focusing on patients with cancer who are beyond National Comprehensive Cancer Network Guidelines. The organization intends to greatly expand its 1000 patients per year with "high touch" engagement with PhD clinical scientists to many thousands by including artificial intelligence. It plans to extend its N-of-One approach to create new knowledge — especially regarding the hundreds of drugs that are FDA-approved for use in treating cancer but have not been further assessed for the utility in actually treating patients with cancer.

The war on cancer is not over. It remains a persistent foe that causes immense disability, pain, and human suffering. With government support depleted, the burden now shifts to the private sector and philanthropic organizations, such as Cancer Commons, to serve as the new vital infrastructure in the fight for a cure. Now, we must redouble our efforts to ensure that these research endeavors are supported if the US government will not do its part.

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

The War on Cancer, declared by President Richard Nixon some 50 years ago, has been canceled during the second Trump administration in 2025 — so saith The New York Times Sunday magazine cover story on September 14, 2025. This war seems now to be best described as "The War on Cancer Research."

To our horror and disbelief, we've witnessed the slow but persistent drift of much of the United States citizenry away from science and the sudden and severe movement of the US government to crush much medical research. But it is not as if we were not warned.

In August 2024, on these pages and without political bias, I urged Medscape readers to pay attention to Project 2025. A great deal of what we as a population are now experiencing was laid out as a carefully constructed plan.

What is surprising is the cruel ruthlessness of the "move fast and break things" approach, taken with little apparent concern about the resultant human tragedies (workforce and patients) and no clear care about the resulting fallout. As we've now learned, destroying something as grand as our cancer research enterprise can be accomplished very quickly. Rebuilding it is certain to be slow and difficult and perhaps can never be accomplished.

In this new anti-science, anti-research, and anti-researcher reality, what can we now do?

First and foremost, we must recognize that the war on cancer is not over. Cancer is not canceled, even if much of the US government's research effort/funding has been. Those of us in medicine and public health often speak in quantification of causes of death of our populations. As such, I'll remind Medscape readers that cancer afflicts some 20 million humans worldwide each year, killing nearly 10 million. Although two-thirds of Americans diagnosed with a potentially lethal malignancy are cured, cancer still kills roughly 600,000 Americans each year. Cancer has been the second most frequent cause of death of Americans for 75 years.

Being inevitable and immutable, death itself is not the enemy. We all die. Disease, disability, pain, and human suffering are the real enemies of us all. Cancer maims, pains, diabetes, and torments some 20 million humans worldwide each year. That is a huge humanitarian problem that should be recognized by individuals of all creeds and backgrounds.

With this depletion of our domestic government basic and applied cancer research program, what can we do?

1. Think globally and look to the international scientific research enterprises — relying on them, much as they have relied on us.
2. Defend the universal importance of reliable and available literature on medical science.
3. Continue to translate and apply the vast amount of available published research in clinical practice and publish the results.
4. Urge private industries to expand their research budgets into areas of study that may not produce quickly tangible positive bottom-line results.
5. Remind the Secretary of the Department of Health and Human Services (for whom chronic diseases seem paramount) that cancer is the second leading American chronic disease by morbidity.
6. Redouble efforts of cancer prevention, especially urging the FDA to ban combustible tobacco and strive more diligently to decrease obesity.
7. Appeal to our vast philanthropic universe to increase its funding of nonprofit organizations active in the cancer investigation, diagnosis, and management space.

One such 501c3 organization is California-based Cancer Commons. (Disclosure: I named it in 2010 and serve as its editor in chief).

A commons is a space shared by a community to use for the common interest. As we originally envisioned it, a cancer commons is an open access internet location where individuals and organizations (eg, corporations, universities, government agencies, philanthropies) will voluntarily share their data to work together to defeat the common enemy of humans: cancer.

On September 8, 2025, Cancer Commons was the 15th annual Lundberg Institute Lecturer at the Commonwealth Club of California in San Francisco. At the lecture, Cancer Commons founder (and long-term survivor of metastatic malignant melanoma), Jay Martin "Martin" Tenenbaum, PhD, spoke of the need for a cancer commons and the founder's vision. Emma Shtivelman, PhD, the long-time compassionate chief scientist, described some of the thousands of patients with advanced cancer that she has helped — all free of charge. And newly named CEO Clifford Reid, MBA, PhD, used his entrepreneurial prowess to envision an ambitious future.

Cancer Commons has always focused on patients with cancer who are beyond standards of curative care. As Cancer Commons evolves, it anticipates focusing on patients with cancer who are beyond National Comprehensive Cancer Network Guidelines. The organization intends to greatly expand its 1000 patients per year with "high touch" engagement with PhD clinical scientists to many thousands by including artificial intelligence. It plans to extend its N-of-One approach to create new knowledge — especially regarding the hundreds of drugs that are FDA-approved for use in treating cancer but have not been further assessed for the utility in actually treating patients with cancer.

The war on cancer is not over. It remains a persistent foe that causes immense disability, pain, and human suffering. With government support depleted, the burden now shifts to the private sector and philanthropic organizations, such as Cancer Commons, to serve as the new vital infrastructure in the fight for a cure. Now, we must redouble our efforts to ensure that these research endeavors are supported if the US government will not do its part.

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

The War on Cancer, declared by President Richard Nixon some 50 years ago, has been canceled during the second Trump administration in 2025 — so saith The New York Times Sunday magazine cover story on September 14, 2025. This war seems now to be best described as "The War on Cancer Research."

To our horror and disbelief, we've witnessed the slow but persistent drift of much of the United States citizenry away from science and the sudden and severe movement of the US government to crush much medical research. But it is not as if we were not warned.

In August 2024, on these pages and without political bias, I urged Medscape readers to pay attention to Project 2025. A great deal of what we as a population are now experiencing was laid out as a carefully constructed plan.

What is surprising is the cruel ruthlessness of the "move fast and break things" approach, taken with little apparent concern about the resultant human tragedies (workforce and patients) and no clear care about the resulting fallout. As we've now learned, destroying something as grand as our cancer research enterprise can be accomplished very quickly. Rebuilding it is certain to be slow and difficult and perhaps can never be accomplished.

In this new anti-science, anti-research, and anti-researcher reality, what can we now do?

First and foremost, we must recognize that the war on cancer is not over. Cancer is not canceled, even if much of the US government's research effort/funding has been. Those of us in medicine and public health often speak in quantification of causes of death of our populations. As such, I'll remind Medscape readers that cancer afflicts some 20 million humans worldwide each year, killing nearly 10 million. Although two-thirds of Americans diagnosed with a potentially lethal malignancy are cured, cancer still kills roughly 600,000 Americans each year. Cancer has been the second most frequent cause of death of Americans for 75 years.

Being inevitable and immutable, death itself is not the enemy. We all die. Disease, disability, pain, and human suffering are the real enemies of us all. Cancer maims, pains, diabetes, and torments some 20 million humans worldwide each year. That is a huge humanitarian problem that should be recognized by individuals of all creeds and backgrounds.

With this depletion of our domestic government basic and applied cancer research program, what can we do?

1. Think globally and look to the international scientific research enterprises — relying on them, much as they have relied on us.
2. Defend the universal importance of reliable and available literature on medical science.
3. Continue to translate and apply the vast amount of available published research in clinical practice and publish the results.
4. Urge private industries to expand their research budgets into areas of study that may not produce quickly tangible positive bottom-line results.
5. Remind the Secretary of the Department of Health and Human Services (for whom chronic diseases seem paramount) that cancer is the second leading American chronic disease by morbidity.
6. Redouble efforts of cancer prevention, especially urging the FDA to ban combustible tobacco and strive more diligently to decrease obesity.
7. Appeal to our vast philanthropic universe to increase its funding of nonprofit organizations active in the cancer investigation, diagnosis, and management space.

One such 501c3 organization is California-based Cancer Commons. (Disclosure: I named it in 2010 and serve as its editor in chief).

A commons is a space shared by a community to use for the common interest. As we originally envisioned it, a cancer commons is an open access internet location where individuals and organizations (eg, corporations, universities, government agencies, philanthropies) will voluntarily share their data to work together to defeat the common enemy of humans: cancer.

On September 8, 2025, Cancer Commons was the 15th annual Lundberg Institute Lecturer at the Commonwealth Club of California in San Francisco. At the lecture, Cancer Commons founder (and long-term survivor of metastatic malignant melanoma), Jay Martin "Martin" Tenenbaum, PhD, spoke of the need for a cancer commons and the founder's vision. Emma Shtivelman, PhD, the long-time compassionate chief scientist, described some of the thousands of patients with advanced cancer that she has helped — all free of charge. And newly named CEO Clifford Reid, MBA, PhD, used his entrepreneurial prowess to envision an ambitious future.

Cancer Commons has always focused on patients with cancer who are beyond standards of curative care. As Cancer Commons evolves, it anticipates focusing on patients with cancer who are beyond National Comprehensive Cancer Network Guidelines. The organization intends to greatly expand its 1000 patients per year with "high touch" engagement with PhD clinical scientists to many thousands by including artificial intelligence. It plans to extend its N-of-One approach to create new knowledge — especially regarding the hundreds of drugs that are FDA-approved for use in treating cancer but have not been further assessed for the utility in actually treating patients with cancer.

The war on cancer is not over. It remains a persistent foe that causes immense disability, pain, and human suffering. With government support depleted, the burden now shifts to the private sector and philanthropic organizations, such as Cancer Commons, to serve as the new vital infrastructure in the fight for a cure. Now, we must redouble our efforts to ensure that these research endeavors are supported if the US government will not do its part.

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

TOPLINE: Agent Orange exposure was associated with a 26% to 71% increased risk for multiple lymphoid cancers in veterans enrolled in the US Department of Veterans Affairs (VA) Million Veterans Program (MVP), while genetic predisposition independently raised risk by 12% to 81% across different lymphoma subtypes. A case-controlled analysis of 255,155 veterans found no significant interaction between genetic risk scores and Agent Orange exposure.

METHODOLOGY:

• A case-control study included 255,155 non-Hispanic White veterans (median age 67 years, 92.5% male) enrolled in the VA MVP with genotype and Agent Orange exposure data.

• Researchers analyzed five lymphoid malignant neoplasm subtypes: chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, marginal zone lymphoma, and multiple myeloma diagnosed from January 1965 through June 2024.

• Agent Orange exposure was determined through self-reported survey responses, while polygenic risk scores were derived from genome-wide association studies of lymphoid malignant neoplasms.

• Analysis included adjustments for age at enrollment, sex, and the first 10 genetic principal components in logistic regression models evaluating Agent Orange exposure, polygenic risk scores, and their potential interaction.

TAKEAWAY:

• Agent Orange exposure significantly increased risk for chronic lymphocytic leukemia (odds ratio [OR], 1.61; 95% CI, 1.40-1.84), diffuse large B-cell lymphoma (OR, 1.26; 95% CI, 1.03-1.53), follicular lymphoma (OR, 1.71; 95% CI, 1.39-2.11), and multiple myeloma (OR, 1.58; 95% CI, 1.35-1.86).

• Polygenic risk scores were independently associated with all lymphoma subtypes, with strongest associations for chronic lymphocytic leukemia (OR, 1.81; 95% CI, 1.70-1.93) and multiple myeloma (OR, 1.41; 95% CI, 1.31-1.52).

• Analysis in African American participants showed similar associations for multiple myeloma with both Agent Orange exposure (OR, 1.56; 95% CI, 1.18-2.07) and polygenic risk scores (OR, 1.31; 95% CI, 1.15-1.49).

• According to the researchers, no significant polygenic risk score and Agent Orange exposure interactions were observed for any lymphoma subtype.

IN PRACTICE: "Our study addressed the public health concerns surrounding Agent Orange exposure and lymphoid malignant neoplasms, finding that both Agent Orange exposure and polygenic risk are independently associated with disease, suggesting potentially distinct and additive pathways that merit further investigation," wrote the authors of the study.

SOURCE: The study was led by researchers at the University of California, Irvine and the Tibor Rubin Veterans Affairs Medical Center, Long Beach, Californiaand was published online on August 13 in JAMA Network Open.

LIMITATIONS: According to the authors, while this represents the largest case-control study of Agent Orange exposure and lymphoid malignant neoplasm risk, the power to detect interaction associations in specific subtypes might be limited. Self-reported Agent Orange exposure data may have introduced survival bias, particularly in aggressive subtypes, as patients with aggressive tumors may have died before joining the MVP. Additionally, about half of the patients were diagnosed with lymphoid malignant neoplasms before self-reporting Agent Orange exposure, potentially introducing recall bias.

DISCLOSURES: The research was supported by a Veterans Affairs Career Development Award Xueyi Teng, PhD, received grants from the George E. Hewitt Foundation for Medical Research Postdoc Fellowship during the study.

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

TOPLINE: Agent Orange exposure was associated with a 26% to 71% increased risk for multiple lymphoid cancers in veterans enrolled in the US Department of Veterans Affairs (VA) Million Veterans Program (MVP), while genetic predisposition independently raised risk by 12% to 81% across different lymphoma subtypes. A case-controlled analysis of 255,155 veterans found no significant interaction between genetic risk scores and Agent Orange exposure.

METHODOLOGY:

• A case-control study included 255,155 non-Hispanic White veterans (median age 67 years, 92.5% male) enrolled in the VA MVP with genotype and Agent Orange exposure data.

• Researchers analyzed five lymphoid malignant neoplasm subtypes: chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, marginal zone lymphoma, and multiple myeloma diagnosed from January 1965 through June 2024.

• Agent Orange exposure was determined through self-reported survey responses, while polygenic risk scores were derived from genome-wide association studies of lymphoid malignant neoplasms.

• Analysis included adjustments for age at enrollment, sex, and the first 10 genetic principal components in logistic regression models evaluating Agent Orange exposure, polygenic risk scores, and their potential interaction.

TAKEAWAY:

• Agent Orange exposure significantly increased risk for chronic lymphocytic leukemia (odds ratio [OR], 1.61; 95% CI, 1.40-1.84), diffuse large B-cell lymphoma (OR, 1.26; 95% CI, 1.03-1.53), follicular lymphoma (OR, 1.71; 95% CI, 1.39-2.11), and multiple myeloma (OR, 1.58; 95% CI, 1.35-1.86).

• Polygenic risk scores were independently associated with all lymphoma subtypes, with strongest associations for chronic lymphocytic leukemia (OR, 1.81; 95% CI, 1.70-1.93) and multiple myeloma (OR, 1.41; 95% CI, 1.31-1.52).

• Analysis in African American participants showed similar associations for multiple myeloma with both Agent Orange exposure (OR, 1.56; 95% CI, 1.18-2.07) and polygenic risk scores (OR, 1.31; 95% CI, 1.15-1.49).

• According to the researchers, no significant polygenic risk score and Agent Orange exposure interactions were observed for any lymphoma subtype.

IN PRACTICE: "Our study addressed the public health concerns surrounding Agent Orange exposure and lymphoid malignant neoplasms, finding that both Agent Orange exposure and polygenic risk are independently associated with disease, suggesting potentially distinct and additive pathways that merit further investigation," wrote the authors of the study.

SOURCE: The study was led by researchers at the University of California, Irvine and the Tibor Rubin Veterans Affairs Medical Center, Long Beach, Californiaand was published online on August 13 in JAMA Network Open.

LIMITATIONS: According to the authors, while this represents the largest case-control study of Agent Orange exposure and lymphoid malignant neoplasm risk, the power to detect interaction associations in specific subtypes might be limited. Self-reported Agent Orange exposure data may have introduced survival bias, particularly in aggressive subtypes, as patients with aggressive tumors may have died before joining the MVP. Additionally, about half of the patients were diagnosed with lymphoid malignant neoplasms before self-reporting Agent Orange exposure, potentially introducing recall bias.

DISCLOSURES: The research was supported by a Veterans Affairs Career Development Award Xueyi Teng, PhD, received grants from the George E. Hewitt Foundation for Medical Research Postdoc Fellowship during the study.

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

TOPLINE: Agent Orange exposure was associated with a 26% to 71% increased risk for multiple lymphoid cancers in veterans enrolled in the US Department of Veterans Affairs (VA) Million Veterans Program (MVP), while genetic predisposition independently raised risk by 12% to 81% across different lymphoma subtypes. A case-controlled analysis of 255,155 veterans found no significant interaction between genetic risk scores and Agent Orange exposure.

METHODOLOGY:

• A case-control study included 255,155 non-Hispanic White veterans (median age 67 years, 92.5% male) enrolled in the VA MVP with genotype and Agent Orange exposure data.

• Researchers analyzed five lymphoid malignant neoplasm subtypes: chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, marginal zone lymphoma, and multiple myeloma diagnosed from January 1965 through June 2024.

• Agent Orange exposure was determined through self-reported survey responses, while polygenic risk scores were derived from genome-wide association studies of lymphoid malignant neoplasms.

• Analysis included adjustments for age at enrollment, sex, and the first 10 genetic principal components in logistic regression models evaluating Agent Orange exposure, polygenic risk scores, and their potential interaction.

TAKEAWAY:

• Agent Orange exposure significantly increased risk for chronic lymphocytic leukemia (odds ratio [OR], 1.61; 95% CI, 1.40-1.84), diffuse large B-cell lymphoma (OR, 1.26; 95% CI, 1.03-1.53), follicular lymphoma (OR, 1.71; 95% CI, 1.39-2.11), and multiple myeloma (OR, 1.58; 95% CI, 1.35-1.86).

• Polygenic risk scores were independently associated with all lymphoma subtypes, with strongest associations for chronic lymphocytic leukemia (OR, 1.81; 95% CI, 1.70-1.93) and multiple myeloma (OR, 1.41; 95% CI, 1.31-1.52).

• Analysis in African American participants showed similar associations for multiple myeloma with both Agent Orange exposure (OR, 1.56; 95% CI, 1.18-2.07) and polygenic risk scores (OR, 1.31; 95% CI, 1.15-1.49).

• According to the researchers, no significant polygenic risk score and Agent Orange exposure interactions were observed for any lymphoma subtype.

IN PRACTICE: "Our study addressed the public health concerns surrounding Agent Orange exposure and lymphoid malignant neoplasms, finding that both Agent Orange exposure and polygenic risk are independently associated with disease, suggesting potentially distinct and additive pathways that merit further investigation," wrote the authors of the study.

SOURCE: The study was led by researchers at the University of California, Irvine and the Tibor Rubin Veterans Affairs Medical Center, Long Beach, Californiaand was published online on August 13 in JAMA Network Open.

LIMITATIONS: According to the authors, while this represents the largest case-control study of Agent Orange exposure and lymphoid malignant neoplasm risk, the power to detect interaction associations in specific subtypes might be limited. Self-reported Agent Orange exposure data may have introduced survival bias, particularly in aggressive subtypes, as patients with aggressive tumors may have died before joining the MVP. Additionally, about half of the patients were diagnosed with lymphoid malignant neoplasms before self-reporting Agent Orange exposure, potentially introducing recall bias.

DISCLOSURES: The research was supported by a Veterans Affairs Career Development Award Xueyi Teng, PhD, received grants from the George E. Hewitt Foundation for Medical Research Postdoc Fellowship during the study.

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

Abiraterone and enzalutamide showed identical survival outcomes when used as first-line treatment for metastatic hormone-sensitive prostate cancer (mHSPC), according to a new study using US Department of Veterans Affairs (VA) data. The report represents the first head-to-head clinical analysis of these commonly used androgen receptor inhibitors.

Among 1258 veterans treated with abiraterone and 311 treated with enzalutamide, median overall survival was 36.2 months for both drugs. Patients were followed for a mean of 28.7 months (abiraterone) and 30.8 months (enzalutamide), reported by Martin W. Schoen, MD, MPH, from Saint Louis University School of Medicine and the St. Louis VA Medical Center, in JAMA Network Open. 

Notably, there was no significant difference in outcomes among Black veterans, who often have poorer outcomes in prostate cancer, and in patients with cardiovascular disease.

“This is the first direct comparison of abiraterone and enzalutamide for mHSPC in a clinical practice setting,” Schoen told Federal Practitioner. “At the population level, there are no differences based on initial treatment choice.”

Abiraterone Is Preferred in the VA Due to Cost

According to Schoen, abiraterone and enzalutamide are the most commonly used androgen receptor inhibitors to treat mHSPC within the VA. A 2025 study by Schoen and colleagues found that 53.7% of veterans with mHSPC in 2022 received androgen receptor inhibitor therapy, up from 16.9% in 2017. 

“In the VA, the preference for most patients is abiraterone since it is the least expensive agent,” he said. A generic version has been available for several years.

Additionally, abiraterone “has been on the market for the longest, and therefore clinicians are familiar with its use,” Schoen said. However, “clinicians have little idea of the comparative efficacy between these 2 agents,” he added.

The authors suggest that the cost and toxicities of the medications should guide clinician decisions, Schoen said. “There is data that abiraterone may worsen diabetes, since it is given with prednisone and could increase the risk of cardiovascular events,” he said.

He added that 2 newer drugs, apalutamide and darolutamide, are also “viable options.” Chemotherapies and certain targeted drugs are also available, “but they are only used in a select group of patients.”

Outside Specialist: Diverse Study Population Is a Plus

Hematologist-oncologist Natalie Reizine, MD, of the University of Illinois College of Medicine, Chicago, who was not involved in the study, told Federal Practitioner that the real-world data are valuable given the limitations of clinical trial populations.

“It’s difficult to compare clinical trials because they enroll different groups of patients,” she said. And, she said, they often exclude patients with significant comorbidities. “If they have bad cardiovascular disease, for instance, or poorly controlled diabetes, they're excluded from the clinical trial. But in real life, many of our patients have other medical problems that we have to manage.”

Reizine also emphasized the significance of the study’s diverse patient population. “Black men are very underrepresented in clinical trials. Many clinical trials that lead to drug approval will have only few or no Black men at all, yet these drugs go on to be widely prescribed to all men with prostate cancer.”

Results Are ‘Reassuring’

Reizine described the overall study findings as “reassuring,” especially in light of “studies that show that abiraterone and prednisone may be associated with worse cardiovascular outcomes. This study showed that in this VA population, even for patients who had cardiovascular disease, there was not a difference in how they did.”

As for choosing between agents, she recommended considering comorbidities and potential drug-drug interactions. “One of the big reasons that you may not be able to safely prescribe enzalutamide, for instance, is if a patient is on an anticoagulant, which is incredibly common in cancer patients. Enzalutamide has more drug-drug interactions than abiraterone and prednisone.” 

Study Demographics and Findings

The study included all patients with mHSPC who initiated abiraterone or enzalutamide between July 2017 and April 2023.

Median ages were 73 (abiraterone) and 74 years (enzalutamide, P = .29). Racial distribution was similar between groups: abiraterone (68.1% White, 25.0% Black, 6.9% other/unknown) and enzalutamide (66.6% White, 27.0% Black, 6.4% other/unknown; P = .74). Ethnicity was 89.2% non-Hispanic, 4.4% Hispanic, and 6.4% unknown in the abiraterone group vs 88.4% non-Hispanic, 3.5% Hispanic, and 8.0% unknown in the enzalutamide group (P = .50).

The groups had similar rates of the most common comorbidities: diabetes (40.5% vs 46.3%, respectively, P = .07), peripheral vascular disease (40.2% vs 37.6%, respectively, P = .44), and chronic pulmonary disease (37.0% vs 40.5%, P = .29).

In an inverse probability weighting analysis with abiraterone as reference, weighted median overall survival was comparable across the entire cohort (36.2 months, P = .32), Black veterans (39.7 months, P = .90), and those with cardiovascular disease (31.5 months, P = .30).

The authors noted limitations such as the observational cohort design and data constraints. 

The study was supported by the American Society of Clinical Oncology Conquer Cancer Foundation, the Prostate Cancer Foundation, and the Blavatnik Family Foundation.

Schoen discloses relationships with the Prostate Cancer Foundation, Astellas, and US Department of Defense. Other authors disclose relationships with the American Society of Clinical Oncology, Pfizer, Exelixis, Eli Lilly, Sanofi, Merck, Seagen, Bellicum, and BMS.

Outside the submitted work. Reizine discloses relationships with the US Department of Defense, Sanofi, Exelexis, Janssen, AstraZeneca, EMD Serono, Janssen, Merck, and Tempus.

Abiraterone and enzalutamide showed identical survival outcomes when used as first-line treatment for metastatic hormone-sensitive prostate cancer (mHSPC), according to a new study using US Department of Veterans Affairs (VA) data. The report represents the first head-to-head clinical analysis of these commonly used androgen receptor inhibitors.

Among 1258 veterans treated with abiraterone and 311 treated with enzalutamide, median overall survival was 36.2 months for both drugs. Patients were followed for a mean of 28.7 months (abiraterone) and 30.8 months (enzalutamide), reported by Martin W. Schoen, MD, MPH, from Saint Louis University School of Medicine and the St. Louis VA Medical Center, in JAMA Network Open. 

Notably, there was no significant difference in outcomes among Black veterans, who often have poorer outcomes in prostate cancer, and in patients with cardiovascular disease.

“This is the first direct comparison of abiraterone and enzalutamide for mHSPC in a clinical practice setting,” Schoen told Federal Practitioner. “At the population level, there are no differences based on initial treatment choice.”

Abiraterone Is Preferred in the VA Due to Cost

According to Schoen, abiraterone and enzalutamide are the most commonly used androgen receptor inhibitors to treat mHSPC within the VA. A 2025 study by Schoen and colleagues found that 53.7% of veterans with mHSPC in 2022 received androgen receptor inhibitor therapy, up from 16.9% in 2017. 

“In the VA, the preference for most patients is abiraterone since it is the least expensive agent,” he said. A generic version has been available for several years.

Additionally, abiraterone “has been on the market for the longest, and therefore clinicians are familiar with its use,” Schoen said. However, “clinicians have little idea of the comparative efficacy between these 2 agents,” he added.

The authors suggest that the cost and toxicities of the medications should guide clinician decisions, Schoen said. “There is data that abiraterone may worsen diabetes, since it is given with prednisone and could increase the risk of cardiovascular events,” he said.

He added that 2 newer drugs, apalutamide and darolutamide, are also “viable options.” Chemotherapies and certain targeted drugs are also available, “but they are only used in a select group of patients.”

Outside Specialist: Diverse Study Population Is a Plus

Hematologist-oncologist Natalie Reizine, MD, of the University of Illinois College of Medicine, Chicago, who was not involved in the study, told Federal Practitioner that the real-world data are valuable given the limitations of clinical trial populations.

“It’s difficult to compare clinical trials because they enroll different groups of patients,” she said. And, she said, they often exclude patients with significant comorbidities. “If they have bad cardiovascular disease, for instance, or poorly controlled diabetes, they're excluded from the clinical trial. But in real life, many of our patients have other medical problems that we have to manage.”

Reizine also emphasized the significance of the study’s diverse patient population. “Black men are very underrepresented in clinical trials. Many clinical trials that lead to drug approval will have only few or no Black men at all, yet these drugs go on to be widely prescribed to all men with prostate cancer.”

Results Are ‘Reassuring’

Reizine described the overall study findings as “reassuring,” especially in light of “studies that show that abiraterone and prednisone may be associated with worse cardiovascular outcomes. This study showed that in this VA population, even for patients who had cardiovascular disease, there was not a difference in how they did.”

As for choosing between agents, she recommended considering comorbidities and potential drug-drug interactions. “One of the big reasons that you may not be able to safely prescribe enzalutamide, for instance, is if a patient is on an anticoagulant, which is incredibly common in cancer patients. Enzalutamide has more drug-drug interactions than abiraterone and prednisone.” 

Study Demographics and Findings

The study included all patients with mHSPC who initiated abiraterone or enzalutamide between July 2017 and April 2023.

Median ages were 73 (abiraterone) and 74 years (enzalutamide, P = .29). Racial distribution was similar between groups: abiraterone (68.1% White, 25.0% Black, 6.9% other/unknown) and enzalutamide (66.6% White, 27.0% Black, 6.4% other/unknown; P = .74). Ethnicity was 89.2% non-Hispanic, 4.4% Hispanic, and 6.4% unknown in the abiraterone group vs 88.4% non-Hispanic, 3.5% Hispanic, and 8.0% unknown in the enzalutamide group (P = .50).

The groups had similar rates of the most common comorbidities: diabetes (40.5% vs 46.3%, respectively, P = .07), peripheral vascular disease (40.2% vs 37.6%, respectively, P = .44), and chronic pulmonary disease (37.0% vs 40.5%, P = .29).

In an inverse probability weighting analysis with abiraterone as reference, weighted median overall survival was comparable across the entire cohort (36.2 months, P = .32), Black veterans (39.7 months, P = .90), and those with cardiovascular disease (31.5 months, P = .30).

The authors noted limitations such as the observational cohort design and data constraints. 

The study was supported by the American Society of Clinical Oncology Conquer Cancer Foundation, the Prostate Cancer Foundation, and the Blavatnik Family Foundation.

Schoen discloses relationships with the Prostate Cancer Foundation, Astellas, and US Department of Defense. Other authors disclose relationships with the American Society of Clinical Oncology, Pfizer, Exelixis, Eli Lilly, Sanofi, Merck, Seagen, Bellicum, and BMS.

Outside the submitted work. Reizine discloses relationships with the US Department of Defense, Sanofi, Exelexis, Janssen, AstraZeneca, EMD Serono, Janssen, Merck, and Tempus.

Abiraterone and enzalutamide showed identical survival outcomes when used as first-line treatment for metastatic hormone-sensitive prostate cancer (mHSPC), according to a new study using US Department of Veterans Affairs (VA) data. The report represents the first head-to-head clinical analysis of these commonly used androgen receptor inhibitors.

Among 1258 veterans treated with abiraterone and 311 treated with enzalutamide, median overall survival was 36.2 months for both drugs. Patients were followed for a mean of 28.7 months (abiraterone) and 30.8 months (enzalutamide), reported by Martin W. Schoen, MD, MPH, from Saint Louis University School of Medicine and the St. Louis VA Medical Center, in JAMA Network Open. 

Notably, there was no significant difference in outcomes among Black veterans, who often have poorer outcomes in prostate cancer, and in patients with cardiovascular disease.

“This is the first direct comparison of abiraterone and enzalutamide for mHSPC in a clinical practice setting,” Schoen told Federal Practitioner. “At the population level, there are no differences based on initial treatment choice.”

Abiraterone Is Preferred in the VA Due to Cost

According to Schoen, abiraterone and enzalutamide are the most commonly used androgen receptor inhibitors to treat mHSPC within the VA. A 2025 study by Schoen and colleagues found that 53.7% of veterans with mHSPC in 2022 received androgen receptor inhibitor therapy, up from 16.9% in 2017. 

“In the VA, the preference for most patients is abiraterone since it is the least expensive agent,” he said. A generic version has been available for several years.

Additionally, abiraterone “has been on the market for the longest, and therefore clinicians are familiar with its use,” Schoen said. However, “clinicians have little idea of the comparative efficacy between these 2 agents,” he added.

The authors suggest that the cost and toxicities of the medications should guide clinician decisions, Schoen said. “There is data that abiraterone may worsen diabetes, since it is given with prednisone and could increase the risk of cardiovascular events,” he said.

He added that 2 newer drugs, apalutamide and darolutamide, are also “viable options.” Chemotherapies and certain targeted drugs are also available, “but they are only used in a select group of patients.”

Outside Specialist: Diverse Study Population Is a Plus

Hematologist-oncologist Natalie Reizine, MD, of the University of Illinois College of Medicine, Chicago, who was not involved in the study, told Federal Practitioner that the real-world data are valuable given the limitations of clinical trial populations.

“It’s difficult to compare clinical trials because they enroll different groups of patients,” she said. And, she said, they often exclude patients with significant comorbidities. “If they have bad cardiovascular disease, for instance, or poorly controlled diabetes, they're excluded from the clinical trial. But in real life, many of our patients have other medical problems that we have to manage.”

Reizine also emphasized the significance of the study’s diverse patient population. “Black men are very underrepresented in clinical trials. Many clinical trials that lead to drug approval will have only few or no Black men at all, yet these drugs go on to be widely prescribed to all men with prostate cancer.”

Results Are ‘Reassuring’

Reizine described the overall study findings as “reassuring,” especially in light of “studies that show that abiraterone and prednisone may be associated with worse cardiovascular outcomes. This study showed that in this VA population, even for patients who had cardiovascular disease, there was not a difference in how they did.”

As for choosing between agents, she recommended considering comorbidities and potential drug-drug interactions. “One of the big reasons that you may not be able to safely prescribe enzalutamide, for instance, is if a patient is on an anticoagulant, which is incredibly common in cancer patients. Enzalutamide has more drug-drug interactions than abiraterone and prednisone.” 

Study Demographics and Findings

The study included all patients with mHSPC who initiated abiraterone or enzalutamide between July 2017 and April 2023.

Median ages were 73 (abiraterone) and 74 years (enzalutamide, P = .29). Racial distribution was similar between groups: abiraterone (68.1% White, 25.0% Black, 6.9% other/unknown) and enzalutamide (66.6% White, 27.0% Black, 6.4% other/unknown; P = .74). Ethnicity was 89.2% non-Hispanic, 4.4% Hispanic, and 6.4% unknown in the abiraterone group vs 88.4% non-Hispanic, 3.5% Hispanic, and 8.0% unknown in the enzalutamide group (P = .50).

The groups had similar rates of the most common comorbidities: diabetes (40.5% vs 46.3%, respectively, P = .07), peripheral vascular disease (40.2% vs 37.6%, respectively, P = .44), and chronic pulmonary disease (37.0% vs 40.5%, P = .29).

In an inverse probability weighting analysis with abiraterone as reference, weighted median overall survival was comparable across the entire cohort (36.2 months, P = .32), Black veterans (39.7 months, P = .90), and those with cardiovascular disease (31.5 months, P = .30).

The authors noted limitations such as the observational cohort design and data constraints. 

The study was supported by the American Society of Clinical Oncology Conquer Cancer Foundation, the Prostate Cancer Foundation, and the Blavatnik Family Foundation.

Schoen discloses relationships with the Prostate Cancer Foundation, Astellas, and US Department of Defense. Other authors disclose relationships with the American Society of Clinical Oncology, Pfizer, Exelixis, Eli Lilly, Sanofi, Merck, Seagen, Bellicum, and BMS.

Outside the submitted work. Reizine discloses relationships with the US Department of Defense, Sanofi, Exelexis, Janssen, AstraZeneca, EMD Serono, Janssen, Merck, and Tempus.

TOPLINE: COVID-19 infection is associated with a 25% reduction in cancer risk over 3 years among veterans who survived the initial infection. This protective effect was observed across sexes and racial groups, with stronger benefits seen in older patients and those with mild disease.

METHODOLOGY: 

• Researchers conducted a retrospective cohort study comparing Veterans who tested positive for COVID-19 between March 15, 2020, and November 30, 2020, to those who tested negative.

• Analysis included 499,396 veterans, with 88,590 (17.2%) COVID-19 positive and 427,566 (82.8%) COVID-19 negative patients, with mean (SD) ages of 57.9 (16.4) and 59.5 (15.8) years, respectively.

• Investigators utilized Cox proportional hazard regression models to determine the hazard ratio of new cancer diagnosis within a three-year follow-up period.

• Patient characteristics included age, race, ethnicity, sex, BMI, smoking status, and various comorbidities as covariates in the analysis.

TAKEAWAY:

• For patients surviving ≥ 30 days after COVID-19 testing, infection was associated with a 25% reduction in cancer hazard (hazard ratio [HR], 0.75; 95% CI, 0.73-0.77).

• The reduction in cancer risk was similar across sexes and races, with the exception of Asians, and showed greater decreases with advancing age above 45 years.

• Patients with mild COVID-19 showed the strongest reduction in cancer risk (adjusted HR, 0.72; 95% CI, 0.70-0.74), while those with moderate COVID-19 showed an 11% reduction (adjusted HR, 0.89; 95% CI, 0.83-0.93), and severe COVID-19 showed no significant reduction in cancer risk.

IN PRACTICE: "Regarding age, the incidence of cancer appeared to decrease with each decade of life in the COVID-19 group com­pared to that in the non-exposed group,” the authors noted. “This is surprising, given that cancer diagnoses typically increase with age.” 

SOURCE: The study was led by researchers at the Miami Veterans Affairs (VA) Healthcare System Geriatric Research, Education, and Clinical Center and was published online on August 25 in PLoS One.

LIMITATIONS: The findings of this retrospective and observational study should be interpreted with caution. Results may not be generalizable beyond the predominantly male, older veteran population. The 3-year follow-up period may be insufficient to fully understand long-term cancer incidence patterns. Researchers could not capture all COVID-19 reinfection cases due to testing occurring outside the Veterans Affairs system, including at-home testing. The impact of vaccination status and reinfection on cancer risk could not be fully assessed, as the initial study cohort was grouped prior to vaccine availability.

DISCLOSURES: The authors report no financial support was received for this study and declare no competing interests.

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

TOPLINE: COVID-19 infection is associated with a 25% reduction in cancer risk over 3 years among veterans who survived the initial infection. This protective effect was observed across sexes and racial groups, with stronger benefits seen in older patients and those with mild disease.

METHODOLOGY: 

• Researchers conducted a retrospective cohort study comparing Veterans who tested positive for COVID-19 between March 15, 2020, and November 30, 2020, to those who tested negative.

• Analysis included 499,396 veterans, with 88,590 (17.2%) COVID-19 positive and 427,566 (82.8%) COVID-19 negative patients, with mean (SD) ages of 57.9 (16.4) and 59.5 (15.8) years, respectively.

• Investigators utilized Cox proportional hazard regression models to determine the hazard ratio of new cancer diagnosis within a three-year follow-up period.

• Patient characteristics included age, race, ethnicity, sex, BMI, smoking status, and various comorbidities as covariates in the analysis.

TAKEAWAY:

• For patients surviving ≥ 30 days after COVID-19 testing, infection was associated with a 25% reduction in cancer hazard (hazard ratio [HR], 0.75; 95% CI, 0.73-0.77).

• The reduction in cancer risk was similar across sexes and races, with the exception of Asians, and showed greater decreases with advancing age above 45 years.

• Patients with mild COVID-19 showed the strongest reduction in cancer risk (adjusted HR, 0.72; 95% CI, 0.70-0.74), while those with moderate COVID-19 showed an 11% reduction (adjusted HR, 0.89; 95% CI, 0.83-0.93), and severe COVID-19 showed no significant reduction in cancer risk.

IN PRACTICE: "Regarding age, the incidence of cancer appeared to decrease with each decade of life in the COVID-19 group com­pared to that in the non-exposed group,” the authors noted. “This is surprising, given that cancer diagnoses typically increase with age.” 

SOURCE: The study was led by researchers at the Miami Veterans Affairs (VA) Healthcare System Geriatric Research, Education, and Clinical Center and was published online on August 25 in PLoS One.

LIMITATIONS: The findings of this retrospective and observational study should be interpreted with caution. Results may not be generalizable beyond the predominantly male, older veteran population. The 3-year follow-up period may be insufficient to fully understand long-term cancer incidence patterns. Researchers could not capture all COVID-19 reinfection cases due to testing occurring outside the Veterans Affairs system, including at-home testing. The impact of vaccination status and reinfection on cancer risk could not be fully assessed, as the initial study cohort was grouped prior to vaccine availability.

DISCLOSURES: The authors report no financial support was received for this study and declare no competing interests.

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

TOPLINE: COVID-19 infection is associated with a 25% reduction in cancer risk over 3 years among veterans who survived the initial infection. This protective effect was observed across sexes and racial groups, with stronger benefits seen in older patients and those with mild disease.

METHODOLOGY: 

• Researchers conducted a retrospective cohort study comparing Veterans who tested positive for COVID-19 between March 15, 2020, and November 30, 2020, to those who tested negative.

• Analysis included 499,396 veterans, with 88,590 (17.2%) COVID-19 positive and 427,566 (82.8%) COVID-19 negative patients, with mean (SD) ages of 57.9 (16.4) and 59.5 (15.8) years, respectively.

• Investigators utilized Cox proportional hazard regression models to determine the hazard ratio of new cancer diagnosis within a three-year follow-up period.

• Patient characteristics included age, race, ethnicity, sex, BMI, smoking status, and various comorbidities as covariates in the analysis.

TAKEAWAY:

• For patients surviving ≥ 30 days after COVID-19 testing, infection was associated with a 25% reduction in cancer hazard (hazard ratio [HR], 0.75; 95% CI, 0.73-0.77).

• The reduction in cancer risk was similar across sexes and races, with the exception of Asians, and showed greater decreases with advancing age above 45 years.

• Patients with mild COVID-19 showed the strongest reduction in cancer risk (adjusted HR, 0.72; 95% CI, 0.70-0.74), while those with moderate COVID-19 showed an 11% reduction (adjusted HR, 0.89; 95% CI, 0.83-0.93), and severe COVID-19 showed no significant reduction in cancer risk.

IN PRACTICE: "Regarding age, the incidence of cancer appeared to decrease with each decade of life in the COVID-19 group com­pared to that in the non-exposed group,” the authors noted. “This is surprising, given that cancer diagnoses typically increase with age.” 

SOURCE: The study was led by researchers at the Miami Veterans Affairs (VA) Healthcare System Geriatric Research, Education, and Clinical Center and was published online on August 25 in PLoS One.

LIMITATIONS: The findings of this retrospective and observational study should be interpreted with caution. Results may not be generalizable beyond the predominantly male, older veteran population. The 3-year follow-up period may be insufficient to fully understand long-term cancer incidence patterns. Researchers could not capture all COVID-19 reinfection cases due to testing occurring outside the Veterans Affairs system, including at-home testing. The impact of vaccination status and reinfection on cancer risk could not be fully assessed, as the initial study cohort was grouped prior to vaccine availability.

DISCLOSURES: The authors report no financial support was received for this study and declare no competing interests.

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

Male veterans with breast cancer may have a more difficult time receiving appropriate health care due to a recently revised US Department of Veterans Affairs (VA) policy that requires each individual to prove the disease’s connection to their service to qualify for coverage. 

According to a VA memo obtained by ProPublica, the change is based on a Jan. 1 presidential order titled “Defending Women from Gender Ideology Extremism and Restoring Biological Truth to the Federal Government.” VA Press Secretary Pete Kasperowicz told ProPublica that the policy was changed because the previous policy “falsely classified male breasts as reproductive organs.” 

In 2024, the VA added male breast cancer (along with urethral cancer and cancer of the paraurethral glands) to its list of presumed service-connected disabilities due to military environmental exposure, such as toxic burn pits. Male breast cancer was added to the category of “reproductive cancer of any type” after experts pointed to the similarity of male and female breast cancers.

Establishing a connection between a variety of cancers and military service has been a years-long fight only resolved recently in the form of the 2022 PACT Act. The VA lists > 20 medical conditions as “presumptive” for service connection, with some caveats, such as area of service. The act reduced the burden of proof needed: The terms “presumptive conditions” and “presumptive-exposure locations” mean veterans only have to provide their military records to show they were in an exposure location to have their care for certain conditions covered. 

Supporters of the PACT Act say the policy change could make it harder for veterans to receive timely care, a serious issue for men with breast cancer who have been “severely underrepresented” in clinical studies and many studies specifically exclude males. The American Cancer Society estimates about 2800 men have been or will be diagnosed with invasive breast cancer in 2025. Less than 1% of breast cancers in the US occur in men, but breast cancer is notably higher among veterans: 11% of 3304 veterans, according to a 2023 study. 

Breast cancer is more aggressive in men—they’re more often diagnosed at Stage IV and tend to be older—and survival rates have been lower than in women. In a 2019 study of 16,025 male and 1,800,708 female patients with breast cancer, men had 19% higher overall mortality.

Treatment for male breast cancer has lagged. A 2021 study found men were less likely than women to receive radiation therapy. However, that’s changing. Since that study, however, the American Cancer Society claims treatments and survival rates have improved. According to the Surveillance, Epidemiology, and End Results database, 5-year survival rates are 97% for localized, 86% for regional, and 31% for distant; 84% for all stages combined.

Screening and treatment have focused on women. But the VA Breast and Gynecologic Oncology System of Excellence (BGSoE) provides cancer care for all veterans diagnosed with breast malignancies. Male veterans with breast cancer do face additional challenges in addressing a cancer that is most often associated with females. “I must admit, it was awkward every time I went [to the Women’s Health Center for postmastectomy follow-ups]” William K. Lewis, described in his patient perspective on male breast cancer treatment in the VA.

Though the policy has changed, Kasperowicz told ProPublica that veterans who previously qualified for coverage can keep it: “The department grants disability benefits compensation claims for male Veterans with breast cancer on an individual basis and will continue to do so. VA encourages any male Veterans with breast cancer who feel their health may have been impacted by their military service to submit a disability compensation claim.”

Male veterans with breast cancer may have a more difficult time receiving appropriate health care due to a recently revised US Department of Veterans Affairs (VA) policy that requires each individual to prove the disease’s connection to their service to qualify for coverage. 

According to a VA memo obtained by ProPublica, the change is based on a Jan. 1 presidential order titled “Defending Women from Gender Ideology Extremism and Restoring Biological Truth to the Federal Government.” VA Press Secretary Pete Kasperowicz told ProPublica that the policy was changed because the previous policy “falsely classified male breasts as reproductive organs.” 

In 2024, the VA added male breast cancer (along with urethral cancer and cancer of the paraurethral glands) to its list of presumed service-connected disabilities due to military environmental exposure, such as toxic burn pits. Male breast cancer was added to the category of “reproductive cancer of any type” after experts pointed to the similarity of male and female breast cancers.

Establishing a connection between a variety of cancers and military service has been a years-long fight only resolved recently in the form of the 2022 PACT Act. The VA lists > 20 medical conditions as “presumptive” for service connection, with some caveats, such as area of service. The act reduced the burden of proof needed: The terms “presumptive conditions” and “presumptive-exposure locations” mean veterans only have to provide their military records to show they were in an exposure location to have their care for certain conditions covered. 

Supporters of the PACT Act say the policy change could make it harder for veterans to receive timely care, a serious issue for men with breast cancer who have been “severely underrepresented” in clinical studies and many studies specifically exclude males. The American Cancer Society estimates about 2800 men have been or will be diagnosed with invasive breast cancer in 2025. Less than 1% of breast cancers in the US occur in men, but breast cancer is notably higher among veterans: 11% of 3304 veterans, according to a 2023 study. 

Breast cancer is more aggressive in men—they’re more often diagnosed at Stage IV and tend to be older—and survival rates have been lower than in women. In a 2019 study of 16,025 male and 1,800,708 female patients with breast cancer, men had 19% higher overall mortality.

Treatment for male breast cancer has lagged. A 2021 study found men were less likely than women to receive radiation therapy. However, that’s changing. Since that study, however, the American Cancer Society claims treatments and survival rates have improved. According to the Surveillance, Epidemiology, and End Results database, 5-year survival rates are 97% for localized, 86% for regional, and 31% for distant; 84% for all stages combined.

Screening and treatment have focused on women. But the VA Breast and Gynecologic Oncology System of Excellence (BGSoE) provides cancer care for all veterans diagnosed with breast malignancies. Male veterans with breast cancer do face additional challenges in addressing a cancer that is most often associated with females. “I must admit, it was awkward every time I went [to the Women’s Health Center for postmastectomy follow-ups]” William K. Lewis, described in his patient perspective on male breast cancer treatment in the VA.

Though the policy has changed, Kasperowicz told ProPublica that veterans who previously qualified for coverage can keep it: “The department grants disability benefits compensation claims for male Veterans with breast cancer on an individual basis and will continue to do so. VA encourages any male Veterans with breast cancer who feel their health may have been impacted by their military service to submit a disability compensation claim.”

Male veterans with breast cancer may have a more difficult time receiving appropriate health care due to a recently revised US Department of Veterans Affairs (VA) policy that requires each individual to prove the disease’s connection to their service to qualify for coverage. 

According to a VA memo obtained by ProPublica, the change is based on a Jan. 1 presidential order titled “Defending Women from Gender Ideology Extremism and Restoring Biological Truth to the Federal Government.” VA Press Secretary Pete Kasperowicz told ProPublica that the policy was changed because the previous policy “falsely classified male breasts as reproductive organs.” 

In 2024, the VA added male breast cancer (along with urethral cancer and cancer of the paraurethral glands) to its list of presumed service-connected disabilities due to military environmental exposure, such as toxic burn pits. Male breast cancer was added to the category of “reproductive cancer of any type” after experts pointed to the similarity of male and female breast cancers.

Establishing a connection between a variety of cancers and military service has been a years-long fight only resolved recently in the form of the 2022 PACT Act. The VA lists > 20 medical conditions as “presumptive” for service connection, with some caveats, such as area of service. The act reduced the burden of proof needed: The terms “presumptive conditions” and “presumptive-exposure locations” mean veterans only have to provide their military records to show they were in an exposure location to have their care for certain conditions covered. 

Supporters of the PACT Act say the policy change could make it harder for veterans to receive timely care, a serious issue for men with breast cancer who have been “severely underrepresented” in clinical studies and many studies specifically exclude males. The American Cancer Society estimates about 2800 men have been or will be diagnosed with invasive breast cancer in 2025. Less than 1% of breast cancers in the US occur in men, but breast cancer is notably higher among veterans: 11% of 3304 veterans, according to a 2023 study. 

Breast cancer is more aggressive in men—they’re more often diagnosed at Stage IV and tend to be older—and survival rates have been lower than in women. In a 2019 study of 16,025 male and 1,800,708 female patients with breast cancer, men had 19% higher overall mortality.

Treatment for male breast cancer has lagged. A 2021 study found men were less likely than women to receive radiation therapy. However, that’s changing. Since that study, however, the American Cancer Society claims treatments and survival rates have improved. According to the Surveillance, Epidemiology, and End Results database, 5-year survival rates are 97% for localized, 86% for regional, and 31% for distant; 84% for all stages combined.

Screening and treatment have focused on women. But the VA Breast and Gynecologic Oncology System of Excellence (BGSoE) provides cancer care for all veterans diagnosed with breast malignancies. Male veterans with breast cancer do face additional challenges in addressing a cancer that is most often associated with females. “I must admit, it was awkward every time I went [to the Women’s Health Center for postmastectomy follow-ups]” William K. Lewis, described in his patient perspective on male breast cancer treatment in the VA.

Though the policy has changed, Kasperowicz told ProPublica that veterans who previously qualified for coverage can keep it: “The department grants disability benefits compensation claims for male Veterans with breast cancer on an individual basis and will continue to do so. VA encourages any male Veterans with breast cancer who feel their health may have been impacted by their military service to submit a disability compensation claim.”

A global analysis challenged the notion that a rise in cancer is disproportionately affecting younger adults, finding instead that several cancer types previously seen rising in younger adults are also increasing in older adults.

More specifically, the analysis found that incidence rates for thyroid cancer, breast cancer, kidney cancer, endometrial cancer, and leukemia increased similarly in both younger and older adults in most countries over a 15-year period. Colorectal cancer (CRC) was the exception, where incidence rates increased in younger adults in most countries but only increased slightly in older adults in about half and decreased in about one quarter.

“Our findings suggest that whatever is triggering the rise in these cancers is more likely to be common across all age groups, rather than specific to cancers in the under 50s, since there were similar increases in younger and older adults,” Amy Berrington de González, DPhil, The Institute of Cancer Research, London, England, who led the study, said in a statement.

The authors of an editorial agreed, adding that the growing “concern about increasing cancer rates should recognize that this increase is not restricted to young adults but affects all generations.”

The study and editorial were published recently in Annals of Internal Medicine.

 

Data Defy Early-Onset Cancer Epidemic Narrative

A growing body of evidence suggests that cancer incidence rates are increasing among younger adults in many countries. However, studies tracking international trends have largely evaluated cancer incidence in younger adults without comparing these trends in older adults or analyses have focused the age comparison in individual countries, Berrington de González and colleagues explained.

To better understand cancer incidence trends across countries and age groups, the researchers evaluated cancer trends in 42 countries between 2003 and 2017, focusing on 13 cancer types previously reported to be climbing in adults younger than age 50 years.

The researchers found that incidence rates for six of the 13 cancer types increased among younger adults (aged 20-49 years) in more than three quarters of the countries studied.

The largest increase was in thyroid cancer (median average annual percentage change [AAPC], 3.57%), followed by kidney cancer (median AAPC, 2.21%), endometrial cancer (median AAPC, 1.66%), CRC (median AAPC, 1.45%), breast cancer (median AAPC, 0.89%), and leukemia (median AAPC, 0.78%).

But with the exception of CRC, incidence rates for these cancers increased to a similar degree in adults aged 50 years or older — with median AAPCs of 3% (vs 3.57%) for thyroid cancer, 1.65% (vs 2.21%) for kidney cancer, 1.20% (vs 1.66%) for endometrial cancer, 0.86% (vs 0.89%) for breast cancer, and 0.61% (vs 0.78%) for leukemia.

In older adults, CRC incidence rates only increased in about half the countries (median AAPC, 0.37%), and the annual percentage change was much greater in younger than older adults in nearly 70% of countries. CRC incidence rates in older individuals also decreased in nearly 25% of countries.

Why is CRC an apparent outlier?

“Bowel cancer screening not only helps detect cancer at earlier stages but also helps prevent cancer through the removal of premalignant lesions,” Berrington de González said. “This could be why bowel cancer cases seem to be rising faster in younger adults — we’re getting better at preventing them developing in older adults.”

The incidence of certain cancers also declined in younger adults. Specifically, rates of liver, oral, esophageal, and stomach cancers decreased in younger adults in more than half of countries assessed, with median AAPCs of -0.14% for liver, -0.42% for oral, -0.92% for esophageal, and -1.62% for stomach cancers.

Over half of countries also saw declining rates of stomach (median AAPC, -2.05%) and esophageal (median AAPC, -0.25%) cancers among older adults, while rates of liver and oral cancers increased in older individuals (median AAPC, 2.17% and 0.49%, respectively).

For gallbladder, pancreatic, and prostate cancers — three other cancers previously found to be increasing in younger adults — the researchers reported that incidence rates increased in younger adults in just over half of countries (median AAPCs, 3.2% for prostate cancer, 0.49% for gallbladder cancer, and 1% for pancreatic cancer). Incidence rates also often increased in older adults but to a lesser extent (median AAPCs, 0.75% for prostate cancer, -0.10% for gallbladder, and 0.96% for pancreatic cancer).

 

True Rise or Increased Scrutiny?

Why are cancer rates increasing?

“Understanding factors that contribute to the increase in incidence across the age spectrum was beyond the scope of the study,” editorialists Christopher Cann, MD, Fox Chase Cancer Center, and Efrat Dotan, MD, University of Pennsylvania Health System, both in Philadelphia, wrote.

Several studies have suggested that rising rates of obesity could help explain increasing cancer incidence, particularly in younger adults. In fact, “the cancers that we identified as increasing are all obesity-related cancers, including endometrial and kidney cancer,” Berrington de González said. However, so far, the evidence on this link remains unclear, she acknowledged.

Weighing in on the study, Gilbert Welch, MD, Brigham and Women’s Hospital, Boston, told this news organization that it’s “critically important” to distinguish between two explanations for rising cancer incidence.

There may be an increase in the true occurrence of clinically meaningful cancer, which “warrants investigation into biologic explanations, better treatment, and perhaps more testing,” Welch said.

But it may instead reflect changes in diagnostic scrutiny. “Simply put, whenever we doctors look harder for cancer, we find more,” Welch said. “And there are lots of ways to look harder: testing more people, testing people more frequently, using tests with increasing ability to detect small irregularities, and using lower diagnostic thresholds for labeling these as cancer.”

If increased incidence is the result of greater diagnostic scrutiny, searching for biologic causes is bound to be unproductive and more testing will only aggravate the problem, he explained.

Welch pointed out that the fastest rising cancer in both younger and older adults was thyroid cancer (AAPC, ≥ 3%), which is “exquisitely sensitive” to diagnostic scrutiny.

Take what happened in South Korea. Around 2000, the government of South Korea started a national screening program for breast, colon, and stomach cancers. Doctors and hospitals often added on ultrasound scans for thyroid cancer for a small additional fee.

“A decade later the rate of thyroid cancer diagnosis had increased 15-fold, turning what was once a rare cancer into the most common cancer in Korea,” Welch said. “But the death rate from thyroid cancer did not change. This was not an epidemic of disease; this was an epidemic of diagnosis.”

Welch also noted that the study authors and editorialists put the finding in perspective by explaining that, despite the rising rates of certain cancers in younger adults, cancer remains rare in these adults.

Welch highlighted that, for younger adults in the US, cancer death rates in young adults have cut in half over the last 30 years. “Cancer accounts for only 10% of deaths in young people in the US — and that number is falling,” Welch said.

The study was funded by the Institute of Cancer Research and the National Institutes of Health Intramural Research Program. Disclosures for authors and editorial writers are available with the original articles. Welch reported receiving royalties from three books including “Should I be tested for cancer?”

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

A global analysis challenged the notion that a rise in cancer is disproportionately affecting younger adults, finding instead that several cancer types previously seen rising in younger adults are also increasing in older adults.

More specifically, the analysis found that incidence rates for thyroid cancer, breast cancer, kidney cancer, endometrial cancer, and leukemia increased similarly in both younger and older adults in most countries over a 15-year period. Colorectal cancer (CRC) was the exception, where incidence rates increased in younger adults in most countries but only increased slightly in older adults in about half and decreased in about one quarter.

“Our findings suggest that whatever is triggering the rise in these cancers is more likely to be common across all age groups, rather than specific to cancers in the under 50s, since there were similar increases in younger and older adults,” Amy Berrington de González, DPhil, The Institute of Cancer Research, London, England, who led the study, said in a statement.

The authors of an editorial agreed, adding that the growing “concern about increasing cancer rates should recognize that this increase is not restricted to young adults but affects all generations.”

The study and editorial were published recently in Annals of Internal Medicine.

 

Data Defy Early-Onset Cancer Epidemic Narrative

A growing body of evidence suggests that cancer incidence rates are increasing among younger adults in many countries. However, studies tracking international trends have largely evaluated cancer incidence in younger adults without comparing these trends in older adults or analyses have focused the age comparison in individual countries, Berrington de González and colleagues explained.

To better understand cancer incidence trends across countries and age groups, the researchers evaluated cancer trends in 42 countries between 2003 and 2017, focusing on 13 cancer types previously reported to be climbing in adults younger than age 50 years.

The researchers found that incidence rates for six of the 13 cancer types increased among younger adults (aged 20-49 years) in more than three quarters of the countries studied.

The largest increase was in thyroid cancer (median average annual percentage change [AAPC], 3.57%), followed by kidney cancer (median AAPC, 2.21%), endometrial cancer (median AAPC, 1.66%), CRC (median AAPC, 1.45%), breast cancer (median AAPC, 0.89%), and leukemia (median AAPC, 0.78%).

But with the exception of CRC, incidence rates for these cancers increased to a similar degree in adults aged 50 years or older — with median AAPCs of 3% (vs 3.57%) for thyroid cancer, 1.65% (vs 2.21%) for kidney cancer, 1.20% (vs 1.66%) for endometrial cancer, 0.86% (vs 0.89%) for breast cancer, and 0.61% (vs 0.78%) for leukemia.

In older adults, CRC incidence rates only increased in about half the countries (median AAPC, 0.37%), and the annual percentage change was much greater in younger than older adults in nearly 70% of countries. CRC incidence rates in older individuals also decreased in nearly 25% of countries.

Why is CRC an apparent outlier?

“Bowel cancer screening not only helps detect cancer at earlier stages but also helps prevent cancer through the removal of premalignant lesions,” Berrington de González said. “This could be why bowel cancer cases seem to be rising faster in younger adults — we’re getting better at preventing them developing in older adults.”

The incidence of certain cancers also declined in younger adults. Specifically, rates of liver, oral, esophageal, and stomach cancers decreased in younger adults in more than half of countries assessed, with median AAPCs of -0.14% for liver, -0.42% for oral, -0.92% for esophageal, and -1.62% for stomach cancers.

Over half of countries also saw declining rates of stomach (median AAPC, -2.05%) and esophageal (median AAPC, -0.25%) cancers among older adults, while rates of liver and oral cancers increased in older individuals (median AAPC, 2.17% and 0.49%, respectively).

For gallbladder, pancreatic, and prostate cancers — three other cancers previously found to be increasing in younger adults — the researchers reported that incidence rates increased in younger adults in just over half of countries (median AAPCs, 3.2% for prostate cancer, 0.49% for gallbladder cancer, and 1% for pancreatic cancer). Incidence rates also often increased in older adults but to a lesser extent (median AAPCs, 0.75% for prostate cancer, -0.10% for gallbladder, and 0.96% for pancreatic cancer).

 

True Rise or Increased Scrutiny?

Why are cancer rates increasing?

“Understanding factors that contribute to the increase in incidence across the age spectrum was beyond the scope of the study,” editorialists Christopher Cann, MD, Fox Chase Cancer Center, and Efrat Dotan, MD, University of Pennsylvania Health System, both in Philadelphia, wrote.

Several studies have suggested that rising rates of obesity could help explain increasing cancer incidence, particularly in younger adults. In fact, “the cancers that we identified as increasing are all obesity-related cancers, including endometrial and kidney cancer,” Berrington de González said. However, so far, the evidence on this link remains unclear, she acknowledged.

Weighing in on the study, Gilbert Welch, MD, Brigham and Women’s Hospital, Boston, told this news organization that it’s “critically important” to distinguish between two explanations for rising cancer incidence.

There may be an increase in the true occurrence of clinically meaningful cancer, which “warrants investigation into biologic explanations, better treatment, and perhaps more testing,” Welch said.

But it may instead reflect changes in diagnostic scrutiny. “Simply put, whenever we doctors look harder for cancer, we find more,” Welch said. “And there are lots of ways to look harder: testing more people, testing people more frequently, using tests with increasing ability to detect small irregularities, and using lower diagnostic thresholds for labeling these as cancer.”

If increased incidence is the result of greater diagnostic scrutiny, searching for biologic causes is bound to be unproductive and more testing will only aggravate the problem, he explained.

Welch pointed out that the fastest rising cancer in both younger and older adults was thyroid cancer (AAPC, ≥ 3%), which is “exquisitely sensitive” to diagnostic scrutiny.

Take what happened in South Korea. Around 2000, the government of South Korea started a national screening program for breast, colon, and stomach cancers. Doctors and hospitals often added on ultrasound scans for thyroid cancer for a small additional fee.

“A decade later the rate of thyroid cancer diagnosis had increased 15-fold, turning what was once a rare cancer into the most common cancer in Korea,” Welch said. “But the death rate from thyroid cancer did not change. This was not an epidemic of disease; this was an epidemic of diagnosis.”

Welch also noted that the study authors and editorialists put the finding in perspective by explaining that, despite the rising rates of certain cancers in younger adults, cancer remains rare in these adults.

Welch highlighted that, for younger adults in the US, cancer death rates in young adults have cut in half over the last 30 years. “Cancer accounts for only 10% of deaths in young people in the US — and that number is falling,” Welch said.

The study was funded by the Institute of Cancer Research and the National Institutes of Health Intramural Research Program. Disclosures for authors and editorial writers are available with the original articles. Welch reported receiving royalties from three books including “Should I be tested for cancer?”

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

A global analysis challenged the notion that a rise in cancer is disproportionately affecting younger adults, finding instead that several cancer types previously seen rising in younger adults are also increasing in older adults.

More specifically, the analysis found that incidence rates for thyroid cancer, breast cancer, kidney cancer, endometrial cancer, and leukemia increased similarly in both younger and older adults in most countries over a 15-year period. Colorectal cancer (CRC) was the exception, where incidence rates increased in younger adults in most countries but only increased slightly in older adults in about half and decreased in about one quarter.

“Our findings suggest that whatever is triggering the rise in these cancers is more likely to be common across all age groups, rather than specific to cancers in the under 50s, since there were similar increases in younger and older adults,” Amy Berrington de González, DPhil, The Institute of Cancer Research, London, England, who led the study, said in a statement.

The authors of an editorial agreed, adding that the growing “concern about increasing cancer rates should recognize that this increase is not restricted to young adults but affects all generations.”

The study and editorial were published recently in Annals of Internal Medicine.

 

Data Defy Early-Onset Cancer Epidemic Narrative

A growing body of evidence suggests that cancer incidence rates are increasing among younger adults in many countries. However, studies tracking international trends have largely evaluated cancer incidence in younger adults without comparing these trends in older adults or analyses have focused the age comparison in individual countries, Berrington de González and colleagues explained.

To better understand cancer incidence trends across countries and age groups, the researchers evaluated cancer trends in 42 countries between 2003 and 2017, focusing on 13 cancer types previously reported to be climbing in adults younger than age 50 years.

The researchers found that incidence rates for six of the 13 cancer types increased among younger adults (aged 20-49 years) in more than three quarters of the countries studied.

The largest increase was in thyroid cancer (median average annual percentage change [AAPC], 3.57%), followed by kidney cancer (median AAPC, 2.21%), endometrial cancer (median AAPC, 1.66%), CRC (median AAPC, 1.45%), breast cancer (median AAPC, 0.89%), and leukemia (median AAPC, 0.78%).

But with the exception of CRC, incidence rates for these cancers increased to a similar degree in adults aged 50 years or older — with median AAPCs of 3% (vs 3.57%) for thyroid cancer, 1.65% (vs 2.21%) for kidney cancer, 1.20% (vs 1.66%) for endometrial cancer, 0.86% (vs 0.89%) for breast cancer, and 0.61% (vs 0.78%) for leukemia.

In older adults, CRC incidence rates only increased in about half the countries (median AAPC, 0.37%), and the annual percentage change was much greater in younger than older adults in nearly 70% of countries. CRC incidence rates in older individuals also decreased in nearly 25% of countries.

Why is CRC an apparent outlier?

“Bowel cancer screening not only helps detect cancer at earlier stages but also helps prevent cancer through the removal of premalignant lesions,” Berrington de González said. “This could be why bowel cancer cases seem to be rising faster in younger adults — we’re getting better at preventing them developing in older adults.”

The incidence of certain cancers also declined in younger adults. Specifically, rates of liver, oral, esophageal, and stomach cancers decreased in younger adults in more than half of countries assessed, with median AAPCs of -0.14% for liver, -0.42% for oral, -0.92% for esophageal, and -1.62% for stomach cancers.

Over half of countries also saw declining rates of stomach (median AAPC, -2.05%) and esophageal (median AAPC, -0.25%) cancers among older adults, while rates of liver and oral cancers increased in older individuals (median AAPC, 2.17% and 0.49%, respectively).

For gallbladder, pancreatic, and prostate cancers — three other cancers previously found to be increasing in younger adults — the researchers reported that incidence rates increased in younger adults in just over half of countries (median AAPCs, 3.2% for prostate cancer, 0.49% for gallbladder cancer, and 1% for pancreatic cancer). Incidence rates also often increased in older adults but to a lesser extent (median AAPCs, 0.75% for prostate cancer, -0.10% for gallbladder, and 0.96% for pancreatic cancer).

 

True Rise or Increased Scrutiny?

Why are cancer rates increasing?

“Understanding factors that contribute to the increase in incidence across the age spectrum was beyond the scope of the study,” editorialists Christopher Cann, MD, Fox Chase Cancer Center, and Efrat Dotan, MD, University of Pennsylvania Health System, both in Philadelphia, wrote.

Several studies have suggested that rising rates of obesity could help explain increasing cancer incidence, particularly in younger adults. In fact, “the cancers that we identified as increasing are all obesity-related cancers, including endometrial and kidney cancer,” Berrington de González said. However, so far, the evidence on this link remains unclear, she acknowledged.

Weighing in on the study, Gilbert Welch, MD, Brigham and Women’s Hospital, Boston, told this news organization that it’s “critically important” to distinguish between two explanations for rising cancer incidence.

There may be an increase in the true occurrence of clinically meaningful cancer, which “warrants investigation into biologic explanations, better treatment, and perhaps more testing,” Welch said.

But it may instead reflect changes in diagnostic scrutiny. “Simply put, whenever we doctors look harder for cancer, we find more,” Welch said. “And there are lots of ways to look harder: testing more people, testing people more frequently, using tests with increasing ability to detect small irregularities, and using lower diagnostic thresholds for labeling these as cancer.”

If increased incidence is the result of greater diagnostic scrutiny, searching for biologic causes is bound to be unproductive and more testing will only aggravate the problem, he explained.

Welch pointed out that the fastest rising cancer in both younger and older adults was thyroid cancer (AAPC, ≥ 3%), which is “exquisitely sensitive” to diagnostic scrutiny.

Take what happened in South Korea. Around 2000, the government of South Korea started a national screening program for breast, colon, and stomach cancers. Doctors and hospitals often added on ultrasound scans for thyroid cancer for a small additional fee.

“A decade later the rate of thyroid cancer diagnosis had increased 15-fold, turning what was once a rare cancer into the most common cancer in Korea,” Welch said. “But the death rate from thyroid cancer did not change. This was not an epidemic of disease; this was an epidemic of diagnosis.”

Welch also noted that the study authors and editorialists put the finding in perspective by explaining that, despite the rising rates of certain cancers in younger adults, cancer remains rare in these adults.

Welch highlighted that, for younger adults in the US, cancer death rates in young adults have cut in half over the last 30 years. “Cancer accounts for only 10% of deaths in young people in the US — and that number is falling,” Welch said.

The study was funded by the Institute of Cancer Research and the National Institutes of Health Intramural Research Program. Disclosures for authors and editorial writers are available with the original articles. Welch reported receiving royalties from three books including “Should I be tested for cancer?”

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