Oncology

The latest glucagon-like peptide 1 (GLP-1) receptor agonists have been heralded for their potential to not only boost weight loss and glucose control but also improve cardiovascular, gastric, hepatic, and renal values.

Throughout 2024, research has also indicated GLP-1 drugs may reduce risks for obesity-related cancer.

In a US study of more than 1.6 million patients with type 2 diabetes, cancer researchers found that patients who took a GLP-1 drug had significant risk reductions for 10 of 13 obesity-associated cancers, as compared with patients who only took insulin.

The research team found a reduction in esophageal, colorectal, endometrial, gallbladder, kidney, liver, ovarian, and pancreatic cancers, as well as meningioma and multiple myeloma. They also saw a declining risk for stomach cancer, though it wasn’t considered statistically significant, but not a reduced risk for postmenopausal breast cancer or thyroid cancer.

The associations make sense, particularly because GLP-1 drugs have unexpected effects on modulating immune functions linked to obesity-associated cancers.

“The protective effects of GLP-1s against obesity-associated cancers likely stem from multiple mechanisms,” said lead author Lindsey Wang, a medical student and research scholar at Case Western Reserve University in Cleveland.

“These drugs promote substantial weight loss, reducing obesity-related cancer risks,” she said. “They also enhance insulin sensitivity and lower insulin levels, decreasing cancer cell growth signals.”

 

Additional GLP-1 Studies

The Case Western team also published a study in December 2023 that found people with type 2 diabetes who took GLP-1s had a 44% lower risk for colorectal cancer than those who took insulin and a 25% lower risk than those who took metformin. The research suggested even greater risk reductions among those with overweight or obesity, with GLP-1 users having a 50% lower risk than those who took insulin and a 42% lower risk than those who took metformin.

In another recent Case Western study, both bariatric surgery and GLP-1 drugs reduced the risk for obesity-related cancers. While those who had bariatric surgery had a 22% risk reduction over 10 years, as compared with those who received no treatment, those taking GLP-1 had a 39% risk reduction.

Other studies worldwide have looked at GLP-1 drugs and tumor effects among various cancer cell lines. In a study using pancreatic cancer cell lines, GLP-1 liraglutide suppressed cancer cell growth and led to cell death. Similarly, a study using breast cancer cells found liraglutide reduced cancer cell viability and the ability for cells to migrate.

As researchers identify additional links between GLP-1s and improvements across organ systems, the knock-on effects could lead to lower cancer risks as well. For example, studies presented at The Liver Meeting in San Diego in November pointed to GLP-1s reducing fatty liver disease, which can slow the progression to liver cancer.

“Separate from obesity, having higher levels of body fat is associated with an increased risk of several forms of cancer,” said Neil Iyengar, MD, an oncologist at Memorial Sloan Kettering Cancer Center in New York City. Iyengar researches the relationship between obesity and cancer.

“I foresee that this class of drugs will revolutionize obesity and the cancer burden that comes with it, if people can get access,” he said. “This really is an exciting development.”

 

Ongoing GLP-1 Research

On the other hand, cancer researchers have also expressed concerns about potential associations between GLP-1s and increased cancer risks. In the obesity-associated cancer study by Case Western researchers, patients with type 2 diabetes taking a GLP-1 drug appeared to have a slightly higher risk for kidney cancer than those taking metformin.

In addition, GLP-1 studies in animals have indicated that the drugs may increase the risks for medullary thyroid cancer and pancreatic cancer. However, the data on increased risks in humans remain inconclusive, and more recent studies refute these findings.

For instance, cancer researchers in India conducted a systematic review and meta-analysis of semaglutide and cancer risks, finding that 37 randomized controlled trials and 19 real-world studies didn’t find increased risks for any cancer, including pancreatic and thyroid cancers.

In another systematic review by Brazilian researchers, 50 trials found GLP-1s didn’t increase the risk for breast cancer or benign breast neoplasms.

In 2025, new retrospective studies will show more nuanced data, especially as more patients — both with and without type 2 diabetes — take semaglutide, tirzepatide, and new GLP-1 drugs in the research pipeline.

“The holy grail has always been getting a medication to treat obesity,” said Anne McTiernan, MD, PhD, an epidemiologist and obesity researcher at the Fred Hutchinson Cancer Center in Seattle.

“There have been trials focused on these medications’ effects on diabetes and cardiovascular disease treatment, but no trials have tested their effects on cancer risk,” she said. “Usually, many years of follow-up of large numbers of patients are needed to see cancer effects of a carcinogen or cancer-preventing intervention.”

Those clinical trials are likely coming soon, she said. Researchers will need to conduct prospective clinical trials to examine the direct relationship between GLP-1 drugs and cancer risks, as well as the underlying mechanisms linked to cancer cell growth, activation of immune cells, and anti-inflammatory properties.

Because GLP-1 medications aren’t intended to be taken forever, researchers will also need to consider the associations with long-term cancer risks. Even so, weight loss and other obesity-related improvements could contribute to overall lower cancer risks in the end.

“If taking these drugs for a limited amount of time can help people lose weight and get on an exercise plan, then that’s helping lower cancer risk long-term,” said Sonali Thosani, MD, associate professor of endocrine neoplasia and hormonal disorders at the University of Texas MD Anderson Cancer Center in Houston.

“But it all comes back to someone making lifestyle changes and sticking to them, even after they stop taking the drugs,” she said. “If they can do that, then you’ll probably see a net positive for long-term cancer risks and other long-term health risks.”

 

A version of this article appeared on Medscape.com.

The latest glucagon-like peptide 1 (GLP-1) receptor agonists have been heralded for their potential to not only boost weight loss and glucose control but also improve cardiovascular, gastric, hepatic, and renal values.

Throughout 2024, research has also indicated GLP-1 drugs may reduce risks for obesity-related cancer.

In a US study of more than 1.6 million patients with type 2 diabetes, cancer researchers found that patients who took a GLP-1 drug had significant risk reductions for 10 of 13 obesity-associated cancers, as compared with patients who only took insulin.

The research team found a reduction in esophageal, colorectal, endometrial, gallbladder, kidney, liver, ovarian, and pancreatic cancers, as well as meningioma and multiple myeloma. They also saw a declining risk for stomach cancer, though it wasn’t considered statistically significant, but not a reduced risk for postmenopausal breast cancer or thyroid cancer.

The associations make sense, particularly because GLP-1 drugs have unexpected effects on modulating immune functions linked to obesity-associated cancers.

“The protective effects of GLP-1s against obesity-associated cancers likely stem from multiple mechanisms,” said lead author Lindsey Wang, a medical student and research scholar at Case Western Reserve University in Cleveland.

“These drugs promote substantial weight loss, reducing obesity-related cancer risks,” she said. “They also enhance insulin sensitivity and lower insulin levels, decreasing cancer cell growth signals.”

 

Additional GLP-1 Studies

The Case Western team also published a study in December 2023 that found people with type 2 diabetes who took GLP-1s had a 44% lower risk for colorectal cancer than those who took insulin and a 25% lower risk than those who took metformin. The research suggested even greater risk reductions among those with overweight or obesity, with GLP-1 users having a 50% lower risk than those who took insulin and a 42% lower risk than those who took metformin.

In another recent Case Western study, both bariatric surgery and GLP-1 drugs reduced the risk for obesity-related cancers. While those who had bariatric surgery had a 22% risk reduction over 10 years, as compared with those who received no treatment, those taking GLP-1 had a 39% risk reduction.

Other studies worldwide have looked at GLP-1 drugs and tumor effects among various cancer cell lines. In a study using pancreatic cancer cell lines, GLP-1 liraglutide suppressed cancer cell growth and led to cell death. Similarly, a study using breast cancer cells found liraglutide reduced cancer cell viability and the ability for cells to migrate.

As researchers identify additional links between GLP-1s and improvements across organ systems, the knock-on effects could lead to lower cancer risks as well. For example, studies presented at The Liver Meeting in San Diego in November pointed to GLP-1s reducing fatty liver disease, which can slow the progression to liver cancer.

“Separate from obesity, having higher levels of body fat is associated with an increased risk of several forms of cancer,” said Neil Iyengar, MD, an oncologist at Memorial Sloan Kettering Cancer Center in New York City. Iyengar researches the relationship between obesity and cancer.

“I foresee that this class of drugs will revolutionize obesity and the cancer burden that comes with it, if people can get access,” he said. “This really is an exciting development.”

 

Ongoing GLP-1 Research

On the other hand, cancer researchers have also expressed concerns about potential associations between GLP-1s and increased cancer risks. In the obesity-associated cancer study by Case Western researchers, patients with type 2 diabetes taking a GLP-1 drug appeared to have a slightly higher risk for kidney cancer than those taking metformin.

In addition, GLP-1 studies in animals have indicated that the drugs may increase the risks for medullary thyroid cancer and pancreatic cancer. However, the data on increased risks in humans remain inconclusive, and more recent studies refute these findings.

For instance, cancer researchers in India conducted a systematic review and meta-analysis of semaglutide and cancer risks, finding that 37 randomized controlled trials and 19 real-world studies didn’t find increased risks for any cancer, including pancreatic and thyroid cancers.

In another systematic review by Brazilian researchers, 50 trials found GLP-1s didn’t increase the risk for breast cancer or benign breast neoplasms.

In 2025, new retrospective studies will show more nuanced data, especially as more patients — both with and without type 2 diabetes — take semaglutide, tirzepatide, and new GLP-1 drugs in the research pipeline.

“The holy grail has always been getting a medication to treat obesity,” said Anne McTiernan, MD, PhD, an epidemiologist and obesity researcher at the Fred Hutchinson Cancer Center in Seattle.

“There have been trials focused on these medications’ effects on diabetes and cardiovascular disease treatment, but no trials have tested their effects on cancer risk,” she said. “Usually, many years of follow-up of large numbers of patients are needed to see cancer effects of a carcinogen or cancer-preventing intervention.”

Those clinical trials are likely coming soon, she said. Researchers will need to conduct prospective clinical trials to examine the direct relationship between GLP-1 drugs and cancer risks, as well as the underlying mechanisms linked to cancer cell growth, activation of immune cells, and anti-inflammatory properties.

Because GLP-1 medications aren’t intended to be taken forever, researchers will also need to consider the associations with long-term cancer risks. Even so, weight loss and other obesity-related improvements could contribute to overall lower cancer risks in the end.

“If taking these drugs for a limited amount of time can help people lose weight and get on an exercise plan, then that’s helping lower cancer risk long-term,” said Sonali Thosani, MD, associate professor of endocrine neoplasia and hormonal disorders at the University of Texas MD Anderson Cancer Center in Houston.

“But it all comes back to someone making lifestyle changes and sticking to them, even after they stop taking the drugs,” she said. “If they can do that, then you’ll probably see a net positive for long-term cancer risks and other long-term health risks.”

 

A version of this article appeared on Medscape.com.

The latest glucagon-like peptide 1 (GLP-1) receptor agonists have been heralded for their potential to not only boost weight loss and glucose control but also improve cardiovascular, gastric, hepatic, and renal values.

Throughout 2024, research has also indicated GLP-1 drugs may reduce risks for obesity-related cancer.

In a US study of more than 1.6 million patients with type 2 diabetes, cancer researchers found that patients who took a GLP-1 drug had significant risk reductions for 10 of 13 obesity-associated cancers, as compared with patients who only took insulin.

The research team found a reduction in esophageal, colorectal, endometrial, gallbladder, kidney, liver, ovarian, and pancreatic cancers, as well as meningioma and multiple myeloma. They also saw a declining risk for stomach cancer, though it wasn’t considered statistically significant, but not a reduced risk for postmenopausal breast cancer or thyroid cancer.

The associations make sense, particularly because GLP-1 drugs have unexpected effects on modulating immune functions linked to obesity-associated cancers.

“The protective effects of GLP-1s against obesity-associated cancers likely stem from multiple mechanisms,” said lead author Lindsey Wang, a medical student and research scholar at Case Western Reserve University in Cleveland.

“These drugs promote substantial weight loss, reducing obesity-related cancer risks,” she said. “They also enhance insulin sensitivity and lower insulin levels, decreasing cancer cell growth signals.”

 

Additional GLP-1 Studies

The Case Western team also published a study in December 2023 that found people with type 2 diabetes who took GLP-1s had a 44% lower risk for colorectal cancer than those who took insulin and a 25% lower risk than those who took metformin. The research suggested even greater risk reductions among those with overweight or obesity, with GLP-1 users having a 50% lower risk than those who took insulin and a 42% lower risk than those who took metformin.

In another recent Case Western study, both bariatric surgery and GLP-1 drugs reduced the risk for obesity-related cancers. While those who had bariatric surgery had a 22% risk reduction over 10 years, as compared with those who received no treatment, those taking GLP-1 had a 39% risk reduction.

Other studies worldwide have looked at GLP-1 drugs and tumor effects among various cancer cell lines. In a study using pancreatic cancer cell lines, GLP-1 liraglutide suppressed cancer cell growth and led to cell death. Similarly, a study using breast cancer cells found liraglutide reduced cancer cell viability and the ability for cells to migrate.

As researchers identify additional links between GLP-1s and improvements across organ systems, the knock-on effects could lead to lower cancer risks as well. For example, studies presented at The Liver Meeting in San Diego in November pointed to GLP-1s reducing fatty liver disease, which can slow the progression to liver cancer.

“Separate from obesity, having higher levels of body fat is associated with an increased risk of several forms of cancer,” said Neil Iyengar, MD, an oncologist at Memorial Sloan Kettering Cancer Center in New York City. Iyengar researches the relationship between obesity and cancer.

“I foresee that this class of drugs will revolutionize obesity and the cancer burden that comes with it, if people can get access,” he said. “This really is an exciting development.”

 

Ongoing GLP-1 Research

On the other hand, cancer researchers have also expressed concerns about potential associations between GLP-1s and increased cancer risks. In the obesity-associated cancer study by Case Western researchers, patients with type 2 diabetes taking a GLP-1 drug appeared to have a slightly higher risk for kidney cancer than those taking metformin.

In addition, GLP-1 studies in animals have indicated that the drugs may increase the risks for medullary thyroid cancer and pancreatic cancer. However, the data on increased risks in humans remain inconclusive, and more recent studies refute these findings.

For instance, cancer researchers in India conducted a systematic review and meta-analysis of semaglutide and cancer risks, finding that 37 randomized controlled trials and 19 real-world studies didn’t find increased risks for any cancer, including pancreatic and thyroid cancers.

In another systematic review by Brazilian researchers, 50 trials found GLP-1s didn’t increase the risk for breast cancer or benign breast neoplasms.

In 2025, new retrospective studies will show more nuanced data, especially as more patients — both with and without type 2 diabetes — take semaglutide, tirzepatide, and new GLP-1 drugs in the research pipeline.

“The holy grail has always been getting a medication to treat obesity,” said Anne McTiernan, MD, PhD, an epidemiologist and obesity researcher at the Fred Hutchinson Cancer Center in Seattle.

“There have been trials focused on these medications’ effects on diabetes and cardiovascular disease treatment, but no trials have tested their effects on cancer risk,” she said. “Usually, many years of follow-up of large numbers of patients are needed to see cancer effects of a carcinogen or cancer-preventing intervention.”

Those clinical trials are likely coming soon, she said. Researchers will need to conduct prospective clinical trials to examine the direct relationship between GLP-1 drugs and cancer risks, as well as the underlying mechanisms linked to cancer cell growth, activation of immune cells, and anti-inflammatory properties.

Because GLP-1 medications aren’t intended to be taken forever, researchers will also need to consider the associations with long-term cancer risks. Even so, weight loss and other obesity-related improvements could contribute to overall lower cancer risks in the end.

“If taking these drugs for a limited amount of time can help people lose weight and get on an exercise plan, then that’s helping lower cancer risk long-term,” said Sonali Thosani, MD, associate professor of endocrine neoplasia and hormonal disorders at the University of Texas MD Anderson Cancer Center in Houston.

“But it all comes back to someone making lifestyle changes and sticking to them, even after they stop taking the drugs,” she said. “If they can do that, then you’ll probably see a net positive for long-term cancer risks and other long-term health risks.”

 

A version of this article appeared on Medscape.com.

The evidence is clear: Alcohol can cause cancer.

Earlier this month, US surgeon general Vivek Murthy, MD, issued an advisory, calling for alcoholic beverages to carry a warning label about cancer risk. The advisory flagged alcohol as the third leading preventable cause of cancer in the United States, after tobacco and obesity, and highlighted people’s limited awareness about the relationship between alcohol and cancer risk.

But, when it comes to cancer risk, are all types of alcohol created equal?

For many years, red wine seemed to be an outlier, with studies indicating that, in moderation, it might even be good for you. Red wine has anti-inflammatory and antioxidant properties — most notably, it contains the antioxidant resveratrol. Starting in the 1990s, research began to hint that the compound might protect against heart disease, aging, and cancer, though much of this work was done in animals or test tubes.

The idea that red wine carries health benefits, however, has been called into question more recently. A recent meta-analysis, for instance, suggests that many previous studies touting the health benefits of more moderate drinking were likely biased, potentially leading to “misleading positive health associations.” And one recent study found that alcohol consumption, largely red wine and beer, at all levels was linked to an increased risk for cardiovascular disease.

Although wine’s health halo is dwindling, there might be an exception: Cancer risk.

Overall, research shows that even light to moderate drinking increases the risk for at least seven types of cancer, but when focusing on red wine, in particular, that risk calculus can look different.

“It’s very complicated and nuanced,” said Timothy Rebbeck, PhD, professor of cancer prevention, Harvard T.H. Chan School of Public Health, Boston. “And ‘complicated and nuanced’ doesn’t work very well in public health messages.”

The Knowns About Alcohol and Cancer Risk

Some things about the relationship between alcohol and cancer risk are crystal clear. “There’s no question that alcohol is a group 1 carcinogen,” Rebbeck said. “Alcohol can cause cancer.”

Groups including the International Agency for Research on Cancer (IARC) and American Cancer Society agree that alcohol use is an established cause of seven types of cancer: Those of the oral cavity, larynx, pharynx, esophagus (squamous cell carcinoma), liver (hepatocellular carcinoma), breast, and colon/rectum. Heavy drinking — at least 8 standard drinks a week for women and 15 for men — and binge drinking — 4 or more drinks in 2 hours for women and 5 or more for men — only amplify that risk. (A “standard” drink has 14 g of alcohol, which translates to a 5-oz glass of wine.)

“We’re most concerned about high-risk drinking — more than 2 drinks a day — and/or binge drinking,” said Noelle LoConte, MD, of the Division of Hematology, Medical Oncology and Palliative Care, University of Wisconsin School of Medicine and Public Health, Madison, who authored a 2018 statement on alcohol and cancer risk from the American Society of Clinical Oncology (ASCO).

Compared with not drinking, heavy drinking is linked with a roughly fivefold increase in the risk for oral cavity, pharyngeal, and esophageal cancers, and a 61% increase in the risk for breast cancer, according to LoConte and colleagues.

Things get murkier when it comes to moderate drinking — defined as up to 1 standard drink per day for women and 2 per day for men. There is evidence, LoConte said, that moderate drinking is associated with increased cancer risks, though the magnitude is generally much less than heavier drinking.

Cancer type also matters. One analysis found that the risk for breast cancer increased with even light to moderate alcohol consumption. Compared with no drinking, light to moderate drinking has also been linked to increased risks for oral cavity, pharynx, larynx, and esophageal cancers.

As for whether the type of alcoholic beverage matters, LoConte said, there’s no clear physiological reason that wine would be less risky than beer or liquor. Research indicates that ethanol is the problematic ingredient: Once ingested, it’s metabolized into acetaldehyde, a DNA-damaging substance that’s considered a probable human carcinogen. Ethanol can also alter circulating levels of estrogens and androgens, LoConte said, which is thought to drive its association with breast cancer risk.

“It likely doesn’t matter how you choose to get your ethanol,” she said. “It’s a question of volume.”

Hints That Wine Is an Outlier

Still, some studies suggest that how people ingest ethanol could make a difference.

A study published in August in JAMA Network Open is a case in point. The study found that, among older adults, light to heavy drinkers had an increased risk of dying from cancer, compared with occasional drinkers (though the increased risk among light to moderate drinkers occurred only among people who also had chronic health conditions, such as diabetes or high blood pressure, or were of lower socioeconomic status).

Wine drinkers fared differently. Most notably, drinkers who “preferred” wine — consuming over 80% of total ethanol from wine — or those who drank only with meals showed a small reduction in their risk for cancer mortality and all-cause mortality (hazard ratio [HR], 0.94 for both). The small protective association was somewhat stronger among people who reported both patterns (HR, 0.88), especially if they were of lower socioeconomic status (HR, 0.79).

The findings are in line with other research suggesting that wine drinkers may be outliers when it comes to cancer risk. A 2023 meta-analysis of 26 observational studies, for instance, found no association between wine consumption and any cancer type, with the caveat that there was «substantial» heterogeneity among the studies.

This heterogeneity caveat speaks to the inherent limitations of observational research, said Tim Stockwell, PhD, of the Canadian Institute for Substance Use Research, University of Victoria in British Columbia, Canada.

“Individual studies of alcohol and cancer risk do find differences by type of drink, or patterns of drinking,” Stockwell said. “But it’s so hard to unpack the confounding that goes along with the type of person who’s a wine drinker or a beer drinker or a spirit drinker. The beverage of choice seems to come with a lot of baggage.”

Compared with people who favor beer or liquor, he noted, wine aficionados are typically higher-income, exercise more often, smoke less, and have different diets, for example. The “best” studies, Rebbeck said, try to adjust for those differences, but it’s challenging.

The authors of the 2023 meta-analysis noted that “many components in wine could have anticarcinogenic effects” that theoretically could counter the ill effects of ethanol. Besides resveratrol, which is mainly found in red wine, the list includes anthocyanins, quercetin, and tannins. However, the authors also acknowledged that they couldn’t account for whether other lifestyle habits might explain why wine drinkers, overall, showed no increased cancer risks and sometimes lower risks.

Still, groups such as the IARC and ASCO hold that there is no known “safe” level, or type, of alcohol when it comes to cancer.

In the latest Canadian guidelines on alcohol use, the scientific panel calculated that people who have 6 drinks a week throughout adulthood (whatever the source of the alcohol) could shave 11 weeks from their life expectancy, on average, said Stockwell, who was on the guideline panel. Compare that with heavy drinking, where 4 drinks a day could rob the average person of 2 or 3 years. “If you’re drinking a lot, you could get huge benefits from cutting down,” Stockwell explained. “If you’re a moderate drinker, the benefits would obviously be less.”

Stockwell said that choices around drinking and breast cancer risk, specifically, can be “tough.” Unlike many of the other alcohol-associated cancers, he noted, breast cancer is common — so even small relative risk increases may be concerning. Based on a 2020 meta-analysis of 22 cohort studies, the risk for breast cancer rises by about 10%, on average, for every 10 g of alcohol a woman drinks per day. This study also found no evidence that wine is any different from other types of alcohol.

In real life, the calculus around wine consumption and cancer risk will probably vary widely from person to person, Rebbeck said. One woman with a family history of breast cancer might decide that having wine with dinner isn’t worth it. Another with the same family history might see that glass of wine as a stress reliever and opt to focus on other ways to reduce her breast cancer risk — by exercising and maintaining a healthy weight, for example.

“The bottom line is, in human studies, the data on light to moderate drinking and cancer are limited and messy, and you can’t draw firm conclusions from them,” Rebbeck said. “It probably raises risk in some people, but we don’t know who those people are. And the risk increases are relatively small.”

A Conversation Few Are Having

Even with many studies highlighting the connection between alcohol consumption and cancer risk, most people remain unaware about this risk.

A 2023 study by the National Cancer Institute found that only a minority of US adults knew that drinking alcohol is linked to increased cancer risk, and they were much less likely to say that was true of wine: Only 20% did, vs 31% who said that liquor can boost cancer risk. Meanwhile, 10% believed that wine helps prevent cancer. Other studies show that even among cancer survivors and patients undergoing active cancer treatment, many drink — often heavily.

“What we know right now is, physicians almost never talk about this,” LoConte said.

That could be due to time constraints, according to Rebbeck, or clinicians’ perceptions that the subject is too complicated and/or their own confusion about the data. There could also be some “cognitive dissonance” at play, LoConte noted, because many doctors drink alcohol.

It’s critical, she said, that conversations about drinking habits become “normalized,” and that should include informing patients that alcohol use is associated with certain cancers. Again, LoConte said, it’s high-risk drinking that’s most concerning and where reducing intake could have the biggest impact on cancer risk and other health outcomes.

“From a cancer prevention standpoint, it’s probably best not to drink,” she said. “But people don’t make choices based solely on cancer risk. We don’t want to come out with recommendations saying no one should drink. I don’t think the data support that, and people would buck against that advice.”

Rebbeck made a similar point. Even if there’s uncertainty about the risks for a daily glass of wine, he said, people can use that information to make decisions. “Everybody’s preferences and choices are going to be different,” Rebbeck said. “And that’s all we can really do.”

A version of this article appeared on Medscape.com.

The evidence is clear: Alcohol can cause cancer.

Earlier this month, US surgeon general Vivek Murthy, MD, issued an advisory, calling for alcoholic beverages to carry a warning label about cancer risk. The advisory flagged alcohol as the third leading preventable cause of cancer in the United States, after tobacco and obesity, and highlighted people’s limited awareness about the relationship between alcohol and cancer risk.

But, when it comes to cancer risk, are all types of alcohol created equal?

For many years, red wine seemed to be an outlier, with studies indicating that, in moderation, it might even be good for you. Red wine has anti-inflammatory and antioxidant properties — most notably, it contains the antioxidant resveratrol. Starting in the 1990s, research began to hint that the compound might protect against heart disease, aging, and cancer, though much of this work was done in animals or test tubes.

The idea that red wine carries health benefits, however, has been called into question more recently. A recent meta-analysis, for instance, suggests that many previous studies touting the health benefits of more moderate drinking were likely biased, potentially leading to “misleading positive health associations.” And one recent study found that alcohol consumption, largely red wine and beer, at all levels was linked to an increased risk for cardiovascular disease.

Although wine’s health halo is dwindling, there might be an exception: Cancer risk.

Overall, research shows that even light to moderate drinking increases the risk for at least seven types of cancer, but when focusing on red wine, in particular, that risk calculus can look different.

“It’s very complicated and nuanced,” said Timothy Rebbeck, PhD, professor of cancer prevention, Harvard T.H. Chan School of Public Health, Boston. “And ‘complicated and nuanced’ doesn’t work very well in public health messages.”

The Knowns About Alcohol and Cancer Risk

Some things about the relationship between alcohol and cancer risk are crystal clear. “There’s no question that alcohol is a group 1 carcinogen,” Rebbeck said. “Alcohol can cause cancer.”

Groups including the International Agency for Research on Cancer (IARC) and American Cancer Society agree that alcohol use is an established cause of seven types of cancer: Those of the oral cavity, larynx, pharynx, esophagus (squamous cell carcinoma), liver (hepatocellular carcinoma), breast, and colon/rectum. Heavy drinking — at least 8 standard drinks a week for women and 15 for men — and binge drinking — 4 or more drinks in 2 hours for women and 5 or more for men — only amplify that risk. (A “standard” drink has 14 g of alcohol, which translates to a 5-oz glass of wine.)

“We’re most concerned about high-risk drinking — more than 2 drinks a day — and/or binge drinking,” said Noelle LoConte, MD, of the Division of Hematology, Medical Oncology and Palliative Care, University of Wisconsin School of Medicine and Public Health, Madison, who authored a 2018 statement on alcohol and cancer risk from the American Society of Clinical Oncology (ASCO).

Compared with not drinking, heavy drinking is linked with a roughly fivefold increase in the risk for oral cavity, pharyngeal, and esophageal cancers, and a 61% increase in the risk for breast cancer, according to LoConte and colleagues.

Things get murkier when it comes to moderate drinking — defined as up to 1 standard drink per day for women and 2 per day for men. There is evidence, LoConte said, that moderate drinking is associated with increased cancer risks, though the magnitude is generally much less than heavier drinking.

Cancer type also matters. One analysis found that the risk for breast cancer increased with even light to moderate alcohol consumption. Compared with no drinking, light to moderate drinking has also been linked to increased risks for oral cavity, pharynx, larynx, and esophageal cancers.

As for whether the type of alcoholic beverage matters, LoConte said, there’s no clear physiological reason that wine would be less risky than beer or liquor. Research indicates that ethanol is the problematic ingredient: Once ingested, it’s metabolized into acetaldehyde, a DNA-damaging substance that’s considered a probable human carcinogen. Ethanol can also alter circulating levels of estrogens and androgens, LoConte said, which is thought to drive its association with breast cancer risk.

“It likely doesn’t matter how you choose to get your ethanol,” she said. “It’s a question of volume.”

Hints That Wine Is an Outlier

Still, some studies suggest that how people ingest ethanol could make a difference.

A study published in August in JAMA Network Open is a case in point. The study found that, among older adults, light to heavy drinkers had an increased risk of dying from cancer, compared with occasional drinkers (though the increased risk among light to moderate drinkers occurred only among people who also had chronic health conditions, such as diabetes or high blood pressure, or were of lower socioeconomic status).

Wine drinkers fared differently. Most notably, drinkers who “preferred” wine — consuming over 80% of total ethanol from wine — or those who drank only with meals showed a small reduction in their risk for cancer mortality and all-cause mortality (hazard ratio [HR], 0.94 for both). The small protective association was somewhat stronger among people who reported both patterns (HR, 0.88), especially if they were of lower socioeconomic status (HR, 0.79).

The findings are in line with other research suggesting that wine drinkers may be outliers when it comes to cancer risk. A 2023 meta-analysis of 26 observational studies, for instance, found no association between wine consumption and any cancer type, with the caveat that there was «substantial» heterogeneity among the studies.

This heterogeneity caveat speaks to the inherent limitations of observational research, said Tim Stockwell, PhD, of the Canadian Institute for Substance Use Research, University of Victoria in British Columbia, Canada.

“Individual studies of alcohol and cancer risk do find differences by type of drink, or patterns of drinking,” Stockwell said. “But it’s so hard to unpack the confounding that goes along with the type of person who’s a wine drinker or a beer drinker or a spirit drinker. The beverage of choice seems to come with a lot of baggage.”

Compared with people who favor beer or liquor, he noted, wine aficionados are typically higher-income, exercise more often, smoke less, and have different diets, for example. The “best” studies, Rebbeck said, try to adjust for those differences, but it’s challenging.

The authors of the 2023 meta-analysis noted that “many components in wine could have anticarcinogenic effects” that theoretically could counter the ill effects of ethanol. Besides resveratrol, which is mainly found in red wine, the list includes anthocyanins, quercetin, and tannins. However, the authors also acknowledged that they couldn’t account for whether other lifestyle habits might explain why wine drinkers, overall, showed no increased cancer risks and sometimes lower risks.

Still, groups such as the IARC and ASCO hold that there is no known “safe” level, or type, of alcohol when it comes to cancer.

In the latest Canadian guidelines on alcohol use, the scientific panel calculated that people who have 6 drinks a week throughout adulthood (whatever the source of the alcohol) could shave 11 weeks from their life expectancy, on average, said Stockwell, who was on the guideline panel. Compare that with heavy drinking, where 4 drinks a day could rob the average person of 2 or 3 years. “If you’re drinking a lot, you could get huge benefits from cutting down,” Stockwell explained. “If you’re a moderate drinker, the benefits would obviously be less.”

Stockwell said that choices around drinking and breast cancer risk, specifically, can be “tough.” Unlike many of the other alcohol-associated cancers, he noted, breast cancer is common — so even small relative risk increases may be concerning. Based on a 2020 meta-analysis of 22 cohort studies, the risk for breast cancer rises by about 10%, on average, for every 10 g of alcohol a woman drinks per day. This study also found no evidence that wine is any different from other types of alcohol.

In real life, the calculus around wine consumption and cancer risk will probably vary widely from person to person, Rebbeck said. One woman with a family history of breast cancer might decide that having wine with dinner isn’t worth it. Another with the same family history might see that glass of wine as a stress reliever and opt to focus on other ways to reduce her breast cancer risk — by exercising and maintaining a healthy weight, for example.

“The bottom line is, in human studies, the data on light to moderate drinking and cancer are limited and messy, and you can’t draw firm conclusions from them,” Rebbeck said. “It probably raises risk in some people, but we don’t know who those people are. And the risk increases are relatively small.”

A Conversation Few Are Having

Even with many studies highlighting the connection between alcohol consumption and cancer risk, most people remain unaware about this risk.

A 2023 study by the National Cancer Institute found that only a minority of US adults knew that drinking alcohol is linked to increased cancer risk, and they were much less likely to say that was true of wine: Only 20% did, vs 31% who said that liquor can boost cancer risk. Meanwhile, 10% believed that wine helps prevent cancer. Other studies show that even among cancer survivors and patients undergoing active cancer treatment, many drink — often heavily.

“What we know right now is, physicians almost never talk about this,” LoConte said.

That could be due to time constraints, according to Rebbeck, or clinicians’ perceptions that the subject is too complicated and/or their own confusion about the data. There could also be some “cognitive dissonance” at play, LoConte noted, because many doctors drink alcohol.

It’s critical, she said, that conversations about drinking habits become “normalized,” and that should include informing patients that alcohol use is associated with certain cancers. Again, LoConte said, it’s high-risk drinking that’s most concerning and where reducing intake could have the biggest impact on cancer risk and other health outcomes.

“From a cancer prevention standpoint, it’s probably best not to drink,” she said. “But people don’t make choices based solely on cancer risk. We don’t want to come out with recommendations saying no one should drink. I don’t think the data support that, and people would buck against that advice.”

Rebbeck made a similar point. Even if there’s uncertainty about the risks for a daily glass of wine, he said, people can use that information to make decisions. “Everybody’s preferences and choices are going to be different,” Rebbeck said. “And that’s all we can really do.”

A version of this article appeared on Medscape.com.

The evidence is clear: Alcohol can cause cancer.

Earlier this month, US surgeon general Vivek Murthy, MD, issued an advisory, calling for alcoholic beverages to carry a warning label about cancer risk. The advisory flagged alcohol as the third leading preventable cause of cancer in the United States, after tobacco and obesity, and highlighted people’s limited awareness about the relationship between alcohol and cancer risk.

But, when it comes to cancer risk, are all types of alcohol created equal?

For many years, red wine seemed to be an outlier, with studies indicating that, in moderation, it might even be good for you. Red wine has anti-inflammatory and antioxidant properties — most notably, it contains the antioxidant resveratrol. Starting in the 1990s, research began to hint that the compound might protect against heart disease, aging, and cancer, though much of this work was done in animals or test tubes.

The idea that red wine carries health benefits, however, has been called into question more recently. A recent meta-analysis, for instance, suggests that many previous studies touting the health benefits of more moderate drinking were likely biased, potentially leading to “misleading positive health associations.” And one recent study found that alcohol consumption, largely red wine and beer, at all levels was linked to an increased risk for cardiovascular disease.

Although wine’s health halo is dwindling, there might be an exception: Cancer risk.

Overall, research shows that even light to moderate drinking increases the risk for at least seven types of cancer, but when focusing on red wine, in particular, that risk calculus can look different.

“It’s very complicated and nuanced,” said Timothy Rebbeck, PhD, professor of cancer prevention, Harvard T.H. Chan School of Public Health, Boston. “And ‘complicated and nuanced’ doesn’t work very well in public health messages.”

The Knowns About Alcohol and Cancer Risk

Some things about the relationship between alcohol and cancer risk are crystal clear. “There’s no question that alcohol is a group 1 carcinogen,” Rebbeck said. “Alcohol can cause cancer.”

Groups including the International Agency for Research on Cancer (IARC) and American Cancer Society agree that alcohol use is an established cause of seven types of cancer: Those of the oral cavity, larynx, pharynx, esophagus (squamous cell carcinoma), liver (hepatocellular carcinoma), breast, and colon/rectum. Heavy drinking — at least 8 standard drinks a week for women and 15 for men — and binge drinking — 4 or more drinks in 2 hours for women and 5 or more for men — only amplify that risk. (A “standard” drink has 14 g of alcohol, which translates to a 5-oz glass of wine.)

“We’re most concerned about high-risk drinking — more than 2 drinks a day — and/or binge drinking,” said Noelle LoConte, MD, of the Division of Hematology, Medical Oncology and Palliative Care, University of Wisconsin School of Medicine and Public Health, Madison, who authored a 2018 statement on alcohol and cancer risk from the American Society of Clinical Oncology (ASCO).

Compared with not drinking, heavy drinking is linked with a roughly fivefold increase in the risk for oral cavity, pharyngeal, and esophageal cancers, and a 61% increase in the risk for breast cancer, according to LoConte and colleagues.

Things get murkier when it comes to moderate drinking — defined as up to 1 standard drink per day for women and 2 per day for men. There is evidence, LoConte said, that moderate drinking is associated with increased cancer risks, though the magnitude is generally much less than heavier drinking.

Cancer type also matters. One analysis found that the risk for breast cancer increased with even light to moderate alcohol consumption. Compared with no drinking, light to moderate drinking has also been linked to increased risks for oral cavity, pharynx, larynx, and esophageal cancers.

As for whether the type of alcoholic beverage matters, LoConte said, there’s no clear physiological reason that wine would be less risky than beer or liquor. Research indicates that ethanol is the problematic ingredient: Once ingested, it’s metabolized into acetaldehyde, a DNA-damaging substance that’s considered a probable human carcinogen. Ethanol can also alter circulating levels of estrogens and androgens, LoConte said, which is thought to drive its association with breast cancer risk.

“It likely doesn’t matter how you choose to get your ethanol,” she said. “It’s a question of volume.”

Hints That Wine Is an Outlier

Still, some studies suggest that how people ingest ethanol could make a difference.

A study published in August in JAMA Network Open is a case in point. The study found that, among older adults, light to heavy drinkers had an increased risk of dying from cancer, compared with occasional drinkers (though the increased risk among light to moderate drinkers occurred only among people who also had chronic health conditions, such as diabetes or high blood pressure, or were of lower socioeconomic status).

Wine drinkers fared differently. Most notably, drinkers who “preferred” wine — consuming over 80% of total ethanol from wine — or those who drank only with meals showed a small reduction in their risk for cancer mortality and all-cause mortality (hazard ratio [HR], 0.94 for both). The small protective association was somewhat stronger among people who reported both patterns (HR, 0.88), especially if they were of lower socioeconomic status (HR, 0.79).

The findings are in line with other research suggesting that wine drinkers may be outliers when it comes to cancer risk. A 2023 meta-analysis of 26 observational studies, for instance, found no association between wine consumption and any cancer type, with the caveat that there was «substantial» heterogeneity among the studies.

This heterogeneity caveat speaks to the inherent limitations of observational research, said Tim Stockwell, PhD, of the Canadian Institute for Substance Use Research, University of Victoria in British Columbia, Canada.

“Individual studies of alcohol and cancer risk do find differences by type of drink, or patterns of drinking,” Stockwell said. “But it’s so hard to unpack the confounding that goes along with the type of person who’s a wine drinker or a beer drinker or a spirit drinker. The beverage of choice seems to come with a lot of baggage.”

Compared with people who favor beer or liquor, he noted, wine aficionados are typically higher-income, exercise more often, smoke less, and have different diets, for example. The “best” studies, Rebbeck said, try to adjust for those differences, but it’s challenging.

The authors of the 2023 meta-analysis noted that “many components in wine could have anticarcinogenic effects” that theoretically could counter the ill effects of ethanol. Besides resveratrol, which is mainly found in red wine, the list includes anthocyanins, quercetin, and tannins. However, the authors also acknowledged that they couldn’t account for whether other lifestyle habits might explain why wine drinkers, overall, showed no increased cancer risks and sometimes lower risks.

Still, groups such as the IARC and ASCO hold that there is no known “safe” level, or type, of alcohol when it comes to cancer.

In the latest Canadian guidelines on alcohol use, the scientific panel calculated that people who have 6 drinks a week throughout adulthood (whatever the source of the alcohol) could shave 11 weeks from their life expectancy, on average, said Stockwell, who was on the guideline panel. Compare that with heavy drinking, where 4 drinks a day could rob the average person of 2 or 3 years. “If you’re drinking a lot, you could get huge benefits from cutting down,” Stockwell explained. “If you’re a moderate drinker, the benefits would obviously be less.”

Stockwell said that choices around drinking and breast cancer risk, specifically, can be “tough.” Unlike many of the other alcohol-associated cancers, he noted, breast cancer is common — so even small relative risk increases may be concerning. Based on a 2020 meta-analysis of 22 cohort studies, the risk for breast cancer rises by about 10%, on average, for every 10 g of alcohol a woman drinks per day. This study also found no evidence that wine is any different from other types of alcohol.

In real life, the calculus around wine consumption and cancer risk will probably vary widely from person to person, Rebbeck said. One woman with a family history of breast cancer might decide that having wine with dinner isn’t worth it. Another with the same family history might see that glass of wine as a stress reliever and opt to focus on other ways to reduce her breast cancer risk — by exercising and maintaining a healthy weight, for example.

“The bottom line is, in human studies, the data on light to moderate drinking and cancer are limited and messy, and you can’t draw firm conclusions from them,” Rebbeck said. “It probably raises risk in some people, but we don’t know who those people are. And the risk increases are relatively small.”

A Conversation Few Are Having

Even with many studies highlighting the connection between alcohol consumption and cancer risk, most people remain unaware about this risk.

A 2023 study by the National Cancer Institute found that only a minority of US adults knew that drinking alcohol is linked to increased cancer risk, and they were much less likely to say that was true of wine: Only 20% did, vs 31% who said that liquor can boost cancer risk. Meanwhile, 10% believed that wine helps prevent cancer. Other studies show that even among cancer survivors and patients undergoing active cancer treatment, many drink — often heavily.

“What we know right now is, physicians almost never talk about this,” LoConte said.

That could be due to time constraints, according to Rebbeck, or clinicians’ perceptions that the subject is too complicated and/or their own confusion about the data. There could also be some “cognitive dissonance” at play, LoConte noted, because many doctors drink alcohol.

It’s critical, she said, that conversations about drinking habits become “normalized,” and that should include informing patients that alcohol use is associated with certain cancers. Again, LoConte said, it’s high-risk drinking that’s most concerning and where reducing intake could have the biggest impact on cancer risk and other health outcomes.

“From a cancer prevention standpoint, it’s probably best not to drink,” she said. “But people don’t make choices based solely on cancer risk. We don’t want to come out with recommendations saying no one should drink. I don’t think the data support that, and people would buck against that advice.”

Rebbeck made a similar point. Even if there’s uncertainty about the risks for a daily glass of wine, he said, people can use that information to make decisions. “Everybody’s preferences and choices are going to be different,” Rebbeck said. “And that’s all we can really do.”

A version of this article appeared on Medscape.com.

SAN ANTONIO — Adding the CDK 4/6 blocker palbociclib to standard endocrine and antihuman epidermal growth factor receptor 2 (HER2) therapies in metastatic hormone receptor (HR)–positive, HER2-positive breast cancer extended patients’ median progression-free survival more than a year, according to the results of the phase 3 PATINA study.

This regimen “may represent a new standard of care” for these patients, said principal investigator and presenter Otto Metzger, MD, a medical breast oncologist at the Dana-Farber Cancer Institute in Boston, Massachusetts, who presented the findings at the San Antonio Breast Cancer Symposium (SABCS) 2024.

The open-label PATINA trial, which was conducted in Europe, Australia, New Zealand, and the United States, included a total of 518 patients. Patients received first-line treatment of six to eight cycles of induction chemotherapy plus anti-HER2 therapy. Researchers then randomized patients to either palbociclib plus anti-HER2 and endocrine therapy (n = 261) or to anti-HER2 and endocrine therapy alone (n = 257).

Patients did not progress on induction therapy, which likely would have signaled early resistance to anti-HER2 treatment. For anti-HER2 therapy, 97.3% received a combination of trastuzumab and pertuzumab. For endocrine therapy, 90.9% received an aromatase inhibitor.

Metzger and colleagues found that median progression-free survival was 1.3 years longer in patients receiving palbociclib — 3.7 years in the palbociclib arm vs 2.4 years in the control group (hazard ratio [HR], 0.74; P = .0074).

Although overall survival outcomes are immature, 5-year survival rates were slightly better in the palbociclib arm — 74.3% with palbociclib vs 69.8% without it — but the difference was not statistically significant.

Grade 3 neutropenia was the most frequent adverse event in the palbociclib arm (63.2% vs 2%). Grades 2 and 3 fatigue, stomatitis, and diarrhea were also more common with palbociclib. Grade 4 adverse events occurred in 12.3% of those receiving palbociclib and 8.9% of those who did not. There were no treatment-related deaths.

“We’re very impressed with the results,” said Metzger.

On the basis of previous studies, it’s believed that CDK 4/6 inhibition counteracts the development of resistance to anti-HER2 and endocrine therapies, which likely explains the benefit found in the trial.

But even without CDK 4/6 inhibition, the progression-free survival of 2.4 years in the control arm “far exceed[ed] our expectations,” Metzger reported. This may have occurred because the control arm received endocrine therapy, something previous trials of anti-HER2 therapy have avoided because of tolerability and other concerns.

These findings, however, support “the common use of endocrine therapy,” Metzger said.

 

‘Incredible’ Results

The progression-free survival as well as overall survival results in the trial are “incredible,” said study discussant Sara Hurvitz, MD, a medical breast oncologist at the Fred Hutch Cancer Center in Seattle, Washington. This is “historic and very important data.”

Hurvitz even suggested the results might mean that patients who fit the PATINA criteria can avoid the toxicity of upfront trastuzumab deruxtecan and use the PATINA regimen instead, potentially preserving their quality of life for longer.

Another study discussant, Virginia Kaklamani, MD, a medical breast oncologist at the University of Texas MD Anderson Cancer Center, San Antonio, had a similar thought.

In PATINA, “we’re talking about patients being on a treatment that’s well tolerated, where patients continue to work and continue with their lives despite being on treatment for metastatic breast cancer for 4 years, which is remarkable,” Kaklamani said.

Many of us have dabbled with giving CDK 4/6 inhibitors in triple-positive breast cancer, but “now we have more definitive data,” she said. The approach can help “maintain the quality of life of our patients for a longer period of time” and delay the use of chemotherapy in the second line, she added.

Metzger said Pfizer, the maker of palbociclib, plans to file for a HER2-positive indication with the Food and Drug Administration based on the trial results.

For now, the CDK 4/6 blocker is only indicated in combination with endocrine therapy for HR-positive, HER2-negative metastatic disease.

In response to a question about using the PATINA regimen in patients who don’t get chemotherapy induction, Metzger noted that, “while the study didn’t test this directly, I would argue that this data is quite compelling” for using palbociclib plus anti-HER2 and endocrine therapy, even without chemotherapy induction.

The work was funded by palbociclib maker Pfizer. Metzger had no disclosures. Hurvitz has numerous industry ties, including being a researcher and advisor to Pfizer. Kaklamani also has numerous industry ties, including reporting personal/consulting fees from Pfizer Canada.

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

SAN ANTONIO — Adding the CDK 4/6 blocker palbociclib to standard endocrine and antihuman epidermal growth factor receptor 2 (HER2) therapies in metastatic hormone receptor (HR)–positive, HER2-positive breast cancer extended patients’ median progression-free survival more than a year, according to the results of the phase 3 PATINA study.

This regimen “may represent a new standard of care” for these patients, said principal investigator and presenter Otto Metzger, MD, a medical breast oncologist at the Dana-Farber Cancer Institute in Boston, Massachusetts, who presented the findings at the San Antonio Breast Cancer Symposium (SABCS) 2024.

The open-label PATINA trial, which was conducted in Europe, Australia, New Zealand, and the United States, included a total of 518 patients. Patients received first-line treatment of six to eight cycles of induction chemotherapy plus anti-HER2 therapy. Researchers then randomized patients to either palbociclib plus anti-HER2 and endocrine therapy (n = 261) or to anti-HER2 and endocrine therapy alone (n = 257).

Patients did not progress on induction therapy, which likely would have signaled early resistance to anti-HER2 treatment. For anti-HER2 therapy, 97.3% received a combination of trastuzumab and pertuzumab. For endocrine therapy, 90.9% received an aromatase inhibitor.

Metzger and colleagues found that median progression-free survival was 1.3 years longer in patients receiving palbociclib — 3.7 years in the palbociclib arm vs 2.4 years in the control group (hazard ratio [HR], 0.74; P = .0074).

Although overall survival outcomes are immature, 5-year survival rates were slightly better in the palbociclib arm — 74.3% with palbociclib vs 69.8% without it — but the difference was not statistically significant.

Grade 3 neutropenia was the most frequent adverse event in the palbociclib arm (63.2% vs 2%). Grades 2 and 3 fatigue, stomatitis, and diarrhea were also more common with palbociclib. Grade 4 adverse events occurred in 12.3% of those receiving palbociclib and 8.9% of those who did not. There were no treatment-related deaths.

“We’re very impressed with the results,” said Metzger.

On the basis of previous studies, it’s believed that CDK 4/6 inhibition counteracts the development of resistance to anti-HER2 and endocrine therapies, which likely explains the benefit found in the trial.

But even without CDK 4/6 inhibition, the progression-free survival of 2.4 years in the control arm “far exceed[ed] our expectations,” Metzger reported. This may have occurred because the control arm received endocrine therapy, something previous trials of anti-HER2 therapy have avoided because of tolerability and other concerns.

These findings, however, support “the common use of endocrine therapy,” Metzger said.

 

‘Incredible’ Results

The progression-free survival as well as overall survival results in the trial are “incredible,” said study discussant Sara Hurvitz, MD, a medical breast oncologist at the Fred Hutch Cancer Center in Seattle, Washington. This is “historic and very important data.”

Hurvitz even suggested the results might mean that patients who fit the PATINA criteria can avoid the toxicity of upfront trastuzumab deruxtecan and use the PATINA regimen instead, potentially preserving their quality of life for longer.

Another study discussant, Virginia Kaklamani, MD, a medical breast oncologist at the University of Texas MD Anderson Cancer Center, San Antonio, had a similar thought.

In PATINA, “we’re talking about patients being on a treatment that’s well tolerated, where patients continue to work and continue with their lives despite being on treatment for metastatic breast cancer for 4 years, which is remarkable,” Kaklamani said.

Many of us have dabbled with giving CDK 4/6 inhibitors in triple-positive breast cancer, but “now we have more definitive data,” she said. The approach can help “maintain the quality of life of our patients for a longer period of time” and delay the use of chemotherapy in the second line, she added.

Metzger said Pfizer, the maker of palbociclib, plans to file for a HER2-positive indication with the Food and Drug Administration based on the trial results.

For now, the CDK 4/6 blocker is only indicated in combination with endocrine therapy for HR-positive, HER2-negative metastatic disease.

In response to a question about using the PATINA regimen in patients who don’t get chemotherapy induction, Metzger noted that, “while the study didn’t test this directly, I would argue that this data is quite compelling” for using palbociclib plus anti-HER2 and endocrine therapy, even without chemotherapy induction.

The work was funded by palbociclib maker Pfizer. Metzger had no disclosures. Hurvitz has numerous industry ties, including being a researcher and advisor to Pfizer. Kaklamani also has numerous industry ties, including reporting personal/consulting fees from Pfizer Canada.

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

SAN ANTONIO — Adding the CDK 4/6 blocker palbociclib to standard endocrine and antihuman epidermal growth factor receptor 2 (HER2) therapies in metastatic hormone receptor (HR)–positive, HER2-positive breast cancer extended patients’ median progression-free survival more than a year, according to the results of the phase 3 PATINA study.

This regimen “may represent a new standard of care” for these patients, said principal investigator and presenter Otto Metzger, MD, a medical breast oncologist at the Dana-Farber Cancer Institute in Boston, Massachusetts, who presented the findings at the San Antonio Breast Cancer Symposium (SABCS) 2024.

The open-label PATINA trial, which was conducted in Europe, Australia, New Zealand, and the United States, included a total of 518 patients. Patients received first-line treatment of six to eight cycles of induction chemotherapy plus anti-HER2 therapy. Researchers then randomized patients to either palbociclib plus anti-HER2 and endocrine therapy (n = 261) or to anti-HER2 and endocrine therapy alone (n = 257).

Patients did not progress on induction therapy, which likely would have signaled early resistance to anti-HER2 treatment. For anti-HER2 therapy, 97.3% received a combination of trastuzumab and pertuzumab. For endocrine therapy, 90.9% received an aromatase inhibitor.

Metzger and colleagues found that median progression-free survival was 1.3 years longer in patients receiving palbociclib — 3.7 years in the palbociclib arm vs 2.4 years in the control group (hazard ratio [HR], 0.74; P = .0074).

Although overall survival outcomes are immature, 5-year survival rates were slightly better in the palbociclib arm — 74.3% with palbociclib vs 69.8% without it — but the difference was not statistically significant.

Grade 3 neutropenia was the most frequent adverse event in the palbociclib arm (63.2% vs 2%). Grades 2 and 3 fatigue, stomatitis, and diarrhea were also more common with palbociclib. Grade 4 adverse events occurred in 12.3% of those receiving palbociclib and 8.9% of those who did not. There were no treatment-related deaths.

“We’re very impressed with the results,” said Metzger.

On the basis of previous studies, it’s believed that CDK 4/6 inhibition counteracts the development of resistance to anti-HER2 and endocrine therapies, which likely explains the benefit found in the trial.

But even without CDK 4/6 inhibition, the progression-free survival of 2.4 years in the control arm “far exceed[ed] our expectations,” Metzger reported. This may have occurred because the control arm received endocrine therapy, something previous trials of anti-HER2 therapy have avoided because of tolerability and other concerns.

These findings, however, support “the common use of endocrine therapy,” Metzger said.

 

‘Incredible’ Results

The progression-free survival as well as overall survival results in the trial are “incredible,” said study discussant Sara Hurvitz, MD, a medical breast oncologist at the Fred Hutch Cancer Center in Seattle, Washington. This is “historic and very important data.”

Hurvitz even suggested the results might mean that patients who fit the PATINA criteria can avoid the toxicity of upfront trastuzumab deruxtecan and use the PATINA regimen instead, potentially preserving their quality of life for longer.

Another study discussant, Virginia Kaklamani, MD, a medical breast oncologist at the University of Texas MD Anderson Cancer Center, San Antonio, had a similar thought.

In PATINA, “we’re talking about patients being on a treatment that’s well tolerated, where patients continue to work and continue with their lives despite being on treatment for metastatic breast cancer for 4 years, which is remarkable,” Kaklamani said.

Many of us have dabbled with giving CDK 4/6 inhibitors in triple-positive breast cancer, but “now we have more definitive data,” she said. The approach can help “maintain the quality of life of our patients for a longer period of time” and delay the use of chemotherapy in the second line, she added.

Metzger said Pfizer, the maker of palbociclib, plans to file for a HER2-positive indication with the Food and Drug Administration based on the trial results.

For now, the CDK 4/6 blocker is only indicated in combination with endocrine therapy for HR-positive, HER2-negative metastatic disease.

In response to a question about using the PATINA regimen in patients who don’t get chemotherapy induction, Metzger noted that, “while the study didn’t test this directly, I would argue that this data is quite compelling” for using palbociclib plus anti-HER2 and endocrine therapy, even without chemotherapy induction.

The work was funded by palbociclib maker Pfizer. Metzger had no disclosures. Hurvitz has numerous industry ties, including being a researcher and advisor to Pfizer. Kaklamani also has numerous industry ties, including reporting personal/consulting fees from Pfizer Canada.

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

A major prospective study of more than half a million UK women conducted over almost 17 years has confirmed an association between dietary calcium intake and decreased risk of colorectal cancer. 

Cancer Research UK (CRUK), which funded the study, said that it demonstrated the benefits of a healthy, balanced diet for lowering cancer risk.

Colorectal cancer is the third most common cancer worldwide. Incidence rates vary markedly, with higher rates observed in high-income countries. The risk increases for individuals who migrate from low- to high-incidence areas, suggesting that lifestyle and environmental factors contribute to its development.

While alcohol and processed meats are established carcinogens, and red meat is classified as probably carcinogenic, there is a lack of consensus regarding the relationships between other dietary factors and colorectal cancer risk. This uncertainty may be due, at least in part, to relatively few studies giving comprehensive results on all food types, as well as dietary measurement errors, and/or small sample sizes.

 

Study Tracked 97 Dietary Factors

To address these gaps, the research team, led by the University of Oxford in England, tracked the intake of 97 dietary factors in 542,778 women from 2001 for an average of 16.6 years. During this period 12,251 participants developed colorectal cancer. The women completed detailed dietary questionnaires at baseline, with 7% participating in at least one subsequent 24-hour online dietary assessment.

Women diagnosed with colorectal cancer were generally older, taller, more likely to have a family history of bowel cancer, and have more adverse health behaviors, compared with participants overall.

 

Calcium Intake Showed the Strongest Protective Association

Relative risks (RR) for colorectal cancer were calculated for intakes of all 97 dietary factors, with significant associations found for 17 of them. Calcium intake showed the strongest protective effect, with each additional 300 mg per day – equivalent to a large glass of milk – associated with a 17% reduced RR. 

Six dairy-related factors associated with calcium – dairy milk, yogurt, riboflavin, magnesium, phosphorus, and potassium intakes – also demonstrated inverse associations with colorectal cancer risk. Weaker protective effects were noted for breakfast cereal, fruit, wholegrains, carbohydrates, fibre, total sugars, folate, and vitamin C. However, the team commented that these inverse associations might reflect residual confounding from other lifestyle or other dietary factors.

Calcium’s protective role was independent of dairy milk intake. The study, published in Nature Communications, concluded that, while “dairy products help protect against colorectal cancer,” that protection is “driven largely or wholly by calcium.”

 

Alcohol and Processed Meat Confirmed as Risk Factors

As expected, alcohol showed the reverse association, with each additional 20 g daily – equivalent to one large glass of wine – associated with a 15% RR increase. Weaker associations were seen for the combined category of red and processed meat, with each additional 30 g per day associated with an 8% increased RR for colorectal cancer. This association was minimally affected by diet and lifestyle factors.

Commenting to the Science Media Centre (SMC), Tom Sanders, professor emeritus of nutrition and dietetics at King’s College London, England, said: “One theory is that the calcium may bind to free bile acids in the gut, preventing the harmful effects of free bile acids on gut mucosa.” However, the lactose content in milk also has effects on large bowel microflora, which may in turn affect risk.

Also commenting to the SMC, David Nunan, senior research fellow at the University of Oxford’s Centre for Evidence Based Medicine, who was not involved in the study, cautioned that the findings were subject to the bias inherent in observational studies. “These biases often inflate the estimated associations compared to controlled experiments,” he said. Nunan advised caution in interpreting the findings, as more robust research, such as randomized controlled trials, would be needed to establish causation.

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

A major prospective study of more than half a million UK women conducted over almost 17 years has confirmed an association between dietary calcium intake and decreased risk of colorectal cancer. 

Cancer Research UK (CRUK), which funded the study, said that it demonstrated the benefits of a healthy, balanced diet for lowering cancer risk.

Colorectal cancer is the third most common cancer worldwide. Incidence rates vary markedly, with higher rates observed in high-income countries. The risk increases for individuals who migrate from low- to high-incidence areas, suggesting that lifestyle and environmental factors contribute to its development.

While alcohol and processed meats are established carcinogens, and red meat is classified as probably carcinogenic, there is a lack of consensus regarding the relationships between other dietary factors and colorectal cancer risk. This uncertainty may be due, at least in part, to relatively few studies giving comprehensive results on all food types, as well as dietary measurement errors, and/or small sample sizes.

 

Study Tracked 97 Dietary Factors

To address these gaps, the research team, led by the University of Oxford in England, tracked the intake of 97 dietary factors in 542,778 women from 2001 for an average of 16.6 years. During this period 12,251 participants developed colorectal cancer. The women completed detailed dietary questionnaires at baseline, with 7% participating in at least one subsequent 24-hour online dietary assessment.

Women diagnosed with colorectal cancer were generally older, taller, more likely to have a family history of bowel cancer, and have more adverse health behaviors, compared with participants overall.

 

Calcium Intake Showed the Strongest Protective Association

Relative risks (RR) for colorectal cancer were calculated for intakes of all 97 dietary factors, with significant associations found for 17 of them. Calcium intake showed the strongest protective effect, with each additional 300 mg per day – equivalent to a large glass of milk – associated with a 17% reduced RR. 

Six dairy-related factors associated with calcium – dairy milk, yogurt, riboflavin, magnesium, phosphorus, and potassium intakes – also demonstrated inverse associations with colorectal cancer risk. Weaker protective effects were noted for breakfast cereal, fruit, wholegrains, carbohydrates, fibre, total sugars, folate, and vitamin C. However, the team commented that these inverse associations might reflect residual confounding from other lifestyle or other dietary factors.

Calcium’s protective role was independent of dairy milk intake. The study, published in Nature Communications, concluded that, while “dairy products help protect against colorectal cancer,” that protection is “driven largely or wholly by calcium.”

 

Alcohol and Processed Meat Confirmed as Risk Factors

As expected, alcohol showed the reverse association, with each additional 20 g daily – equivalent to one large glass of wine – associated with a 15% RR increase. Weaker associations were seen for the combined category of red and processed meat, with each additional 30 g per day associated with an 8% increased RR for colorectal cancer. This association was minimally affected by diet and lifestyle factors.

Commenting to the Science Media Centre (SMC), Tom Sanders, professor emeritus of nutrition and dietetics at King’s College London, England, said: “One theory is that the calcium may bind to free bile acids in the gut, preventing the harmful effects of free bile acids on gut mucosa.” However, the lactose content in milk also has effects on large bowel microflora, which may in turn affect risk.

Also commenting to the SMC, David Nunan, senior research fellow at the University of Oxford’s Centre for Evidence Based Medicine, who was not involved in the study, cautioned that the findings were subject to the bias inherent in observational studies. “These biases often inflate the estimated associations compared to controlled experiments,” he said. Nunan advised caution in interpreting the findings, as more robust research, such as randomized controlled trials, would be needed to establish causation.

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

A major prospective study of more than half a million UK women conducted over almost 17 years has confirmed an association between dietary calcium intake and decreased risk of colorectal cancer. 

Cancer Research UK (CRUK), which funded the study, said that it demonstrated the benefits of a healthy, balanced diet for lowering cancer risk.

Colorectal cancer is the third most common cancer worldwide. Incidence rates vary markedly, with higher rates observed in high-income countries. The risk increases for individuals who migrate from low- to high-incidence areas, suggesting that lifestyle and environmental factors contribute to its development.

While alcohol and processed meats are established carcinogens, and red meat is classified as probably carcinogenic, there is a lack of consensus regarding the relationships between other dietary factors and colorectal cancer risk. This uncertainty may be due, at least in part, to relatively few studies giving comprehensive results on all food types, as well as dietary measurement errors, and/or small sample sizes.

 

Study Tracked 97 Dietary Factors

To address these gaps, the research team, led by the University of Oxford in England, tracked the intake of 97 dietary factors in 542,778 women from 2001 for an average of 16.6 years. During this period 12,251 participants developed colorectal cancer. The women completed detailed dietary questionnaires at baseline, with 7% participating in at least one subsequent 24-hour online dietary assessment.

Women diagnosed with colorectal cancer were generally older, taller, more likely to have a family history of bowel cancer, and have more adverse health behaviors, compared with participants overall.

 

Calcium Intake Showed the Strongest Protective Association

Relative risks (RR) for colorectal cancer were calculated for intakes of all 97 dietary factors, with significant associations found for 17 of them. Calcium intake showed the strongest protective effect, with each additional 300 mg per day – equivalent to a large glass of milk – associated with a 17% reduced RR. 

Six dairy-related factors associated with calcium – dairy milk, yogurt, riboflavin, magnesium, phosphorus, and potassium intakes – also demonstrated inverse associations with colorectal cancer risk. Weaker protective effects were noted for breakfast cereal, fruit, wholegrains, carbohydrates, fibre, total sugars, folate, and vitamin C. However, the team commented that these inverse associations might reflect residual confounding from other lifestyle or other dietary factors.

Calcium’s protective role was independent of dairy milk intake. The study, published in Nature Communications, concluded that, while “dairy products help protect against colorectal cancer,” that protection is “driven largely or wholly by calcium.”

 

Alcohol and Processed Meat Confirmed as Risk Factors

As expected, alcohol showed the reverse association, with each additional 20 g daily – equivalent to one large glass of wine – associated with a 15% RR increase. Weaker associations were seen for the combined category of red and processed meat, with each additional 30 g per day associated with an 8% increased RR for colorectal cancer. This association was minimally affected by diet and lifestyle factors.

Commenting to the Science Media Centre (SMC), Tom Sanders, professor emeritus of nutrition and dietetics at King’s College London, England, said: “One theory is that the calcium may bind to free bile acids in the gut, preventing the harmful effects of free bile acids on gut mucosa.” However, the lactose content in milk also has effects on large bowel microflora, which may in turn affect risk.

Also commenting to the SMC, David Nunan, senior research fellow at the University of Oxford’s Centre for Evidence Based Medicine, who was not involved in the study, cautioned that the findings were subject to the bias inherent in observational studies. “These biases often inflate the estimated associations compared to controlled experiments,” he said. Nunan advised caution in interpreting the findings, as more robust research, such as randomized controlled trials, would be needed to establish causation.

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

MRI-invisible prostate lesions. It sounds like the stuff of science fiction and fantasy, a creation from the minds of H.G. Wells, who wrote The Invisible Man, or J.K. Rowling, who authored the Harry Potter series.

But MRI-invisible prostate lesions are real. And what these lesions may, or may not, indicate is the subject of intense debate.

MRI plays an increasingly important role in detecting and diagnosing prostate cancer, staging prostate cancer as well as monitoring disease progression. However, on occasion, a puzzling phenomenon arises. Certain prostate lesions that appear when pathologists examine biopsied tissue samples under a microscope are not visible on MRI. The prostate tissue will, instead, appear normal to a radiologist’s eye.

Why are certain lesions invisible with MRI? And is it dangerous for patients if these lesions are not detected? 

Some experts believe these MRI-invisible lesions are nothing to worry about.

If the clinician can’t see the cancer on MRI, then it simply isn’t a threat, according to Mark Emberton, MD, a pioneer in prostate MRIs and director of interventional oncology at University College London, England.

Laurence Klotz, MD, of the University of Toronto, Ontario, Canada, agreed, noting that “invisible cancers are clinically insignificant and don’t require systematic biopsies.”

Emberton and Klotz compared MRI-invisible lesions to grade group 1 prostate cancer (Gleason score ≤ 6) — the least aggressive category that indicates the cancer that is not likely to spread or kill. For patients on active surveillance, those with MRI-invisible cancers do drastically better than those with visible cancers, Klotz explained.

But other experts in the field are skeptical that MRI-invisible lesions are truly innocuous.

Although statistically an MRI-visible prostate lesion indicates a more aggressive tumor, that is not always the case for every individual, said Brian Helfand, MD, PhD, chief of urology at NorthShore University Health System, Evanston, Illinois.

MRIs can lead to false negatives in about 10%-20% of patients who have clinically significant prostate cancer, though estimates vary.

In one analysis, 16% of men with no suspicious lesions on MRI had clinically significant prostate cancer identified after undergoing a systematic biopsy. Another analysis found that about 35% of MRI-invisible prostate cancers identified via biopsy were clinically significant.

Other studies, however, have indicated that negative MRI results accurately indicate patients at low risk of developing clinically significant cancers. A recent JAMA Oncology analysis, for instance, found that only seven of 233 men (3%) with negative MRI results at baseline who completed 3 years of monitoring were diagnosed with clinically significant prostate cancer.

When a patient has an MRI-invisible prostate tumor, there are a couple of reasons the MRI may not be picking it up, said urologic oncologist Alexander Putnam Cole, MD, assistant professor of surgery, Harvard Medical School, Boston, Massachusetts. “One is that the cancer is aggressive but just very small,” said Cole.

“Another possibility is that the cancer looks very similar to background prostate tissue, which is something that you might expect if you think about more of a low-grade cancer,” he explained.

The experience level of the radiologist interpreting the MRI can also play into the accuracy of the reading.

But Cole agreed that “in general, MRI visibility is associated with molecular and histologic features of progression and aggressiveness and non-visible cancers are less likely to have aggressive features.”

The genomic profiles of MRI-visible and -invisible cancers bear this out.

According to Todd Morgan, MD, chief of urologic oncology at Michigan Medicine, University of Michigan, Ann Arbor, the gene expression in visible disease tends to be linked to more aggressive prostate tumors whereas gene expression in invisible disease does not.

In one analysis, for instance, researchers found that four genes — PHYHD1, CENPF, ALDH2, and GDF15 — associated with worse progression-free survival and metastasis-free survival in prostate cancer also predicted MRI visibility.

“Genes that are associated with visibility are essentially the same genes that are associated with aggressive cancers,” Klotz said.

 

Next Steps After Negative MRI Result

What do MRI-invisible lesions mean for patient care? If, for instance, a patient has elevated PSA levels but a normal MRI, is a targeted or systematic biopsy warranted?

The overarching message, according to Klotz, is that “you don’t need to find them.” Klotz noted, however, that patients with a negative MRI result should still be followed with periodic repeat imaging.

Several trials support this approach of using MRI to decide who needs a biopsy and delaying a biopsy in men with normal MRIs.

The recent JAMA Oncology analysis found that, among men with negative MRI results, 86% avoided a biopsy over 3 years, with clinically significant prostate cancer detected in only 4% of men across the study period — four in the initial diagnostic phase and seven in the 3-year monitoring phase. However, during the initial diagnostic phase, more than half the men with positive MRI findings had clinically significant prostate cancer detected.

Another recent study found that patients with negative MRI results were much less likely to upgrade to higher Gleason scores over time. Among 522 patients who underwent a systematic and targeted biopsy within 18 months of their grade group 1 designation, 9.2% with negative MRI findings had tumors reclassified as grade group 2 or higher vs 27% with positive MRI findings, and 2.3% with negative MRI findings had tumors reclassified as grade group 3 or higher vs 7.8% with positive MRI findings.

These data suggest that men with grade group 1 cancer and negative MRI result “may be able to avoid confirmatory biopsies until a routine surveillance biopsy in 2-3 years,” according to study author Christian Pavlovich, MD, professor of urologic oncology at the Johns Hopkins University School of Medicine, Baltimore.

Cole used MRI findings to triage who gets a biopsy. When a biopsy is warranted, “I usually recommend adding in some systematic sampling of the other side to assess for nonvisible cancers,” he noted.

Sampling prostate tissue outside the target area “adds maybe 1-2 minutes to the procedure and doesn’t drastically increase the morbidity or risks,” Cole said. It also can help “confirm there is cancer in the MRI target and also confirm there is no cancer in the nonvisible areas.” 

According to Klotz, if imaging demonstrates progression, patients should receive a biopsy — in most cases, a targeted biopsy only. And, Klotz noted, skipping routine prostate biopsies in men with negative MRI results can save thousands of men from these procedures, which carry risks for infections and sepsis.

Looking beyond Gleason scores for risk prediction, MRI “visibility is a very powerful risk stratifier,” he said.

A version of this article appeared on Medscape.com.

MRI-invisible prostate lesions. It sounds like the stuff of science fiction and fantasy, a creation from the minds of H.G. Wells, who wrote The Invisible Man, or J.K. Rowling, who authored the Harry Potter series.

But MRI-invisible prostate lesions are real. And what these lesions may, or may not, indicate is the subject of intense debate.

MRI plays an increasingly important role in detecting and diagnosing prostate cancer, staging prostate cancer as well as monitoring disease progression. However, on occasion, a puzzling phenomenon arises. Certain prostate lesions that appear when pathologists examine biopsied tissue samples under a microscope are not visible on MRI. The prostate tissue will, instead, appear normal to a radiologist’s eye.

Why are certain lesions invisible with MRI? And is it dangerous for patients if these lesions are not detected? 

Some experts believe these MRI-invisible lesions are nothing to worry about.

If the clinician can’t see the cancer on MRI, then it simply isn’t a threat, according to Mark Emberton, MD, a pioneer in prostate MRIs and director of interventional oncology at University College London, England.

Laurence Klotz, MD, of the University of Toronto, Ontario, Canada, agreed, noting that “invisible cancers are clinically insignificant and don’t require systematic biopsies.”

Emberton and Klotz compared MRI-invisible lesions to grade group 1 prostate cancer (Gleason score ≤ 6) — the least aggressive category that indicates the cancer that is not likely to spread or kill. For patients on active surveillance, those with MRI-invisible cancers do drastically better than those with visible cancers, Klotz explained.

But other experts in the field are skeptical that MRI-invisible lesions are truly innocuous.

Although statistically an MRI-visible prostate lesion indicates a more aggressive tumor, that is not always the case for every individual, said Brian Helfand, MD, PhD, chief of urology at NorthShore University Health System, Evanston, Illinois.

MRIs can lead to false negatives in about 10%-20% of patients who have clinically significant prostate cancer, though estimates vary.

In one analysis, 16% of men with no suspicious lesions on MRI had clinically significant prostate cancer identified after undergoing a systematic biopsy. Another analysis found that about 35% of MRI-invisible prostate cancers identified via biopsy were clinically significant.

Other studies, however, have indicated that negative MRI results accurately indicate patients at low risk of developing clinically significant cancers. A recent JAMA Oncology analysis, for instance, found that only seven of 233 men (3%) with negative MRI results at baseline who completed 3 years of monitoring were diagnosed with clinically significant prostate cancer.

When a patient has an MRI-invisible prostate tumor, there are a couple of reasons the MRI may not be picking it up, said urologic oncologist Alexander Putnam Cole, MD, assistant professor of surgery, Harvard Medical School, Boston, Massachusetts. “One is that the cancer is aggressive but just very small,” said Cole.

“Another possibility is that the cancer looks very similar to background prostate tissue, which is something that you might expect if you think about more of a low-grade cancer,” he explained.

The experience level of the radiologist interpreting the MRI can also play into the accuracy of the reading.

But Cole agreed that “in general, MRI visibility is associated with molecular and histologic features of progression and aggressiveness and non-visible cancers are less likely to have aggressive features.”

The genomic profiles of MRI-visible and -invisible cancers bear this out.

According to Todd Morgan, MD, chief of urologic oncology at Michigan Medicine, University of Michigan, Ann Arbor, the gene expression in visible disease tends to be linked to more aggressive prostate tumors whereas gene expression in invisible disease does not.

In one analysis, for instance, researchers found that four genes — PHYHD1, CENPF, ALDH2, and GDF15 — associated with worse progression-free survival and metastasis-free survival in prostate cancer also predicted MRI visibility.

“Genes that are associated with visibility are essentially the same genes that are associated with aggressive cancers,” Klotz said.

 

Next Steps After Negative MRI Result

What do MRI-invisible lesions mean for patient care? If, for instance, a patient has elevated PSA levels but a normal MRI, is a targeted or systematic biopsy warranted?

The overarching message, according to Klotz, is that “you don’t need to find them.” Klotz noted, however, that patients with a negative MRI result should still be followed with periodic repeat imaging.

Several trials support this approach of using MRI to decide who needs a biopsy and delaying a biopsy in men with normal MRIs.

The recent JAMA Oncology analysis found that, among men with negative MRI results, 86% avoided a biopsy over 3 years, with clinically significant prostate cancer detected in only 4% of men across the study period — four in the initial diagnostic phase and seven in the 3-year monitoring phase. However, during the initial diagnostic phase, more than half the men with positive MRI findings had clinically significant prostate cancer detected.

Another recent study found that patients with negative MRI results were much less likely to upgrade to higher Gleason scores over time. Among 522 patients who underwent a systematic and targeted biopsy within 18 months of their grade group 1 designation, 9.2% with negative MRI findings had tumors reclassified as grade group 2 or higher vs 27% with positive MRI findings, and 2.3% with negative MRI findings had tumors reclassified as grade group 3 or higher vs 7.8% with positive MRI findings.

These data suggest that men with grade group 1 cancer and negative MRI result “may be able to avoid confirmatory biopsies until a routine surveillance biopsy in 2-3 years,” according to study author Christian Pavlovich, MD, professor of urologic oncology at the Johns Hopkins University School of Medicine, Baltimore.

Cole used MRI findings to triage who gets a biopsy. When a biopsy is warranted, “I usually recommend adding in some systematic sampling of the other side to assess for nonvisible cancers,” he noted.

Sampling prostate tissue outside the target area “adds maybe 1-2 minutes to the procedure and doesn’t drastically increase the morbidity or risks,” Cole said. It also can help “confirm there is cancer in the MRI target and also confirm there is no cancer in the nonvisible areas.” 

According to Klotz, if imaging demonstrates progression, patients should receive a biopsy — in most cases, a targeted biopsy only. And, Klotz noted, skipping routine prostate biopsies in men with negative MRI results can save thousands of men from these procedures, which carry risks for infections and sepsis.

Looking beyond Gleason scores for risk prediction, MRI “visibility is a very powerful risk stratifier,” he said.

A version of this article appeared on Medscape.com.

MRI-invisible prostate lesions. It sounds like the stuff of science fiction and fantasy, a creation from the minds of H.G. Wells, who wrote The Invisible Man, or J.K. Rowling, who authored the Harry Potter series.

But MRI-invisible prostate lesions are real. And what these lesions may, or may not, indicate is the subject of intense debate.

MRI plays an increasingly important role in detecting and diagnosing prostate cancer, staging prostate cancer as well as monitoring disease progression. However, on occasion, a puzzling phenomenon arises. Certain prostate lesions that appear when pathologists examine biopsied tissue samples under a microscope are not visible on MRI. The prostate tissue will, instead, appear normal to a radiologist’s eye.

Why are certain lesions invisible with MRI? And is it dangerous for patients if these lesions are not detected? 

Some experts believe these MRI-invisible lesions are nothing to worry about.

If the clinician can’t see the cancer on MRI, then it simply isn’t a threat, according to Mark Emberton, MD, a pioneer in prostate MRIs and director of interventional oncology at University College London, England.

Laurence Klotz, MD, of the University of Toronto, Ontario, Canada, agreed, noting that “invisible cancers are clinically insignificant and don’t require systematic biopsies.”

Emberton and Klotz compared MRI-invisible lesions to grade group 1 prostate cancer (Gleason score ≤ 6) — the least aggressive category that indicates the cancer that is not likely to spread or kill. For patients on active surveillance, those with MRI-invisible cancers do drastically better than those with visible cancers, Klotz explained.

But other experts in the field are skeptical that MRI-invisible lesions are truly innocuous.

Although statistically an MRI-visible prostate lesion indicates a more aggressive tumor, that is not always the case for every individual, said Brian Helfand, MD, PhD, chief of urology at NorthShore University Health System, Evanston, Illinois.

MRIs can lead to false negatives in about 10%-20% of patients who have clinically significant prostate cancer, though estimates vary.

In one analysis, 16% of men with no suspicious lesions on MRI had clinically significant prostate cancer identified after undergoing a systematic biopsy. Another analysis found that about 35% of MRI-invisible prostate cancers identified via biopsy were clinically significant.

Other studies, however, have indicated that negative MRI results accurately indicate patients at low risk of developing clinically significant cancers. A recent JAMA Oncology analysis, for instance, found that only seven of 233 men (3%) with negative MRI results at baseline who completed 3 years of monitoring were diagnosed with clinically significant prostate cancer.

When a patient has an MRI-invisible prostate tumor, there are a couple of reasons the MRI may not be picking it up, said urologic oncologist Alexander Putnam Cole, MD, assistant professor of surgery, Harvard Medical School, Boston, Massachusetts. “One is that the cancer is aggressive but just very small,” said Cole.

“Another possibility is that the cancer looks very similar to background prostate tissue, which is something that you might expect if you think about more of a low-grade cancer,” he explained.

The experience level of the radiologist interpreting the MRI can also play into the accuracy of the reading.

But Cole agreed that “in general, MRI visibility is associated with molecular and histologic features of progression and aggressiveness and non-visible cancers are less likely to have aggressive features.”

The genomic profiles of MRI-visible and -invisible cancers bear this out.

According to Todd Morgan, MD, chief of urologic oncology at Michigan Medicine, University of Michigan, Ann Arbor, the gene expression in visible disease tends to be linked to more aggressive prostate tumors whereas gene expression in invisible disease does not.

In one analysis, for instance, researchers found that four genes — PHYHD1, CENPF, ALDH2, and GDF15 — associated with worse progression-free survival and metastasis-free survival in prostate cancer also predicted MRI visibility.

“Genes that are associated with visibility are essentially the same genes that are associated with aggressive cancers,” Klotz said.

 

Next Steps After Negative MRI Result

What do MRI-invisible lesions mean for patient care? If, for instance, a patient has elevated PSA levels but a normal MRI, is a targeted or systematic biopsy warranted?

The overarching message, according to Klotz, is that “you don’t need to find them.” Klotz noted, however, that patients with a negative MRI result should still be followed with periodic repeat imaging.

Several trials support this approach of using MRI to decide who needs a biopsy and delaying a biopsy in men with normal MRIs.

The recent JAMA Oncology analysis found that, among men with negative MRI results, 86% avoided a biopsy over 3 years, with clinically significant prostate cancer detected in only 4% of men across the study period — four in the initial diagnostic phase and seven in the 3-year monitoring phase. However, during the initial diagnostic phase, more than half the men with positive MRI findings had clinically significant prostate cancer detected.

Another recent study found that patients with negative MRI results were much less likely to upgrade to higher Gleason scores over time. Among 522 patients who underwent a systematic and targeted biopsy within 18 months of their grade group 1 designation, 9.2% with negative MRI findings had tumors reclassified as grade group 2 or higher vs 27% with positive MRI findings, and 2.3% with negative MRI findings had tumors reclassified as grade group 3 or higher vs 7.8% with positive MRI findings.

These data suggest that men with grade group 1 cancer and negative MRI result “may be able to avoid confirmatory biopsies until a routine surveillance biopsy in 2-3 years,” according to study author Christian Pavlovich, MD, professor of urologic oncology at the Johns Hopkins University School of Medicine, Baltimore.

Cole used MRI findings to triage who gets a biopsy. When a biopsy is warranted, “I usually recommend adding in some systematic sampling of the other side to assess for nonvisible cancers,” he noted.

Sampling prostate tissue outside the target area “adds maybe 1-2 minutes to the procedure and doesn’t drastically increase the morbidity or risks,” Cole said. It also can help “confirm there is cancer in the MRI target and also confirm there is no cancer in the nonvisible areas.” 

According to Klotz, if imaging demonstrates progression, patients should receive a biopsy — in most cases, a targeted biopsy only. And, Klotz noted, skipping routine prostate biopsies in men with negative MRI results can save thousands of men from these procedures, which carry risks for infections and sepsis.

Looking beyond Gleason scores for risk prediction, MRI “visibility is a very powerful risk stratifier,” he said.

A version of this article appeared on Medscape.com.

For millennia in medicine, alcohol, particularly red wine, carried a health halo; in small doses, it has historically been thought to have cardioprotective benefits. Michael Farkouh, MD, a professor of cardiology at Cedars-Sinai, estimates half the physicians still accept people having a drink or two a day. “That is still in practice, though the numbers are reducing,” he said.

But Farkouh no longer drinks alcohol, a position he has come to after getting more involved in research into the substance and his realization that many of the studies touting alcohol’s health benefits were flawed.

Today, alcohol sits alongside asbestos and tobacco as class 1 carcinogens. According to the World Health Organization, it has no known safe ingestible amount. In 2018, a blockbuster report in The Lancet found no amount of any kind of alcohol improves health. In early January, US Surgeon General Vivek Murthy called for adding cancer warnings to alcohol labels.

But the way doctors drink is far from black and white. For physicians, drinking habits are tied up in personal values, professional understanding of a substance with a confusing research history, and the fact alcohol is deeply ingrained in the social fabric of society — and in medicine. As thinking on alcohol shifts, this news organization spoke with physicians about their own drinking habits, how they counsel patients on it, and alcohol’s place in a field that works to keep people healthy.

 

Cultural Currency

From the days of Hippocrates, who believed alcohol could cure virtually every ailment, alcohol has held a large role in medicine. Through much of the 19th century, patent remedies like Hamlin’s Wizard Oil and the Seven Sutherland Sisters Hair Grower, contained alcohol — sometimes in concentrations exceeding 50%.

The first American Pharmacopoeia, published in 1820, even contained nine wine-based medicines. Throughout the second half of the 19th century, physicians largely debated alcohol’s role in medicine. However, a 1922 poll of members of the American Medical Association found that physicians were still using alcohol as a medicine for everything from heart attacks to animal bites.

Today, alcohol’s presence in medicine is, in some ways, representative of a realized cognitive dissonance.

“In my mind, alcohol has completely lost any illusion of benefit. It is a poison to almost every single organ in our body. Yet I’m currently engaged in a duel of being a physician who drinks in moderation and constantly judging myself for it,” said Tyra Fainstad, MD, an internist and an associate professor at CU Medicine in Denver.

Fainstad said every academic national conference she has attended has had a reception with multiple cash bars — and professional recruitment dinners regularly include at least the offering of alcohol. Private hospitals often have open bars at events.

“Drinking has historically been a way that people unwind, even in medicine,” said addiction psychiatrist Alexis Ritvo, MD. Ritvo — who said she drinks occasionally but much less than she used to after paying attention to how alcohol makes her feel and the harm alcohol can cause — noted that some occasions where alcohol is present socially in medicine don’t bother her. Alcohol is even an option at the addiction psychiatry conference, where attendees can exchange tickets for drinks. But last year, the event provided separate bars for alcoholic and nonalcoholic drinks.

“Our life is full of things that are contradictory or at odds,” Ritvo said. “We want things to either be wrong or right, appropriate or inappropriate, but just like all things, everything’s pretty nuanced.”

But there are examples of alcohol being a part of an event that are downright inappropriate, such as when she attended a fundraiser for a recovery facility that had an open bar.

Farkouh said alcohol at events can exclude others. (He recommends that instead of calling a social gathering “going out for drinks,” someone might say, “We’re getting together.”) He drinks mocktails or nonalcoholic beer at work events where alcohol is served.

Brian Dwinnell, MD, associate dean of student life at CU Medicine, said alcohol can quickly become the focus of an event — something he noticed at an annual kickball game between first- and second-year students that has historically served beer.

In recent years, school leadership has removed alcohol from his institution’s match day celebration and the kickball game. “Initially, there was some pushback from students,” he said of making these events dry, “but now, it’s just sort of accepted, and the events have been just as great as they were when we did provide alcohol.”

 

How Doctors Drink

Physicians may have a greater understanding of alcohol’s health harms. Still, they don’t necessarily drink less because of it, and whether they should becomes a question not just of health but also of the standards to which society holds medical professionals.

Data suggest physicians tend to drink at rates similar to those among the general population. A recent Medscape Medical News survey found nearly 60% of physicians have started drinking less.

Dwinnell said he is a long-time “wine connoisseur” and drinks on occasion. But he admitted that while he thinks about the health implications of alcohol more — and he has nixed it from various events for medical students — he does not believe his drinking habits have changed much.

Navya Mysore, MD, a family physician in New York City, said she has become interested in wine over the past few years, even taking classes to learn more about it. “I like understanding how it’s made, the regions it’s from, and how to pair it with food,” she said. Mysore admits she drank a little more than usual throughout the pandemic, yet today, she said her relationship with alcohol in moderation is related to family, community, and connection.

Fainstad, who drinks socially, said: “I think there’s an immeasurable quality to the social ritual of it. I think for better or worse — probably for worse — for many generations, alcohol has been a part of many meaningful traditions and rituals that we hold.”

Farkouh was quick to underscore the importance of social connection, and that alcohol reduces stress for some people. “I don’t want to take that away from people,” he said. But he also stated the importance of finding other ways to find social fulfillment and enjoyment — and said it’s essential for societal norms to shift to reflect this.

With emerging data, alcohol’s image in society is shifting. Ireland recently became the first country to pass regulation requiring all alcohol sold there to come with a cancer warning. All the clinicians interviewed for this article spoke about the increased acceptability of choosing not to drink for whatever reason.

In the context of alcohol, Dwinnell often asks his students, “What if you were out at a restaurant and you saw your mother’s surgeon there and they were intoxicated? Are you going to feel comfortable with that individual operating on your mother tomorrow or any time?” He added: “Physicians are held to a higher professional standard than those in other fields — and they should be. This is a high-stakes business.”

Dwinnell’s hypothetical question to students is a good one, albeit perhaps not always a fair one. “It’s important for people to realize that physicians are humans,” Mysore said. “We are people, we have lives, and we may choose to have habits that are not necessarily the healthiest for us.”

Fainstad said there’s no shame in medical professionals drinking on occasion. “You can’t be held accountable for something you don’t know about,” she said, acknowledging the known harms of alcohol and that there is still more to learn. But she does wonder how doctors who drank might be perceived in years to come. “I can imagine in a couple of decades, people could say, ‘Even doctors used to have a glass of wine with dinner.’”

 

‘Physicians Should Tighten Their Stances on Alcohol’

The 2020-2025 Dietary Guidelines suggest limiting intake to two alcoholic drinks or less daily for men and one drink or less for women or to choose not to drink. Farkouh said he skews toward the latter, encouraging patients to drink as little as possible or nothing at all. “If you take a holistic approach, physicians should tighten their stances on alcohol,” he said.

Ultimately, he said a randomized trial is warranted to address the risk for cardiovascular disease, in particular.

Of course, physicians vary in how they discuss the topic with patients.

Mysore said she regularly educates patients about pour size and ways to swap out alcoholic drinks with nonalcoholic ones. Outside of cases of addiction, she favors the idea of moderation. “I don’t really subscribe to all-or-nothing mindsets. If there’s something that you enjoy having as a part of your life, I don’t think there’s any reason why you need to eliminate it,” she said. “You just need to figure out what moderation looks like for you.”

Ritvo favors motivational interviewing and tries to understand someone’s relationship with alcohol.

Fainstad provides the Dietary Guidelines’ cutoffs to patients and educates them on the poisonous nature of the substance.

Clearer guidance from large governing bodies — potential changes around alcohol in the 2025-230 revision of the US Dietary Guidelines or cancer warnings on booze sold in the United States — are coming and could help streamline messaging.

And although he speaks with urgency about alcohol’s dangers, Farkouh emphasized the need for a judgment-free and patient-centered approach to conversations around drinking: “People have grown up with alcohol being acceptable, and it’s going to take time to change that.”

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

For millennia in medicine, alcohol, particularly red wine, carried a health halo; in small doses, it has historically been thought to have cardioprotective benefits. Michael Farkouh, MD, a professor of cardiology at Cedars-Sinai, estimates half the physicians still accept people having a drink or two a day. “That is still in practice, though the numbers are reducing,” he said.

But Farkouh no longer drinks alcohol, a position he has come to after getting more involved in research into the substance and his realization that many of the studies touting alcohol’s health benefits were flawed.

Today, alcohol sits alongside asbestos and tobacco as class 1 carcinogens. According to the World Health Organization, it has no known safe ingestible amount. In 2018, a blockbuster report in The Lancet found no amount of any kind of alcohol improves health. In early January, US Surgeon General Vivek Murthy called for adding cancer warnings to alcohol labels.

But the way doctors drink is far from black and white. For physicians, drinking habits are tied up in personal values, professional understanding of a substance with a confusing research history, and the fact alcohol is deeply ingrained in the social fabric of society — and in medicine. As thinking on alcohol shifts, this news organization spoke with physicians about their own drinking habits, how they counsel patients on it, and alcohol’s place in a field that works to keep people healthy.

 

Cultural Currency

From the days of Hippocrates, who believed alcohol could cure virtually every ailment, alcohol has held a large role in medicine. Through much of the 19th century, patent remedies like Hamlin’s Wizard Oil and the Seven Sutherland Sisters Hair Grower, contained alcohol — sometimes in concentrations exceeding 50%.

The first American Pharmacopoeia, published in 1820, even contained nine wine-based medicines. Throughout the second half of the 19th century, physicians largely debated alcohol’s role in medicine. However, a 1922 poll of members of the American Medical Association found that physicians were still using alcohol as a medicine for everything from heart attacks to animal bites.

Today, alcohol’s presence in medicine is, in some ways, representative of a realized cognitive dissonance.

“In my mind, alcohol has completely lost any illusion of benefit. It is a poison to almost every single organ in our body. Yet I’m currently engaged in a duel of being a physician who drinks in moderation and constantly judging myself for it,” said Tyra Fainstad, MD, an internist and an associate professor at CU Medicine in Denver.

Fainstad said every academic national conference she has attended has had a reception with multiple cash bars — and professional recruitment dinners regularly include at least the offering of alcohol. Private hospitals often have open bars at events.

“Drinking has historically been a way that people unwind, even in medicine,” said addiction psychiatrist Alexis Ritvo, MD. Ritvo — who said she drinks occasionally but much less than she used to after paying attention to how alcohol makes her feel and the harm alcohol can cause — noted that some occasions where alcohol is present socially in medicine don’t bother her. Alcohol is even an option at the addiction psychiatry conference, where attendees can exchange tickets for drinks. But last year, the event provided separate bars for alcoholic and nonalcoholic drinks.

“Our life is full of things that are contradictory or at odds,” Ritvo said. “We want things to either be wrong or right, appropriate or inappropriate, but just like all things, everything’s pretty nuanced.”

But there are examples of alcohol being a part of an event that are downright inappropriate, such as when she attended a fundraiser for a recovery facility that had an open bar.

Farkouh said alcohol at events can exclude others. (He recommends that instead of calling a social gathering “going out for drinks,” someone might say, “We’re getting together.”) He drinks mocktails or nonalcoholic beer at work events where alcohol is served.

Brian Dwinnell, MD, associate dean of student life at CU Medicine, said alcohol can quickly become the focus of an event — something he noticed at an annual kickball game between first- and second-year students that has historically served beer.

In recent years, school leadership has removed alcohol from his institution’s match day celebration and the kickball game. “Initially, there was some pushback from students,” he said of making these events dry, “but now, it’s just sort of accepted, and the events have been just as great as they were when we did provide alcohol.”

 

How Doctors Drink

Physicians may have a greater understanding of alcohol’s health harms. Still, they don’t necessarily drink less because of it, and whether they should becomes a question not just of health but also of the standards to which society holds medical professionals.

Data suggest physicians tend to drink at rates similar to those among the general population. A recent Medscape Medical News survey found nearly 60% of physicians have started drinking less.

Dwinnell said he is a long-time “wine connoisseur” and drinks on occasion. But he admitted that while he thinks about the health implications of alcohol more — and he has nixed it from various events for medical students — he does not believe his drinking habits have changed much.

Navya Mysore, MD, a family physician in New York City, said she has become interested in wine over the past few years, even taking classes to learn more about it. “I like understanding how it’s made, the regions it’s from, and how to pair it with food,” she said. Mysore admits she drank a little more than usual throughout the pandemic, yet today, she said her relationship with alcohol in moderation is related to family, community, and connection.

Fainstad, who drinks socially, said: “I think there’s an immeasurable quality to the social ritual of it. I think for better or worse — probably for worse — for many generations, alcohol has been a part of many meaningful traditions and rituals that we hold.”

Farkouh was quick to underscore the importance of social connection, and that alcohol reduces stress for some people. “I don’t want to take that away from people,” he said. But he also stated the importance of finding other ways to find social fulfillment and enjoyment — and said it’s essential for societal norms to shift to reflect this.

With emerging data, alcohol’s image in society is shifting. Ireland recently became the first country to pass regulation requiring all alcohol sold there to come with a cancer warning. All the clinicians interviewed for this article spoke about the increased acceptability of choosing not to drink for whatever reason.

In the context of alcohol, Dwinnell often asks his students, “What if you were out at a restaurant and you saw your mother’s surgeon there and they were intoxicated? Are you going to feel comfortable with that individual operating on your mother tomorrow or any time?” He added: “Physicians are held to a higher professional standard than those in other fields — and they should be. This is a high-stakes business.”

Dwinnell’s hypothetical question to students is a good one, albeit perhaps not always a fair one. “It’s important for people to realize that physicians are humans,” Mysore said. “We are people, we have lives, and we may choose to have habits that are not necessarily the healthiest for us.”

Fainstad said there’s no shame in medical professionals drinking on occasion. “You can’t be held accountable for something you don’t know about,” she said, acknowledging the known harms of alcohol and that there is still more to learn. But she does wonder how doctors who drank might be perceived in years to come. “I can imagine in a couple of decades, people could say, ‘Even doctors used to have a glass of wine with dinner.’”

 

‘Physicians Should Tighten Their Stances on Alcohol’

The 2020-2025 Dietary Guidelines suggest limiting intake to two alcoholic drinks or less daily for men and one drink or less for women or to choose not to drink. Farkouh said he skews toward the latter, encouraging patients to drink as little as possible or nothing at all. “If you take a holistic approach, physicians should tighten their stances on alcohol,” he said.

Ultimately, he said a randomized trial is warranted to address the risk for cardiovascular disease, in particular.

Of course, physicians vary in how they discuss the topic with patients.

Mysore said she regularly educates patients about pour size and ways to swap out alcoholic drinks with nonalcoholic ones. Outside of cases of addiction, she favors the idea of moderation. “I don’t really subscribe to all-or-nothing mindsets. If there’s something that you enjoy having as a part of your life, I don’t think there’s any reason why you need to eliminate it,” she said. “You just need to figure out what moderation looks like for you.”

Ritvo favors motivational interviewing and tries to understand someone’s relationship with alcohol.

Fainstad provides the Dietary Guidelines’ cutoffs to patients and educates them on the poisonous nature of the substance.

Clearer guidance from large governing bodies — potential changes around alcohol in the 2025-230 revision of the US Dietary Guidelines or cancer warnings on booze sold in the United States — are coming and could help streamline messaging.

And although he speaks with urgency about alcohol’s dangers, Farkouh emphasized the need for a judgment-free and patient-centered approach to conversations around drinking: “People have grown up with alcohol being acceptable, and it’s going to take time to change that.”

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

For millennia in medicine, alcohol, particularly red wine, carried a health halo; in small doses, it has historically been thought to have cardioprotective benefits. Michael Farkouh, MD, a professor of cardiology at Cedars-Sinai, estimates half the physicians still accept people having a drink or two a day. “That is still in practice, though the numbers are reducing,” he said.

But Farkouh no longer drinks alcohol, a position he has come to after getting more involved in research into the substance and his realization that many of the studies touting alcohol’s health benefits were flawed.

Today, alcohol sits alongside asbestos and tobacco as class 1 carcinogens. According to the World Health Organization, it has no known safe ingestible amount. In 2018, a blockbuster report in The Lancet found no amount of any kind of alcohol improves health. In early January, US Surgeon General Vivek Murthy called for adding cancer warnings to alcohol labels.

But the way doctors drink is far from black and white. For physicians, drinking habits are tied up in personal values, professional understanding of a substance with a confusing research history, and the fact alcohol is deeply ingrained in the social fabric of society — and in medicine. As thinking on alcohol shifts, this news organization spoke with physicians about their own drinking habits, how they counsel patients on it, and alcohol’s place in a field that works to keep people healthy.

 

Cultural Currency

From the days of Hippocrates, who believed alcohol could cure virtually every ailment, alcohol has held a large role in medicine. Through much of the 19th century, patent remedies like Hamlin’s Wizard Oil and the Seven Sutherland Sisters Hair Grower, contained alcohol — sometimes in concentrations exceeding 50%.

The first American Pharmacopoeia, published in 1820, even contained nine wine-based medicines. Throughout the second half of the 19th century, physicians largely debated alcohol’s role in medicine. However, a 1922 poll of members of the American Medical Association found that physicians were still using alcohol as a medicine for everything from heart attacks to animal bites.

Today, alcohol’s presence in medicine is, in some ways, representative of a realized cognitive dissonance.

“In my mind, alcohol has completely lost any illusion of benefit. It is a poison to almost every single organ in our body. Yet I’m currently engaged in a duel of being a physician who drinks in moderation and constantly judging myself for it,” said Tyra Fainstad, MD, an internist and an associate professor at CU Medicine in Denver.

Fainstad said every academic national conference she has attended has had a reception with multiple cash bars — and professional recruitment dinners regularly include at least the offering of alcohol. Private hospitals often have open bars at events.

“Drinking has historically been a way that people unwind, even in medicine,” said addiction psychiatrist Alexis Ritvo, MD. Ritvo — who said she drinks occasionally but much less than she used to after paying attention to how alcohol makes her feel and the harm alcohol can cause — noted that some occasions where alcohol is present socially in medicine don’t bother her. Alcohol is even an option at the addiction psychiatry conference, where attendees can exchange tickets for drinks. But last year, the event provided separate bars for alcoholic and nonalcoholic drinks.

“Our life is full of things that are contradictory or at odds,” Ritvo said. “We want things to either be wrong or right, appropriate or inappropriate, but just like all things, everything’s pretty nuanced.”

But there are examples of alcohol being a part of an event that are downright inappropriate, such as when she attended a fundraiser for a recovery facility that had an open bar.

Farkouh said alcohol at events can exclude others. (He recommends that instead of calling a social gathering “going out for drinks,” someone might say, “We’re getting together.”) He drinks mocktails or nonalcoholic beer at work events where alcohol is served.

Brian Dwinnell, MD, associate dean of student life at CU Medicine, said alcohol can quickly become the focus of an event — something he noticed at an annual kickball game between first- and second-year students that has historically served beer.

In recent years, school leadership has removed alcohol from his institution’s match day celebration and the kickball game. “Initially, there was some pushback from students,” he said of making these events dry, “but now, it’s just sort of accepted, and the events have been just as great as they were when we did provide alcohol.”

 

How Doctors Drink

Physicians may have a greater understanding of alcohol’s health harms. Still, they don’t necessarily drink less because of it, and whether they should becomes a question not just of health but also of the standards to which society holds medical professionals.

Data suggest physicians tend to drink at rates similar to those among the general population. A recent Medscape Medical News survey found nearly 60% of physicians have started drinking less.

Dwinnell said he is a long-time “wine connoisseur” and drinks on occasion. But he admitted that while he thinks about the health implications of alcohol more — and he has nixed it from various events for medical students — he does not believe his drinking habits have changed much.

Navya Mysore, MD, a family physician in New York City, said she has become interested in wine over the past few years, even taking classes to learn more about it. “I like understanding how it’s made, the regions it’s from, and how to pair it with food,” she said. Mysore admits she drank a little more than usual throughout the pandemic, yet today, she said her relationship with alcohol in moderation is related to family, community, and connection.

Fainstad, who drinks socially, said: “I think there’s an immeasurable quality to the social ritual of it. I think for better or worse — probably for worse — for many generations, alcohol has been a part of many meaningful traditions and rituals that we hold.”

Farkouh was quick to underscore the importance of social connection, and that alcohol reduces stress for some people. “I don’t want to take that away from people,” he said. But he also stated the importance of finding other ways to find social fulfillment and enjoyment — and said it’s essential for societal norms to shift to reflect this.

With emerging data, alcohol’s image in society is shifting. Ireland recently became the first country to pass regulation requiring all alcohol sold there to come with a cancer warning. All the clinicians interviewed for this article spoke about the increased acceptability of choosing not to drink for whatever reason.

In the context of alcohol, Dwinnell often asks his students, “What if you were out at a restaurant and you saw your mother’s surgeon there and they were intoxicated? Are you going to feel comfortable with that individual operating on your mother tomorrow or any time?” He added: “Physicians are held to a higher professional standard than those in other fields — and they should be. This is a high-stakes business.”

Dwinnell’s hypothetical question to students is a good one, albeit perhaps not always a fair one. “It’s important for people to realize that physicians are humans,” Mysore said. “We are people, we have lives, and we may choose to have habits that are not necessarily the healthiest for us.”

Fainstad said there’s no shame in medical professionals drinking on occasion. “You can’t be held accountable for something you don’t know about,” she said, acknowledging the known harms of alcohol and that there is still more to learn. But she does wonder how doctors who drank might be perceived in years to come. “I can imagine in a couple of decades, people could say, ‘Even doctors used to have a glass of wine with dinner.’”

 

‘Physicians Should Tighten Their Stances on Alcohol’

The 2020-2025 Dietary Guidelines suggest limiting intake to two alcoholic drinks or less daily for men and one drink or less for women or to choose not to drink. Farkouh said he skews toward the latter, encouraging patients to drink as little as possible or nothing at all. “If you take a holistic approach, physicians should tighten their stances on alcohol,” he said.

Ultimately, he said a randomized trial is warranted to address the risk for cardiovascular disease, in particular.

Of course, physicians vary in how they discuss the topic with patients.

Mysore said she regularly educates patients about pour size and ways to swap out alcoholic drinks with nonalcoholic ones. Outside of cases of addiction, she favors the idea of moderation. “I don’t really subscribe to all-or-nothing mindsets. If there’s something that you enjoy having as a part of your life, I don’t think there’s any reason why you need to eliminate it,” she said. “You just need to figure out what moderation looks like for you.”

Ritvo favors motivational interviewing and tries to understand someone’s relationship with alcohol.

Fainstad provides the Dietary Guidelines’ cutoffs to patients and educates them on the poisonous nature of the substance.

Clearer guidance from large governing bodies — potential changes around alcohol in the 2025-230 revision of the US Dietary Guidelines or cancer warnings on booze sold in the United States — are coming and could help streamline messaging.

And although he speaks with urgency about alcohol’s dangers, Farkouh emphasized the need for a judgment-free and patient-centered approach to conversations around drinking: “People have grown up with alcohol being acceptable, and it’s going to take time to change that.”

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

TOPLINE: 

Prostate-specific membrane antigen (PSMA)–PET detected metastatic disease in 46% of patients with high-risk prostate cancer previously classified as nonmetastatic by conventional imaging. Results were positive in 84% of patients, with polymetastatic disease found in 24% of cases.

METHODOLOGY:

• Recurrent nonmetastatic hormone-sensitive prostate cancer is characterized by increasing prostate-specific antigen (PSA) levels while naive or responsive to androgen deprivation therapy, without evidence of metastasis on conventional imaging.
• A post hoc, retrospective, cross-sectional analysis included 182 patients from four prospective studies conducted from September 2016 to September 2021, with participants having recurrent prostate cancer after radical prostatectomy, definitive radiotherapy, or salvage radiotherapy.
• Inclusion criteria encompassed PSA levels > 1.0 ng/mL after radical prostatectomy and salvage radiotherapy or > 2.0 ng/mL above nadir after definitive radiotherapy, PSA doubling time ≤ 9 months, and serum testosterone ≥ 150 ng/dL.
• Researchers at the University of California, Los Angeles, performed Gallium-68-PSMA-11 PET/CT imaging with a median injection of 5.0 mCi and uptake time of 61 minutes, with 98% of patients receiving CT contrast.

TAKEAWAY:

• PSMA-PET findings were positive in 80% of patients after radical prostatectomy, 92% after definitive radiotherapy, 85% after radical prostatectomy and salvage radiotherapy, and 84% overall (153 of 182 patients).
• Distant metastatic disease was detected in 34% of patients after radical prostatectomy, 56% after definitive radiotherapy, 60% after radical prostatectomy and salvage radiotherapy, and 46% overall.
• Polymetastatic disease (≥ 5 lesions) was identified in 19% of patients after radical prostatectomy, 36% after definitive radiotherapy, 23% after radical prostatectomy and salvage radiotherapy, and 24% overall.
• According to the authors, these findings suggest that patients’ high-risk nonmetastatic hormone-sensitive prostate cancers are understaged by conventional imaging.

IN PRACTICE:

“In a cohort of patients with high-risk hormone-sensitive prostate cancer without evidence of metastatic disease by conventional imaging, PSMA-PET results were positive in 84% of patients, detected M1 disease stage in 46% of patients, and found polymetastatic disease in 24% of patients. ... The results challenge the interpretation of previous studies, such as the EMBARK trial, and support the evolving role of PSMA-PET for patient selection in clinical and trial interventions in prostate cancer,” the authors of the new paper wrote. “Further studies are needed to assess its independent prognostic value and use for treatment guidance.”

SOURCE:

This study was led by Adrien Holzgreve, MD, and Wesley R. Armstrong, BS, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles. It was published online on January 3 in JAMA Network Open.

LIMITATIONS:

The analysis included significantly fewer patients treated with combined radical prostatectomy and salvage radiotherapy than the original EMBARK trial (29% vs 49%). Patients in this study had a lower median PSA doubling time and serum PSA level at enrollment than those in the EMBARK study. The retrospective nature of this study precluded systematic baseline imaging that would be standard for clinical trial enrollment. Additionally, while PSMA-PET offers the best diagnostic accuracy for prostate cancer staging, it can produce false-positive findings, particularly in bone metastases, with a positive predictive value of 0.84% in biochemical recurrence.

DISCLOSURES:

Holzgreve reported receiving personal fees from ABX advanced biochemical compounds outside the submitted work. This study was supported by grants from the Deutsche Forschungsgemeinschaft, the Prostate Cancer Foundation, and the Society of Nuclear Medicine and Molecular Imaging. 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: 

Prostate-specific membrane antigen (PSMA)–PET detected metastatic disease in 46% of patients with high-risk prostate cancer previously classified as nonmetastatic by conventional imaging. Results were positive in 84% of patients, with polymetastatic disease found in 24% of cases.

METHODOLOGY:

• Recurrent nonmetastatic hormone-sensitive prostate cancer is characterized by increasing prostate-specific antigen (PSA) levels while naive or responsive to androgen deprivation therapy, without evidence of metastasis on conventional imaging.
• A post hoc, retrospective, cross-sectional analysis included 182 patients from four prospective studies conducted from September 2016 to September 2021, with participants having recurrent prostate cancer after radical prostatectomy, definitive radiotherapy, or salvage radiotherapy.
• Inclusion criteria encompassed PSA levels > 1.0 ng/mL after radical prostatectomy and salvage radiotherapy or > 2.0 ng/mL above nadir after definitive radiotherapy, PSA doubling time ≤ 9 months, and serum testosterone ≥ 150 ng/dL.
• Researchers at the University of California, Los Angeles, performed Gallium-68-PSMA-11 PET/CT imaging with a median injection of 5.0 mCi and uptake time of 61 minutes, with 98% of patients receiving CT contrast.

TAKEAWAY:

• PSMA-PET findings were positive in 80% of patients after radical prostatectomy, 92% after definitive radiotherapy, 85% after radical prostatectomy and salvage radiotherapy, and 84% overall (153 of 182 patients).
• Distant metastatic disease was detected in 34% of patients after radical prostatectomy, 56% after definitive radiotherapy, 60% after radical prostatectomy and salvage radiotherapy, and 46% overall.
• Polymetastatic disease (≥ 5 lesions) was identified in 19% of patients after radical prostatectomy, 36% after definitive radiotherapy, 23% after radical prostatectomy and salvage radiotherapy, and 24% overall.
• According to the authors, these findings suggest that patients’ high-risk nonmetastatic hormone-sensitive prostate cancers are understaged by conventional imaging.

IN PRACTICE:

“In a cohort of patients with high-risk hormone-sensitive prostate cancer without evidence of metastatic disease by conventional imaging, PSMA-PET results were positive in 84% of patients, detected M1 disease stage in 46% of patients, and found polymetastatic disease in 24% of patients. ... The results challenge the interpretation of previous studies, such as the EMBARK trial, and support the evolving role of PSMA-PET for patient selection in clinical and trial interventions in prostate cancer,” the authors of the new paper wrote. “Further studies are needed to assess its independent prognostic value and use for treatment guidance.”

SOURCE:

This study was led by Adrien Holzgreve, MD, and Wesley R. Armstrong, BS, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles. It was published online on January 3 in JAMA Network Open.

LIMITATIONS:

The analysis included significantly fewer patients treated with combined radical prostatectomy and salvage radiotherapy than the original EMBARK trial (29% vs 49%). Patients in this study had a lower median PSA doubling time and serum PSA level at enrollment than those in the EMBARK study. The retrospective nature of this study precluded systematic baseline imaging that would be standard for clinical trial enrollment. Additionally, while PSMA-PET offers the best diagnostic accuracy for prostate cancer staging, it can produce false-positive findings, particularly in bone metastases, with a positive predictive value of 0.84% in biochemical recurrence.

DISCLOSURES:

Holzgreve reported receiving personal fees from ABX advanced biochemical compounds outside the submitted work. This study was supported by grants from the Deutsche Forschungsgemeinschaft, the Prostate Cancer Foundation, and the Society of Nuclear Medicine and Molecular Imaging. 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: 

Prostate-specific membrane antigen (PSMA)–PET detected metastatic disease in 46% of patients with high-risk prostate cancer previously classified as nonmetastatic by conventional imaging. Results were positive in 84% of patients, with polymetastatic disease found in 24% of cases.

METHODOLOGY:

• Recurrent nonmetastatic hormone-sensitive prostate cancer is characterized by increasing prostate-specific antigen (PSA) levels while naive or responsive to androgen deprivation therapy, without evidence of metastasis on conventional imaging.
• A post hoc, retrospective, cross-sectional analysis included 182 patients from four prospective studies conducted from September 2016 to September 2021, with participants having recurrent prostate cancer after radical prostatectomy, definitive radiotherapy, or salvage radiotherapy.
• Inclusion criteria encompassed PSA levels > 1.0 ng/mL after radical prostatectomy and salvage radiotherapy or > 2.0 ng/mL above nadir after definitive radiotherapy, PSA doubling time ≤ 9 months, and serum testosterone ≥ 150 ng/dL.
• Researchers at the University of California, Los Angeles, performed Gallium-68-PSMA-11 PET/CT imaging with a median injection of 5.0 mCi and uptake time of 61 minutes, with 98% of patients receiving CT contrast.

TAKEAWAY:

• PSMA-PET findings were positive in 80% of patients after radical prostatectomy, 92% after definitive radiotherapy, 85% after radical prostatectomy and salvage radiotherapy, and 84% overall (153 of 182 patients).
• Distant metastatic disease was detected in 34% of patients after radical prostatectomy, 56% after definitive radiotherapy, 60% after radical prostatectomy and salvage radiotherapy, and 46% overall.
• Polymetastatic disease (≥ 5 lesions) was identified in 19% of patients after radical prostatectomy, 36% after definitive radiotherapy, 23% after radical prostatectomy and salvage radiotherapy, and 24% overall.
• According to the authors, these findings suggest that patients’ high-risk nonmetastatic hormone-sensitive prostate cancers are understaged by conventional imaging.

IN PRACTICE:

“In a cohort of patients with high-risk hormone-sensitive prostate cancer without evidence of metastatic disease by conventional imaging, PSMA-PET results were positive in 84% of patients, detected M1 disease stage in 46% of patients, and found polymetastatic disease in 24% of patients. ... The results challenge the interpretation of previous studies, such as the EMBARK trial, and support the evolving role of PSMA-PET for patient selection in clinical and trial interventions in prostate cancer,” the authors of the new paper wrote. “Further studies are needed to assess its independent prognostic value and use for treatment guidance.”

SOURCE:

This study was led by Adrien Holzgreve, MD, and Wesley R. Armstrong, BS, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles. It was published online on January 3 in JAMA Network Open.

LIMITATIONS:

The analysis included significantly fewer patients treated with combined radical prostatectomy and salvage radiotherapy than the original EMBARK trial (29% vs 49%). Patients in this study had a lower median PSA doubling time and serum PSA level at enrollment than those in the EMBARK study. The retrospective nature of this study precluded systematic baseline imaging that would be standard for clinical trial enrollment. Additionally, while PSMA-PET offers the best diagnostic accuracy for prostate cancer staging, it can produce false-positive findings, particularly in bone metastases, with a positive predictive value of 0.84% in biochemical recurrence.

DISCLOSURES:

Holzgreve reported receiving personal fees from ABX advanced biochemical compounds outside the submitted work. This study was supported by grants from the Deutsche Forschungsgemeinschaft, the Prostate Cancer Foundation, and the Society of Nuclear Medicine and Molecular Imaging. 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.

Results from the British COLO-DETECT trial add to the growing body of evidence supporting the use of artificial intelligence (AI)–aided colonoscopy to increase premalignant colorectal polyp detection in routine colonoscopy practice.

Colin J. Rees, a professor of gastroenterology in the Faculty of Medical Sciences at Newcastle University in Newcastle upon Tyne, England, and colleagues compared the real-world clinical effectiveness of computer-aided detection (CADe)–assisted colonoscopy using an “intelligent” module with that of standard colonoscopy in a study in The Lancet Gastroenterology & Hepatology.

They found the GI Genius Intelligent Endoscopy Module (Medtronic) increased the mean number of adenomas detected per procedure and the adenoma detection rate, especially for small, flat (type 0-IIa) polyps, and sessile serrated lesions, which are more likely to be missed.

“Missed sessile serrated lesions disproportionately increase the risk of post-colonoscopy colorectal cancer, thus the adoption of GI Genius into routine colonoscopy practice could not only increase polyp detection but also reduce the incidence of post-colonoscopy colorectal cancer,” the investigators wrote.

“AI is going to have a major impact upon most aspects of healthcare. Some areas of medical practice are now well established, and some are still in evolution,” Rees, who is also president of the British Society of Gastroenterology, said in an interview. “Within gastroenterology, the role of AI in endoscopic diagnostics is also evolving. The COLO-DETECT trial demonstrates that AI increases detection of lesions, and work is ongoing to see how AI might help with characterization and other elements of endoscopic practice.”

 

Study Details

The multicenter, open-label, parallel-arm, pragmatic randomized controlled trial was conducted at 12 National Health Service hospitals in England. The study cohort consisted of adults ≥ 18 years undergoing colorectal cancer (CRC) screening or colonoscopy for gastrointestinal symptom surveillance owing to personal or family history.

Recruiting staff, participants, and colonoscopists were unmasked to allocation, whereas histopathologists, cochief investigators, and trial statisticians were masked.

CADe-assisted colonoscopy consisted of standard colonoscopy plus the GI Genius module active for at least the entire inspection phase of colonoscope withdrawal.

The primary outcome was mean adenomas per procedure (total number of adenomas detected divided by total number of procedures). The key secondary outcome was adenoma detection rate (proportion of colonoscopies with at least one adenoma).

From March 2021 to April 2023, the investigators recruited 2032 participants, 55.7% men, with a mean cohort age of 62.4 years and randomly assigned them to CADe-assisted colonoscopy (n = 1015) or to standard colonoscopy (n = 1017). Of these, 60.6% were undergoing screening and 39.4% had symptomatic indications.

Mean adenomas per procedure were 1.56 (SD, 2.82; n = 1001 participants with data) in the CADe-assisted group vs 1.21 (n = 1009) in the standard group, for an adjusted mean difference of 0.36 (95% CI, 0.14-0.57; adjusted incidence rate ratio, 1.30; 95% CI, 1.15-1.47; P < .0001).

Adenomas were detected in 555 (56.6%) of 980 participants in the CADe-assisted group vs 477 (48.4%) of 986 in the standard group, representing a proportion difference of 8.3% (95% CI, 3.9-12.7; adjusted odds ratio, 1.47; 95% CI, 1.21-1.78; P < .0001).

As to safety, adverse events were numerically comparable in both the intervention and control groups, with overall events 25 vs 19 and serious events 4 vs 6. On independent review, no adverse events in the CADe-assisted colonoscopy group were related to GI Genius.

 

Offering a US perspective on the study, Nabil M. Mansour, MD, an associate professor and director of the McNair General GI Clinic at Baylor College of Medicine in Houston, Texas, said GI Genius and other CADe systems represent a significant advance over standard colonoscopy for identifying premalignant polyps. “While the data have been mixed, most studies, particularly randomized controlled trials have shown significant improvements with CADe in detection both terms of in adenomas per colonoscopy and reductions in adenoma miss rate,” he said in an interview.

He added that the main utility of CADe is for asymptomatic patients undergoing average-risk screening and surveillance colonoscopy for CRC screening and prevention, as well as for those with positive stool-based screening tests, “though there is no downside to using it in symptomatic patients as well.” Though AI colonoscopy likely still stands at < 50% of endoscopy centers overall, and is used mainly at academic centers, his clinic has been using it for the past year.

The main question, Mansour cautioned, is whether increased detection of small polyps will actually reduce CRC incidence or mortality, and it will likely be several years before clear, concrete data can answer that.

“Most studies have shown the improvement in adenoma detection is mainly for diminutive polyps < 5 mm in diameter, but whether that will actually translate to substantive improvements in hard outcomes is as yet unknown,” he said. “But if gastroenterologists are interested in doing everything they can today to help improve detection rates and lower miss rates of premalignant polyps, serious consideration should be given to adopting the use of CADe in practice.”

This study was supported by Medtronic. Rees reported receiving grant funding from ARC Medical, Norgine, Medtronic, 3-D Matrix, and Olympus Medical, and has been an expert witness for ARC Medical. Other authors disclosed receiving research funding, honoraria, or travel expenses from Medtronic or other private companies. Mansour had no competing interests to declare.

A version of this article appeared on Medscape.com.

Results from the British COLO-DETECT trial add to the growing body of evidence supporting the use of artificial intelligence (AI)–aided colonoscopy to increase premalignant colorectal polyp detection in routine colonoscopy practice.

Colin J. Rees, a professor of gastroenterology in the Faculty of Medical Sciences at Newcastle University in Newcastle upon Tyne, England, and colleagues compared the real-world clinical effectiveness of computer-aided detection (CADe)–assisted colonoscopy using an “intelligent” module with that of standard colonoscopy in a study in The Lancet Gastroenterology & Hepatology.

They found the GI Genius Intelligent Endoscopy Module (Medtronic) increased the mean number of adenomas detected per procedure and the adenoma detection rate, especially for small, flat (type 0-IIa) polyps, and sessile serrated lesions, which are more likely to be missed.

“Missed sessile serrated lesions disproportionately increase the risk of post-colonoscopy colorectal cancer, thus the adoption of GI Genius into routine colonoscopy practice could not only increase polyp detection but also reduce the incidence of post-colonoscopy colorectal cancer,” the investigators wrote.

“AI is going to have a major impact upon most aspects of healthcare. Some areas of medical practice are now well established, and some are still in evolution,” Rees, who is also president of the British Society of Gastroenterology, said in an interview. “Within gastroenterology, the role of AI in endoscopic diagnostics is also evolving. The COLO-DETECT trial demonstrates that AI increases detection of lesions, and work is ongoing to see how AI might help with characterization and other elements of endoscopic practice.”

 

Study Details

The multicenter, open-label, parallel-arm, pragmatic randomized controlled trial was conducted at 12 National Health Service hospitals in England. The study cohort consisted of adults ≥ 18 years undergoing colorectal cancer (CRC) screening or colonoscopy for gastrointestinal symptom surveillance owing to personal or family history.

Recruiting staff, participants, and colonoscopists were unmasked to allocation, whereas histopathologists, cochief investigators, and trial statisticians were masked.

CADe-assisted colonoscopy consisted of standard colonoscopy plus the GI Genius module active for at least the entire inspection phase of colonoscope withdrawal.

The primary outcome was mean adenomas per procedure (total number of adenomas detected divided by total number of procedures). The key secondary outcome was adenoma detection rate (proportion of colonoscopies with at least one adenoma).

From March 2021 to April 2023, the investigators recruited 2032 participants, 55.7% men, with a mean cohort age of 62.4 years and randomly assigned them to CADe-assisted colonoscopy (n = 1015) or to standard colonoscopy (n = 1017). Of these, 60.6% were undergoing screening and 39.4% had symptomatic indications.

Mean adenomas per procedure were 1.56 (SD, 2.82; n = 1001 participants with data) in the CADe-assisted group vs 1.21 (n = 1009) in the standard group, for an adjusted mean difference of 0.36 (95% CI, 0.14-0.57; adjusted incidence rate ratio, 1.30; 95% CI, 1.15-1.47; P < .0001).

Adenomas were detected in 555 (56.6%) of 980 participants in the CADe-assisted group vs 477 (48.4%) of 986 in the standard group, representing a proportion difference of 8.3% (95% CI, 3.9-12.7; adjusted odds ratio, 1.47; 95% CI, 1.21-1.78; P < .0001).

As to safety, adverse events were numerically comparable in both the intervention and control groups, with overall events 25 vs 19 and serious events 4 vs 6. On independent review, no adverse events in the CADe-assisted colonoscopy group were related to GI Genius.

 

Offering a US perspective on the study, Nabil M. Mansour, MD, an associate professor and director of the McNair General GI Clinic at Baylor College of Medicine in Houston, Texas, said GI Genius and other CADe systems represent a significant advance over standard colonoscopy for identifying premalignant polyps. “While the data have been mixed, most studies, particularly randomized controlled trials have shown significant improvements with CADe in detection both terms of in adenomas per colonoscopy and reductions in adenoma miss rate,” he said in an interview.

He added that the main utility of CADe is for asymptomatic patients undergoing average-risk screening and surveillance colonoscopy for CRC screening and prevention, as well as for those with positive stool-based screening tests, “though there is no downside to using it in symptomatic patients as well.” Though AI colonoscopy likely still stands at < 50% of endoscopy centers overall, and is used mainly at academic centers, his clinic has been using it for the past year.

The main question, Mansour cautioned, is whether increased detection of small polyps will actually reduce CRC incidence or mortality, and it will likely be several years before clear, concrete data can answer that.

“Most studies have shown the improvement in adenoma detection is mainly for diminutive polyps < 5 mm in diameter, but whether that will actually translate to substantive improvements in hard outcomes is as yet unknown,” he said. “But if gastroenterologists are interested in doing everything they can today to help improve detection rates and lower miss rates of premalignant polyps, serious consideration should be given to adopting the use of CADe in practice.”

This study was supported by Medtronic. Rees reported receiving grant funding from ARC Medical, Norgine, Medtronic, 3-D Matrix, and Olympus Medical, and has been an expert witness for ARC Medical. Other authors disclosed receiving research funding, honoraria, or travel expenses from Medtronic or other private companies. Mansour had no competing interests to declare.

A version of this article appeared on Medscape.com.

Results from the British COLO-DETECT trial add to the growing body of evidence supporting the use of artificial intelligence (AI)–aided colonoscopy to increase premalignant colorectal polyp detection in routine colonoscopy practice.

Colin J. Rees, a professor of gastroenterology in the Faculty of Medical Sciences at Newcastle University in Newcastle upon Tyne, England, and colleagues compared the real-world clinical effectiveness of computer-aided detection (CADe)–assisted colonoscopy using an “intelligent” module with that of standard colonoscopy in a study in The Lancet Gastroenterology & Hepatology.

They found the GI Genius Intelligent Endoscopy Module (Medtronic) increased the mean number of adenomas detected per procedure and the adenoma detection rate, especially for small, flat (type 0-IIa) polyps, and sessile serrated lesions, which are more likely to be missed.

“Missed sessile serrated lesions disproportionately increase the risk of post-colonoscopy colorectal cancer, thus the adoption of GI Genius into routine colonoscopy practice could not only increase polyp detection but also reduce the incidence of post-colonoscopy colorectal cancer,” the investigators wrote.

“AI is going to have a major impact upon most aspects of healthcare. Some areas of medical practice are now well established, and some are still in evolution,” Rees, who is also president of the British Society of Gastroenterology, said in an interview. “Within gastroenterology, the role of AI in endoscopic diagnostics is also evolving. The COLO-DETECT trial demonstrates that AI increases detection of lesions, and work is ongoing to see how AI might help with characterization and other elements of endoscopic practice.”

 

Study Details

The multicenter, open-label, parallel-arm, pragmatic randomized controlled trial was conducted at 12 National Health Service hospitals in England. The study cohort consisted of adults ≥ 18 years undergoing colorectal cancer (CRC) screening or colonoscopy for gastrointestinal symptom surveillance owing to personal or family history.

Recruiting staff, participants, and colonoscopists were unmasked to allocation, whereas histopathologists, cochief investigators, and trial statisticians were masked.

CADe-assisted colonoscopy consisted of standard colonoscopy plus the GI Genius module active for at least the entire inspection phase of colonoscope withdrawal.

The primary outcome was mean adenomas per procedure (total number of adenomas detected divided by total number of procedures). The key secondary outcome was adenoma detection rate (proportion of colonoscopies with at least one adenoma).

From March 2021 to April 2023, the investigators recruited 2032 participants, 55.7% men, with a mean cohort age of 62.4 years and randomly assigned them to CADe-assisted colonoscopy (n = 1015) or to standard colonoscopy (n = 1017). Of these, 60.6% were undergoing screening and 39.4% had symptomatic indications.

Mean adenomas per procedure were 1.56 (SD, 2.82; n = 1001 participants with data) in the CADe-assisted group vs 1.21 (n = 1009) in the standard group, for an adjusted mean difference of 0.36 (95% CI, 0.14-0.57; adjusted incidence rate ratio, 1.30; 95% CI, 1.15-1.47; P < .0001).

Adenomas were detected in 555 (56.6%) of 980 participants in the CADe-assisted group vs 477 (48.4%) of 986 in the standard group, representing a proportion difference of 8.3% (95% CI, 3.9-12.7; adjusted odds ratio, 1.47; 95% CI, 1.21-1.78; P < .0001).

As to safety, adverse events were numerically comparable in both the intervention and control groups, with overall events 25 vs 19 and serious events 4 vs 6. On independent review, no adverse events in the CADe-assisted colonoscopy group were related to GI Genius.

 

Offering a US perspective on the study, Nabil M. Mansour, MD, an associate professor and director of the McNair General GI Clinic at Baylor College of Medicine in Houston, Texas, said GI Genius and other CADe systems represent a significant advance over standard colonoscopy for identifying premalignant polyps. “While the data have been mixed, most studies, particularly randomized controlled trials have shown significant improvements with CADe in detection both terms of in adenomas per colonoscopy and reductions in adenoma miss rate,” he said in an interview.

He added that the main utility of CADe is for asymptomatic patients undergoing average-risk screening and surveillance colonoscopy for CRC screening and prevention, as well as for those with positive stool-based screening tests, “though there is no downside to using it in symptomatic patients as well.” Though AI colonoscopy likely still stands at < 50% of endoscopy centers overall, and is used mainly at academic centers, his clinic has been using it for the past year.

The main question, Mansour cautioned, is whether increased detection of small polyps will actually reduce CRC incidence or mortality, and it will likely be several years before clear, concrete data can answer that.

“Most studies have shown the improvement in adenoma detection is mainly for diminutive polyps < 5 mm in diameter, but whether that will actually translate to substantive improvements in hard outcomes is as yet unknown,” he said. “But if gastroenterologists are interested in doing everything they can today to help improve detection rates and lower miss rates of premalignant polyps, serious consideration should be given to adopting the use of CADe in practice.”

This study was supported by Medtronic. Rees reported receiving grant funding from ARC Medical, Norgine, Medtronic, 3-D Matrix, and Olympus Medical, and has been an expert witness for ARC Medical. Other authors disclosed receiving research funding, honoraria, or travel expenses from Medtronic or other private companies. Mansour had no competing interests to declare.

A version of this article appeared on Medscape.com.

Recently, a 40-year-old woman took to Facebook to announce that she had died.

Rachel Davies, of Wales, wrote: “If you’re reading this, then it means I’m no longer here. What a life I’ve had, and surprisingly, since cancer entered my life. When I look through my photos, I’ve done and seen so much since cancer, and probably some of my best memories are from this period. In so many ways, I have to thank it for learning how to live fully. What I wish is that everyone can experience the same but without needing cancer. Get out there, experience life fully, and wear that dress!!! I’m so sad to leave my family and friends, I wish I never had to go. I’m so grateful to have had Charlie young so that I’ve watched him grow into the man he is today. I’m unbelievably proud of him. I am thankful I had the opportunity to have Kacey and Jacob in my life. Lastly, I was blessed to meet the love of my life, my husband, and my best friend. I have no regrets, I have had a wonderful life. So to all of you, don’t be sad I’ve gone. Live your life and live it well. Love, Rachel x.”

 

I didn’t know Ms. Davies, but am likely among many who wish I had. In a terrible situation she kept trying.

She had HER2 metastatic breast cancer, which can respond to the drug Enhertu (trastuzumab). Unfortunately, she never had the chance, because it wasn’t available to her in Wales. In the United Kingdom it’s available only in Scotland.

I’m not saying it was a cure. Statistically, it likely would have bought her another 6 months of family time. But that’s still another half year.

I’m not blaming the Welsh NHS, though they made the decision not to cover it because of cost. The jobs of such committees is a thankless one, trying to decide where the limited money goes — vaccines for many children that are proven to lessen morbidity and mortality over the course of a lifetime, or to add 6 months to the lives of comparatively fewer women with HER2 metastatic breast cancer.

I’m not blaming the company that makes Enhertu, though it was the cost that kept her from getting it. Bringing a drug to market, with all the labs and clinical research behind it, ain’t cheap. If the company can’t keep the lights on they’re not going to able to develop future pharmaceuticals to help others, though I do wonder if a better price could have been negotiated. (I’m not trying to justify the salaries of insurance CEOs — don’t even get me started on those.)

Money is always limited, and human suffering is infinite. Every health care organization, public or private, has to face that simple fact. There is no right place to draw the line, so we use the greatest good for the greatest many as our best guess.

In her last post, though, Ms. Davies didn’t dwell on any of this. She reflected on her joys and blessings, and encouraged others to live life fully. Things we should all focus on.

In a world that often seems to have gone mad, it’s good to keep in mind that there is more good than bad out there. 

Thank you, Ms. Davies, for the reminder.

Allan M. Block, MD, has a solo neurology practice in Scottsdale, Arizona.

Recently, a 40-year-old woman took to Facebook to announce that she had died.

Rachel Davies, of Wales, wrote: “If you’re reading this, then it means I’m no longer here. What a life I’ve had, and surprisingly, since cancer entered my life. When I look through my photos, I’ve done and seen so much since cancer, and probably some of my best memories are from this period. In so many ways, I have to thank it for learning how to live fully. What I wish is that everyone can experience the same but without needing cancer. Get out there, experience life fully, and wear that dress!!! I’m so sad to leave my family and friends, I wish I never had to go. I’m so grateful to have had Charlie young so that I’ve watched him grow into the man he is today. I’m unbelievably proud of him. I am thankful I had the opportunity to have Kacey and Jacob in my life. Lastly, I was blessed to meet the love of my life, my husband, and my best friend. I have no regrets, I have had a wonderful life. So to all of you, don’t be sad I’ve gone. Live your life and live it well. Love, Rachel x.”

 

I didn’t know Ms. Davies, but am likely among many who wish I had. In a terrible situation she kept trying.

She had HER2 metastatic breast cancer, which can respond to the drug Enhertu (trastuzumab). Unfortunately, she never had the chance, because it wasn’t available to her in Wales. In the United Kingdom it’s available only in Scotland.

I’m not saying it was a cure. Statistically, it likely would have bought her another 6 months of family time. But that’s still another half year.

I’m not blaming the Welsh NHS, though they made the decision not to cover it because of cost. The jobs of such committees is a thankless one, trying to decide where the limited money goes — vaccines for many children that are proven to lessen morbidity and mortality over the course of a lifetime, or to add 6 months to the lives of comparatively fewer women with HER2 metastatic breast cancer.

I’m not blaming the company that makes Enhertu, though it was the cost that kept her from getting it. Bringing a drug to market, with all the labs and clinical research behind it, ain’t cheap. If the company can’t keep the lights on they’re not going to able to develop future pharmaceuticals to help others, though I do wonder if a better price could have been negotiated. (I’m not trying to justify the salaries of insurance CEOs — don’t even get me started on those.)

Money is always limited, and human suffering is infinite. Every health care organization, public or private, has to face that simple fact. There is no right place to draw the line, so we use the greatest good for the greatest many as our best guess.

In her last post, though, Ms. Davies didn’t dwell on any of this. She reflected on her joys and blessings, and encouraged others to live life fully. Things we should all focus on.

In a world that often seems to have gone mad, it’s good to keep in mind that there is more good than bad out there. 

Thank you, Ms. Davies, for the reminder.

Allan M. Block, MD, has a solo neurology practice in Scottsdale, Arizona.

Recently, a 40-year-old woman took to Facebook to announce that she had died.

Rachel Davies, of Wales, wrote: “If you’re reading this, then it means I’m no longer here. What a life I’ve had, and surprisingly, since cancer entered my life. When I look through my photos, I’ve done and seen so much since cancer, and probably some of my best memories are from this period. In so many ways, I have to thank it for learning how to live fully. What I wish is that everyone can experience the same but without needing cancer. Get out there, experience life fully, and wear that dress!!! I’m so sad to leave my family and friends, I wish I never had to go. I’m so grateful to have had Charlie young so that I’ve watched him grow into the man he is today. I’m unbelievably proud of him. I am thankful I had the opportunity to have Kacey and Jacob in my life. Lastly, I was blessed to meet the love of my life, my husband, and my best friend. I have no regrets, I have had a wonderful life. So to all of you, don’t be sad I’ve gone. Live your life and live it well. Love, Rachel x.”

 

I didn’t know Ms. Davies, but am likely among many who wish I had. In a terrible situation she kept trying.

She had HER2 metastatic breast cancer, which can respond to the drug Enhertu (trastuzumab). Unfortunately, she never had the chance, because it wasn’t available to her in Wales. In the United Kingdom it’s available only in Scotland.

I’m not saying it was a cure. Statistically, it likely would have bought her another 6 months of family time. But that’s still another half year.

I’m not blaming the Welsh NHS, though they made the decision not to cover it because of cost. The jobs of such committees is a thankless one, trying to decide where the limited money goes — vaccines for many children that are proven to lessen morbidity and mortality over the course of a lifetime, or to add 6 months to the lives of comparatively fewer women with HER2 metastatic breast cancer.

I’m not blaming the company that makes Enhertu, though it was the cost that kept her from getting it. Bringing a drug to market, with all the labs and clinical research behind it, ain’t cheap. If the company can’t keep the lights on they’re not going to able to develop future pharmaceuticals to help others, though I do wonder if a better price could have been negotiated. (I’m not trying to justify the salaries of insurance CEOs — don’t even get me started on those.)

Money is always limited, and human suffering is infinite. Every health care organization, public or private, has to face that simple fact. There is no right place to draw the line, so we use the greatest good for the greatest many as our best guess.

In her last post, though, Ms. Davies didn’t dwell on any of this. She reflected on her joys and blessings, and encouraged others to live life fully. Things we should all focus on.

In a world that often seems to have gone mad, it’s good to keep in mind that there is more good than bad out there. 

Thank you, Ms. Davies, for the reminder.

Allan M. Block, MD, has a solo neurology practice in Scottsdale, Arizona.

TOPLINE:

Aggressive margin reduction with MRI-guided stereotactic body radiotherapy (SBRT) led to a significantly lower incidence of late genitourinary and gastrointestinal toxicities at 2 years compared with CT-guided SBRT in men with localized prostate cancer, new data showed.

METHODOLOGY:

• MRI-guided SBRT is known to reduce planning margins in prostate cancer and lead to less acute toxicity compared with standard CT-guided SBRT. However, the long-term benefits of the MRI-guided approach remain unclear.
• To find out, researchers conducted the phase 3 MIRAGE trial, in which 156 patients with localized prostate cancer were randomly assigned to receive either MRI-guided SBRT with 2-mm margins or CT-guided SBRT with 4-mm margins.
• The MIRAGE trial initially reported the primary outcome of acute genitourinary grade ≥ 2 toxicity within 90 days of SBRT.
• In this secondary analysis, researchers evaluated physician-reported late genitourinary and gastrointestinal toxicity, along with changes in various patient-reported quality-of-life scores over a 2-year follow-up period.

TAKEAWAY:

• Over a period of 2 years, MRI-guided SBRT was associated with a significantly lower cumulative incidence of grade ≥ 2 genitourinary toxicities compared with CT-guided SBRT (27% vs 51%; P = .004). Similar outcomes were noted for grade ≥ 2 gastrointestinal toxicities (1.4% with MRI vs 9.5% with CT; P = .025).
• Fewer patients who received MRI-guided SBRT reported deterioration in urinary irritation between 6 and 24 months after radiotherapy — 14 of 73 patients (19.2%) in the MRI group vs 24 of 68 patients (35.3%) in the CT group (P = .031).
• Patients receiving MRI-guided SBRT were also less likely to experience clinically relevant deterioration in bowel function (odds ratio [OR], 0.444; P = .035) and sexual health score (OR, 0.366; P = .03).
• Between 6 and 24 months after radiotherapy, 26.4% of patients (19 of 72) in the MRI group vs 42.3% (30 of 71) in the CT group reported clinically relevant deterioration in bowel function.

IN PRACTICE:

“Our secondary analysis of a randomized trial revealed that aggressive planning for margin reduction with MRI guidance vs CT guidance for prostate SBRT led to lower physician-scored genitourinary and gastrointestinal toxicity and better bowel and sexual quality-of-life metrics over 2 years of follow-up,” the authors wrote.

SOURCE:

This study, led by Amar U. Kishan, University of California Los Angeles, was published online in European Urology.

LIMITATIONS:

The absence of blinding in this study may have influenced both physician-scored toxicity assessments and patient-reported quality-of-life outcomes. The MIRAGE trial was not specifically designed with sufficient statistical power to evaluate the secondary analyses presented in this study.

DISCLOSURES:

This study was supported by grants from the US Department of Defense. Several authors reported receiving grants or personal fees among other ties with various sources.

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:

Aggressive margin reduction with MRI-guided stereotactic body radiotherapy (SBRT) led to a significantly lower incidence of late genitourinary and gastrointestinal toxicities at 2 years compared with CT-guided SBRT in men with localized prostate cancer, new data showed.

METHODOLOGY:

• MRI-guided SBRT is known to reduce planning margins in prostate cancer and lead to less acute toxicity compared with standard CT-guided SBRT. However, the long-term benefits of the MRI-guided approach remain unclear.
• To find out, researchers conducted the phase 3 MIRAGE trial, in which 156 patients with localized prostate cancer were randomly assigned to receive either MRI-guided SBRT with 2-mm margins or CT-guided SBRT with 4-mm margins.
• The MIRAGE trial initially reported the primary outcome of acute genitourinary grade ≥ 2 toxicity within 90 days of SBRT.
• In this secondary analysis, researchers evaluated physician-reported late genitourinary and gastrointestinal toxicity, along with changes in various patient-reported quality-of-life scores over a 2-year follow-up period.

TAKEAWAY:

• Over a period of 2 years, MRI-guided SBRT was associated with a significantly lower cumulative incidence of grade ≥ 2 genitourinary toxicities compared with CT-guided SBRT (27% vs 51%; P = .004). Similar outcomes were noted for grade ≥ 2 gastrointestinal toxicities (1.4% with MRI vs 9.5% with CT; P = .025).
• Fewer patients who received MRI-guided SBRT reported deterioration in urinary irritation between 6 and 24 months after radiotherapy — 14 of 73 patients (19.2%) in the MRI group vs 24 of 68 patients (35.3%) in the CT group (P = .031).
• Patients receiving MRI-guided SBRT were also less likely to experience clinically relevant deterioration in bowel function (odds ratio [OR], 0.444; P = .035) and sexual health score (OR, 0.366; P = .03).
• Between 6 and 24 months after radiotherapy, 26.4% of patients (19 of 72) in the MRI group vs 42.3% (30 of 71) in the CT group reported clinically relevant deterioration in bowel function.

IN PRACTICE:

“Our secondary analysis of a randomized trial revealed that aggressive planning for margin reduction with MRI guidance vs CT guidance for prostate SBRT led to lower physician-scored genitourinary and gastrointestinal toxicity and better bowel and sexual quality-of-life metrics over 2 years of follow-up,” the authors wrote.

SOURCE:

This study, led by Amar U. Kishan, University of California Los Angeles, was published online in European Urology.

LIMITATIONS:

The absence of blinding in this study may have influenced both physician-scored toxicity assessments and patient-reported quality-of-life outcomes. The MIRAGE trial was not specifically designed with sufficient statistical power to evaluate the secondary analyses presented in this study.

DISCLOSURES:

This study was supported by grants from the US Department of Defense. Several authors reported receiving grants or personal fees among other ties with various sources.

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:

Aggressive margin reduction with MRI-guided stereotactic body radiotherapy (SBRT) led to a significantly lower incidence of late genitourinary and gastrointestinal toxicities at 2 years compared with CT-guided SBRT in men with localized prostate cancer, new data showed.

METHODOLOGY:

• MRI-guided SBRT is known to reduce planning margins in prostate cancer and lead to less acute toxicity compared with standard CT-guided SBRT. However, the long-term benefits of the MRI-guided approach remain unclear.
• To find out, researchers conducted the phase 3 MIRAGE trial, in which 156 patients with localized prostate cancer were randomly assigned to receive either MRI-guided SBRT with 2-mm margins or CT-guided SBRT with 4-mm margins.
• The MIRAGE trial initially reported the primary outcome of acute genitourinary grade ≥ 2 toxicity within 90 days of SBRT.
• In this secondary analysis, researchers evaluated physician-reported late genitourinary and gastrointestinal toxicity, along with changes in various patient-reported quality-of-life scores over a 2-year follow-up period.

TAKEAWAY:

• Over a period of 2 years, MRI-guided SBRT was associated with a significantly lower cumulative incidence of grade ≥ 2 genitourinary toxicities compared with CT-guided SBRT (27% vs 51%; P = .004). Similar outcomes were noted for grade ≥ 2 gastrointestinal toxicities (1.4% with MRI vs 9.5% with CT; P = .025).
• Fewer patients who received MRI-guided SBRT reported deterioration in urinary irritation between 6 and 24 months after radiotherapy — 14 of 73 patients (19.2%) in the MRI group vs 24 of 68 patients (35.3%) in the CT group (P = .031).
• Patients receiving MRI-guided SBRT were also less likely to experience clinically relevant deterioration in bowel function (odds ratio [OR], 0.444; P = .035) and sexual health score (OR, 0.366; P = .03).
• Between 6 and 24 months after radiotherapy, 26.4% of patients (19 of 72) in the MRI group vs 42.3% (30 of 71) in the CT group reported clinically relevant deterioration in bowel function.

IN PRACTICE:

“Our secondary analysis of a randomized trial revealed that aggressive planning for margin reduction with MRI guidance vs CT guidance for prostate SBRT led to lower physician-scored genitourinary and gastrointestinal toxicity and better bowel and sexual quality-of-life metrics over 2 years of follow-up,” the authors wrote.

SOURCE:

This study, led by Amar U. Kishan, University of California Los Angeles, was published online in European Urology.

LIMITATIONS:

The absence of blinding in this study may have influenced both physician-scored toxicity assessments and patient-reported quality-of-life outcomes. The MIRAGE trial was not specifically designed with sufficient statistical power to evaluate the secondary analyses presented in this study.

DISCLOSURES:

This study was supported by grants from the US Department of Defense. Several authors reported receiving grants or personal fees among other ties with various sources.

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.