Dr. Shailja Shah is a gastroenterologist and clinical researcher at VA San Diego and the University of California, San Diego. Dr. Shah leads a multidisciplinary research program anchored in defining non-genetic, genetic, and systems-level determinants of H. pylori treatment- and disease-related clinical outcomes, including gastric cancer, among high-risk populations. She is also actively involved in research and public policy initiatives to promote gastric cancer prevention and early detection efforts. Dr. Shah’s current and prior sources of funding include the US Dept of Veterans Affairs, AHRQ, NIH, and the American Gastroenterological Association (AGA).

As a gastroenterologist and physician scientist at UCSD/VA San Diego and Moores Cancer Center, when you think about early detection and surveillance of gastric cancer, what are some of the signs and symptoms you look for and how would you factor in risk-based screenings?

Dr. Shah: In the United States, gastric cancer is overlooked because it is thought of as a rare cancer when, in fact, it's more common than esophageal cancer and in certain groups even approaches rates of colorectal cancer. This is important because we have clear guidelines on who to screen for esophageal and colorectal cancer, but we don't have these guidelines for gastric cancer.

The majority of gastric cancer cases in the United States is non-cardia gastric cancer, which refers to the location in the stomach that this type of cancer occurs. This is in comparison to gastric cancer of the cardia which makes up a much smaller percentage. I mention this up front because the risk factor profiles for these two cancers based on anatomic location are different. Cardia gastric cancer mostly tracks with risk factors for esophageal adenocarcinoma while non-cardia gastric cancer is more common in non-white groups who share a disproportionate burden—with some groups as much as 13.5-fold higher than non-Hispanic whites.

The key to the discussion of risk-based screening for non-cardia gastric cancer is that gastric cancer is typically asymptomatic or presents with only non-specific symptoms until it's in the more advanced stages. There's no cure for gastric cancer once it is in this advanced stage, which is really when symptoms prompt the diagnostic workup. When gastric cancer is caught in the early stage where it is asymptomatic or associated with non-specific symptoms that might not prompt an immediate diagnostic workup—this is the stage that resection would be curative.

There are countries such as Japan and South Korea where endoscopic screening for gastric cancer routinely occurs. This has translated into significant reductions in gastric cancer mortality, although notably has not substantially decreased the actual incidence of cancer. This again suggests that the benefit is early detection and the opportunity for curative resection—which can be accomplished either endoscopically or surgically. The United States population overall is not universally high risk for gastric cancer; however, there are certain identifiable high-risk groups who might benefit from endoscopy for early detection. These include non-white groups and immigrants from high risk countries for gastric cancer, people with a family history of gastric cancer, as well as people with gastric precancerous changes such as atrophic gastritis and intestinal metaplasia. These precancerous changes most often are the result of chronic H. pylori infection.

We don't have very precise risk stratification models, and this is a much-needed area of research. We do, however, have evidence from cost-effectiveness analyses that upper endoscopy for gastric cancer screening at the time of colonoscopy for colorectal cancer screening might be cost effective for non-white race and ethnic groups. At the very least, data from these modeling studies can form a starting point when we think of risk-based screening; ideally, we will have data from prospective studies to guide our approach to gastric cancer screening.

Since H. pylori is one of the strongest risk factors for non-cardia gastric cancer, what is your detailed approach to diagnosis and management?

Dr. Shah: H. pylori is a gram-negative bacterium and, globally, it is the most common chronic bacterial infection. Some studies estimate that over half the world's population is infected with H. pylori. It is difficult to get a precise estimate of the global burden of H. pylori, since many times this infection is asymptomatic and it is not one that is routinely screened for in most parts of the world, including the United States. Generally, testing for H. pylori is triggered by GI symptoms such as dyspepsia, abdominal discomfort, or in patients who don't have symptoms, the things that might trigger testing would be a family history of gastric cancer, unexplained iron deficiency, long term NSAID use, and a few other situations.

It is important to diagnose H. pylori because chronic untreated infection is associated with gastric inflammation, which in some cases can progress to loss of the normal gastric glands, a condition known as atrophic gastritis, and, if replaced by intestinal-type tissue, intestinal metaplasia. Such conditions are associated with significantly higher risk of gastric dysplasia and cancer, particularly if there is ongoing H. pylori infection. This stepwise cascade from chronic gastritis to atrophic gastritis, intestinal metaplasia, dysplasia, and intestinal-type gastric adenocarcinoma is known as the correa cascade, for which H. pylori is the most common trigger.

We know that H. pylori eradication with antibiotics and high dose acid suppression does improve that inflammation and reduces the risk of gastric cancer. But the key here is that the biggest benefit of H. pylori eradication is eradicating H. pylori prior to the development severe atrophic gastritis and intestinal metaplasia. Therefore, simply testing and treating for H. pylori is not enough for gastric cancer prevention since some people might already have these advanced changes, since these typically don't cause symptoms. This forms the basis for endoscopic surveillance of these precancerous conditions, which is detailed in the most recent AGA guidelines and clinical practice update on intestinal metaplasia and atrophic gastritis, respectively.

H. pylori eradication still a cornerstone of gastric cancer prevention and risk reduction. Careful treatment selection and ensuring that eradication is confirmed warrants emphasis, particularly in the face of rising rates of H. pylori eradication failure. My key takeaway points for H. pylori eradication therapy is that prior to prescribing treatment, it's very important to review patients prior antibiotic exposures specifically macrolides and fluoroquinolones, since patients who have had treatment with these antibiotics for any condition are more likely to be colonized with resistant H. pylori strains. Clarithromycin-triple therapy should not be used unless patients are confirmed to be colonized with clarithromycin susceptible H. pylori. Bismuth-based quadruple therapy is really the preferred first line treatment instead of clarithromycin-based triple therapy given the high rates of clarithromycin resistance. It's also important to provide patients with anticipatory guidance regarding both the importance of completing the full course, as well as some expected possible side effects of antibiotics such as GI upset, nausea. The other tenant therapy is ensuring appropriate gastric acid suppression, which is a point emphasized in the recently published AGA clinical practice update on H. pylori management. All patients should have repeat non-serological H. pylori testing to ensure that eradication was successful. To reduce false positive or false negative results, this repeat testing should be done at least 2-4 weeks after completion of therapy and with patients off PPI therapy for at least 1-2 weeks.

What have you found to be some of the key disparities in gastric cancer particularly as it pertains to the racial and ethnic groups in the United States?

Dr. Shah: Racial and ethnic differences in gastric cancer incidence is a defining factor for gastric cancer in the United States. Our team recently conducted a population-based analysis of the California Cancer Registry, which is one of, if not the largest and most diverse of the SEER cancer registries. The results of this study highlighted the disparity in risk of gastric cancer based on race/ethnicity. All non-white groups in the US had a significantly higher risk of non-cardia gastric cancer compared to non-Hispanic whites. This was particularly striking in the age group that we generally consider for cancer screening, where there was anywhere from 2-fold up to 13.5-fold higher risk of non-cardia gastric cancer compared to the reference non-Hispanic whites. In some of these groups for example, Korean American men above the age of 50, these rates were on par with colorectal cancer rates. Even more concerning, it is possible that these estimates are actually underestimating the true burden of disease, since early cancer is asymptomatic most of the time and might go undiagnosed in the absence of screening.

We also know that immigrants from countries where gastric cancer incidence is high, also retain that increased risk and mortality even when they immigrate to countries gastric cancer incidence is low overall. Admittedly, this risk varies depending on immigrant generation and level of acculturation, including dietary practices, and other factors. The risk is observed to decrease over subsequent generations and depending on acculturation, which underscores opportunities for research into interventions and initiatives to address modifiable risk factors.

Given that immigrants from countries of high gastric cancer, including Asian Americans and Hispanics, comprise the vast majority of population growth in the United States, the public health implications are enormous if we continue to be complacent on gastric cancer prevention and early detection efforts.

As the fifth most common cancer and the third most common cause of cancer related deaths, based on recent studies and your personal experiences as a medical practitioner, also considering the gastric cancer does not cause symptoms until it is in the advanced stage, what are your recommendations as it relates to early detection and improving gastric cancer related outcomes?

Dr. Shah: The first step in my opinion, is recognizing that gastric cancer disproportionately affects certain populations in the US like I mentioned, especially racial and ethnic minorities and other under-represented populations, including US veterans. As a VA clinician and a VA investigator, we see that risk factors for gastric cancer, including H. pylori, disproportionately affect our veterans. The reasons are not fully understood but might relate to differential risk factors and exposures among veterans compared to civilian populations.

Gastric cancer is potentially preventable but is almost certainly curable if detected at an early stage, which really provides the rationale for risk-based screening. Unfortunately, gastric cancer has not been a research priority and there are currently no prospective trials investigating patient outcomes associated with screening versus no screening, nor studies investigating surveillance versus no surveillance of conditions like atrophic gastritis and intestinal metaplasia or  defining appropriate surveillance and screening intervals.  The AGA recently published guidelines and clinical practice updates for intestinal metaplasia and atrophic gastritis management. But one common thread that these documents specifically called attention to, was the lack of high-quality data informing practice, especially practice in the United States. Other research priority areas include risk factors and risk stratification algorithms both for incident and fatal gastric cancer, as well as progression of atrophic gastritis and intestinal metaplasia. Having a better understanding of these factors would really help to fine tune our algorithms, and potentially identify factors that can even be intervened on to halt progression.

The last point that I'll highlight actually relates to non-H. pylori associated gastric cancer. We spend a lot of time focused on H. pylori associated gastric cancer, but an increasing number of gastric cancers are being diagnosed in people without evidence of H. pylori infection. Better understanding the interaction between genetic and environmental triggers and how this differs from H. pylori associated gastric cancer is critical to our approach to control and prevention since there certainly could be important nuances.

Dr. Shailja Shah is a gastroenterologist and clinical researcher at VA San Diego and the University of California, San Diego. Dr. Shah leads a multidisciplinary research program anchored in defining non-genetic, genetic, and systems-level determinants of H. pylori treatment- and disease-related clinical outcomes, including gastric cancer, among high-risk populations. She is also actively involved in research and public policy initiatives to promote gastric cancer prevention and early detection efforts. Dr. Shah’s current and prior sources of funding include the US Dept of Veterans Affairs, AHRQ, NIH, and the American Gastroenterological Association (AGA).

As a gastroenterologist and physician scientist at UCSD/VA San Diego and Moores Cancer Center, when you think about early detection and surveillance of gastric cancer, what are some of the signs and symptoms you look for and how would you factor in risk-based screenings?

Dr. Shah: In the United States, gastric cancer is overlooked because it is thought of as a rare cancer when, in fact, it's more common than esophageal cancer and in certain groups even approaches rates of colorectal cancer. This is important because we have clear guidelines on who to screen for esophageal and colorectal cancer, but we don't have these guidelines for gastric cancer.

The majority of gastric cancer cases in the United States is non-cardia gastric cancer, which refers to the location in the stomach that this type of cancer occurs. This is in comparison to gastric cancer of the cardia which makes up a much smaller percentage. I mention this up front because the risk factor profiles for these two cancers based on anatomic location are different. Cardia gastric cancer mostly tracks with risk factors for esophageal adenocarcinoma while non-cardia gastric cancer is more common in non-white groups who share a disproportionate burden—with some groups as much as 13.5-fold higher than non-Hispanic whites.

The key to the discussion of risk-based screening for non-cardia gastric cancer is that gastric cancer is typically asymptomatic or presents with only non-specific symptoms until it's in the more advanced stages. There's no cure for gastric cancer once it is in this advanced stage, which is really when symptoms prompt the diagnostic workup. When gastric cancer is caught in the early stage where it is asymptomatic or associated with non-specific symptoms that might not prompt an immediate diagnostic workup—this is the stage that resection would be curative.

There are countries such as Japan and South Korea where endoscopic screening for gastric cancer routinely occurs. This has translated into significant reductions in gastric cancer mortality, although notably has not substantially decreased the actual incidence of cancer. This again suggests that the benefit is early detection and the opportunity for curative resection—which can be accomplished either endoscopically or surgically. The United States population overall is not universally high risk for gastric cancer; however, there are certain identifiable high-risk groups who might benefit from endoscopy for early detection. These include non-white groups and immigrants from high risk countries for gastric cancer, people with a family history of gastric cancer, as well as people with gastric precancerous changes such as atrophic gastritis and intestinal metaplasia. These precancerous changes most often are the result of chronic H. pylori infection.

We don't have very precise risk stratification models, and this is a much-needed area of research. We do, however, have evidence from cost-effectiveness analyses that upper endoscopy for gastric cancer screening at the time of colonoscopy for colorectal cancer screening might be cost effective for non-white race and ethnic groups. At the very least, data from these modeling studies can form a starting point when we think of risk-based screening; ideally, we will have data from prospective studies to guide our approach to gastric cancer screening.

Since H. pylori is one of the strongest risk factors for non-cardia gastric cancer, what is your detailed approach to diagnosis and management?

Dr. Shah: H. pylori is a gram-negative bacterium and, globally, it is the most common chronic bacterial infection. Some studies estimate that over half the world's population is infected with H. pylori. It is difficult to get a precise estimate of the global burden of H. pylori, since many times this infection is asymptomatic and it is not one that is routinely screened for in most parts of the world, including the United States. Generally, testing for H. pylori is triggered by GI symptoms such as dyspepsia, abdominal discomfort, or in patients who don't have symptoms, the things that might trigger testing would be a family history of gastric cancer, unexplained iron deficiency, long term NSAID use, and a few other situations.

It is important to diagnose H. pylori because chronic untreated infection is associated with gastric inflammation, which in some cases can progress to loss of the normal gastric glands, a condition known as atrophic gastritis, and, if replaced by intestinal-type tissue, intestinal metaplasia. Such conditions are associated with significantly higher risk of gastric dysplasia and cancer, particularly if there is ongoing H. pylori infection. This stepwise cascade from chronic gastritis to atrophic gastritis, intestinal metaplasia, dysplasia, and intestinal-type gastric adenocarcinoma is known as the correa cascade, for which H. pylori is the most common trigger.

We know that H. pylori eradication with antibiotics and high dose acid suppression does improve that inflammation and reduces the risk of gastric cancer. But the key here is that the biggest benefit of H. pylori eradication is eradicating H. pylori prior to the development severe atrophic gastritis and intestinal metaplasia. Therefore, simply testing and treating for H. pylori is not enough for gastric cancer prevention since some people might already have these advanced changes, since these typically don't cause symptoms. This forms the basis for endoscopic surveillance of these precancerous conditions, which is detailed in the most recent AGA guidelines and clinical practice update on intestinal metaplasia and atrophic gastritis, respectively.

H. pylori eradication still a cornerstone of gastric cancer prevention and risk reduction. Careful treatment selection and ensuring that eradication is confirmed warrants emphasis, particularly in the face of rising rates of H. pylori eradication failure. My key takeaway points for H. pylori eradication therapy is that prior to prescribing treatment, it's very important to review patients prior antibiotic exposures specifically macrolides and fluoroquinolones, since patients who have had treatment with these antibiotics for any condition are more likely to be colonized with resistant H. pylori strains. Clarithromycin-triple therapy should not be used unless patients are confirmed to be colonized with clarithromycin susceptible H. pylori. Bismuth-based quadruple therapy is really the preferred first line treatment instead of clarithromycin-based triple therapy given the high rates of clarithromycin resistance. It's also important to provide patients with anticipatory guidance regarding both the importance of completing the full course, as well as some expected possible side effects of antibiotics such as GI upset, nausea. The other tenant therapy is ensuring appropriate gastric acid suppression, which is a point emphasized in the recently published AGA clinical practice update on H. pylori management. All patients should have repeat non-serological H. pylori testing to ensure that eradication was successful. To reduce false positive or false negative results, this repeat testing should be done at least 2-4 weeks after completion of therapy and with patients off PPI therapy for at least 1-2 weeks.

What have you found to be some of the key disparities in gastric cancer particularly as it pertains to the racial and ethnic groups in the United States?

Dr. Shah: Racial and ethnic differences in gastric cancer incidence is a defining factor for gastric cancer in the United States. Our team recently conducted a population-based analysis of the California Cancer Registry, which is one of, if not the largest and most diverse of the SEER cancer registries. The results of this study highlighted the disparity in risk of gastric cancer based on race/ethnicity. All non-white groups in the US had a significantly higher risk of non-cardia gastric cancer compared to non-Hispanic whites. This was particularly striking in the age group that we generally consider for cancer screening, where there was anywhere from 2-fold up to 13.5-fold higher risk of non-cardia gastric cancer compared to the reference non-Hispanic whites. In some of these groups for example, Korean American men above the age of 50, these rates were on par with colorectal cancer rates. Even more concerning, it is possible that these estimates are actually underestimating the true burden of disease, since early cancer is asymptomatic most of the time and might go undiagnosed in the absence of screening.

We also know that immigrants from countries where gastric cancer incidence is high, also retain that increased risk and mortality even when they immigrate to countries gastric cancer incidence is low overall. Admittedly, this risk varies depending on immigrant generation and level of acculturation, including dietary practices, and other factors. The risk is observed to decrease over subsequent generations and depending on acculturation, which underscores opportunities for research into interventions and initiatives to address modifiable risk factors.

Given that immigrants from countries of high gastric cancer, including Asian Americans and Hispanics, comprise the vast majority of population growth in the United States, the public health implications are enormous if we continue to be complacent on gastric cancer prevention and early detection efforts.

As the fifth most common cancer and the third most common cause of cancer related deaths, based on recent studies and your personal experiences as a medical practitioner, also considering the gastric cancer does not cause symptoms until it is in the advanced stage, what are your recommendations as it relates to early detection and improving gastric cancer related outcomes?

Dr. Shah: The first step in my opinion, is recognizing that gastric cancer disproportionately affects certain populations in the US like I mentioned, especially racial and ethnic minorities and other under-represented populations, including US veterans. As a VA clinician and a VA investigator, we see that risk factors for gastric cancer, including H. pylori, disproportionately affect our veterans. The reasons are not fully understood but might relate to differential risk factors and exposures among veterans compared to civilian populations.

Gastric cancer is potentially preventable but is almost certainly curable if detected at an early stage, which really provides the rationale for risk-based screening. Unfortunately, gastric cancer has not been a research priority and there are currently no prospective trials investigating patient outcomes associated with screening versus no screening, nor studies investigating surveillance versus no surveillance of conditions like atrophic gastritis and intestinal metaplasia or  defining appropriate surveillance and screening intervals.  The AGA recently published guidelines and clinical practice updates for intestinal metaplasia and atrophic gastritis management. But one common thread that these documents specifically called attention to, was the lack of high-quality data informing practice, especially practice in the United States. Other research priority areas include risk factors and risk stratification algorithms both for incident and fatal gastric cancer, as well as progression of atrophic gastritis and intestinal metaplasia. Having a better understanding of these factors would really help to fine tune our algorithms, and potentially identify factors that can even be intervened on to halt progression.

The last point that I'll highlight actually relates to non-H. pylori associated gastric cancer. We spend a lot of time focused on H. pylori associated gastric cancer, but an increasing number of gastric cancers are being diagnosed in people without evidence of H. pylori infection. Better understanding the interaction between genetic and environmental triggers and how this differs from H. pylori associated gastric cancer is critical to our approach to control and prevention since there certainly could be important nuances.

Dr. Shailja Shah is a gastroenterologist and clinical researcher at VA San Diego and the University of California, San Diego. Dr. Shah leads a multidisciplinary research program anchored in defining non-genetic, genetic, and systems-level determinants of H. pylori treatment- and disease-related clinical outcomes, including gastric cancer, among high-risk populations. She is also actively involved in research and public policy initiatives to promote gastric cancer prevention and early detection efforts. Dr. Shah’s current and prior sources of funding include the US Dept of Veterans Affairs, AHRQ, NIH, and the American Gastroenterological Association (AGA).

As a gastroenterologist and physician scientist at UCSD/VA San Diego and Moores Cancer Center, when you think about early detection and surveillance of gastric cancer, what are some of the signs and symptoms you look for and how would you factor in risk-based screenings?

Dr. Shah: In the United States, gastric cancer is overlooked because it is thought of as a rare cancer when, in fact, it's more common than esophageal cancer and in certain groups even approaches rates of colorectal cancer. This is important because we have clear guidelines on who to screen for esophageal and colorectal cancer, but we don't have these guidelines for gastric cancer.

The majority of gastric cancer cases in the United States is non-cardia gastric cancer, which refers to the location in the stomach that this type of cancer occurs. This is in comparison to gastric cancer of the cardia which makes up a much smaller percentage. I mention this up front because the risk factor profiles for these two cancers based on anatomic location are different. Cardia gastric cancer mostly tracks with risk factors for esophageal adenocarcinoma while non-cardia gastric cancer is more common in non-white groups who share a disproportionate burden—with some groups as much as 13.5-fold higher than non-Hispanic whites.

The key to the discussion of risk-based screening for non-cardia gastric cancer is that gastric cancer is typically asymptomatic or presents with only non-specific symptoms until it's in the more advanced stages. There's no cure for gastric cancer once it is in this advanced stage, which is really when symptoms prompt the diagnostic workup. When gastric cancer is caught in the early stage where it is asymptomatic or associated with non-specific symptoms that might not prompt an immediate diagnostic workup—this is the stage that resection would be curative.

There are countries such as Japan and South Korea where endoscopic screening for gastric cancer routinely occurs. This has translated into significant reductions in gastric cancer mortality, although notably has not substantially decreased the actual incidence of cancer. This again suggests that the benefit is early detection and the opportunity for curative resection—which can be accomplished either endoscopically or surgically. The United States population overall is not universally high risk for gastric cancer; however, there are certain identifiable high-risk groups who might benefit from endoscopy for early detection. These include non-white groups and immigrants from high risk countries for gastric cancer, people with a family history of gastric cancer, as well as people with gastric precancerous changes such as atrophic gastritis and intestinal metaplasia. These precancerous changes most often are the result of chronic H. pylori infection.

We don't have very precise risk stratification models, and this is a much-needed area of research. We do, however, have evidence from cost-effectiveness analyses that upper endoscopy for gastric cancer screening at the time of colonoscopy for colorectal cancer screening might be cost effective for non-white race and ethnic groups. At the very least, data from these modeling studies can form a starting point when we think of risk-based screening; ideally, we will have data from prospective studies to guide our approach to gastric cancer screening.

Since H. pylori is one of the strongest risk factors for non-cardia gastric cancer, what is your detailed approach to diagnosis and management?

Dr. Shah: H. pylori is a gram-negative bacterium and, globally, it is the most common chronic bacterial infection. Some studies estimate that over half the world's population is infected with H. pylori. It is difficult to get a precise estimate of the global burden of H. pylori, since many times this infection is asymptomatic and it is not one that is routinely screened for in most parts of the world, including the United States. Generally, testing for H. pylori is triggered by GI symptoms such as dyspepsia, abdominal discomfort, or in patients who don't have symptoms, the things that might trigger testing would be a family history of gastric cancer, unexplained iron deficiency, long term NSAID use, and a few other situations.

It is important to diagnose H. pylori because chronic untreated infection is associated with gastric inflammation, which in some cases can progress to loss of the normal gastric glands, a condition known as atrophic gastritis, and, if replaced by intestinal-type tissue, intestinal metaplasia. Such conditions are associated with significantly higher risk of gastric dysplasia and cancer, particularly if there is ongoing H. pylori infection. This stepwise cascade from chronic gastritis to atrophic gastritis, intestinal metaplasia, dysplasia, and intestinal-type gastric adenocarcinoma is known as the correa cascade, for which H. pylori is the most common trigger.

We know that H. pylori eradication with antibiotics and high dose acid suppression does improve that inflammation and reduces the risk of gastric cancer. But the key here is that the biggest benefit of H. pylori eradication is eradicating H. pylori prior to the development severe atrophic gastritis and intestinal metaplasia. Therefore, simply testing and treating for H. pylori is not enough for gastric cancer prevention since some people might already have these advanced changes, since these typically don't cause symptoms. This forms the basis for endoscopic surveillance of these precancerous conditions, which is detailed in the most recent AGA guidelines and clinical practice update on intestinal metaplasia and atrophic gastritis, respectively.

H. pylori eradication still a cornerstone of gastric cancer prevention and risk reduction. Careful treatment selection and ensuring that eradication is confirmed warrants emphasis, particularly in the face of rising rates of H. pylori eradication failure. My key takeaway points for H. pylori eradication therapy is that prior to prescribing treatment, it's very important to review patients prior antibiotic exposures specifically macrolides and fluoroquinolones, since patients who have had treatment with these antibiotics for any condition are more likely to be colonized with resistant H. pylori strains. Clarithromycin-triple therapy should not be used unless patients are confirmed to be colonized with clarithromycin susceptible H. pylori. Bismuth-based quadruple therapy is really the preferred first line treatment instead of clarithromycin-based triple therapy given the high rates of clarithromycin resistance. It's also important to provide patients with anticipatory guidance regarding both the importance of completing the full course, as well as some expected possible side effects of antibiotics such as GI upset, nausea. The other tenant therapy is ensuring appropriate gastric acid suppression, which is a point emphasized in the recently published AGA clinical practice update on H. pylori management. All patients should have repeat non-serological H. pylori testing to ensure that eradication was successful. To reduce false positive or false negative results, this repeat testing should be done at least 2-4 weeks after completion of therapy and with patients off PPI therapy for at least 1-2 weeks.

What have you found to be some of the key disparities in gastric cancer particularly as it pertains to the racial and ethnic groups in the United States?

Dr. Shah: Racial and ethnic differences in gastric cancer incidence is a defining factor for gastric cancer in the United States. Our team recently conducted a population-based analysis of the California Cancer Registry, which is one of, if not the largest and most diverse of the SEER cancer registries. The results of this study highlighted the disparity in risk of gastric cancer based on race/ethnicity. All non-white groups in the US had a significantly higher risk of non-cardia gastric cancer compared to non-Hispanic whites. This was particularly striking in the age group that we generally consider for cancer screening, where there was anywhere from 2-fold up to 13.5-fold higher risk of non-cardia gastric cancer compared to the reference non-Hispanic whites. In some of these groups for example, Korean American men above the age of 50, these rates were on par with colorectal cancer rates. Even more concerning, it is possible that these estimates are actually underestimating the true burden of disease, since early cancer is asymptomatic most of the time and might go undiagnosed in the absence of screening.

We also know that immigrants from countries where gastric cancer incidence is high, also retain that increased risk and mortality even when they immigrate to countries gastric cancer incidence is low overall. Admittedly, this risk varies depending on immigrant generation and level of acculturation, including dietary practices, and other factors. The risk is observed to decrease over subsequent generations and depending on acculturation, which underscores opportunities for research into interventions and initiatives to address modifiable risk factors.

Given that immigrants from countries of high gastric cancer, including Asian Americans and Hispanics, comprise the vast majority of population growth in the United States, the public health implications are enormous if we continue to be complacent on gastric cancer prevention and early detection efforts.

As the fifth most common cancer and the third most common cause of cancer related deaths, based on recent studies and your personal experiences as a medical practitioner, also considering the gastric cancer does not cause symptoms until it is in the advanced stage, what are your recommendations as it relates to early detection and improving gastric cancer related outcomes?

Dr. Shah: The first step in my opinion, is recognizing that gastric cancer disproportionately affects certain populations in the US like I mentioned, especially racial and ethnic minorities and other under-represented populations, including US veterans. As a VA clinician and a VA investigator, we see that risk factors for gastric cancer, including H. pylori, disproportionately affect our veterans. The reasons are not fully understood but might relate to differential risk factors and exposures among veterans compared to civilian populations.

Gastric cancer is potentially preventable but is almost certainly curable if detected at an early stage, which really provides the rationale for risk-based screening. Unfortunately, gastric cancer has not been a research priority and there are currently no prospective trials investigating patient outcomes associated with screening versus no screening, nor studies investigating surveillance versus no surveillance of conditions like atrophic gastritis and intestinal metaplasia or  defining appropriate surveillance and screening intervals.  The AGA recently published guidelines and clinical practice updates for intestinal metaplasia and atrophic gastritis management. But one common thread that these documents specifically called attention to, was the lack of high-quality data informing practice, especially practice in the United States. Other research priority areas include risk factors and risk stratification algorithms both for incident and fatal gastric cancer, as well as progression of atrophic gastritis and intestinal metaplasia. Having a better understanding of these factors would really help to fine tune our algorithms, and potentially identify factors that can even be intervened on to halt progression.

The last point that I'll highlight actually relates to non-H. pylori associated gastric cancer. We spend a lot of time focused on H. pylori associated gastric cancer, but an increasing number of gastric cancers are being diagnosed in people without evidence of H. pylori infection. Better understanding the interaction between genetic and environmental triggers and how this differs from H. pylori associated gastric cancer is critical to our approach to control and prevention since there certainly could be important nuances.

A potential new urine biomarker for prostate cancer not only spots the presence of aggressive tumors, it also indicates the amount of these tumors, according to a recent report.

In a study of biopsy and prostatectomy samples, researchers found that the multigene Prostate Urine Risk-4 (PUR-4) signature was strongly associated with the presence and amount of Gleason pattern 4 tumors, but not tumors of less aggressive histology.

Given that increased Gleason pattern 4 tumor burden is associated with disease progression in men at intermediate risk, the results suggest that “PUR can show us which men at intermediate risk may require treatment and which may instead be managed conservatively with surveillance,” said senior author Jeremy Clark, PhD, of the University of East Anglia, Norwich, England. “PUR will also be useful for monitoring disease in men that do not currently require treatment and flag up the emergence and expansion of aggressive disease.”

The study by Dr. Clark and colleagues was published online on Nov. 3, 2021, in Life.

Tests using the traditional blood-based biomarker for prostate cancer – prostate-specific antigen (PSA) – have limited sensitivity and specificity, leading to unnecessary biopsies and overtreatment.

The PUR biomarker, one of several emerging alternatives to PSA, is a four-group classifier based on 36 genes, Dr. Clark and colleagues explained. Its categories correspond to the probabilities of the presence of normal tissue (PUR-1), and D’Amico low-risk (PUR-2), intermediate-risk (PUR-3), and high-risk (PUR-4) prostate cancer.

Dr. Clark’s team found in earlier research that the PUR-4 signature was able to predict disease progression in men on active surveillance for prostate cancer up to 5 years after a single urine sample. For their latest study, they sought to understand the relationship between PUR-4 and the amount and grade of tumor.

On the basis of biopsy samples from 215 men with prostate cancer, the researchers found that PUR-4 signature values correlated significantly with increasing Gleason grade.

There was no significant difference in PSA level by tumor volume for Gleason grade 1, 2, or 3. The same was true for PUR-4 and Gleason grade 1 tumors, which only contain less clinically significant Gleason pattern 3 cancer. However, PUR-4 values in men with Gleason grade 2 tumors larger than the median were significantly greater than for smaller tumors. PUR-4 values for large Gleason grade 3 tumors were also greater than for smaller ones, although the difference did not reach statistical significance.

“Since [Gleason grade] 2 and [Gleason grade] 3 contain both Gleason pattern 3 and 4 cancer these observations suggest that Gleason Pattern 4 cancer may be contributing to PUR-4 status,” the authors wrote.

The researchers also examined radical-prostatectomy specimens from nine men – three with Gleason grade 1, four with Gleason grade 2, and two with Gleason grade 3 tumors, as determined on the basis of presurgical biopsy.

There was no significant correlation between PUR-4 and PSA levels, nor were PUR-4 values linked to total tumor area or Gleason pattern 3 tumor area. But the amount of Gleason pattern 4 tumors showed a strong correlation with PUR-4 values, which did not change after adjusting for total prostate size.

“Our study shows that the PUR test can assess the amount of Gleason pattern 4 without the need for a biopsy,” Dr. Clark said in an interview. “It could therefore be a very useful tool indeed for assessing a man’s risk of dying from prostate cancer.”

Jack Schalken, PhD, a professor of experimental urology at Radboud University Medical Center in Nijmegen, the Netherlands, called PUR “another test” for prostate cancer the performance of which is in the same range as that of existing products.

“In fact, several tests are commercially available, but the clinical use is surprisingly low,” he told this news organization. Dr. Schalken, who was not involved in the new study, has reviewed several biomarkers for prostate cancer.

The PUR test is now undergoing validation in an international study that is expected to last another 2 years, Dr. Clark said. If successful, the test would stand out for several reasons.

First, it is based on many genes, so it is able to spot malignancies that other tests, which rely on just a few genes, may not pick up. In addition, although it is sensitive to the amount of Gleason pattern 4 tumor, it does not seem to detect the clinically less significant Gleason pattern 3 cancers.

“We have an at-home collection kit – the men do not have to come to a hospital to provide a urine sample,” Dr. Clark said.

The study did not receive commercial funding. Dr. Clark and two coauthors have filed a patent application related to their research.
 

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

A potential new urine biomarker for prostate cancer not only spots the presence of aggressive tumors, it also indicates the amount of these tumors, according to a recent report.

In a study of biopsy and prostatectomy samples, researchers found that the multigene Prostate Urine Risk-4 (PUR-4) signature was strongly associated with the presence and amount of Gleason pattern 4 tumors, but not tumors of less aggressive histology.

Given that increased Gleason pattern 4 tumor burden is associated with disease progression in men at intermediate risk, the results suggest that “PUR can show us which men at intermediate risk may require treatment and which may instead be managed conservatively with surveillance,” said senior author Jeremy Clark, PhD, of the University of East Anglia, Norwich, England. “PUR will also be useful for monitoring disease in men that do not currently require treatment and flag up the emergence and expansion of aggressive disease.”

The study by Dr. Clark and colleagues was published online on Nov. 3, 2021, in Life.

Tests using the traditional blood-based biomarker for prostate cancer – prostate-specific antigen (PSA) – have limited sensitivity and specificity, leading to unnecessary biopsies and overtreatment.

The PUR biomarker, one of several emerging alternatives to PSA, is a four-group classifier based on 36 genes, Dr. Clark and colleagues explained. Its categories correspond to the probabilities of the presence of normal tissue (PUR-1), and D’Amico low-risk (PUR-2), intermediate-risk (PUR-3), and high-risk (PUR-4) prostate cancer.

Dr. Clark’s team found in earlier research that the PUR-4 signature was able to predict disease progression in men on active surveillance for prostate cancer up to 5 years after a single urine sample. For their latest study, they sought to understand the relationship between PUR-4 and the amount and grade of tumor.

On the basis of biopsy samples from 215 men with prostate cancer, the researchers found that PUR-4 signature values correlated significantly with increasing Gleason grade.

There was no significant difference in PSA level by tumor volume for Gleason grade 1, 2, or 3. The same was true for PUR-4 and Gleason grade 1 tumors, which only contain less clinically significant Gleason pattern 3 cancer. However, PUR-4 values in men with Gleason grade 2 tumors larger than the median were significantly greater than for smaller tumors. PUR-4 values for large Gleason grade 3 tumors were also greater than for smaller ones, although the difference did not reach statistical significance.

“Since [Gleason grade] 2 and [Gleason grade] 3 contain both Gleason pattern 3 and 4 cancer these observations suggest that Gleason Pattern 4 cancer may be contributing to PUR-4 status,” the authors wrote.

The researchers also examined radical-prostatectomy specimens from nine men – three with Gleason grade 1, four with Gleason grade 2, and two with Gleason grade 3 tumors, as determined on the basis of presurgical biopsy.

There was no significant correlation between PUR-4 and PSA levels, nor were PUR-4 values linked to total tumor area or Gleason pattern 3 tumor area. But the amount of Gleason pattern 4 tumors showed a strong correlation with PUR-4 values, which did not change after adjusting for total prostate size.

“Our study shows that the PUR test can assess the amount of Gleason pattern 4 without the need for a biopsy,” Dr. Clark said in an interview. “It could therefore be a very useful tool indeed for assessing a man’s risk of dying from prostate cancer.”

Jack Schalken, PhD, a professor of experimental urology at Radboud University Medical Center in Nijmegen, the Netherlands, called PUR “another test” for prostate cancer the performance of which is in the same range as that of existing products.

“In fact, several tests are commercially available, but the clinical use is surprisingly low,” he told this news organization. Dr. Schalken, who was not involved in the new study, has reviewed several biomarkers for prostate cancer.

The PUR test is now undergoing validation in an international study that is expected to last another 2 years, Dr. Clark said. If successful, the test would stand out for several reasons.

First, it is based on many genes, so it is able to spot malignancies that other tests, which rely on just a few genes, may not pick up. In addition, although it is sensitive to the amount of Gleason pattern 4 tumor, it does not seem to detect the clinically less significant Gleason pattern 3 cancers.

“We have an at-home collection kit – the men do not have to come to a hospital to provide a urine sample,” Dr. Clark said.

The study did not receive commercial funding. Dr. Clark and two coauthors have filed a patent application related to their research.
 

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

A potential new urine biomarker for prostate cancer not only spots the presence of aggressive tumors, it also indicates the amount of these tumors, according to a recent report.

In a study of biopsy and prostatectomy samples, researchers found that the multigene Prostate Urine Risk-4 (PUR-4) signature was strongly associated with the presence and amount of Gleason pattern 4 tumors, but not tumors of less aggressive histology.

Given that increased Gleason pattern 4 tumor burden is associated with disease progression in men at intermediate risk, the results suggest that “PUR can show us which men at intermediate risk may require treatment and which may instead be managed conservatively with surveillance,” said senior author Jeremy Clark, PhD, of the University of East Anglia, Norwich, England. “PUR will also be useful for monitoring disease in men that do not currently require treatment and flag up the emergence and expansion of aggressive disease.”

The study by Dr. Clark and colleagues was published online on Nov. 3, 2021, in Life.

Tests using the traditional blood-based biomarker for prostate cancer – prostate-specific antigen (PSA) – have limited sensitivity and specificity, leading to unnecessary biopsies and overtreatment.

The PUR biomarker, one of several emerging alternatives to PSA, is a four-group classifier based on 36 genes, Dr. Clark and colleagues explained. Its categories correspond to the probabilities of the presence of normal tissue (PUR-1), and D’Amico low-risk (PUR-2), intermediate-risk (PUR-3), and high-risk (PUR-4) prostate cancer.

Dr. Clark’s team found in earlier research that the PUR-4 signature was able to predict disease progression in men on active surveillance for prostate cancer up to 5 years after a single urine sample. For their latest study, they sought to understand the relationship between PUR-4 and the amount and grade of tumor.

On the basis of biopsy samples from 215 men with prostate cancer, the researchers found that PUR-4 signature values correlated significantly with increasing Gleason grade.

There was no significant difference in PSA level by tumor volume for Gleason grade 1, 2, or 3. The same was true for PUR-4 and Gleason grade 1 tumors, which only contain less clinically significant Gleason pattern 3 cancer. However, PUR-4 values in men with Gleason grade 2 tumors larger than the median were significantly greater than for smaller tumors. PUR-4 values for large Gleason grade 3 tumors were also greater than for smaller ones, although the difference did not reach statistical significance.

“Since [Gleason grade] 2 and [Gleason grade] 3 contain both Gleason pattern 3 and 4 cancer these observations suggest that Gleason Pattern 4 cancer may be contributing to PUR-4 status,” the authors wrote.

The researchers also examined radical-prostatectomy specimens from nine men – three with Gleason grade 1, four with Gleason grade 2, and two with Gleason grade 3 tumors, as determined on the basis of presurgical biopsy.

There was no significant correlation between PUR-4 and PSA levels, nor were PUR-4 values linked to total tumor area or Gleason pattern 3 tumor area. But the amount of Gleason pattern 4 tumors showed a strong correlation with PUR-4 values, which did not change after adjusting for total prostate size.

“Our study shows that the PUR test can assess the amount of Gleason pattern 4 without the need for a biopsy,” Dr. Clark said in an interview. “It could therefore be a very useful tool indeed for assessing a man’s risk of dying from prostate cancer.”

Jack Schalken, PhD, a professor of experimental urology at Radboud University Medical Center in Nijmegen, the Netherlands, called PUR “another test” for prostate cancer the performance of which is in the same range as that of existing products.

“In fact, several tests are commercially available, but the clinical use is surprisingly low,” he told this news organization. Dr. Schalken, who was not involved in the new study, has reviewed several biomarkers for prostate cancer.

The PUR test is now undergoing validation in an international study that is expected to last another 2 years, Dr. Clark said. If successful, the test would stand out for several reasons.

First, it is based on many genes, so it is able to spot malignancies that other tests, which rely on just a few genes, may not pick up. In addition, although it is sensitive to the amount of Gleason pattern 4 tumor, it does not seem to detect the clinically less significant Gleason pattern 3 cancers.

“We have an at-home collection kit – the men do not have to come to a hospital to provide a urine sample,” Dr. Clark said.

The study did not receive commercial funding. Dr. Clark and two coauthors have filed a patent application related to their research.
 

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

The risk of occult gastric adenocarcinoma is highly prevalent in hereditary lobular breast cancer (HLBC) families who harbor any type of CDH1 variant and this risk remains high in patients with no family history of gastric cancer, a prospective cohort study has shown.

“In short, what we are putting forward with these data is that pathogenic/likely pathogenic (P/LP) variants in the CDH1 gene confer a very high risk, at the very least, of occult early-stage gastric cancer in patients with HLBC,” said Jeremy Davis, MD, of the surgical oncology program, Center for Cancer Research at the National Cancer Institute.

“So patients that are referred to as ‘HLBC’ due to a CDH1 variant should at least undergo annual endoscopic surveillance but the real questions is whether or not they should also consider prophylactic total gastrectomy – as many patients in our study did,” he said.

The study, which was published online Oct. 13, 2021, in JAMA Surgery, included a cohort of 151 families totaling 283 patients with a CDH1 pathogenic or likely pathogenic (P/LP) variant. Analyses were conducted on three patient groups, which included those with HLBC and a family history of breast cancer but no gastric cancer, those with hereditary diffuse gastric cancer (HDGC) but no history of breast cancer, and those with a family history of both gastric and breast cancer in the mixed group. Of these, 15.5% had a history of HLBC, 16.2% had a history of HDGC, and 52.6% made up the mixed group.

“We examined the HLBC group with specific attention to CDH1 genotype and prevalence of occult gastric cancer,” the authors explained. The group consisted of 31 families with 19 CDH1 variants, 10 of which were also present in the HDGC and mixed groups.

Among this group of patients, almost 73% underwent one or more surveillance endoscopies and on endoscopy, occult signet ring cell carcinoma was detected in over one-third of patients.

The median age at the time of endoscopic carcinoma detection was only 33 years.

“Nearly all of the patients with HLBC (93.8%) ... who elected for risk-reducing total gastrectomy owing to their underlying CDH1 P/LP variant harbored occult signet ring cell gastric adenocarcinoma on final pathology,” investigators observed.

The median age at the time patients elected to undergo total gastrectomy was 50 years.

The prevalence of occult gastric cancer among asymptomatic patients in the HDGC group was similarly high, affecting almost 95% of this group of patients.

Some 18 out of 19 CDH1 P/LP variants were responsible for this high prevalence of occult gastric cancer, as the investigators pointed out.

“Hereditary cancer risk is informed by the presence of a germline gene variant more so than by family history of cancer,” the authors stressed. “[And we found that] germline CDH1 P/LP variants appear to have a highly penetrant gastric phenotype irrespective of family history.”

Given this finding, the authors stressed that it is “paramount” patients previously assigned a diagnosis of HLBC not be excluded from undergoing gastric cancer risk assessment and counseling.

Furthermore, “the mere presence of a germline CDH1 P/LP variant, regardless of family history, may be reason enough to consider prophylactic total gastrectomy,” the authors wrote.

Limitations of the study included the fact that the disease phenotype was established from family pedigrees which has the potential for recall bias by family members.

The study was supported in part by the Intramural Research Program of the National Cancer Institute. None of the authors had conflicts of interest to disclose.

The risk of occult gastric adenocarcinoma is highly prevalent in hereditary lobular breast cancer (HLBC) families who harbor any type of CDH1 variant and this risk remains high in patients with no family history of gastric cancer, a prospective cohort study has shown.

“In short, what we are putting forward with these data is that pathogenic/likely pathogenic (P/LP) variants in the CDH1 gene confer a very high risk, at the very least, of occult early-stage gastric cancer in patients with HLBC,” said Jeremy Davis, MD, of the surgical oncology program, Center for Cancer Research at the National Cancer Institute.

“So patients that are referred to as ‘HLBC’ due to a CDH1 variant should at least undergo annual endoscopic surveillance but the real questions is whether or not they should also consider prophylactic total gastrectomy – as many patients in our study did,” he said.

The study, which was published online Oct. 13, 2021, in JAMA Surgery, included a cohort of 151 families totaling 283 patients with a CDH1 pathogenic or likely pathogenic (P/LP) variant. Analyses were conducted on three patient groups, which included those with HLBC and a family history of breast cancer but no gastric cancer, those with hereditary diffuse gastric cancer (HDGC) but no history of breast cancer, and those with a family history of both gastric and breast cancer in the mixed group. Of these, 15.5% had a history of HLBC, 16.2% had a history of HDGC, and 52.6% made up the mixed group.

“We examined the HLBC group with specific attention to CDH1 genotype and prevalence of occult gastric cancer,” the authors explained. The group consisted of 31 families with 19 CDH1 variants, 10 of which were also present in the HDGC and mixed groups.

Among this group of patients, almost 73% underwent one or more surveillance endoscopies and on endoscopy, occult signet ring cell carcinoma was detected in over one-third of patients.

The median age at the time of endoscopic carcinoma detection was only 33 years.

“Nearly all of the patients with HLBC (93.8%) ... who elected for risk-reducing total gastrectomy owing to their underlying CDH1 P/LP variant harbored occult signet ring cell gastric adenocarcinoma on final pathology,” investigators observed.

The median age at the time patients elected to undergo total gastrectomy was 50 years.

The prevalence of occult gastric cancer among asymptomatic patients in the HDGC group was similarly high, affecting almost 95% of this group of patients.

Some 18 out of 19 CDH1 P/LP variants were responsible for this high prevalence of occult gastric cancer, as the investigators pointed out.

“Hereditary cancer risk is informed by the presence of a germline gene variant more so than by family history of cancer,” the authors stressed. “[And we found that] germline CDH1 P/LP variants appear to have a highly penetrant gastric phenotype irrespective of family history.”

Given this finding, the authors stressed that it is “paramount” patients previously assigned a diagnosis of HLBC not be excluded from undergoing gastric cancer risk assessment and counseling.

Furthermore, “the mere presence of a germline CDH1 P/LP variant, regardless of family history, may be reason enough to consider prophylactic total gastrectomy,” the authors wrote.

Limitations of the study included the fact that the disease phenotype was established from family pedigrees which has the potential for recall bias by family members.

The study was supported in part by the Intramural Research Program of the National Cancer Institute. None of the authors had conflicts of interest to disclose.

The risk of occult gastric adenocarcinoma is highly prevalent in hereditary lobular breast cancer (HLBC) families who harbor any type of CDH1 variant and this risk remains high in patients with no family history of gastric cancer, a prospective cohort study has shown.

“In short, what we are putting forward with these data is that pathogenic/likely pathogenic (P/LP) variants in the CDH1 gene confer a very high risk, at the very least, of occult early-stage gastric cancer in patients with HLBC,” said Jeremy Davis, MD, of the surgical oncology program, Center for Cancer Research at the National Cancer Institute.

“So patients that are referred to as ‘HLBC’ due to a CDH1 variant should at least undergo annual endoscopic surveillance but the real questions is whether or not they should also consider prophylactic total gastrectomy – as many patients in our study did,” he said.

The study, which was published online Oct. 13, 2021, in JAMA Surgery, included a cohort of 151 families totaling 283 patients with a CDH1 pathogenic or likely pathogenic (P/LP) variant. Analyses were conducted on three patient groups, which included those with HLBC and a family history of breast cancer but no gastric cancer, those with hereditary diffuse gastric cancer (HDGC) but no history of breast cancer, and those with a family history of both gastric and breast cancer in the mixed group. Of these, 15.5% had a history of HLBC, 16.2% had a history of HDGC, and 52.6% made up the mixed group.

“We examined the HLBC group with specific attention to CDH1 genotype and prevalence of occult gastric cancer,” the authors explained. The group consisted of 31 families with 19 CDH1 variants, 10 of which were also present in the HDGC and mixed groups.

Among this group of patients, almost 73% underwent one or more surveillance endoscopies and on endoscopy, occult signet ring cell carcinoma was detected in over one-third of patients.

The median age at the time of endoscopic carcinoma detection was only 33 years.

“Nearly all of the patients with HLBC (93.8%) ... who elected for risk-reducing total gastrectomy owing to their underlying CDH1 P/LP variant harbored occult signet ring cell gastric adenocarcinoma on final pathology,” investigators observed.

The median age at the time patients elected to undergo total gastrectomy was 50 years.

The prevalence of occult gastric cancer among asymptomatic patients in the HDGC group was similarly high, affecting almost 95% of this group of patients.

Some 18 out of 19 CDH1 P/LP variants were responsible for this high prevalence of occult gastric cancer, as the investigators pointed out.

“Hereditary cancer risk is informed by the presence of a germline gene variant more so than by family history of cancer,” the authors stressed. “[And we found that] germline CDH1 P/LP variants appear to have a highly penetrant gastric phenotype irrespective of family history.”

Given this finding, the authors stressed that it is “paramount” patients previously assigned a diagnosis of HLBC not be excluded from undergoing gastric cancer risk assessment and counseling.

Furthermore, “the mere presence of a germline CDH1 P/LP variant, regardless of family history, may be reason enough to consider prophylactic total gastrectomy,” the authors wrote.

Limitations of the study included the fact that the disease phenotype was established from family pedigrees which has the potential for recall bias by family members.

The study was supported in part by the Intramural Research Program of the National Cancer Institute. None of the authors had conflicts of interest to disclose.

In Australia, where they know a thing or two about skin cancer, authors of a large prospective population-based cohort study found that melanomas detected through routine skin checks were associated with lower all-cause mortality, but not melanoma-specific mortality.

Among patients in New South Wales diagnosed with melanoma in 2006 or 2007 and followed for nearly 12 years, there was no significant difference in the rate of melanoma-specific death associated with either patient-detected or clinician-detected melanomas in an analysis adjusted for prognostic factors.

Although melanomas found through routine clinician-performed skin checks were associated with a 25% reduction in all-cause mortality compared with patient-detected lesions (P = .006), this difference may have been due to the tendency of health-oriented patients to participate in screening programs.

The study – one of the largest to date and performed in an area of the world where there is a high incidence of skin cancer and high degree of public awareness of the risks of too much sun exposure – could not fully answer its central question: Can routine skin checks, a proxy for skin cancer screening, significantly decrease the incidence of melanoma-related deaths?

“A large randomized clinical trial is needed to provide definitive evidence that screening for skin cancer reduces melanoma-specific and all-cause mortality among people invited (vs. not invited) to screen, but there are concerns about feasibility. Our findings could be used to estimate the sample size for a future trial,” wrote Caroline G. Watts, PhD, of the University of Sydney, Australia, and colleagues. Their study was published online Nov. 3 in JAMA Dermatology.

In an editorial accompanying the study, dermatologists Allan C. Halpern, MD, and Michael A. Marchetti, MD, of Memorial Sloan-Kettering Cancer Center in New York, point out that “there has never been a randomized clinical trial of melanoma screening, nor is there one currently ongoing or planned. Even if one were to be initiated immediately, such a trial would take well over a decade to conduct.

“Thus, for the foreseeable future, our approaches to melanoma secondary prevention need to be based on indirect evidence and our understanding of biology and epidemiology,” they wrote.

A dermatology researcher who was not involved in the study said that while it doesn’t solve the screening conundrum, it does highlight the value of public health campaigns.

“The way that I interpret the data, especially the fact that it’s coming out of Australia, is that if education about self-examination is done properly, that can also be effective in terms of detecting these skin cancers,” said Shawn Demehri, MD, PhD, principal investigator at the Cutaneous Biology Research Center at Massachusetts General Hospital, Boston. Dr. Demehri was asked to comment on the study.

“I would argue that the results would probably have been different if the study had been conducted in the U.S. rather than Australia, because the education in terms of self-examination is much more advanced and organized in Australia,” he said in an interview.

Study details

To assess melanoma-specific and all-cause mortality associated with melanoma identified through routine skin checks, Dr. Watts and colleagues followed patients diagnosed with melanoma from October 2006 through October 2007 who were enrolled in the Melanoma Patterns of Care Study. The patients were followed until 2018 (mean follow-up 11.9 years).

Of the 2,452 patients for whom data were available, 291 had an initial diagnosis of primary melanoma in situ (MIS), and 2,161 were diagnosed with invasive cutaneous melanoma.

The median age at diagnosis was 65 years, ranging from 16 to 98 years. Nearly two-thirds of the patients (61%) were men.

Among all patients, 858 (35%) had melanoma detected during a routine skin check, 1,148 (47%) detected the lesions themselves, 293 (12%) had incidentally-detected melanomas, and 153 (6%) had lesions detected by other, unspecified means.

In analyses adjusted for age and sex, the investigators found that compared with patient-detected lesions, melanomas detected during routine skin checks were associated with a 59% lower risk for melanoma-specific mortality (subhazard ratio, 0.41, P < .001) and 36% lower risk for all-cause mortality (hazard ratio, 0.64, P < .001).

But after adjustment for melanoma prognostic factors such as ulceration and mitotic rate, the association of skin check–detected lesions with melanoma-specific mortality was no longer statistically significant. The association with lower all-cause mortality was somewhat attenuated, but remained significant (HR, 0.75, P = .006).

Factors associated with a higher likelihood of melanoma detection during routine skin checks included males vs. females, a history of melanoma, having multiple moles, age 50 or older, and residence in a urban vs. rural areas.
 

Screen with care

In their editorial, Dr. Halpern and Dr. Marchetti propose methods for screening that find a balance between detection of significant disease and potential harm to patients from unnecessary biopsy or invasive procedures.

“For many lesions, we could use serial photography and dermoscopy in lieu of tissue biopsy to identify those that are truly dynamic outliers and likely to be of greater risk to the patient. An analogous approach is already used for the management of small lung nodules detected incidentally and through screening,” they wrote.

They also raise the issue of potential overdiagnosis and overtreatment of MIS, and recommend an approach similar to that used for some older patients with prostate cancer, for example.

“The consequences of MIS treatment differ greatly based on the type, anatomic location, and size of the tumor; these factors should be considered in shared decision-making with patients. Options such as active surveillance and topical therapy should be discussed, particularly in those with significant comorbidities or advanced age,” they wrote.

The study was supported by grants from the Australian National Health and Medical Research Council, Cancer Institute New South Wales, and the New South Wales State Government. Dr. Watts, Dr. Halpern, Dr. Marchetti, and Dr. Demehri reported having no conflicts of interest.

In Australia, where they know a thing or two about skin cancer, authors of a large prospective population-based cohort study found that melanomas detected through routine skin checks were associated with lower all-cause mortality, but not melanoma-specific mortality.

Among patients in New South Wales diagnosed with melanoma in 2006 or 2007 and followed for nearly 12 years, there was no significant difference in the rate of melanoma-specific death associated with either patient-detected or clinician-detected melanomas in an analysis adjusted for prognostic factors.

Although melanomas found through routine clinician-performed skin checks were associated with a 25% reduction in all-cause mortality compared with patient-detected lesions (P = .006), this difference may have been due to the tendency of health-oriented patients to participate in screening programs.

The study – one of the largest to date and performed in an area of the world where there is a high incidence of skin cancer and high degree of public awareness of the risks of too much sun exposure – could not fully answer its central question: Can routine skin checks, a proxy for skin cancer screening, significantly decrease the incidence of melanoma-related deaths?

“A large randomized clinical trial is needed to provide definitive evidence that screening for skin cancer reduces melanoma-specific and all-cause mortality among people invited (vs. not invited) to screen, but there are concerns about feasibility. Our findings could be used to estimate the sample size for a future trial,” wrote Caroline G. Watts, PhD, of the University of Sydney, Australia, and colleagues. Their study was published online Nov. 3 in JAMA Dermatology.

In an editorial accompanying the study, dermatologists Allan C. Halpern, MD, and Michael A. Marchetti, MD, of Memorial Sloan-Kettering Cancer Center in New York, point out that “there has never been a randomized clinical trial of melanoma screening, nor is there one currently ongoing or planned. Even if one were to be initiated immediately, such a trial would take well over a decade to conduct.

“Thus, for the foreseeable future, our approaches to melanoma secondary prevention need to be based on indirect evidence and our understanding of biology and epidemiology,” they wrote.

A dermatology researcher who was not involved in the study said that while it doesn’t solve the screening conundrum, it does highlight the value of public health campaigns.

“The way that I interpret the data, especially the fact that it’s coming out of Australia, is that if education about self-examination is done properly, that can also be effective in terms of detecting these skin cancers,” said Shawn Demehri, MD, PhD, principal investigator at the Cutaneous Biology Research Center at Massachusetts General Hospital, Boston. Dr. Demehri was asked to comment on the study.

“I would argue that the results would probably have been different if the study had been conducted in the U.S. rather than Australia, because the education in terms of self-examination is much more advanced and organized in Australia,” he said in an interview.

Study details

To assess melanoma-specific and all-cause mortality associated with melanoma identified through routine skin checks, Dr. Watts and colleagues followed patients diagnosed with melanoma from October 2006 through October 2007 who were enrolled in the Melanoma Patterns of Care Study. The patients were followed until 2018 (mean follow-up 11.9 years).

Of the 2,452 patients for whom data were available, 291 had an initial diagnosis of primary melanoma in situ (MIS), and 2,161 were diagnosed with invasive cutaneous melanoma.

The median age at diagnosis was 65 years, ranging from 16 to 98 years. Nearly two-thirds of the patients (61%) were men.

Among all patients, 858 (35%) had melanoma detected during a routine skin check, 1,148 (47%) detected the lesions themselves, 293 (12%) had incidentally-detected melanomas, and 153 (6%) had lesions detected by other, unspecified means.

In analyses adjusted for age and sex, the investigators found that compared with patient-detected lesions, melanomas detected during routine skin checks were associated with a 59% lower risk for melanoma-specific mortality (subhazard ratio, 0.41, P < .001) and 36% lower risk for all-cause mortality (hazard ratio, 0.64, P < .001).

But after adjustment for melanoma prognostic factors such as ulceration and mitotic rate, the association of skin check–detected lesions with melanoma-specific mortality was no longer statistically significant. The association with lower all-cause mortality was somewhat attenuated, but remained significant (HR, 0.75, P = .006).

Factors associated with a higher likelihood of melanoma detection during routine skin checks included males vs. females, a history of melanoma, having multiple moles, age 50 or older, and residence in a urban vs. rural areas.
 

Screen with care

In their editorial, Dr. Halpern and Dr. Marchetti propose methods for screening that find a balance between detection of significant disease and potential harm to patients from unnecessary biopsy or invasive procedures.

“For many lesions, we could use serial photography and dermoscopy in lieu of tissue biopsy to identify those that are truly dynamic outliers and likely to be of greater risk to the patient. An analogous approach is already used for the management of small lung nodules detected incidentally and through screening,” they wrote.

They also raise the issue of potential overdiagnosis and overtreatment of MIS, and recommend an approach similar to that used for some older patients with prostate cancer, for example.

“The consequences of MIS treatment differ greatly based on the type, anatomic location, and size of the tumor; these factors should be considered in shared decision-making with patients. Options such as active surveillance and topical therapy should be discussed, particularly in those with significant comorbidities or advanced age,” they wrote.

The study was supported by grants from the Australian National Health and Medical Research Council, Cancer Institute New South Wales, and the New South Wales State Government. Dr. Watts, Dr. Halpern, Dr. Marchetti, and Dr. Demehri reported having no conflicts of interest.

In Australia, where they know a thing or two about skin cancer, authors of a large prospective population-based cohort study found that melanomas detected through routine skin checks were associated with lower all-cause mortality, but not melanoma-specific mortality.

Among patients in New South Wales diagnosed with melanoma in 2006 or 2007 and followed for nearly 12 years, there was no significant difference in the rate of melanoma-specific death associated with either patient-detected or clinician-detected melanomas in an analysis adjusted for prognostic factors.

Although melanomas found through routine clinician-performed skin checks were associated with a 25% reduction in all-cause mortality compared with patient-detected lesions (P = .006), this difference may have been due to the tendency of health-oriented patients to participate in screening programs.

The study – one of the largest to date and performed in an area of the world where there is a high incidence of skin cancer and high degree of public awareness of the risks of too much sun exposure – could not fully answer its central question: Can routine skin checks, a proxy for skin cancer screening, significantly decrease the incidence of melanoma-related deaths?

“A large randomized clinical trial is needed to provide definitive evidence that screening for skin cancer reduces melanoma-specific and all-cause mortality among people invited (vs. not invited) to screen, but there are concerns about feasibility. Our findings could be used to estimate the sample size for a future trial,” wrote Caroline G. Watts, PhD, of the University of Sydney, Australia, and colleagues. Their study was published online Nov. 3 in JAMA Dermatology.

In an editorial accompanying the study, dermatologists Allan C. Halpern, MD, and Michael A. Marchetti, MD, of Memorial Sloan-Kettering Cancer Center in New York, point out that “there has never been a randomized clinical trial of melanoma screening, nor is there one currently ongoing or planned. Even if one were to be initiated immediately, such a trial would take well over a decade to conduct.

“Thus, for the foreseeable future, our approaches to melanoma secondary prevention need to be based on indirect evidence and our understanding of biology and epidemiology,” they wrote.

A dermatology researcher who was not involved in the study said that while it doesn’t solve the screening conundrum, it does highlight the value of public health campaigns.

“The way that I interpret the data, especially the fact that it’s coming out of Australia, is that if education about self-examination is done properly, that can also be effective in terms of detecting these skin cancers,” said Shawn Demehri, MD, PhD, principal investigator at the Cutaneous Biology Research Center at Massachusetts General Hospital, Boston. Dr. Demehri was asked to comment on the study.

“I would argue that the results would probably have been different if the study had been conducted in the U.S. rather than Australia, because the education in terms of self-examination is much more advanced and organized in Australia,” he said in an interview.

Study details

To assess melanoma-specific and all-cause mortality associated with melanoma identified through routine skin checks, Dr. Watts and colleagues followed patients diagnosed with melanoma from October 2006 through October 2007 who were enrolled in the Melanoma Patterns of Care Study. The patients were followed until 2018 (mean follow-up 11.9 years).

Of the 2,452 patients for whom data were available, 291 had an initial diagnosis of primary melanoma in situ (MIS), and 2,161 were diagnosed with invasive cutaneous melanoma.

The median age at diagnosis was 65 years, ranging from 16 to 98 years. Nearly two-thirds of the patients (61%) were men.

Among all patients, 858 (35%) had melanoma detected during a routine skin check, 1,148 (47%) detected the lesions themselves, 293 (12%) had incidentally-detected melanomas, and 153 (6%) had lesions detected by other, unspecified means.

In analyses adjusted for age and sex, the investigators found that compared with patient-detected lesions, melanomas detected during routine skin checks were associated with a 59% lower risk for melanoma-specific mortality (subhazard ratio, 0.41, P < .001) and 36% lower risk for all-cause mortality (hazard ratio, 0.64, P < .001).

But after adjustment for melanoma prognostic factors such as ulceration and mitotic rate, the association of skin check–detected lesions with melanoma-specific mortality was no longer statistically significant. The association with lower all-cause mortality was somewhat attenuated, but remained significant (HR, 0.75, P = .006).

Factors associated with a higher likelihood of melanoma detection during routine skin checks included males vs. females, a history of melanoma, having multiple moles, age 50 or older, and residence in a urban vs. rural areas.
 

Screen with care

In their editorial, Dr. Halpern and Dr. Marchetti propose methods for screening that find a balance between detection of significant disease and potential harm to patients from unnecessary biopsy or invasive procedures.

“For many lesions, we could use serial photography and dermoscopy in lieu of tissue biopsy to identify those that are truly dynamic outliers and likely to be of greater risk to the patient. An analogous approach is already used for the management of small lung nodules detected incidentally and through screening,” they wrote.

They also raise the issue of potential overdiagnosis and overtreatment of MIS, and recommend an approach similar to that used for some older patients with prostate cancer, for example.

“The consequences of MIS treatment differ greatly based on the type, anatomic location, and size of the tumor; these factors should be considered in shared decision-making with patients. Options such as active surveillance and topical therapy should be discussed, particularly in those with significant comorbidities or advanced age,” they wrote.

The study was supported by grants from the Australian National Health and Medical Research Council, Cancer Institute New South Wales, and the New South Wales State Government. Dr. Watts, Dr. Halpern, Dr. Marchetti, and Dr. Demehri reported having no conflicts of interest.

In patients with metastatic urothelial carcinoma, immunotherapy, antibody drug conjugates and targeted agents are being added to the potential treatment options for this incurable condition, which has a limited life expectancy. This is according to a review of the recent therapeutic advances and ongoing clinical trials in metastatic urothelial carcinoma.

“Survival in the metastatic setting is 12-15 months with cisplatin-based combination chemotherapy, but only 3-6 months if left untreated,” wrote Srikala S. Sridhar, MD, of the University of Toronto, and colleagues. Their report is in Therapeutic Advances in Medical Oncology. “More recently, with the advent of immunotherapy, antibody-drug conjugates, and targeted agents, the treatment landscape has changed significantly, with overall survival now approaching two years.”

Both the incidence and mortality from bladder cancer have risen over the past few decades. Around 5% of patients are metastatic at presentation, but nearly half of patients with muscle-invasive bladder cancer will eventually relapse and develop metastatic disease.

For first-line treatment in metastatic urothelial carcinoma, cisplatin-based chemotherapy remains the preferred option with response rates up to 72%, but durability is an issue with most patients experiencing disease progression. In patients with locally advanced or metastatic disease, who are not eligible for cisplatin-based chemotherapy and whose tumors express PD-L1, or patients who are not eligible for any platinum-based regimen regardless of PD-L1 status, the immune checkpoint inhibitors atezolizumab and pembrolizumab have received accelerated Food and Drug administration approval. More recently, pembrolizumab gained full FDA approval for use in patients not eligible to receive platinum-based chemotherapy.

While phase 3 studies are evaluating chemotherapy combined with atezolizumab or pembrolizumab, the results have not been promising. Moreover, the decreased survival observed in the immunotherapy-alone arms of these trials led the FDA to issue a warning that single agent immunotherapy should be used only in patients who are not eligible for cisplatin-based therapy and have PD-L1 expression, or in those not eligible for any platinum-based regimens regardless of PD-L1 expression.

“More intensive treatment in metastatic urothelial carcinoma is not always better,” the authors wrote. “Some of the reasons for this could be that chemotherapy and immunotherapy are targeting a similar population of cells, or that chemotherapy and immunotherapy are antagonistic on some level.”

Maintenance strategies are considered standard of care for other advanced solid tumors. In patients with bladder cancer without disease progression after a first line platinum-based chemotherapy, maintenance avelumab, an anti PD-L1, has shown an overall survival of 21.4 months versus 14.3 months with best supportive care, a finding that the authors described as “practice changing.” Meanwhile, a separate trial showed increased progression-free survival with maintenance pembrolizumab, but no increased overall survival.

For second-line treatment, immunotherapy is currently the standard of care in patients with disease progression during or after platinum-based chemotherapy. While the efficiency of five anti PD-1 and PD-L1 antibodies has been reported in the second-line setting, pembrolizumab is the only immune checkpoint inhibitor to receive full FDA approval. Atezolizumab, nivolumab, avelumab, and durvalumab have received accelerated approval.

“In urothelial carcinomas, PD-1 appears to have an advantage over anti PD-L1 in the second-line setting, but in the maintenance setting, it seems to be the opposite,” the authors wrote.

Erdafitinib is the only fibroblast growth factor receptor (FGFR) inhibitor approved for locally advanced or metastatic urothelial carcinoma, progressing on platinum-based chemotherapy. The oral potent tyrosine kinase inhibitor of FGFR 1-4 is approved for use only in patients with susceptible FGFR3 gene mutations or FGFR2/3 gene fusions. Despite being approved for second-line treatment, erdafitinib is used mainly in third-line treatment after progression on immunotherapy. 

The antibody drug conjugates sacituzumab govitecan and enfortumab vedotin, which have gained accelerated FDA approval, provide other options for patients with metastatic urothelial carcinoma resistant to chemotherapy and checkpoint inhibitors. As these antibody drug conjugates have different mechanisms of action and toxicity profiles, they could be used in the same patient throughout the disease course, but further research is needed. Meanwhile, many chemotherapy options, including docetaxel, gemcitabine, ifosfamide, and pemetrexed, have been tested in metastatic urothelial carcinoma with some response after platinum-based treatment.

“A number of studies evaluating promising therapeutic strategies are still ongoing and will hopefully provide information for some important unanswered questions and further guide treatment sequencing in advanced urothelial carcinoma,” the authors wrote.

They declared that there are no conflicts of interest.

In patients with metastatic urothelial carcinoma, immunotherapy, antibody drug conjugates and targeted agents are being added to the potential treatment options for this incurable condition, which has a limited life expectancy. This is according to a review of the recent therapeutic advances and ongoing clinical trials in metastatic urothelial carcinoma.

“Survival in the metastatic setting is 12-15 months with cisplatin-based combination chemotherapy, but only 3-6 months if left untreated,” wrote Srikala S. Sridhar, MD, of the University of Toronto, and colleagues. Their report is in Therapeutic Advances in Medical Oncology. “More recently, with the advent of immunotherapy, antibody-drug conjugates, and targeted agents, the treatment landscape has changed significantly, with overall survival now approaching two years.”

Both the incidence and mortality from bladder cancer have risen over the past few decades. Around 5% of patients are metastatic at presentation, but nearly half of patients with muscle-invasive bladder cancer will eventually relapse and develop metastatic disease.

For first-line treatment in metastatic urothelial carcinoma, cisplatin-based chemotherapy remains the preferred option with response rates up to 72%, but durability is an issue with most patients experiencing disease progression. In patients with locally advanced or metastatic disease, who are not eligible for cisplatin-based chemotherapy and whose tumors express PD-L1, or patients who are not eligible for any platinum-based regimen regardless of PD-L1 status, the immune checkpoint inhibitors atezolizumab and pembrolizumab have received accelerated Food and Drug administration approval. More recently, pembrolizumab gained full FDA approval for use in patients not eligible to receive platinum-based chemotherapy.

While phase 3 studies are evaluating chemotherapy combined with atezolizumab or pembrolizumab, the results have not been promising. Moreover, the decreased survival observed in the immunotherapy-alone arms of these trials led the FDA to issue a warning that single agent immunotherapy should be used only in patients who are not eligible for cisplatin-based therapy and have PD-L1 expression, or in those not eligible for any platinum-based regimens regardless of PD-L1 expression.

“More intensive treatment in metastatic urothelial carcinoma is not always better,” the authors wrote. “Some of the reasons for this could be that chemotherapy and immunotherapy are targeting a similar population of cells, or that chemotherapy and immunotherapy are antagonistic on some level.”

Maintenance strategies are considered standard of care for other advanced solid tumors. In patients with bladder cancer without disease progression after a first line platinum-based chemotherapy, maintenance avelumab, an anti PD-L1, has shown an overall survival of 21.4 months versus 14.3 months with best supportive care, a finding that the authors described as “practice changing.” Meanwhile, a separate trial showed increased progression-free survival with maintenance pembrolizumab, but no increased overall survival.

For second-line treatment, immunotherapy is currently the standard of care in patients with disease progression during or after platinum-based chemotherapy. While the efficiency of five anti PD-1 and PD-L1 antibodies has been reported in the second-line setting, pembrolizumab is the only immune checkpoint inhibitor to receive full FDA approval. Atezolizumab, nivolumab, avelumab, and durvalumab have received accelerated approval.

“In urothelial carcinomas, PD-1 appears to have an advantage over anti PD-L1 in the second-line setting, but in the maintenance setting, it seems to be the opposite,” the authors wrote.

Erdafitinib is the only fibroblast growth factor receptor (FGFR) inhibitor approved for locally advanced or metastatic urothelial carcinoma, progressing on platinum-based chemotherapy. The oral potent tyrosine kinase inhibitor of FGFR 1-4 is approved for use only in patients with susceptible FGFR3 gene mutations or FGFR2/3 gene fusions. Despite being approved for second-line treatment, erdafitinib is used mainly in third-line treatment after progression on immunotherapy. 

The antibody drug conjugates sacituzumab govitecan and enfortumab vedotin, which have gained accelerated FDA approval, provide other options for patients with metastatic urothelial carcinoma resistant to chemotherapy and checkpoint inhibitors. As these antibody drug conjugates have different mechanisms of action and toxicity profiles, they could be used in the same patient throughout the disease course, but further research is needed. Meanwhile, many chemotherapy options, including docetaxel, gemcitabine, ifosfamide, and pemetrexed, have been tested in metastatic urothelial carcinoma with some response after platinum-based treatment.

“A number of studies evaluating promising therapeutic strategies are still ongoing and will hopefully provide information for some important unanswered questions and further guide treatment sequencing in advanced urothelial carcinoma,” the authors wrote.

They declared that there are no conflicts of interest.

In patients with metastatic urothelial carcinoma, immunotherapy, antibody drug conjugates and targeted agents are being added to the potential treatment options for this incurable condition, which has a limited life expectancy. This is according to a review of the recent therapeutic advances and ongoing clinical trials in metastatic urothelial carcinoma.

“Survival in the metastatic setting is 12-15 months with cisplatin-based combination chemotherapy, but only 3-6 months if left untreated,” wrote Srikala S. Sridhar, MD, of the University of Toronto, and colleagues. Their report is in Therapeutic Advances in Medical Oncology. “More recently, with the advent of immunotherapy, antibody-drug conjugates, and targeted agents, the treatment landscape has changed significantly, with overall survival now approaching two years.”

Both the incidence and mortality from bladder cancer have risen over the past few decades. Around 5% of patients are metastatic at presentation, but nearly half of patients with muscle-invasive bladder cancer will eventually relapse and develop metastatic disease.

For first-line treatment in metastatic urothelial carcinoma, cisplatin-based chemotherapy remains the preferred option with response rates up to 72%, but durability is an issue with most patients experiencing disease progression. In patients with locally advanced or metastatic disease, who are not eligible for cisplatin-based chemotherapy and whose tumors express PD-L1, or patients who are not eligible for any platinum-based regimen regardless of PD-L1 status, the immune checkpoint inhibitors atezolizumab and pembrolizumab have received accelerated Food and Drug administration approval. More recently, pembrolizumab gained full FDA approval for use in patients not eligible to receive platinum-based chemotherapy.

While phase 3 studies are evaluating chemotherapy combined with atezolizumab or pembrolizumab, the results have not been promising. Moreover, the decreased survival observed in the immunotherapy-alone arms of these trials led the FDA to issue a warning that single agent immunotherapy should be used only in patients who are not eligible for cisplatin-based therapy and have PD-L1 expression, or in those not eligible for any platinum-based regimens regardless of PD-L1 expression.

“More intensive treatment in metastatic urothelial carcinoma is not always better,” the authors wrote. “Some of the reasons for this could be that chemotherapy and immunotherapy are targeting a similar population of cells, or that chemotherapy and immunotherapy are antagonistic on some level.”

Maintenance strategies are considered standard of care for other advanced solid tumors. In patients with bladder cancer without disease progression after a first line platinum-based chemotherapy, maintenance avelumab, an anti PD-L1, has shown an overall survival of 21.4 months versus 14.3 months with best supportive care, a finding that the authors described as “practice changing.” Meanwhile, a separate trial showed increased progression-free survival with maintenance pembrolizumab, but no increased overall survival.

For second-line treatment, immunotherapy is currently the standard of care in patients with disease progression during or after platinum-based chemotherapy. While the efficiency of five anti PD-1 and PD-L1 antibodies has been reported in the second-line setting, pembrolizumab is the only immune checkpoint inhibitor to receive full FDA approval. Atezolizumab, nivolumab, avelumab, and durvalumab have received accelerated approval.

“In urothelial carcinomas, PD-1 appears to have an advantage over anti PD-L1 in the second-line setting, but in the maintenance setting, it seems to be the opposite,” the authors wrote.

Erdafitinib is the only fibroblast growth factor receptor (FGFR) inhibitor approved for locally advanced or metastatic urothelial carcinoma, progressing on platinum-based chemotherapy. The oral potent tyrosine kinase inhibitor of FGFR 1-4 is approved for use only in patients with susceptible FGFR3 gene mutations or FGFR2/3 gene fusions. Despite being approved for second-line treatment, erdafitinib is used mainly in third-line treatment after progression on immunotherapy. 

The antibody drug conjugates sacituzumab govitecan and enfortumab vedotin, which have gained accelerated FDA approval, provide other options for patients with metastatic urothelial carcinoma resistant to chemotherapy and checkpoint inhibitors. As these antibody drug conjugates have different mechanisms of action and toxicity profiles, they could be used in the same patient throughout the disease course, but further research is needed. Meanwhile, many chemotherapy options, including docetaxel, gemcitabine, ifosfamide, and pemetrexed, have been tested in metastatic urothelial carcinoma with some response after platinum-based treatment.

“A number of studies evaluating promising therapeutic strategies are still ongoing and will hopefully provide information for some important unanswered questions and further guide treatment sequencing in advanced urothelial carcinoma,” the authors wrote.

They declared that there are no conflicts of interest.

U.S. regulators have made it easier for physicians, patients, and researchers to determine the status of cancer medicines cleared for sale based on limited evidence, including a public list detailing cases where accelerated approvals have been rescinded for lack of evidence.

On Oct. 29, the Food and Drug Administration posted new websites detailing the status of oncology medicines given these special clearances:

• Ongoing | Cancer Accelerated Approvals 
• Verified Clinical Benefit | Cancer Accelerated Approvals
• Withdrawn | Cancer Accelerated Approvals

The FDA’s cancer center also has created a web page called Project Confirm to provide more information on the way it uses accelerated approvals.

There has been increased concern about medicines cleared by accelerated approvals in recent years, culminating in an uproar over the controversial June approval of aducanumab (Aduhelm) for Alzheimer’s disease. This drew more attention to a debate already underway about how much data supports some of the indications for some cancer drugs.

Federal and state officials and advisers are putting more pressure on pharmaceutical companies to prove that medicines that are put on the market through accelerated approval do deliver meaningful benefits for patients.

In addition, earlier this month two of the top health advisers in Barack Obama’s administration proposed a new model through which Medicare could reduce payments for certain cancer drugs cleared through accelerated approvals – and even cut off reimbursements in cases where companies fail to deliver confirmatory evidence for expected benefits.

This “Pay for Drugs That Work Model” was proposed by Richard Frank, PhD, and Ezekiel Emanuel, MD, PhD, in a recent JAMA article. In their view, the FDA’s accelerated drug approval process allows for too many delays in obtaining answers as to whether medicines cleared this way provide expected benefits.

“The proposed Pay for Drugs That Work model could test a modified approach for incentivizing rapid completion of confirmatory trials to inform clinicians and patients about the true risks and benefits of new drugs and improve the value for money of cancer drugs that receive accelerated approval,” they wrote.
 

Excel files, regular updates

For the FDA, accelerated approvals require balancing an estimated potential benefit for people facing serious diseases (for example, cancer) against serious risks, including potentially exposing patients to costly, toxic drugs that will later be shown not to work for their conditions.

For many years, there has been significant pressure on the FDA to lean toward speedier approvals, with members of Congress, advocacy groups, and drugmakers advocating for broad use of surrogate data in deciding on clearances. The FDA posts biannual reports on its website that highlight how quickly approvals have been granted. But these biannual reports don’t provide much information on the status of accelerated-approval drugs, other than to say if they have been given full approval or withdrawn.

The newly created websites from the FDA’s oncology division appear to reflect growing public interest in knowing what standards the agency sets for confirmatory trials and what deadlines companies face to deliver evidence of significant benefit for their drugs.

The new sortable websites also include details on trials and have links to Excel files which will help researchers and others seeking to track patterns with accelerated approvals. The FDA said in an interview that it intends to update these sites when there are developments with accelerated approvals for cancer drugs, such as new clearances of this type, conversions to regular approvals, and withdrawn approvals.

Julia Beaver, MD, chief of medical oncology at the FDA’s Oncology Center of Excellence, and acting deputy director of the Office of Oncologic Diseases of the FDA’s Center for Drug Evaluation and Research, described the new websites as part of a “commitment to preserve the integrity” of the accelerated approval program.

“These new web pages will make information on our accelerated approvals more transparent,” Dr. Beaver said in an email to this news organization.

The FDA has been able to speed many medicines to market and clear additional uses for drugs already sold through the program, giving people earlier access in many cases to critical medicines, Dr. Beaver said.

More than 165 oncology indications have received accelerated approval, with almost half converted to regular approval in a median of 3 years. Less than 10% of these indications were withdrawn, Dr. Beaver said.

“Of those accelerated approvals that were converted to regular approval, many demonstrated survival advantages to patients with several types of cancer or provided meaningful therapeutic options where none previously existed,” she said.

However, Dr. Beaver also has made public the FDA’s concerns with what she and Richard Pazdur, MD, director of the Oncology Center of Excellence, have described as “dangling” accelerated approvals. 

These are cases where the required trials did not end up confirming benefit for a medicine, yet the manufacturer did not move to withdraw an accelerated approval. The FDA’s cancer center has already announced that it is doing an “industry-wide evaluation of accelerated approvals in oncology in which confirmatory trials did not confirm clinical benefit.”

This stems in part from what can be called the FDA’s “growing pains” in its efforts to manage the rapidly changing landscape for these immunotherapy checkpoint inhibitors. This field of medicine has experienced an “unprecedented level of drug development” in recent years, FDA officials said in briefing materials for an Oncologic Drugs Advisory Committee (ODAC) meeting last April on dangling accelerated approvals.

A newly posted chart on withdrawn oncology accelerated approvals, posted by the FDA’s cancer division, makes it clear that the pace of these rescinded clearances has picked up. The chart lists a total 14 withdrawn indications of oncology accelerated approvals.

Six of these withdrawals happened this year.

There were two withdrawals in 2020, including the December withdrawal of nivolumab, (Opdivo) for a form of metastatic lung cancer.

Then there was a significant gap, with no withdrawals going back to 2013 (when there was one). There were two withdrawals in 2012 and three in 2011.

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

U.S. regulators have made it easier for physicians, patients, and researchers to determine the status of cancer medicines cleared for sale based on limited evidence, including a public list detailing cases where accelerated approvals have been rescinded for lack of evidence.

On Oct. 29, the Food and Drug Administration posted new websites detailing the status of oncology medicines given these special clearances:

• Ongoing | Cancer Accelerated Approvals 
• Verified Clinical Benefit | Cancer Accelerated Approvals
• Withdrawn | Cancer Accelerated Approvals

The FDA’s cancer center also has created a web page called Project Confirm to provide more information on the way it uses accelerated approvals.

There has been increased concern about medicines cleared by accelerated approvals in recent years, culminating in an uproar over the controversial June approval of aducanumab (Aduhelm) for Alzheimer’s disease. This drew more attention to a debate already underway about how much data supports some of the indications for some cancer drugs.

Federal and state officials and advisers are putting more pressure on pharmaceutical companies to prove that medicines that are put on the market through accelerated approval do deliver meaningful benefits for patients.

In addition, earlier this month two of the top health advisers in Barack Obama’s administration proposed a new model through which Medicare could reduce payments for certain cancer drugs cleared through accelerated approvals – and even cut off reimbursements in cases where companies fail to deliver confirmatory evidence for expected benefits.

This “Pay for Drugs That Work Model” was proposed by Richard Frank, PhD, and Ezekiel Emanuel, MD, PhD, in a recent JAMA article. In their view, the FDA’s accelerated drug approval process allows for too many delays in obtaining answers as to whether medicines cleared this way provide expected benefits.

“The proposed Pay for Drugs That Work model could test a modified approach for incentivizing rapid completion of confirmatory trials to inform clinicians and patients about the true risks and benefits of new drugs and improve the value for money of cancer drugs that receive accelerated approval,” they wrote.
 

Excel files, regular updates

For the FDA, accelerated approvals require balancing an estimated potential benefit for people facing serious diseases (for example, cancer) against serious risks, including potentially exposing patients to costly, toxic drugs that will later be shown not to work for their conditions.

For many years, there has been significant pressure on the FDA to lean toward speedier approvals, with members of Congress, advocacy groups, and drugmakers advocating for broad use of surrogate data in deciding on clearances. The FDA posts biannual reports on its website that highlight how quickly approvals have been granted. But these biannual reports don’t provide much information on the status of accelerated-approval drugs, other than to say if they have been given full approval or withdrawn.

The newly created websites from the FDA’s oncology division appear to reflect growing public interest in knowing what standards the agency sets for confirmatory trials and what deadlines companies face to deliver evidence of significant benefit for their drugs.

The new sortable websites also include details on trials and have links to Excel files which will help researchers and others seeking to track patterns with accelerated approvals. The FDA said in an interview that it intends to update these sites when there are developments with accelerated approvals for cancer drugs, such as new clearances of this type, conversions to regular approvals, and withdrawn approvals.

Julia Beaver, MD, chief of medical oncology at the FDA’s Oncology Center of Excellence, and acting deputy director of the Office of Oncologic Diseases of the FDA’s Center for Drug Evaluation and Research, described the new websites as part of a “commitment to preserve the integrity” of the accelerated approval program.

“These new web pages will make information on our accelerated approvals more transparent,” Dr. Beaver said in an email to this news organization.

The FDA has been able to speed many medicines to market and clear additional uses for drugs already sold through the program, giving people earlier access in many cases to critical medicines, Dr. Beaver said.

More than 165 oncology indications have received accelerated approval, with almost half converted to regular approval in a median of 3 years. Less than 10% of these indications were withdrawn, Dr. Beaver said.

“Of those accelerated approvals that were converted to regular approval, many demonstrated survival advantages to patients with several types of cancer or provided meaningful therapeutic options where none previously existed,” she said.

However, Dr. Beaver also has made public the FDA’s concerns with what she and Richard Pazdur, MD, director of the Oncology Center of Excellence, have described as “dangling” accelerated approvals. 

These are cases where the required trials did not end up confirming benefit for a medicine, yet the manufacturer did not move to withdraw an accelerated approval. The FDA’s cancer center has already announced that it is doing an “industry-wide evaluation of accelerated approvals in oncology in which confirmatory trials did not confirm clinical benefit.”

This stems in part from what can be called the FDA’s “growing pains” in its efforts to manage the rapidly changing landscape for these immunotherapy checkpoint inhibitors. This field of medicine has experienced an “unprecedented level of drug development” in recent years, FDA officials said in briefing materials for an Oncologic Drugs Advisory Committee (ODAC) meeting last April on dangling accelerated approvals.

A newly posted chart on withdrawn oncology accelerated approvals, posted by the FDA’s cancer division, makes it clear that the pace of these rescinded clearances has picked up. The chart lists a total 14 withdrawn indications of oncology accelerated approvals.

Six of these withdrawals happened this year.

There were two withdrawals in 2020, including the December withdrawal of nivolumab, (Opdivo) for a form of metastatic lung cancer.

Then there was a significant gap, with no withdrawals going back to 2013 (when there was one). There were two withdrawals in 2012 and three in 2011.

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

U.S. regulators have made it easier for physicians, patients, and researchers to determine the status of cancer medicines cleared for sale based on limited evidence, including a public list detailing cases where accelerated approvals have been rescinded for lack of evidence.

On Oct. 29, the Food and Drug Administration posted new websites detailing the status of oncology medicines given these special clearances:

• Ongoing | Cancer Accelerated Approvals 
• Verified Clinical Benefit | Cancer Accelerated Approvals
• Withdrawn | Cancer Accelerated Approvals

The FDA’s cancer center also has created a web page called Project Confirm to provide more information on the way it uses accelerated approvals.

There has been increased concern about medicines cleared by accelerated approvals in recent years, culminating in an uproar over the controversial June approval of aducanumab (Aduhelm) for Alzheimer’s disease. This drew more attention to a debate already underway about how much data supports some of the indications for some cancer drugs.

Federal and state officials and advisers are putting more pressure on pharmaceutical companies to prove that medicines that are put on the market through accelerated approval do deliver meaningful benefits for patients.

In addition, earlier this month two of the top health advisers in Barack Obama’s administration proposed a new model through which Medicare could reduce payments for certain cancer drugs cleared through accelerated approvals – and even cut off reimbursements in cases where companies fail to deliver confirmatory evidence for expected benefits.

This “Pay for Drugs That Work Model” was proposed by Richard Frank, PhD, and Ezekiel Emanuel, MD, PhD, in a recent JAMA article. In their view, the FDA’s accelerated drug approval process allows for too many delays in obtaining answers as to whether medicines cleared this way provide expected benefits.

“The proposed Pay for Drugs That Work model could test a modified approach for incentivizing rapid completion of confirmatory trials to inform clinicians and patients about the true risks and benefits of new drugs and improve the value for money of cancer drugs that receive accelerated approval,” they wrote.
 

Excel files, regular updates

For the FDA, accelerated approvals require balancing an estimated potential benefit for people facing serious diseases (for example, cancer) against serious risks, including potentially exposing patients to costly, toxic drugs that will later be shown not to work for their conditions.

For many years, there has been significant pressure on the FDA to lean toward speedier approvals, with members of Congress, advocacy groups, and drugmakers advocating for broad use of surrogate data in deciding on clearances. The FDA posts biannual reports on its website that highlight how quickly approvals have been granted. But these biannual reports don’t provide much information on the status of accelerated-approval drugs, other than to say if they have been given full approval or withdrawn.

The newly created websites from the FDA’s oncology division appear to reflect growing public interest in knowing what standards the agency sets for confirmatory trials and what deadlines companies face to deliver evidence of significant benefit for their drugs.

The new sortable websites also include details on trials and have links to Excel files which will help researchers and others seeking to track patterns with accelerated approvals. The FDA said in an interview that it intends to update these sites when there are developments with accelerated approvals for cancer drugs, such as new clearances of this type, conversions to regular approvals, and withdrawn approvals.

Julia Beaver, MD, chief of medical oncology at the FDA’s Oncology Center of Excellence, and acting deputy director of the Office of Oncologic Diseases of the FDA’s Center for Drug Evaluation and Research, described the new websites as part of a “commitment to preserve the integrity” of the accelerated approval program.

“These new web pages will make information on our accelerated approvals more transparent,” Dr. Beaver said in an email to this news organization.

The FDA has been able to speed many medicines to market and clear additional uses for drugs already sold through the program, giving people earlier access in many cases to critical medicines, Dr. Beaver said.

More than 165 oncology indications have received accelerated approval, with almost half converted to regular approval in a median of 3 years. Less than 10% of these indications were withdrawn, Dr. Beaver said.

“Of those accelerated approvals that were converted to regular approval, many demonstrated survival advantages to patients with several types of cancer or provided meaningful therapeutic options where none previously existed,” she said.

However, Dr. Beaver also has made public the FDA’s concerns with what she and Richard Pazdur, MD, director of the Oncology Center of Excellence, have described as “dangling” accelerated approvals. 

These are cases where the required trials did not end up confirming benefit for a medicine, yet the manufacturer did not move to withdraw an accelerated approval. The FDA’s cancer center has already announced that it is doing an “industry-wide evaluation of accelerated approvals in oncology in which confirmatory trials did not confirm clinical benefit.”

This stems in part from what can be called the FDA’s “growing pains” in its efforts to manage the rapidly changing landscape for these immunotherapy checkpoint inhibitors. This field of medicine has experienced an “unprecedented level of drug development” in recent years, FDA officials said in briefing materials for an Oncologic Drugs Advisory Committee (ODAC) meeting last April on dangling accelerated approvals.

A newly posted chart on withdrawn oncology accelerated approvals, posted by the FDA’s cancer division, makes it clear that the pace of these rescinded clearances has picked up. The chart lists a total 14 withdrawn indications of oncology accelerated approvals.

Six of these withdrawals happened this year.

There were two withdrawals in 2020, including the December withdrawal of nivolumab, (Opdivo) for a form of metastatic lung cancer.

Then there was a significant gap, with no withdrawals going back to 2013 (when there was one). There were two withdrawals in 2012 and three in 2011.

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

In patients with advanced cancer who are prescribed immune checkpoint inhibitors, comedications must be carefully assessed before patients start ICI therapy, most notably proton pump inhibitors, glucocorticoids, antibiotics, and psychotropic drugs.

“Our results confirm the detrimental impact on oncological outcomes of antibiotics and glucocorticoids at a dosage ≥10 mg/day when given within 1 month before or after ICI onset,” Marie Kostine, MD, of Bordeaux (France) University Hospital, and colleagues wrote in the European Journal of Cancer. “Moreover, we show that other comedications may significantly alter the antitumoral response of ICI, such as proton pump inhibitors, psychotropic drugs, morphine, aspirin, and insulin, whereas others seem to have no impact.”

While immune checkpoint inhibitors are transforming the treatment of advanced cancers, gut microbiota composition is an important determinant of response to ICIs. Antibiotic treatments are known to alter the gut microbiota. Other drugs, such as proton pump inhibitors, antidiabetic agents, aspirin, NSAIDs, glucocorticoids, immunomodulators, psychotropic drugs, and analgesics, have been associated with changes in microbiome composition. Since many patients with advanced cancer are exposed to such drugs, this study looked at the possible influence of these comedications on the antitumor effect and safety of ICIs.

The observational study included 635 patients with advanced cancer treated with ICIs between May 2015 and September 2017. Comedications given within 1 month before or 1 month after the first administration of an ICI were reviewed from medical records. Psychotropic drugs, proton pump inhibitors, ACE inhibitors and/or angiotensin II receptor blockers (ARBs), glucocorticoids, antibiotics, statins, and morphine were the most prescribed comedications.

Baseline use of antibiotics, glucocorticoids greater than 10 mg/day, proton pump inhibitors, psychotropic drugs, morphine, and insulin was associated with decreased overall survival and tumor response. However, the coadministration of statins, ACE inhibitors and/or ARBs, NSAIDs, aspirin, and oral diabetes drugs did not impact patient outcomes. Additionally, treatments that altered the response to ICIs were associated with a decreased incidence of immune-related adverse events.

“These results suggest some practical advice in a patient candidate to ICIs,” the authors wrote. “First, antibiotic treatment should be limited to documented infections,” and “withdrawal of proton pump inhibitors and psychotropic drugs should be considered.

“Regarding baseline glucocorticoids use, the cutoff of 10 mg/day should be respected, considering the deleterious effect of higher dosage. Moreover, because of the lack of impact of inhaled or topical glucocorticoids, local routes should be preferred,” the authors wrote. “Conversely, our study brings reassuring data regarding the use of glucocorticoids for the management of immune-related adverse events, which did not alter ICI efficacy, confirming previous reports.”

The authors noted that the observational nature of the study does not allow any causal conclusion, adding that it remains unknown whether the effect of comedications “on cancer outcomes is thoroughly mediated by changes in microbiota or other immunomodulatory properties.”

Along with the retrospective design, study limitations included reporting bias and missing data on baseline comedications, specific prognostic factors and cancer outcomes.

The authors noted no conflicts of interest.

In patients with advanced cancer who are prescribed immune checkpoint inhibitors, comedications must be carefully assessed before patients start ICI therapy, most notably proton pump inhibitors, glucocorticoids, antibiotics, and psychotropic drugs.

“Our results confirm the detrimental impact on oncological outcomes of antibiotics and glucocorticoids at a dosage ≥10 mg/day when given within 1 month before or after ICI onset,” Marie Kostine, MD, of Bordeaux (France) University Hospital, and colleagues wrote in the European Journal of Cancer. “Moreover, we show that other comedications may significantly alter the antitumoral response of ICI, such as proton pump inhibitors, psychotropic drugs, morphine, aspirin, and insulin, whereas others seem to have no impact.”

While immune checkpoint inhibitors are transforming the treatment of advanced cancers, gut microbiota composition is an important determinant of response to ICIs. Antibiotic treatments are known to alter the gut microbiota. Other drugs, such as proton pump inhibitors, antidiabetic agents, aspirin, NSAIDs, glucocorticoids, immunomodulators, psychotropic drugs, and analgesics, have been associated with changes in microbiome composition. Since many patients with advanced cancer are exposed to such drugs, this study looked at the possible influence of these comedications on the antitumor effect and safety of ICIs.

The observational study included 635 patients with advanced cancer treated with ICIs between May 2015 and September 2017. Comedications given within 1 month before or 1 month after the first administration of an ICI were reviewed from medical records. Psychotropic drugs, proton pump inhibitors, ACE inhibitors and/or angiotensin II receptor blockers (ARBs), glucocorticoids, antibiotics, statins, and morphine were the most prescribed comedications.

Baseline use of antibiotics, glucocorticoids greater than 10 mg/day, proton pump inhibitors, psychotropic drugs, morphine, and insulin was associated with decreased overall survival and tumor response. However, the coadministration of statins, ACE inhibitors and/or ARBs, NSAIDs, aspirin, and oral diabetes drugs did not impact patient outcomes. Additionally, treatments that altered the response to ICIs were associated with a decreased incidence of immune-related adverse events.

“These results suggest some practical advice in a patient candidate to ICIs,” the authors wrote. “First, antibiotic treatment should be limited to documented infections,” and “withdrawal of proton pump inhibitors and psychotropic drugs should be considered.

“Regarding baseline glucocorticoids use, the cutoff of 10 mg/day should be respected, considering the deleterious effect of higher dosage. Moreover, because of the lack of impact of inhaled or topical glucocorticoids, local routes should be preferred,” the authors wrote. “Conversely, our study brings reassuring data regarding the use of glucocorticoids for the management of immune-related adverse events, which did not alter ICI efficacy, confirming previous reports.”

The authors noted that the observational nature of the study does not allow any causal conclusion, adding that it remains unknown whether the effect of comedications “on cancer outcomes is thoroughly mediated by changes in microbiota or other immunomodulatory properties.”

Along with the retrospective design, study limitations included reporting bias and missing data on baseline comedications, specific prognostic factors and cancer outcomes.

The authors noted no conflicts of interest.

In patients with advanced cancer who are prescribed immune checkpoint inhibitors, comedications must be carefully assessed before patients start ICI therapy, most notably proton pump inhibitors, glucocorticoids, antibiotics, and psychotropic drugs.

“Our results confirm the detrimental impact on oncological outcomes of antibiotics and glucocorticoids at a dosage ≥10 mg/day when given within 1 month before or after ICI onset,” Marie Kostine, MD, of Bordeaux (France) University Hospital, and colleagues wrote in the European Journal of Cancer. “Moreover, we show that other comedications may significantly alter the antitumoral response of ICI, such as proton pump inhibitors, psychotropic drugs, morphine, aspirin, and insulin, whereas others seem to have no impact.”

While immune checkpoint inhibitors are transforming the treatment of advanced cancers, gut microbiota composition is an important determinant of response to ICIs. Antibiotic treatments are known to alter the gut microbiota. Other drugs, such as proton pump inhibitors, antidiabetic agents, aspirin, NSAIDs, glucocorticoids, immunomodulators, psychotropic drugs, and analgesics, have been associated with changes in microbiome composition. Since many patients with advanced cancer are exposed to such drugs, this study looked at the possible influence of these comedications on the antitumor effect and safety of ICIs.

The observational study included 635 patients with advanced cancer treated with ICIs between May 2015 and September 2017. Comedications given within 1 month before or 1 month after the first administration of an ICI were reviewed from medical records. Psychotropic drugs, proton pump inhibitors, ACE inhibitors and/or angiotensin II receptor blockers (ARBs), glucocorticoids, antibiotics, statins, and morphine were the most prescribed comedications.

Baseline use of antibiotics, glucocorticoids greater than 10 mg/day, proton pump inhibitors, psychotropic drugs, morphine, and insulin was associated with decreased overall survival and tumor response. However, the coadministration of statins, ACE inhibitors and/or ARBs, NSAIDs, aspirin, and oral diabetes drugs did not impact patient outcomes. Additionally, treatments that altered the response to ICIs were associated with a decreased incidence of immune-related adverse events.

“These results suggest some practical advice in a patient candidate to ICIs,” the authors wrote. “First, antibiotic treatment should be limited to documented infections,” and “withdrawal of proton pump inhibitors and psychotropic drugs should be considered.

“Regarding baseline glucocorticoids use, the cutoff of 10 mg/day should be respected, considering the deleterious effect of higher dosage. Moreover, because of the lack of impact of inhaled or topical glucocorticoids, local routes should be preferred,” the authors wrote. “Conversely, our study brings reassuring data regarding the use of glucocorticoids for the management of immune-related adverse events, which did not alter ICI efficacy, confirming previous reports.”

The authors noted that the observational nature of the study does not allow any causal conclusion, adding that it remains unknown whether the effect of comedications “on cancer outcomes is thoroughly mediated by changes in microbiota or other immunomodulatory properties.”

Along with the retrospective design, study limitations included reporting bias and missing data on baseline comedications, specific prognostic factors and cancer outcomes.

The authors noted no conflicts of interest.

Can treatment or removal of high-grade squamous intraepithelial lesions (HSIL) reduce the likelihood of developing anal cancer in people living with HIV (PLHIV)?

“In theory, looking for and treating high-grade disease (like we know works in the cervix) is a potential way to prevent anal cancer in high-risk individuals,” Joel Palefsky, MD, lead investigator of the Anal Cancer/HSIL Outcomes Research (ANCHOR) study and founder/director of the University of California, San Francisco’s Anal Neoplasia Clinic, told this news organization. “But we’ve never had any direct evidence that it worked,” he said.

Initial findings from ANCHOR – the first randomized trial to demonstrate that anal cancer can be prevented in high-risk, HIV-infected patients – promise to change that paradigm and may even portend a new standard of care.

Undoubtedly, this is welcome news for the HIV community, who are not only at increased risk for anal HSIL overall, but among whom anal cancer cases have been rising over the past decade. This is especially true for women who are expected to bear a large portion of overall burden of human papillomavirus (HPV)–associated anal squamous cell carcinoma over the next 10 to 20 years.

In the study, 4,446 PLHIV ages 35 and older with precursor anal HSIL were randomly assigned to topical (imiquimod intra-anally, perianally, or both, or fluorouracil) or ablative (infrared coagulation, hyfrecation/electrocautery) treatment, or active surveillance, and followed every 6 months for 5 years. The study population was broadly representative, including men who have sex with men (MSM), women, transgender people, and historically underrepresented minorities, a factor that reinforces the study’s importance in this specific population.

Because the primary endpoint was reached (that is, to determine if HSIL treatment and removal effectively reduces anal cancer incidence in HIV-infected men and women), the Data Safety Board halted accrual and recommended that participants in the surveillance group be offered treatment moving forward. While the investigators are currently working on publication of the results, the study is ongoing.

Still, the ANCHOR study, which is one of the largest malignancy screening studies conducted in PLHIV, has also highlighted significant challenges in how anal cancer is approached in general.

“Anal cancer has many similarities to cervical cancer, where screening for precancerous lesions and treatment have been shown to substantially reduce morbidity and mortality,” said Joseph Sparano, MD, a medical oncologist specializing in HIV and breast cancer at Icahn School of Medicine at Mount Sinai, New York. Dr. Sparano is chair and principal investigator of the AIDS Malignancy Consortium but was not involved in the ANCHOR study.

But, he explained in an interview, “it’s much more difficult and technically challenging to screen for and evaluate the anal canal histology,” noting that New York is currently the only U.S. state to recommend screening for anal dysplasia with high-resolution anoscopy in HIV-infected men and women.

Availability and access to high-resolution anoscopy is limited, said Robert Yarchoan, MD, chief of the HIV and AIDS Malignancy Branch at the National Cancer Institute’s Clinical Cancer Research Division and director of the Office of HIV and AIDS Malignancy (which, incidentally, cosponsored ANCHOR).

“There are relatively few people that do this at this time,” he added in an interview, pointing out that among those who do, most are obstetricians/gynecologists.

A bit of digging into ANCHOR’s backstory revealed that this was a point of contention at the study’s onset. While physicians participating in the study received extensive training in high-resolution anoscopy, ob/gyns were the fastest to achieve competency and/or had the most prior experience, namely because of their experience in cervical cancer screening in women.

But initial objections by the American Board of Obstetricians and Gynecologists (which at the time, insisted that its members only treat women and threatened to remove their certification if they participated in the research), almost threw a wrench into the study’s start, according to a report in The New York Times. While rational minds prevailed and the board reversed its earlier statements, lack of ample training in the procedure may signal future barriers to treatment.

Another challenge lies in how study findings might be applicable to other groups outside of the HIV/AIDS population, such as people with other forms of immunosuppression who have HSIL, or even healthy women or men who are at risk as a result of penetrative/nonpenetrative sexual or nonsexual (for example, vaginal discharge to the anus) contact.

Although he was unable to share specifics at this time, Dr. Palefsky said that when they designed the ANCHOR study, they were aware that “merely showing efficacy wouldn’t necessarily be sufficient for establishing a standard of care, where[as] other pieces of information undoubtedly would be considered by entities that make guidelines” (for example, an examination of adverse events, risks/benefits, and factors that influence quality of life).

“With that in mind, we are doing a quality-of-life study and, in fact, have [collaborated on], developed, and validated what I think is the first anal disease-specific, quality of life instrument,” Dr. Palefsky said. “The work is still ongoing because we did not complete enrollment in the study, but we are continuing it as part of the follow up.”

Study investigators have also collected samples for a biorepository of specimens that will hopefully facilitate a better understanding of the molecular events driving progression from precancer to cancer. “A lot of people with HIV have these high-grade lesions,” Dr. Palefsky said. “If we were able to identify who’s at highest risk of all of them, that would be very important, because we prefer not to treat everybody with high-grade disease,” he noted, adding that the “underlying hope is that the biomarkers we find in the setting will also be relevant for other HPV-related cancers,” especially in women.

Dr. Yarchoan concurred. “One of the challenges is going to be to digest this information and see how to use it to potentially address the growing problem of females with HIV,” he said.

Dr. Palefsky, Dr. Sparano, and Dr. Yarchoan have disclosed no relevant financial relationships.

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

Can treatment or removal of high-grade squamous intraepithelial lesions (HSIL) reduce the likelihood of developing anal cancer in people living with HIV (PLHIV)?

“In theory, looking for and treating high-grade disease (like we know works in the cervix) is a potential way to prevent anal cancer in high-risk individuals,” Joel Palefsky, MD, lead investigator of the Anal Cancer/HSIL Outcomes Research (ANCHOR) study and founder/director of the University of California, San Francisco’s Anal Neoplasia Clinic, told this news organization. “But we’ve never had any direct evidence that it worked,” he said.

Initial findings from ANCHOR – the first randomized trial to demonstrate that anal cancer can be prevented in high-risk, HIV-infected patients – promise to change that paradigm and may even portend a new standard of care.

Undoubtedly, this is welcome news for the HIV community, who are not only at increased risk for anal HSIL overall, but among whom anal cancer cases have been rising over the past decade. This is especially true for women who are expected to bear a large portion of overall burden of human papillomavirus (HPV)–associated anal squamous cell carcinoma over the next 10 to 20 years.

In the study, 4,446 PLHIV ages 35 and older with precursor anal HSIL were randomly assigned to topical (imiquimod intra-anally, perianally, or both, or fluorouracil) or ablative (infrared coagulation, hyfrecation/electrocautery) treatment, or active surveillance, and followed every 6 months for 5 years. The study population was broadly representative, including men who have sex with men (MSM), women, transgender people, and historically underrepresented minorities, a factor that reinforces the study’s importance in this specific population.

Because the primary endpoint was reached (that is, to determine if HSIL treatment and removal effectively reduces anal cancer incidence in HIV-infected men and women), the Data Safety Board halted accrual and recommended that participants in the surveillance group be offered treatment moving forward. While the investigators are currently working on publication of the results, the study is ongoing.

Still, the ANCHOR study, which is one of the largest malignancy screening studies conducted in PLHIV, has also highlighted significant challenges in how anal cancer is approached in general.

“Anal cancer has many similarities to cervical cancer, where screening for precancerous lesions and treatment have been shown to substantially reduce morbidity and mortality,” said Joseph Sparano, MD, a medical oncologist specializing in HIV and breast cancer at Icahn School of Medicine at Mount Sinai, New York. Dr. Sparano is chair and principal investigator of the AIDS Malignancy Consortium but was not involved in the ANCHOR study.

But, he explained in an interview, “it’s much more difficult and technically challenging to screen for and evaluate the anal canal histology,” noting that New York is currently the only U.S. state to recommend screening for anal dysplasia with high-resolution anoscopy in HIV-infected men and women.

Availability and access to high-resolution anoscopy is limited, said Robert Yarchoan, MD, chief of the HIV and AIDS Malignancy Branch at the National Cancer Institute’s Clinical Cancer Research Division and director of the Office of HIV and AIDS Malignancy (which, incidentally, cosponsored ANCHOR).

“There are relatively few people that do this at this time,” he added in an interview, pointing out that among those who do, most are obstetricians/gynecologists.

A bit of digging into ANCHOR’s backstory revealed that this was a point of contention at the study’s onset. While physicians participating in the study received extensive training in high-resolution anoscopy, ob/gyns were the fastest to achieve competency and/or had the most prior experience, namely because of their experience in cervical cancer screening in women.

But initial objections by the American Board of Obstetricians and Gynecologists (which at the time, insisted that its members only treat women and threatened to remove their certification if they participated in the research), almost threw a wrench into the study’s start, according to a report in The New York Times. While rational minds prevailed and the board reversed its earlier statements, lack of ample training in the procedure may signal future barriers to treatment.

Another challenge lies in how study findings might be applicable to other groups outside of the HIV/AIDS population, such as people with other forms of immunosuppression who have HSIL, or even healthy women or men who are at risk as a result of penetrative/nonpenetrative sexual or nonsexual (for example, vaginal discharge to the anus) contact.

Although he was unable to share specifics at this time, Dr. Palefsky said that when they designed the ANCHOR study, they were aware that “merely showing efficacy wouldn’t necessarily be sufficient for establishing a standard of care, where[as] other pieces of information undoubtedly would be considered by entities that make guidelines” (for example, an examination of adverse events, risks/benefits, and factors that influence quality of life).

“With that in mind, we are doing a quality-of-life study and, in fact, have [collaborated on], developed, and validated what I think is the first anal disease-specific, quality of life instrument,” Dr. Palefsky said. “The work is still ongoing because we did not complete enrollment in the study, but we are continuing it as part of the follow up.”

Study investigators have also collected samples for a biorepository of specimens that will hopefully facilitate a better understanding of the molecular events driving progression from precancer to cancer. “A lot of people with HIV have these high-grade lesions,” Dr. Palefsky said. “If we were able to identify who’s at highest risk of all of them, that would be very important, because we prefer not to treat everybody with high-grade disease,” he noted, adding that the “underlying hope is that the biomarkers we find in the setting will also be relevant for other HPV-related cancers,” especially in women.

Dr. Yarchoan concurred. “One of the challenges is going to be to digest this information and see how to use it to potentially address the growing problem of females with HIV,” he said.

Dr. Palefsky, Dr. Sparano, and Dr. Yarchoan have disclosed no relevant financial relationships.

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

Can treatment or removal of high-grade squamous intraepithelial lesions (HSIL) reduce the likelihood of developing anal cancer in people living with HIV (PLHIV)?

“In theory, looking for and treating high-grade disease (like we know works in the cervix) is a potential way to prevent anal cancer in high-risk individuals,” Joel Palefsky, MD, lead investigator of the Anal Cancer/HSIL Outcomes Research (ANCHOR) study and founder/director of the University of California, San Francisco’s Anal Neoplasia Clinic, told this news organization. “But we’ve never had any direct evidence that it worked,” he said.

Initial findings from ANCHOR – the first randomized trial to demonstrate that anal cancer can be prevented in high-risk, HIV-infected patients – promise to change that paradigm and may even portend a new standard of care.

Undoubtedly, this is welcome news for the HIV community, who are not only at increased risk for anal HSIL overall, but among whom anal cancer cases have been rising over the past decade. This is especially true for women who are expected to bear a large portion of overall burden of human papillomavirus (HPV)–associated anal squamous cell carcinoma over the next 10 to 20 years.

In the study, 4,446 PLHIV ages 35 and older with precursor anal HSIL were randomly assigned to topical (imiquimod intra-anally, perianally, or both, or fluorouracil) or ablative (infrared coagulation, hyfrecation/electrocautery) treatment, or active surveillance, and followed every 6 months for 5 years. The study population was broadly representative, including men who have sex with men (MSM), women, transgender people, and historically underrepresented minorities, a factor that reinforces the study’s importance in this specific population.

Because the primary endpoint was reached (that is, to determine if HSIL treatment and removal effectively reduces anal cancer incidence in HIV-infected men and women), the Data Safety Board halted accrual and recommended that participants in the surveillance group be offered treatment moving forward. While the investigators are currently working on publication of the results, the study is ongoing.

Still, the ANCHOR study, which is one of the largest malignancy screening studies conducted in PLHIV, has also highlighted significant challenges in how anal cancer is approached in general.

“Anal cancer has many similarities to cervical cancer, where screening for precancerous lesions and treatment have been shown to substantially reduce morbidity and mortality,” said Joseph Sparano, MD, a medical oncologist specializing in HIV and breast cancer at Icahn School of Medicine at Mount Sinai, New York. Dr. Sparano is chair and principal investigator of the AIDS Malignancy Consortium but was not involved in the ANCHOR study.

But, he explained in an interview, “it’s much more difficult and technically challenging to screen for and evaluate the anal canal histology,” noting that New York is currently the only U.S. state to recommend screening for anal dysplasia with high-resolution anoscopy in HIV-infected men and women.

Availability and access to high-resolution anoscopy is limited, said Robert Yarchoan, MD, chief of the HIV and AIDS Malignancy Branch at the National Cancer Institute’s Clinical Cancer Research Division and director of the Office of HIV and AIDS Malignancy (which, incidentally, cosponsored ANCHOR).

“There are relatively few people that do this at this time,” he added in an interview, pointing out that among those who do, most are obstetricians/gynecologists.

A bit of digging into ANCHOR’s backstory revealed that this was a point of contention at the study’s onset. While physicians participating in the study received extensive training in high-resolution anoscopy, ob/gyns were the fastest to achieve competency and/or had the most prior experience, namely because of their experience in cervical cancer screening in women.

But initial objections by the American Board of Obstetricians and Gynecologists (which at the time, insisted that its members only treat women and threatened to remove their certification if they participated in the research), almost threw a wrench into the study’s start, according to a report in The New York Times. While rational minds prevailed and the board reversed its earlier statements, lack of ample training in the procedure may signal future barriers to treatment.

Another challenge lies in how study findings might be applicable to other groups outside of the HIV/AIDS population, such as people with other forms of immunosuppression who have HSIL, or even healthy women or men who are at risk as a result of penetrative/nonpenetrative sexual or nonsexual (for example, vaginal discharge to the anus) contact.

Although he was unable to share specifics at this time, Dr. Palefsky said that when they designed the ANCHOR study, they were aware that “merely showing efficacy wouldn’t necessarily be sufficient for establishing a standard of care, where[as] other pieces of information undoubtedly would be considered by entities that make guidelines” (for example, an examination of adverse events, risks/benefits, and factors that influence quality of life).

“With that in mind, we are doing a quality-of-life study and, in fact, have [collaborated on], developed, and validated what I think is the first anal disease-specific, quality of life instrument,” Dr. Palefsky said. “The work is still ongoing because we did not complete enrollment in the study, but we are continuing it as part of the follow up.”

Study investigators have also collected samples for a biorepository of specimens that will hopefully facilitate a better understanding of the molecular events driving progression from precancer to cancer. “A lot of people with HIV have these high-grade lesions,” Dr. Palefsky said. “If we were able to identify who’s at highest risk of all of them, that would be very important, because we prefer not to treat everybody with high-grade disease,” he noted, adding that the “underlying hope is that the biomarkers we find in the setting will also be relevant for other HPV-related cancers,” especially in women.

Dr. Yarchoan concurred. “One of the challenges is going to be to digest this information and see how to use it to potentially address the growing problem of females with HIV,” he said.

Dr. Palefsky, Dr. Sparano, and Dr. Yarchoan have disclosed no relevant financial relationships.

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

Lung cancer screening reduces mortality, but patient adherence to screening intervals is suboptimal in the United States, according to a review and meta-analysis published in the Journal of Thoracic Oncology.

“Lung cancer screening is effective in reducing mortality, particularly when patients adhere to follow-up recommendations standardized by the Lung CT Screening Reporting & Data System (Lung-RADS),” Yannan Lin, MD, MPH, of the University of California, Los Angeles, and colleagues wrote. ”Patient adherence to Lung-RADS–recommended screening intervals is suboptimal across clinical lung cancer screening programs in the U.S., especially among patients with Lung-RADS category 1-2 results.”

Lung cancer screening can identify tumors at earlier, more treatable stages, but patients with lung cancer diagnoses based on new nodules at incidence screening have shown shortened survivals. The National Lung Screening Trial (NLST) has shown a 20% relative reduction in lung cancer mortality with low-dose chest CT screening relative to chest radiography. The Lung-RADS guidelines to standardize the reporting of lung cancer screening were developed based on findings from the NLST and other screening studies, partly to reduce false-positive rates. Lung-RADS scores are based upon nodule size, characteristics and location, with management guidelines specific to Lung-RADS categories, ranging from low-dose chest CT in 12 months for Lung-RADS 1-2 to chest CT, PET/CT, or tissue sampling for Lung-RADS 4B/X.

The rate of adherence to lung cancer screening based on Lung-RADS guidelines is unclear. This systematic review and meta-analysis looked at patient adherence to Lung-RADS recommended screening intervals in clinical practice.

The meta-analysis included 21 studies. The pooled adherence rate was 57% for defined adherence, which included an annual incidence screen performed within 15 months, among 6,689 patients and 65% for anytime adherence among 5,085 patients. The authors noted that overall rates of adherence to Lung-RADS recommended screening intervals in clinical practices is low as compared with the over 90% adherence seen in the NLST, adversely affecting the mortality benefits of lung cancer screening.

Higher adherence rates were found in patients with Lung-RADS 3 (risk for lung cancer, 1%-2%) and 4 (risk, >5%) than Lung-RADS 1 and 2 (risk, <1%; P < .05), which the authors said suggests that tailored interventions based on Lung-RADS categories may be beneficial.

“It is likely that patients and referrers are more concerned about nodules at a higher risk for lung cancer, prompting greater adherence to recommended screening intervals in Lung-RADS 3-4,” the authors wrote. “It is crucial that patients and referrers alike understand that screening is most effective when performed regularly, including for those with negative baseline screens, as de novo nodules, those detected after a negative screen, are more aggressive than those detected at baseline screen.”

These low adherence rates seen in the clinical practices could be explained by patient characteristics, insurance coverage and interventions to ensure adherence, among other factors.

Further, inconsistent reporting of adherence rates was observed. Standardized reporting of adherence rates to lung cancer screening is needed to identify interventions to improve adherence, the authors wrote.

The authors of this study noted no conflicts of interest.

Lung cancer screening reduces mortality, but patient adherence to screening intervals is suboptimal in the United States, according to a review and meta-analysis published in the Journal of Thoracic Oncology.

“Lung cancer screening is effective in reducing mortality, particularly when patients adhere to follow-up recommendations standardized by the Lung CT Screening Reporting & Data System (Lung-RADS),” Yannan Lin, MD, MPH, of the University of California, Los Angeles, and colleagues wrote. ”Patient adherence to Lung-RADS–recommended screening intervals is suboptimal across clinical lung cancer screening programs in the U.S., especially among patients with Lung-RADS category 1-2 results.”

Lung cancer screening can identify tumors at earlier, more treatable stages, but patients with lung cancer diagnoses based on new nodules at incidence screening have shown shortened survivals. The National Lung Screening Trial (NLST) has shown a 20% relative reduction in lung cancer mortality with low-dose chest CT screening relative to chest radiography. The Lung-RADS guidelines to standardize the reporting of lung cancer screening were developed based on findings from the NLST and other screening studies, partly to reduce false-positive rates. Lung-RADS scores are based upon nodule size, characteristics and location, with management guidelines specific to Lung-RADS categories, ranging from low-dose chest CT in 12 months for Lung-RADS 1-2 to chest CT, PET/CT, or tissue sampling for Lung-RADS 4B/X.

The rate of adherence to lung cancer screening based on Lung-RADS guidelines is unclear. This systematic review and meta-analysis looked at patient adherence to Lung-RADS recommended screening intervals in clinical practice.

The meta-analysis included 21 studies. The pooled adherence rate was 57% for defined adherence, which included an annual incidence screen performed within 15 months, among 6,689 patients and 65% for anytime adherence among 5,085 patients. The authors noted that overall rates of adherence to Lung-RADS recommended screening intervals in clinical practices is low as compared with the over 90% adherence seen in the NLST, adversely affecting the mortality benefits of lung cancer screening.

Higher adherence rates were found in patients with Lung-RADS 3 (risk for lung cancer, 1%-2%) and 4 (risk, >5%) than Lung-RADS 1 and 2 (risk, <1%; P < .05), which the authors said suggests that tailored interventions based on Lung-RADS categories may be beneficial.

“It is likely that patients and referrers are more concerned about nodules at a higher risk for lung cancer, prompting greater adherence to recommended screening intervals in Lung-RADS 3-4,” the authors wrote. “It is crucial that patients and referrers alike understand that screening is most effective when performed regularly, including for those with negative baseline screens, as de novo nodules, those detected after a negative screen, are more aggressive than those detected at baseline screen.”

These low adherence rates seen in the clinical practices could be explained by patient characteristics, insurance coverage and interventions to ensure adherence, among other factors.

Further, inconsistent reporting of adherence rates was observed. Standardized reporting of adherence rates to lung cancer screening is needed to identify interventions to improve adherence, the authors wrote.

The authors of this study noted no conflicts of interest.

Lung cancer screening reduces mortality, but patient adherence to screening intervals is suboptimal in the United States, according to a review and meta-analysis published in the Journal of Thoracic Oncology.

“Lung cancer screening is effective in reducing mortality, particularly when patients adhere to follow-up recommendations standardized by the Lung CT Screening Reporting & Data System (Lung-RADS),” Yannan Lin, MD, MPH, of the University of California, Los Angeles, and colleagues wrote. ”Patient adherence to Lung-RADS–recommended screening intervals is suboptimal across clinical lung cancer screening programs in the U.S., especially among patients with Lung-RADS category 1-2 results.”

Lung cancer screening can identify tumors at earlier, more treatable stages, but patients with lung cancer diagnoses based on new nodules at incidence screening have shown shortened survivals. The National Lung Screening Trial (NLST) has shown a 20% relative reduction in lung cancer mortality with low-dose chest CT screening relative to chest radiography. The Lung-RADS guidelines to standardize the reporting of lung cancer screening were developed based on findings from the NLST and other screening studies, partly to reduce false-positive rates. Lung-RADS scores are based upon nodule size, characteristics and location, with management guidelines specific to Lung-RADS categories, ranging from low-dose chest CT in 12 months for Lung-RADS 1-2 to chest CT, PET/CT, or tissue sampling for Lung-RADS 4B/X.

The rate of adherence to lung cancer screening based on Lung-RADS guidelines is unclear. This systematic review and meta-analysis looked at patient adherence to Lung-RADS recommended screening intervals in clinical practice.

The meta-analysis included 21 studies. The pooled adherence rate was 57% for defined adherence, which included an annual incidence screen performed within 15 months, among 6,689 patients and 65% for anytime adherence among 5,085 patients. The authors noted that overall rates of adherence to Lung-RADS recommended screening intervals in clinical practices is low as compared with the over 90% adherence seen in the NLST, adversely affecting the mortality benefits of lung cancer screening.

Higher adherence rates were found in patients with Lung-RADS 3 (risk for lung cancer, 1%-2%) and 4 (risk, >5%) than Lung-RADS 1 and 2 (risk, <1%; P < .05), which the authors said suggests that tailored interventions based on Lung-RADS categories may be beneficial.

“It is likely that patients and referrers are more concerned about nodules at a higher risk for lung cancer, prompting greater adherence to recommended screening intervals in Lung-RADS 3-4,” the authors wrote. “It is crucial that patients and referrers alike understand that screening is most effective when performed regularly, including for those with negative baseline screens, as de novo nodules, those detected after a negative screen, are more aggressive than those detected at baseline screen.”

These low adherence rates seen in the clinical practices could be explained by patient characteristics, insurance coverage and interventions to ensure adherence, among other factors.

Further, inconsistent reporting of adherence rates was observed. Standardized reporting of adherence rates to lung cancer screening is needed to identify interventions to improve adherence, the authors wrote.

The authors of this study noted no conflicts of interest.

Approximately 12,000 new cases of cervical cancer are diagnosed in women in the United States each year, based on data from the Centers for Disease Control and Prevention, said B.J. Rimel, MD, of Cedars-Sinai Medical Center, Los Angeles, in a presentation at the virtual Advancing NIH Research on the Health of Women conference sponsored by the National Institutes of Health.

Despite increased cervical cancer prevention and screening efforts, the incidence of, and mortality from, cervical cancer has remained stable for the past 2 decades, said Dr. Rimel.

Cervical cancer is the only cancer that can be prevented by vaccination, Dr. Rimel noted. It is essential to identify the women who are dying from cervical cancer, as well as who gets screened, who gets vaccinated, and who ends up in clinical trials, she said.

Novel agents for treating cervical cancer suggest that improvement in stagnant mortality rates is possible, said Dr. Rimel. She noted recent studies of cemiplimab, tisotumab vedotin, and a combination therapy involving pembrolizumab and platinum/paclitaxel, with and without bevacizumab.

Dr. Rimel suggested several opportunities to improve the identification and treatment of cervical cancer: Treat it like a rare disease; address structural racism through clinical trials; create opportunities for low–socioeconomic status patients to be involved in research; and develop solutions according to location (urban vs. rural), she said.

Compared with other cancers, cervical cancer is relatively rare in the United States, Dr. Rimel said. However, “It is important that those with cervical cancer can get treated and get healed from the disease,” she said. To better identify the women with cervical cancer who need treatment and to get them into clinical trials, she suggested using strategies employed by rare disease groups, such as seeking out patient support groups and registries.

Significant racial and ethnic disparities persist in cervical cancer, Dr. Rimel emphasized. Data from the CDC show that Black and Hispanic women in the United States are diagnosed with cervical cancer more frequently than women of other races and ethnicities and are less likely to survive.

“Reimagine cervical cancer as a disease of patients who are historically underrepresented due to race, language, poverty, and location,” she said.

Improving equity in cervical cancer care involves structural and trial-specific issues, said Dr. Rimel. Structural issues start with addressing how women enter into the health care system, she said. Consider where women receive care, and whether women have the opportunity to be vaccinated, and later screened, she said. Consider barriers to cervical cancer trials in centers with larger underserved populations, not only cost or insurance, but also issues of language and trust between patients and health care providers, she noted.

To improve the equity of cervical cancer clinical trials, consider potential barriers to enrollment, she added.

“Low English fluency is a barrier to trial enrollment,” said Dr. Rimel. In-person translation is essential for consent to participate in a trial, and “clinical trial budgets must reflect this requirement,” she added. Patient-reported outcomes need to be in the patient’s preferred language, “this includes online content,” Dr. Rimel said.

Dr. Rimel presented other strategies for clinical trial designs to improve equity.

“Compensate patients for their travel, or provide them with tech to allow for off-site monitoring,” she proposed. Patients of lower socioeconomic status in rural and urban areas have different barriers to enrollment, but virtual visits might be an option for those able to access the Internet when given a device. For others, smaller trial sites closer to home, combined with compensation for travel or missed work, might create more opportunities to participate, Dr. Rimel said. Finally, researchers should consider potential roles for smaller or broader studies that involve less travel and testing that would be feasible for more patients who might not otherwise participate in a clinical trial, she concluded.

Dr. Rimel had no financial conflicts to disclose.

Approximately 12,000 new cases of cervical cancer are diagnosed in women in the United States each year, based on data from the Centers for Disease Control and Prevention, said B.J. Rimel, MD, of Cedars-Sinai Medical Center, Los Angeles, in a presentation at the virtual Advancing NIH Research on the Health of Women conference sponsored by the National Institutes of Health.

Despite increased cervical cancer prevention and screening efforts, the incidence of, and mortality from, cervical cancer has remained stable for the past 2 decades, said Dr. Rimel.

Cervical cancer is the only cancer that can be prevented by vaccination, Dr. Rimel noted. It is essential to identify the women who are dying from cervical cancer, as well as who gets screened, who gets vaccinated, and who ends up in clinical trials, she said.

Novel agents for treating cervical cancer suggest that improvement in stagnant mortality rates is possible, said Dr. Rimel. She noted recent studies of cemiplimab, tisotumab vedotin, and a combination therapy involving pembrolizumab and platinum/paclitaxel, with and without bevacizumab.

Dr. Rimel suggested several opportunities to improve the identification and treatment of cervical cancer: Treat it like a rare disease; address structural racism through clinical trials; create opportunities for low–socioeconomic status patients to be involved in research; and develop solutions according to location (urban vs. rural), she said.

Compared with other cancers, cervical cancer is relatively rare in the United States, Dr. Rimel said. However, “It is important that those with cervical cancer can get treated and get healed from the disease,” she said. To better identify the women with cervical cancer who need treatment and to get them into clinical trials, she suggested using strategies employed by rare disease groups, such as seeking out patient support groups and registries.

Significant racial and ethnic disparities persist in cervical cancer, Dr. Rimel emphasized. Data from the CDC show that Black and Hispanic women in the United States are diagnosed with cervical cancer more frequently than women of other races and ethnicities and are less likely to survive.

“Reimagine cervical cancer as a disease of patients who are historically underrepresented due to race, language, poverty, and location,” she said.

Improving equity in cervical cancer care involves structural and trial-specific issues, said Dr. Rimel. Structural issues start with addressing how women enter into the health care system, she said. Consider where women receive care, and whether women have the opportunity to be vaccinated, and later screened, she said. Consider barriers to cervical cancer trials in centers with larger underserved populations, not only cost or insurance, but also issues of language and trust between patients and health care providers, she noted.

To improve the equity of cervical cancer clinical trials, consider potential barriers to enrollment, she added.

“Low English fluency is a barrier to trial enrollment,” said Dr. Rimel. In-person translation is essential for consent to participate in a trial, and “clinical trial budgets must reflect this requirement,” she added. Patient-reported outcomes need to be in the patient’s preferred language, “this includes online content,” Dr. Rimel said.

Dr. Rimel presented other strategies for clinical trial designs to improve equity.

“Compensate patients for their travel, or provide them with tech to allow for off-site monitoring,” she proposed. Patients of lower socioeconomic status in rural and urban areas have different barriers to enrollment, but virtual visits might be an option for those able to access the Internet when given a device. For others, smaller trial sites closer to home, combined with compensation for travel or missed work, might create more opportunities to participate, Dr. Rimel said. Finally, researchers should consider potential roles for smaller or broader studies that involve less travel and testing that would be feasible for more patients who might not otherwise participate in a clinical trial, she concluded.

Dr. Rimel had no financial conflicts to disclose.

Approximately 12,000 new cases of cervical cancer are diagnosed in women in the United States each year, based on data from the Centers for Disease Control and Prevention, said B.J. Rimel, MD, of Cedars-Sinai Medical Center, Los Angeles, in a presentation at the virtual Advancing NIH Research on the Health of Women conference sponsored by the National Institutes of Health.

Despite increased cervical cancer prevention and screening efforts, the incidence of, and mortality from, cervical cancer has remained stable for the past 2 decades, said Dr. Rimel.

Cervical cancer is the only cancer that can be prevented by vaccination, Dr. Rimel noted. It is essential to identify the women who are dying from cervical cancer, as well as who gets screened, who gets vaccinated, and who ends up in clinical trials, she said.

Novel agents for treating cervical cancer suggest that improvement in stagnant mortality rates is possible, said Dr. Rimel. She noted recent studies of cemiplimab, tisotumab vedotin, and a combination therapy involving pembrolizumab and platinum/paclitaxel, with and without bevacizumab.

Dr. Rimel suggested several opportunities to improve the identification and treatment of cervical cancer: Treat it like a rare disease; address structural racism through clinical trials; create opportunities for low–socioeconomic status patients to be involved in research; and develop solutions according to location (urban vs. rural), she said.

Compared with other cancers, cervical cancer is relatively rare in the United States, Dr. Rimel said. However, “It is important that those with cervical cancer can get treated and get healed from the disease,” she said. To better identify the women with cervical cancer who need treatment and to get them into clinical trials, she suggested using strategies employed by rare disease groups, such as seeking out patient support groups and registries.

Significant racial and ethnic disparities persist in cervical cancer, Dr. Rimel emphasized. Data from the CDC show that Black and Hispanic women in the United States are diagnosed with cervical cancer more frequently than women of other races and ethnicities and are less likely to survive.

“Reimagine cervical cancer as a disease of patients who are historically underrepresented due to race, language, poverty, and location,” she said.

Improving equity in cervical cancer care involves structural and trial-specific issues, said Dr. Rimel. Structural issues start with addressing how women enter into the health care system, she said. Consider where women receive care, and whether women have the opportunity to be vaccinated, and later screened, she said. Consider barriers to cervical cancer trials in centers with larger underserved populations, not only cost or insurance, but also issues of language and trust between patients and health care providers, she noted.

To improve the equity of cervical cancer clinical trials, consider potential barriers to enrollment, she added.

“Low English fluency is a barrier to trial enrollment,” said Dr. Rimel. In-person translation is essential for consent to participate in a trial, and “clinical trial budgets must reflect this requirement,” she added. Patient-reported outcomes need to be in the patient’s preferred language, “this includes online content,” Dr. Rimel said.

Dr. Rimel presented other strategies for clinical trial designs to improve equity.

“Compensate patients for their travel, or provide them with tech to allow for off-site monitoring,” she proposed. Patients of lower socioeconomic status in rural and urban areas have different barriers to enrollment, but virtual visits might be an option for those able to access the Internet when given a device. For others, smaller trial sites closer to home, combined with compensation for travel or missed work, might create more opportunities to participate, Dr. Rimel said. Finally, researchers should consider potential roles for smaller or broader studies that involve less travel and testing that would be feasible for more patients who might not otherwise participate in a clinical trial, she concluded.

Dr. Rimel had no financial conflicts to disclose.