Oncology

Hello. I’m Dr. David Johnson, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School and Old Dominion University in Norfolk, Virginia. 

The American College of Gastroenterology (ACG) recently issued a clinical guideline on the diagnosis and management of gastric premalignant conditions. 

Coincidentally, earlier this year, the ACG and the American Society for Gastrointestinal Endoscopy (ASGE) collaborated to issue recommendations on quality indicators for upper endoscopy. 

In this overview, I’ll focus on gastric premalignant conditions while drawing upon some of the quality indicators from ACG/ASGE. Together, these publications highlight several things that we may be overlooking and clearly need to do better at addressing, given the emerging data in this area.

 

Gastric Premalignant Conditions: Increased Risk for Progression

Gastric premalignant conditions are common and include atrophic gastritis, gastric intestinal metaplasia, dysplasia, and certain gastric epithelial polyps. 

The increased risk for progression to gastric adenocarcinoma in the United States is quite striking. It also reveals an important cancer disparity in certain high-risk groups. 

The incidence rates of gastric cancer are two- to 13-fold greater in non-White individuals, particularly among immigrants from high-risk areas. The rates exceed those for esophageal cancer and approach those for colorectal cancer. We have had a dramatic oversight in recognizing the risk for gastric carcinoma in underserved areas. 

Gastric carcinoma is not a good diagnosis. The 5-year survival rate is 36%. Approximately 40% of cases are metastatic at the time of diagnosis; only about 15% are caught at a curable early stage. 

These rates are in far contrast to Asia and areas that do programmatic screening, where the numbers are dramatically reduced. However, in the United States, we’re simply not there yet.

 

Endoscopic Evaluation

There are three phases of endoscopic evaluation for gastric premalignant conditions on which I’d like to focus: pre-endoscopy, intra-endoscopy, and post-endoscopy.

Pre-endoscopy — that is, before you even put in the endoscope — it’s important to assess patients’ potential risk for certain conditions, regardless of the reason for performing the endoscopy. 

Gastric carcinoma is in the top eight leading causes of cancer death in the United States, with the risk being particularly high in Hispanics and Asians. 

According to 2020 data, 40 million people living in the United States were born in another country, with over 70% coming from areas that have a high incidence of gastric carcinoma. 

Accounting for the increased risk in these groups will become even more important. By 2065, it is projected that Asian and Hispanic individuals — the immigrant groups with the highest risk for gastric cancer — will comprise 70% of the US population. Therefore, we need to do a better job on pre-endoscopic assessment if we want to address this major cancer disparity in the United States. 

However, it’s a potentially fixable problem because, in most cases, gastric carcinoma is preceded by a typical asymptomatic precancerous cascade known as the “Correa’s cascade.” It is analogous to what we see in Barrett’s esophagus or even in colorectal neoplasia as it evolves. 

This histologic cascade is important to recognize in patients before they get to the stage of progression. Doing so is highly dependent on the assessment prior to the endoscopy. 

You should also be thinking about high-risk groups before a pre-endoscopy evaluation.

During intra-endoscopy, it’s important to plan your actions while performing the procedure, even if you are not specifically screening for gastric carcinoma. We must be held accountable to established recommendations, standards, and best practices for accurately defining observations, determining appropriate actions, and effectively implementing screening protocols.

A high-quality evaluation of the gastric mucosa is critically important, as an estimated 5%-11% of neoplastic lesions are missed on upper endoscopy completed within 3 years of a gastric cancer diagnosis. With less-experienced endoscopists, the rate of missed neoplastic lesions may be as high as 25%. 

A quality endoscopy begins (as it would in the colon) with mucosal cleaning. This may not be achieved by water alone and requires the use of mucolytic and defoaming agents, such as simethicone or N-acetylcysteine, which can be inordinately helpful. 

Complete mucosal evaluation entails using insufflation to adequately distend the gastric folds.

Atrophic gastritis is observed in a high percentage of patients, and I’m always on the lookout for it when performing endoscopies. One way to identify atrophic gastritis is to look for the loss of gastric folds, which has an approximate sensitivity of 67% and specificity of 85%. The increased visibility of the submucosal venules is another sign of atrophic gastritis, although its sensitivity and specificity are relatively lower at 48% and 87%, respectively. 

Full photo documentation of the gastric mucosa should be included. It is an important part of the intra-endoscopy procedure and also is mentioned as part of the recently published quality indicators for upper endoscopy from ACG/ASGE. 

Recognizing which patients require a biopsy is important. Appropriate biopsy samples should be obtained in patients with recognizable abnormalities. We’re often looking for changes that may be quite subtle. Dysplasia and even adenocarcinoma in the stomach sometimes just cannot be appreciated based on pure endoscopic evaluation.

When it comes to the biopsy protocol, the recommendation is to follow the Sydney system, which was developed in the 1990s. Simply put, this protocol calls for the biopsy samples to be obtained and placed in two separate jars. You look at the greater and lesser curvature of the antrum and the incisura (jar one), and the greater and lesser curvature of the corpus (jar two) in any identified incidental focused biopsy. This is what we do in the colon and the esophagus. 

You should do this after you appropriately clean the mucosa and distend the gastric lumen, ideally using CO2, to avoid the retention of gas. 

Time is another important quality measure. This is similar to the colon, where we see that withdrawal times have increased from 6 minutes to 8-9 minutes. In the stomach, there were initial data about a minimum of 2-3 minutes. However, more recent data in the ACG guideline and the ACG/ASGE quality indicators indicate that detection rates increase after mucosal clearance and dissension when the gastric evaluation is 6-7 minutes. These are numbers we need to pay attention to. The ACG guideline notes that a 2- to 3-minute withdrawal time for upper endoscopy is substandard and not acceptable. If you’re still at that level, then you’re below the standard of care. 

Again, consider time and photo documentation while examining four to six specific areas of both the greater and lesser curvature of the antrum and corpus, and the incisura angularis. It is ideal to use high-definition endoscopy along with the available virtual imaging enhancers. This is the basic requirement for achieving high-quality assessments. 

When it comes to post-endoscopy, it’s essential to talk to your pathologist about using validated instruments of reporting what gastric precancerous lesions involve. There are two different systems: the Operative Link for Gastritis Assessment (OLGA) and the Operative Link on Gastric Intestinal Metaplasia (OLGIM). Although not routinely used in the United States, they are the best recommendations we have for validated histologic scoring systems.

Your pathologist needs to be up to speed on understanding how to report the extent of intestinal metaplasia (complete, incomplete, and mixed) and identifying the areas of focality or abnormalities. It defines what the subsequent surveillance recommendations should be.

 

Know What’s Required

Let’s review what’s required when it comes to diagnosing and managing gastric premalignant conditions.

First, pre-endoscopy must involve the assessment of risk. Before we put in the endoscope, it’s critical to know, regardless of why the patient is there, who needs to be assessed for gastric premalignant conditions. 

Second, during the intra-endoscopy phase, don’t forget the assessments and documentation. If you’re assessing for gastric intestinal metaplasia, use the Sydney system.

Time is a big component. Withdrawal times are discussed much more frequently now, with the takeaway being that longer is better. Aiming for 6-7 minutes is best, according to recommendations from international endoscopy societies and quality measures from the United States. The ACG guideline says that withdrawal times of 2-3 minutes are not best practice and fall short of standard of care. 

For post-endoscopy, talk to your pathologist to ensure better communication and understanding. Make sure that you have a quality gastrointestinal pathologist interpreting these lesions so patients can either enter surveillance or discontinue surveillance after potentially two exams negative for evidence of progressive change.

To do better, we need to understand these guidelines, which are all applicable now. 

I’m Dr. David Johnson. Thanks for listening. See you next time.

David A. Johnson, MD, a regular contributor to Medscape, is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease.

He has disclosed the relevant financial relationships: Advisor to ISOTHRIVE.

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

Hello. I’m Dr. David Johnson, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School and Old Dominion University in Norfolk, Virginia. 

The American College of Gastroenterology (ACG) recently issued a clinical guideline on the diagnosis and management of gastric premalignant conditions. 

Coincidentally, earlier this year, the ACG and the American Society for Gastrointestinal Endoscopy (ASGE) collaborated to issue recommendations on quality indicators for upper endoscopy. 

In this overview, I’ll focus on gastric premalignant conditions while drawing upon some of the quality indicators from ACG/ASGE. Together, these publications highlight several things that we may be overlooking and clearly need to do better at addressing, given the emerging data in this area.

 

Gastric Premalignant Conditions: Increased Risk for Progression

Gastric premalignant conditions are common and include atrophic gastritis, gastric intestinal metaplasia, dysplasia, and certain gastric epithelial polyps. 

The increased risk for progression to gastric adenocarcinoma in the United States is quite striking. It also reveals an important cancer disparity in certain high-risk groups. 

The incidence rates of gastric cancer are two- to 13-fold greater in non-White individuals, particularly among immigrants from high-risk areas. The rates exceed those for esophageal cancer and approach those for colorectal cancer. We have had a dramatic oversight in recognizing the risk for gastric carcinoma in underserved areas. 

Gastric carcinoma is not a good diagnosis. The 5-year survival rate is 36%. Approximately 40% of cases are metastatic at the time of diagnosis; only about 15% are caught at a curable early stage. 

These rates are in far contrast to Asia and areas that do programmatic screening, where the numbers are dramatically reduced. However, in the United States, we’re simply not there yet.

 

Endoscopic Evaluation

There are three phases of endoscopic evaluation for gastric premalignant conditions on which I’d like to focus: pre-endoscopy, intra-endoscopy, and post-endoscopy.

Pre-endoscopy — that is, before you even put in the endoscope — it’s important to assess patients’ potential risk for certain conditions, regardless of the reason for performing the endoscopy. 

Gastric carcinoma is in the top eight leading causes of cancer death in the United States, with the risk being particularly high in Hispanics and Asians. 

According to 2020 data, 40 million people living in the United States were born in another country, with over 70% coming from areas that have a high incidence of gastric carcinoma. 

Accounting for the increased risk in these groups will become even more important. By 2065, it is projected that Asian and Hispanic individuals — the immigrant groups with the highest risk for gastric cancer — will comprise 70% of the US population. Therefore, we need to do a better job on pre-endoscopic assessment if we want to address this major cancer disparity in the United States. 

However, it’s a potentially fixable problem because, in most cases, gastric carcinoma is preceded by a typical asymptomatic precancerous cascade known as the “Correa’s cascade.” It is analogous to what we see in Barrett’s esophagus or even in colorectal neoplasia as it evolves. 

This histologic cascade is important to recognize in patients before they get to the stage of progression. Doing so is highly dependent on the assessment prior to the endoscopy. 

You should also be thinking about high-risk groups before a pre-endoscopy evaluation.

During intra-endoscopy, it’s important to plan your actions while performing the procedure, even if you are not specifically screening for gastric carcinoma. We must be held accountable to established recommendations, standards, and best practices for accurately defining observations, determining appropriate actions, and effectively implementing screening protocols.

A high-quality evaluation of the gastric mucosa is critically important, as an estimated 5%-11% of neoplastic lesions are missed on upper endoscopy completed within 3 years of a gastric cancer diagnosis. With less-experienced endoscopists, the rate of missed neoplastic lesions may be as high as 25%. 

A quality endoscopy begins (as it would in the colon) with mucosal cleaning. This may not be achieved by water alone and requires the use of mucolytic and defoaming agents, such as simethicone or N-acetylcysteine, which can be inordinately helpful. 

Complete mucosal evaluation entails using insufflation to adequately distend the gastric folds.

Atrophic gastritis is observed in a high percentage of patients, and I’m always on the lookout for it when performing endoscopies. One way to identify atrophic gastritis is to look for the loss of gastric folds, which has an approximate sensitivity of 67% and specificity of 85%. The increased visibility of the submucosal venules is another sign of atrophic gastritis, although its sensitivity and specificity are relatively lower at 48% and 87%, respectively. 

Full photo documentation of the gastric mucosa should be included. It is an important part of the intra-endoscopy procedure and also is mentioned as part of the recently published quality indicators for upper endoscopy from ACG/ASGE. 

Recognizing which patients require a biopsy is important. Appropriate biopsy samples should be obtained in patients with recognizable abnormalities. We’re often looking for changes that may be quite subtle. Dysplasia and even adenocarcinoma in the stomach sometimes just cannot be appreciated based on pure endoscopic evaluation.

When it comes to the biopsy protocol, the recommendation is to follow the Sydney system, which was developed in the 1990s. Simply put, this protocol calls for the biopsy samples to be obtained and placed in two separate jars. You look at the greater and lesser curvature of the antrum and the incisura (jar one), and the greater and lesser curvature of the corpus (jar two) in any identified incidental focused biopsy. This is what we do in the colon and the esophagus. 

You should do this after you appropriately clean the mucosa and distend the gastric lumen, ideally using CO2, to avoid the retention of gas. 

Time is another important quality measure. This is similar to the colon, where we see that withdrawal times have increased from 6 minutes to 8-9 minutes. In the stomach, there were initial data about a minimum of 2-3 minutes. However, more recent data in the ACG guideline and the ACG/ASGE quality indicators indicate that detection rates increase after mucosal clearance and dissension when the gastric evaluation is 6-7 minutes. These are numbers we need to pay attention to. The ACG guideline notes that a 2- to 3-minute withdrawal time for upper endoscopy is substandard and not acceptable. If you’re still at that level, then you’re below the standard of care. 

Again, consider time and photo documentation while examining four to six specific areas of both the greater and lesser curvature of the antrum and corpus, and the incisura angularis. It is ideal to use high-definition endoscopy along with the available virtual imaging enhancers. This is the basic requirement for achieving high-quality assessments. 

When it comes to post-endoscopy, it’s essential to talk to your pathologist about using validated instruments of reporting what gastric precancerous lesions involve. There are two different systems: the Operative Link for Gastritis Assessment (OLGA) and the Operative Link on Gastric Intestinal Metaplasia (OLGIM). Although not routinely used in the United States, they are the best recommendations we have for validated histologic scoring systems.

Your pathologist needs to be up to speed on understanding how to report the extent of intestinal metaplasia (complete, incomplete, and mixed) and identifying the areas of focality or abnormalities. It defines what the subsequent surveillance recommendations should be.

 

Know What’s Required

Let’s review what’s required when it comes to diagnosing and managing gastric premalignant conditions.

First, pre-endoscopy must involve the assessment of risk. Before we put in the endoscope, it’s critical to know, regardless of why the patient is there, who needs to be assessed for gastric premalignant conditions. 

Second, during the intra-endoscopy phase, don’t forget the assessments and documentation. If you’re assessing for gastric intestinal metaplasia, use the Sydney system.

Time is a big component. Withdrawal times are discussed much more frequently now, with the takeaway being that longer is better. Aiming for 6-7 minutes is best, according to recommendations from international endoscopy societies and quality measures from the United States. The ACG guideline says that withdrawal times of 2-3 minutes are not best practice and fall short of standard of care. 

For post-endoscopy, talk to your pathologist to ensure better communication and understanding. Make sure that you have a quality gastrointestinal pathologist interpreting these lesions so patients can either enter surveillance or discontinue surveillance after potentially two exams negative for evidence of progressive change.

To do better, we need to understand these guidelines, which are all applicable now. 

I’m Dr. David Johnson. Thanks for listening. See you next time.

David A. Johnson, MD, a regular contributor to Medscape, is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease.

He has disclosed the relevant financial relationships: Advisor to ISOTHRIVE.

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

Hello. I’m Dr. David Johnson, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School and Old Dominion University in Norfolk, Virginia. 

The American College of Gastroenterology (ACG) recently issued a clinical guideline on the diagnosis and management of gastric premalignant conditions. 

Coincidentally, earlier this year, the ACG and the American Society for Gastrointestinal Endoscopy (ASGE) collaborated to issue recommendations on quality indicators for upper endoscopy. 

In this overview, I’ll focus on gastric premalignant conditions while drawing upon some of the quality indicators from ACG/ASGE. Together, these publications highlight several things that we may be overlooking and clearly need to do better at addressing, given the emerging data in this area.

 

Gastric Premalignant Conditions: Increased Risk for Progression

Gastric premalignant conditions are common and include atrophic gastritis, gastric intestinal metaplasia, dysplasia, and certain gastric epithelial polyps. 

The increased risk for progression to gastric adenocarcinoma in the United States is quite striking. It also reveals an important cancer disparity in certain high-risk groups. 

The incidence rates of gastric cancer are two- to 13-fold greater in non-White individuals, particularly among immigrants from high-risk areas. The rates exceed those for esophageal cancer and approach those for colorectal cancer. We have had a dramatic oversight in recognizing the risk for gastric carcinoma in underserved areas. 

Gastric carcinoma is not a good diagnosis. The 5-year survival rate is 36%. Approximately 40% of cases are metastatic at the time of diagnosis; only about 15% are caught at a curable early stage. 

These rates are in far contrast to Asia and areas that do programmatic screening, where the numbers are dramatically reduced. However, in the United States, we’re simply not there yet.

 

Endoscopic Evaluation

There are three phases of endoscopic evaluation for gastric premalignant conditions on which I’d like to focus: pre-endoscopy, intra-endoscopy, and post-endoscopy.

Pre-endoscopy — that is, before you even put in the endoscope — it’s important to assess patients’ potential risk for certain conditions, regardless of the reason for performing the endoscopy. 

Gastric carcinoma is in the top eight leading causes of cancer death in the United States, with the risk being particularly high in Hispanics and Asians. 

According to 2020 data, 40 million people living in the United States were born in another country, with over 70% coming from areas that have a high incidence of gastric carcinoma. 

Accounting for the increased risk in these groups will become even more important. By 2065, it is projected that Asian and Hispanic individuals — the immigrant groups with the highest risk for gastric cancer — will comprise 70% of the US population. Therefore, we need to do a better job on pre-endoscopic assessment if we want to address this major cancer disparity in the United States. 

However, it’s a potentially fixable problem because, in most cases, gastric carcinoma is preceded by a typical asymptomatic precancerous cascade known as the “Correa’s cascade.” It is analogous to what we see in Barrett’s esophagus or even in colorectal neoplasia as it evolves. 

This histologic cascade is important to recognize in patients before they get to the stage of progression. Doing so is highly dependent on the assessment prior to the endoscopy. 

You should also be thinking about high-risk groups before a pre-endoscopy evaluation.

During intra-endoscopy, it’s important to plan your actions while performing the procedure, even if you are not specifically screening for gastric carcinoma. We must be held accountable to established recommendations, standards, and best practices for accurately defining observations, determining appropriate actions, and effectively implementing screening protocols.

A high-quality evaluation of the gastric mucosa is critically important, as an estimated 5%-11% of neoplastic lesions are missed on upper endoscopy completed within 3 years of a gastric cancer diagnosis. With less-experienced endoscopists, the rate of missed neoplastic lesions may be as high as 25%. 

A quality endoscopy begins (as it would in the colon) with mucosal cleaning. This may not be achieved by water alone and requires the use of mucolytic and defoaming agents, such as simethicone or N-acetylcysteine, which can be inordinately helpful. 

Complete mucosal evaluation entails using insufflation to adequately distend the gastric folds.

Atrophic gastritis is observed in a high percentage of patients, and I’m always on the lookout for it when performing endoscopies. One way to identify atrophic gastritis is to look for the loss of gastric folds, which has an approximate sensitivity of 67% and specificity of 85%. The increased visibility of the submucosal venules is another sign of atrophic gastritis, although its sensitivity and specificity are relatively lower at 48% and 87%, respectively. 

Full photo documentation of the gastric mucosa should be included. It is an important part of the intra-endoscopy procedure and also is mentioned as part of the recently published quality indicators for upper endoscopy from ACG/ASGE. 

Recognizing which patients require a biopsy is important. Appropriate biopsy samples should be obtained in patients with recognizable abnormalities. We’re often looking for changes that may be quite subtle. Dysplasia and even adenocarcinoma in the stomach sometimes just cannot be appreciated based on pure endoscopic evaluation.

When it comes to the biopsy protocol, the recommendation is to follow the Sydney system, which was developed in the 1990s. Simply put, this protocol calls for the biopsy samples to be obtained and placed in two separate jars. You look at the greater and lesser curvature of the antrum and the incisura (jar one), and the greater and lesser curvature of the corpus (jar two) in any identified incidental focused biopsy. This is what we do in the colon and the esophagus. 

You should do this after you appropriately clean the mucosa and distend the gastric lumen, ideally using CO2, to avoid the retention of gas. 

Time is another important quality measure. This is similar to the colon, where we see that withdrawal times have increased from 6 minutes to 8-9 minutes. In the stomach, there were initial data about a minimum of 2-3 minutes. However, more recent data in the ACG guideline and the ACG/ASGE quality indicators indicate that detection rates increase after mucosal clearance and dissension when the gastric evaluation is 6-7 minutes. These are numbers we need to pay attention to. The ACG guideline notes that a 2- to 3-minute withdrawal time for upper endoscopy is substandard and not acceptable. If you’re still at that level, then you’re below the standard of care. 

Again, consider time and photo documentation while examining four to six specific areas of both the greater and lesser curvature of the antrum and corpus, and the incisura angularis. It is ideal to use high-definition endoscopy along with the available virtual imaging enhancers. This is the basic requirement for achieving high-quality assessments. 

When it comes to post-endoscopy, it’s essential to talk to your pathologist about using validated instruments of reporting what gastric precancerous lesions involve. There are two different systems: the Operative Link for Gastritis Assessment (OLGA) and the Operative Link on Gastric Intestinal Metaplasia (OLGIM). Although not routinely used in the United States, they are the best recommendations we have for validated histologic scoring systems.

Your pathologist needs to be up to speed on understanding how to report the extent of intestinal metaplasia (complete, incomplete, and mixed) and identifying the areas of focality or abnormalities. It defines what the subsequent surveillance recommendations should be.

 

Know What’s Required

Let’s review what’s required when it comes to diagnosing and managing gastric premalignant conditions.

First, pre-endoscopy must involve the assessment of risk. Before we put in the endoscope, it’s critical to know, regardless of why the patient is there, who needs to be assessed for gastric premalignant conditions. 

Second, during the intra-endoscopy phase, don’t forget the assessments and documentation. If you’re assessing for gastric intestinal metaplasia, use the Sydney system.

Time is a big component. Withdrawal times are discussed much more frequently now, with the takeaway being that longer is better. Aiming for 6-7 minutes is best, according to recommendations from international endoscopy societies and quality measures from the United States. The ACG guideline says that withdrawal times of 2-3 minutes are not best practice and fall short of standard of care. 

For post-endoscopy, talk to your pathologist to ensure better communication and understanding. Make sure that you have a quality gastrointestinal pathologist interpreting these lesions so patients can either enter surveillance or discontinue surveillance after potentially two exams negative for evidence of progressive change.

To do better, we need to understand these guidelines, which are all applicable now. 

I’m Dr. David Johnson. Thanks for listening. See you next time.

David A. Johnson, MD, a regular contributor to Medscape, is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease.

He has disclosed the relevant financial relationships: Advisor to ISOTHRIVE.

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

Incorporating a polygenic risk score into prostate cancer screening could enhance the detection of clinically significant prostate cancer that conventional screening may miss, according to results of the BARCODE 1 clinical trial conducted in the United Kingdom.

The study found that about 72% of participants with high polygenic risk scores were diagnosed with clinically significant prostate cancers, which would not have been detected with prostate-specific antigen (PSA) testing or MRI.

“With this test, it could be possible to turn the tide on prostate cancer,” study author Ros Eeles, PhD, professor of oncogenetics at The Institute of Cancer Research, London, England, said in a statement following the publication of the analysis in The New England Journal of Medicine.

Prostate cancer remains the second most commonly diagnosed cancer among men. As a screening tool, PSA testing has been criticized for leading to a high rate of false positive results and overdiagnosis — defined as a screen-detected cancer that would take longer to progress to clinical cancer than the patient’s lifetime. Both issues can result in overtreatment.

Given prostate cancer’s high heritability and the proliferation of genome-wide association studies identifying common genetic variants, there has been growing interest in using polygenic risk scores to improve risk stratification and guide screening.

“Building on decades of research into the genetic markers of prostate cancer, our study shows that the theory does work in practice — we can identify men at risk of aggressive cancers who need further tests and spare the men who are at lower risk from unnecessary treatments,” said Eeles.

 

An Adjunct to Screening?

The BARCODE 1 study, conducted in the United Kingdom, tested the clinical utility of a polygenic risk score as an adjunct to screening.

The researchers recruited men aged 55-69 years from primary care centers in the United Kingdom. Using germline DNA extracted from saliva, they derived polygenic risk scores from 130 genetic variants known to be associated with an increased risk for prostate cancer.

Among a total of 6393 men who had their scores calculated, 745 (12%) had a score in the top 10% of genetic risk (≥ 90th percentile) and were invited to undergo further screening.

Of these, 468 (63%) accepted the invite and underwent multiparametric MRI and transperineal prostate biopsy, irrespective of the PSA level. Overall, 187 (40%) were diagnosed with prostate cancer following biopsy. Of the 187 men with prostate cancer, 55% (n = 103) had disease classified as intermediate or high risk (Gleason score ≥ 7) per National Comprehensive Cancer Network criteria and therefore warranted further treatment.

Researchers then compared screening that incorporated polygenic risk scores with standard screening with PSA levels and MRI.

When participants’ risk was stratified by their polygenic risk score, 103 patients (55%) with prostate cancer could be classified as intermediate or higher risk, thus warranting treatment. Overall, 74 (71.8%) of those cancers would have been missed using the standard diagnostic pathway in the United Kingdom, which requires patients to have a high PSA level (> 3.0 μg/L) as well as a positive MRI result. These 74 patients either had PSA levels ≤ 3.0 μg/L or negative MRIs, which would mean these patients would typically fall below the action threshold for further testing.

Of the 103 participants warranting treatment, 40 of these men would have been classified as unfavorable intermediate, high, or very high risk, which would require radical treatment. Among this group, roughly 43% would have been missed using the UK diagnostic pathway. 

However, the investigators estimated a rate of overdiagnosis with the use of polygenic risk scores of 16%-21%, similar to the overdiagnosis estimates in two prior PSA-based screening studies, signaling that the addition of polygenic risk scores does not necessarily reduce the risk for overdiagnosis.

Overall, “this study is the strongest evidence to date on the clinical utility of a polygenic score for prostate cancer screening,” commented Michael Inouye, professor of systems genomics & population health, University of Cambridge, Cambridge, England, in a statement from the UK nonprofit Science Media Centre (SMC).

“I suspect we will look back on this as a landmark study that really made the clinical case for polygenic scores as a new tool that moved health systems from disease management to early detection and prevention,” said Inouye, who was not involved in the study.

However, other experts were more cautious about the findings.

Dusko Ilic, MD, professor of stem cell sciences, King’s College London, London, England, said the results are “promising, especially in identifying significant cancers that would otherwise be missed,” but cautioned that “there is no direct evidence yet that using [polygenic risk scores] improves long-term outcomes such as mortality or quality-adjusted life years.”

“Modeling suggests benefit, but empirical confirmation is needed,” Ilic said in the SMC statement.

The hope is that the recently launched TRANSFORM trial will help answer some of these outstanding questions.

The current study suggests that polygenic risk scores for prostate cancer “would be a useful component of a multimodality screening program that assesses age, family history of prostate cancer, PSA, and MRI results as triage tools before biopsy is recommended,” David Hunter, MPH, ScD, with Harvard T. H. Chan School of Public Health, Boston, and University of Oxford, Oxford, England, wrote in an editorial accompanying the study.

“To make this integrated program a reality, however, changes to infrastructure would be needed to make running and analyzing a regulated genome array as easy as requesting a PSA level or ordering an MRI. Clearly, we are far from that future,” Hunter cautioned. 

“A possible first step that would require less infrastructure could be to order a polygenic risk score only for men with a positive PSA result, then use the polygenic risk score to determine who should undergo an MRI, and then use all the information to determine whether biopsy is recommended,” Hunter said.

In his view, the current study is a “first step on a long road to evaluating new components of any disease screening pathway.”

The research received funding from the European Research Council, the Bob Willis Fund, Cancer Research UK, the Peacock Trust, and the National Institute for Health and Care Research Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research. Disclosures for authors and editorialists are available with the original article. Inouye and Ilic reported no relevant disclosures.

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

Incorporating a polygenic risk score into prostate cancer screening could enhance the detection of clinically significant prostate cancer that conventional screening may miss, according to results of the BARCODE 1 clinical trial conducted in the United Kingdom.

The study found that about 72% of participants with high polygenic risk scores were diagnosed with clinically significant prostate cancers, which would not have been detected with prostate-specific antigen (PSA) testing or MRI.

“With this test, it could be possible to turn the tide on prostate cancer,” study author Ros Eeles, PhD, professor of oncogenetics at The Institute of Cancer Research, London, England, said in a statement following the publication of the analysis in The New England Journal of Medicine.

Prostate cancer remains the second most commonly diagnosed cancer among men. As a screening tool, PSA testing has been criticized for leading to a high rate of false positive results and overdiagnosis — defined as a screen-detected cancer that would take longer to progress to clinical cancer than the patient’s lifetime. Both issues can result in overtreatment.

Given prostate cancer’s high heritability and the proliferation of genome-wide association studies identifying common genetic variants, there has been growing interest in using polygenic risk scores to improve risk stratification and guide screening.

“Building on decades of research into the genetic markers of prostate cancer, our study shows that the theory does work in practice — we can identify men at risk of aggressive cancers who need further tests and spare the men who are at lower risk from unnecessary treatments,” said Eeles.

 

An Adjunct to Screening?

The BARCODE 1 study, conducted in the United Kingdom, tested the clinical utility of a polygenic risk score as an adjunct to screening.

The researchers recruited men aged 55-69 years from primary care centers in the United Kingdom. Using germline DNA extracted from saliva, they derived polygenic risk scores from 130 genetic variants known to be associated with an increased risk for prostate cancer.

Among a total of 6393 men who had their scores calculated, 745 (12%) had a score in the top 10% of genetic risk (≥ 90th percentile) and were invited to undergo further screening.

Of these, 468 (63%) accepted the invite and underwent multiparametric MRI and transperineal prostate biopsy, irrespective of the PSA level. Overall, 187 (40%) were diagnosed with prostate cancer following biopsy. Of the 187 men with prostate cancer, 55% (n = 103) had disease classified as intermediate or high risk (Gleason score ≥ 7) per National Comprehensive Cancer Network criteria and therefore warranted further treatment.

Researchers then compared screening that incorporated polygenic risk scores with standard screening with PSA levels and MRI.

When participants’ risk was stratified by their polygenic risk score, 103 patients (55%) with prostate cancer could be classified as intermediate or higher risk, thus warranting treatment. Overall, 74 (71.8%) of those cancers would have been missed using the standard diagnostic pathway in the United Kingdom, which requires patients to have a high PSA level (> 3.0 μg/L) as well as a positive MRI result. These 74 patients either had PSA levels ≤ 3.0 μg/L or negative MRIs, which would mean these patients would typically fall below the action threshold for further testing.

Of the 103 participants warranting treatment, 40 of these men would have been classified as unfavorable intermediate, high, or very high risk, which would require radical treatment. Among this group, roughly 43% would have been missed using the UK diagnostic pathway. 

However, the investigators estimated a rate of overdiagnosis with the use of polygenic risk scores of 16%-21%, similar to the overdiagnosis estimates in two prior PSA-based screening studies, signaling that the addition of polygenic risk scores does not necessarily reduce the risk for overdiagnosis.

Overall, “this study is the strongest evidence to date on the clinical utility of a polygenic score for prostate cancer screening,” commented Michael Inouye, professor of systems genomics & population health, University of Cambridge, Cambridge, England, in a statement from the UK nonprofit Science Media Centre (SMC).

“I suspect we will look back on this as a landmark study that really made the clinical case for polygenic scores as a new tool that moved health systems from disease management to early detection and prevention,” said Inouye, who was not involved in the study.

However, other experts were more cautious about the findings.

Dusko Ilic, MD, professor of stem cell sciences, King’s College London, London, England, said the results are “promising, especially in identifying significant cancers that would otherwise be missed,” but cautioned that “there is no direct evidence yet that using [polygenic risk scores] improves long-term outcomes such as mortality or quality-adjusted life years.”

“Modeling suggests benefit, but empirical confirmation is needed,” Ilic said in the SMC statement.

The hope is that the recently launched TRANSFORM trial will help answer some of these outstanding questions.

The current study suggests that polygenic risk scores for prostate cancer “would be a useful component of a multimodality screening program that assesses age, family history of prostate cancer, PSA, and MRI results as triage tools before biopsy is recommended,” David Hunter, MPH, ScD, with Harvard T. H. Chan School of Public Health, Boston, and University of Oxford, Oxford, England, wrote in an editorial accompanying the study.

“To make this integrated program a reality, however, changes to infrastructure would be needed to make running and analyzing a regulated genome array as easy as requesting a PSA level or ordering an MRI. Clearly, we are far from that future,” Hunter cautioned. 

“A possible first step that would require less infrastructure could be to order a polygenic risk score only for men with a positive PSA result, then use the polygenic risk score to determine who should undergo an MRI, and then use all the information to determine whether biopsy is recommended,” Hunter said.

In his view, the current study is a “first step on a long road to evaluating new components of any disease screening pathway.”

The research received funding from the European Research Council, the Bob Willis Fund, Cancer Research UK, the Peacock Trust, and the National Institute for Health and Care Research Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research. Disclosures for authors and editorialists are available with the original article. Inouye and Ilic reported no relevant disclosures.

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

Incorporating a polygenic risk score into prostate cancer screening could enhance the detection of clinically significant prostate cancer that conventional screening may miss, according to results of the BARCODE 1 clinical trial conducted in the United Kingdom.

The study found that about 72% of participants with high polygenic risk scores were diagnosed with clinically significant prostate cancers, which would not have been detected with prostate-specific antigen (PSA) testing or MRI.

“With this test, it could be possible to turn the tide on prostate cancer,” study author Ros Eeles, PhD, professor of oncogenetics at The Institute of Cancer Research, London, England, said in a statement following the publication of the analysis in The New England Journal of Medicine.

Prostate cancer remains the second most commonly diagnosed cancer among men. As a screening tool, PSA testing has been criticized for leading to a high rate of false positive results and overdiagnosis — defined as a screen-detected cancer that would take longer to progress to clinical cancer than the patient’s lifetime. Both issues can result in overtreatment.

Given prostate cancer’s high heritability and the proliferation of genome-wide association studies identifying common genetic variants, there has been growing interest in using polygenic risk scores to improve risk stratification and guide screening.

“Building on decades of research into the genetic markers of prostate cancer, our study shows that the theory does work in practice — we can identify men at risk of aggressive cancers who need further tests and spare the men who are at lower risk from unnecessary treatments,” said Eeles.

 

An Adjunct to Screening?

The BARCODE 1 study, conducted in the United Kingdom, tested the clinical utility of a polygenic risk score as an adjunct to screening.

The researchers recruited men aged 55-69 years from primary care centers in the United Kingdom. Using germline DNA extracted from saliva, they derived polygenic risk scores from 130 genetic variants known to be associated with an increased risk for prostate cancer.

Among a total of 6393 men who had their scores calculated, 745 (12%) had a score in the top 10% of genetic risk (≥ 90th percentile) and were invited to undergo further screening.

Of these, 468 (63%) accepted the invite and underwent multiparametric MRI and transperineal prostate biopsy, irrespective of the PSA level. Overall, 187 (40%) were diagnosed with prostate cancer following biopsy. Of the 187 men with prostate cancer, 55% (n = 103) had disease classified as intermediate or high risk (Gleason score ≥ 7) per National Comprehensive Cancer Network criteria and therefore warranted further treatment.

Researchers then compared screening that incorporated polygenic risk scores with standard screening with PSA levels and MRI.

When participants’ risk was stratified by their polygenic risk score, 103 patients (55%) with prostate cancer could be classified as intermediate or higher risk, thus warranting treatment. Overall, 74 (71.8%) of those cancers would have been missed using the standard diagnostic pathway in the United Kingdom, which requires patients to have a high PSA level (> 3.0 μg/L) as well as a positive MRI result. These 74 patients either had PSA levels ≤ 3.0 μg/L or negative MRIs, which would mean these patients would typically fall below the action threshold for further testing.

Of the 103 participants warranting treatment, 40 of these men would have been classified as unfavorable intermediate, high, or very high risk, which would require radical treatment. Among this group, roughly 43% would have been missed using the UK diagnostic pathway. 

However, the investigators estimated a rate of overdiagnosis with the use of polygenic risk scores of 16%-21%, similar to the overdiagnosis estimates in two prior PSA-based screening studies, signaling that the addition of polygenic risk scores does not necessarily reduce the risk for overdiagnosis.

Overall, “this study is the strongest evidence to date on the clinical utility of a polygenic score for prostate cancer screening,” commented Michael Inouye, professor of systems genomics & population health, University of Cambridge, Cambridge, England, in a statement from the UK nonprofit Science Media Centre (SMC).

“I suspect we will look back on this as a landmark study that really made the clinical case for polygenic scores as a new tool that moved health systems from disease management to early detection and prevention,” said Inouye, who was not involved in the study.

However, other experts were more cautious about the findings.

Dusko Ilic, MD, professor of stem cell sciences, King’s College London, London, England, said the results are “promising, especially in identifying significant cancers that would otherwise be missed,” but cautioned that “there is no direct evidence yet that using [polygenic risk scores] improves long-term outcomes such as mortality or quality-adjusted life years.”

“Modeling suggests benefit, but empirical confirmation is needed,” Ilic said in the SMC statement.

The hope is that the recently launched TRANSFORM trial will help answer some of these outstanding questions.

The current study suggests that polygenic risk scores for prostate cancer “would be a useful component of a multimodality screening program that assesses age, family history of prostate cancer, PSA, and MRI results as triage tools before biopsy is recommended,” David Hunter, MPH, ScD, with Harvard T. H. Chan School of Public Health, Boston, and University of Oxford, Oxford, England, wrote in an editorial accompanying the study.

“To make this integrated program a reality, however, changes to infrastructure would be needed to make running and analyzing a regulated genome array as easy as requesting a PSA level or ordering an MRI. Clearly, we are far from that future,” Hunter cautioned. 

“A possible first step that would require less infrastructure could be to order a polygenic risk score only for men with a positive PSA result, then use the polygenic risk score to determine who should undergo an MRI, and then use all the information to determine whether biopsy is recommended,” Hunter said.

In his view, the current study is a “first step on a long road to evaluating new components of any disease screening pathway.”

The research received funding from the European Research Council, the Bob Willis Fund, Cancer Research UK, the Peacock Trust, and the National Institute for Health and Care Research Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research. Disclosures for authors and editorialists are available with the original article. Inouye and Ilic reported no relevant disclosures.

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

This transcript has been edited for clarity. 

Hello. I’m Maurie Markman, from City of Hope. I want to briefly discuss a very interesting paper that is probably a bit controversial, but nevertheless, I want to point out the data. The paper is “Alcohol Consumption Patterns and Mortality Among Older Adults With Health-Related or Socioeconomic Risk Factors,” published in JAMA Network Open. 

This involved a little over 135,000 individual participants in a large, multiyear [research project] in the UK; it’s part of the UK Biobank. This is a population-based cohort that they were looking at here and is only a small part of this huge effort in the UK. 

The particular participants that they were looking at here were 60 years or older and defined as current drinkers; that could be occasional all the way up to heavy. Again, that’s the 135,000 individuals I’m referring to. 

The data were analyzed from September 2023 to May 2024. They divided the population into four groups, including what they call occasional drinkers, which I guess are social drinkers; it was not clear how they defined that. Then they defined three other categories, which were low risk, moderate risk, and high risk, which was much more clearly defined as it was stated in the paper the amount of alcohol consumption each individual had per day.

The question there was about the relationship between how much alcohol an individual stated they drank compared with the occasional drinker, and the risk for cancer in each group. The answer is that there was no protection from cancer by only being a low-risk or a low-level drinker. 

All of the populations had a higher risk for cancer compared with the occasional drinkers. The low-risk group was not protected. The high-risk group had a hazard ratio of 1.39, which is a 39% increase. For the moderate-risk group, the hazard ratio was 1.15, and for the low-risk group, 1.11. 

The risk was higher the more an individual drank. However, the point to be made is that if someone says, “Oh, I drink a certain amount each day, but there’s no impact on my risk for cancer,” these data do not support that conclusion. 

There is much more to be discussed about this topic. It’s an interesting, large population-based, very carefully controlled analysis being done here, but an important point for future conversation. 

Thank you for your attention.

Maurie Markman, MD, has disclosed the following relevant financial relationships: Received income in an amount equal to or greater than $250 from: GlaxoSmithKline; AstraZeneca.

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

This transcript has been edited for clarity. 

Hello. I’m Maurie Markman, from City of Hope. I want to briefly discuss a very interesting paper that is probably a bit controversial, but nevertheless, I want to point out the data. The paper is “Alcohol Consumption Patterns and Mortality Among Older Adults With Health-Related or Socioeconomic Risk Factors,” published in JAMA Network Open. 

This involved a little over 135,000 individual participants in a large, multiyear [research project] in the UK; it’s part of the UK Biobank. This is a population-based cohort that they were looking at here and is only a small part of this huge effort in the UK. 

The particular participants that they were looking at here were 60 years or older and defined as current drinkers; that could be occasional all the way up to heavy. Again, that’s the 135,000 individuals I’m referring to. 

The data were analyzed from September 2023 to May 2024. They divided the population into four groups, including what they call occasional drinkers, which I guess are social drinkers; it was not clear how they defined that. Then they defined three other categories, which were low risk, moderate risk, and high risk, which was much more clearly defined as it was stated in the paper the amount of alcohol consumption each individual had per day.

The question there was about the relationship between how much alcohol an individual stated they drank compared with the occasional drinker, and the risk for cancer in each group. The answer is that there was no protection from cancer by only being a low-risk or a low-level drinker. 

All of the populations had a higher risk for cancer compared with the occasional drinkers. The low-risk group was not protected. The high-risk group had a hazard ratio of 1.39, which is a 39% increase. For the moderate-risk group, the hazard ratio was 1.15, and for the low-risk group, 1.11. 

The risk was higher the more an individual drank. However, the point to be made is that if someone says, “Oh, I drink a certain amount each day, but there’s no impact on my risk for cancer,” these data do not support that conclusion. 

There is much more to be discussed about this topic. It’s an interesting, large population-based, very carefully controlled analysis being done here, but an important point for future conversation. 

Thank you for your attention.

Maurie Markman, MD, has disclosed the following relevant financial relationships: Received income in an amount equal to or greater than $250 from: GlaxoSmithKline; AstraZeneca.

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

This transcript has been edited for clarity. 

Hello. I’m Maurie Markman, from City of Hope. I want to briefly discuss a very interesting paper that is probably a bit controversial, but nevertheless, I want to point out the data. The paper is “Alcohol Consumption Patterns and Mortality Among Older Adults With Health-Related or Socioeconomic Risk Factors,” published in JAMA Network Open. 

This involved a little over 135,000 individual participants in a large, multiyear [research project] in the UK; it’s part of the UK Biobank. This is a population-based cohort that they were looking at here and is only a small part of this huge effort in the UK. 

The particular participants that they were looking at here were 60 years or older and defined as current drinkers; that could be occasional all the way up to heavy. Again, that’s the 135,000 individuals I’m referring to. 

The data were analyzed from September 2023 to May 2024. They divided the population into four groups, including what they call occasional drinkers, which I guess are social drinkers; it was not clear how they defined that. Then they defined three other categories, which were low risk, moderate risk, and high risk, which was much more clearly defined as it was stated in the paper the amount of alcohol consumption each individual had per day.

The question there was about the relationship between how much alcohol an individual stated they drank compared with the occasional drinker, and the risk for cancer in each group. The answer is that there was no protection from cancer by only being a low-risk or a low-level drinker. 

All of the populations had a higher risk for cancer compared with the occasional drinkers. The low-risk group was not protected. The high-risk group had a hazard ratio of 1.39, which is a 39% increase. For the moderate-risk group, the hazard ratio was 1.15, and for the low-risk group, 1.11. 

The risk was higher the more an individual drank. However, the point to be made is that if someone says, “Oh, I drink a certain amount each day, but there’s no impact on my risk for cancer,” these data do not support that conclusion. 

There is much more to be discussed about this topic. It’s an interesting, large population-based, very carefully controlled analysis being done here, but an important point for future conversation. 

Thank you for your attention.

Maurie Markman, MD, has disclosed the following relevant financial relationships: Received income in an amount equal to or greater than $250 from: GlaxoSmithKline; AstraZeneca.

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

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