AVAHO

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.

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.

The United States Food and Drug Administration (FDA) has approved bevacizumab-nwgd (Jobevne, Biocon Biologics Ltd), a biosimilar to bevacizumab (Avastin, Genentech), for intravenous use across multiple cancer types.

Approval was based on “a comprehensive package of comparative pharmacokinetic, safety, efficacy, nonclinical, structural, analytical and functional data, which confirmed the Jobevne is highly similar to Avastin,” according to a Biocon Biologics Ltd press release. 

“The data demonstrated that there were no clinically meaningful differences between Jobevne and Avastin in terms of pharmacokinetics, safety, efficacy, and immunogenicity,” the company stated.

The biosimilar agent is indicated as part of various combinations for the treatment of metastatic colorectal cancer, certain types of non-squamous non–small cell lung cancer, recurrent glioblastoma, metastatic renal cell carcinoma, certain advanced cervical cancers, and epithelial ovarian, fallopian tube, or primary peritoneal cancers, the company noted.

The agent is not indicated for adjuvant treatment of colon cancer, according to the press release, which includes detailed information about the indications, as well as a list of warnings and precautions.

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

The United States Food and Drug Administration (FDA) has approved bevacizumab-nwgd (Jobevne, Biocon Biologics Ltd), a biosimilar to bevacizumab (Avastin, Genentech), for intravenous use across multiple cancer types.

Approval was based on “a comprehensive package of comparative pharmacokinetic, safety, efficacy, nonclinical, structural, analytical and functional data, which confirmed the Jobevne is highly similar to Avastin,” according to a Biocon Biologics Ltd press release. 

“The data demonstrated that there were no clinically meaningful differences between Jobevne and Avastin in terms of pharmacokinetics, safety, efficacy, and immunogenicity,” the company stated.

The biosimilar agent is indicated as part of various combinations for the treatment of metastatic colorectal cancer, certain types of non-squamous non–small cell lung cancer, recurrent glioblastoma, metastatic renal cell carcinoma, certain advanced cervical cancers, and epithelial ovarian, fallopian tube, or primary peritoneal cancers, the company noted.

The agent is not indicated for adjuvant treatment of colon cancer, according to the press release, which includes detailed information about the indications, as well as a list of warnings and precautions.

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

The United States Food and Drug Administration (FDA) has approved bevacizumab-nwgd (Jobevne, Biocon Biologics Ltd), a biosimilar to bevacizumab (Avastin, Genentech), for intravenous use across multiple cancer types.

Approval was based on “a comprehensive package of comparative pharmacokinetic, safety, efficacy, nonclinical, structural, analytical and functional data, which confirmed the Jobevne is highly similar to Avastin,” according to a Biocon Biologics Ltd press release. 

“The data demonstrated that there were no clinically meaningful differences between Jobevne and Avastin in terms of pharmacokinetics, safety, efficacy, and immunogenicity,” the company stated.

The biosimilar agent is indicated as part of various combinations for the treatment of metastatic colorectal cancer, certain types of non-squamous non–small cell lung cancer, recurrent glioblastoma, metastatic renal cell carcinoma, certain advanced cervical cancers, and epithelial ovarian, fallopian tube, or primary peritoneal cancers, the company noted.

The agent is not indicated for adjuvant treatment of colon cancer, according to the press release, which includes detailed information about the indications, as well as a list of warnings and precautions.

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

Adam DuVall, MD, MPH, is a rare medical oncologist who trained in both adult and pediatric hematology/oncology.

This distinction, which DuVall said he shares with only a handful of oncologists in the world, matches his role at University of Chicago (UChicago) Medicine, Chicago. Since joining UChicago in 2020, DuVall has helped expand its Adolescent and Young Adult (AYA) Oncology Program, which aims to provide comprehensive, one-stop care and support for patients with cancer aged from 15 to 39 years.

Started in 2012, the program is one of the oldest in a growing array of initiatives nationwide that seek to address the specific psychosocial and other support needs of patients with cancer who fall into the gap between young children and the older patients who more typically have cancer. Along with DuVall and other oncologists, UChicago’s AYA Program offers dedicated nurse practitioners, social workers, psychologists, a physical therapist, and a program administrator. A community health worker, who does home visits, helps patients coordinate travel, works with their insurance, and generally navigates the medical system, DuVall added.

The program receives about 1500-2000 visits a year, according to DuVall. What the young adult population with cancer has in common that distinguishes it from other age cohorts, he said, are its members’ particular psychosocial needs. “Going through adolescence and young adulthood without cancer, there’s plenty of things that are hard,” DuVall observed. “Put cancer on top of that, and it impacts every aspect of life.”

‘Millennials Have Higher Risk’

The proliferation of AYA programs comes as more and more studies have been published recently showing that young adults are increasingly getting cancer.

According to American Cancer Society research published in December in The Lancet Oncology, incidence rates of colorectal cancer (CRC) among young adults aged 25-49 years rose in the decade through 2017 in more than half of the 50 countries and territories examined. For the past 5 years studied, the incidence rate of early-onset CRC was highest in Australia, Puerto Rico, New Zealand, the United States, and South Korea. At the same time, the study found, rates among older adults in all of those places except South Korea were stable or declining.

Hyuna Sung, PhD, the study’s lead author, said, “Research has shown that Gen X and millennials have higher risk of multiple types of cancer compared to the older generations.”

Some of the cancers found to be increasing among younger adults are linked to “excess body obesity,” Sung said, including not only CRC but also cancers of the uterine corpus, gallbladder, kidney, pancreas, breast, and stomach cardia, as well as myeloma. Early onset of cancers not linked to obesity, such as testicular cancer and small intestinal cancer, has also been shown to be on the rise, Sung noted.

As cancer rates among young adults have risen, nonprofits have stepped in to help medical institutions open programs geared to their needs. Teen Cancer America, founded by members of rock band The Who, has partnered with 64 hospitals in 36 cities to develop AYA-focused programs, funding 85 hospital positions, according to a spokesperson. The Los Angeles–based nonprofit has also provided free consultation to 130 hospitals without formally providing a grant, the spokesperson said.

A map on Teen Cancer America’s website illustrates the nationwide spread of AYA programs, from UCLA Santa Monica Medical Center to Memorial Sloan Kettering Cancer Center in New York City, with more in between.

‘Setting Them Up for a Life of Meaning’

Michael Roth, MD, co-director of the AYA Program at the University of Texas MD Anderson Cancer Center in Houston, likes to say, “If you’ve seen one AYA Program, you’ve seen one AYA Program.”

In other words, offerings vary. “Most centers do not have comprehensive AYA programs,” Roth said, noting that at many sites the AYA Program might consist of oncofertility support. “That said, programs are doing the best they can, knowing that the AYA population is growing exponentially globally.”

Almost 90,000 AYA patients are diagnosed with cancer each year, and 85% will be at least 5-year survivors, Roth said. There are more than 2 million survivors of AYA cancer, he added, and if the median age of diagnosis is 30, they can live five decades beyond their cancer treatment. “Their life matters,” Roth said. “It matters during treatment. Their life after cancer matters.”

The AYA Program at MD Anderson began in 2017, and it sees more than 2000 AYAs diagnosed with cancer every year, according to Roth. The program is designed to complement the care that patients with cancer aged from 15 to 39 years or older may already be receiving from their primary treatment teams. New patients see a medical provider, a social worker, and a vocational counselor for discussions about their needs and concerns, and they have access to a nutritionist and genetic counselor.

The program offers psychosocial and supportive care for patients who may be facing challenges with school, work, relationships, having young children, and mental health, Roth said. Along with assessments and counseling around fertility risks and genetic predisposition, MD Anderson also provides patients in the program with a long-term survivorship plan.

“It’s not just increasing cures,” Roth observed. “We’re also setting them up for a life of meaning and happiness and productivity and health.”

Almost 40% of visits to the program are conducted virtually, according to Roth. “Our goal is to meet the patients where they are,” he said. “We want to be convenient, not be a burden.”

‘The Face of Cancer Has Changed’

Patients with AYA cancer diagnoses may be finishing up school or starting a job, developing their body image and sexual identity, or caring for young children or older parents.

“They feel incredibly isolated,” said Ann LaCasce, MD, MMSc, co-director of the Center for Adolescent and Young Adult Oncology at Dana-Farber Cancer Institute in Boston. “They go into the cancer center or their community practice, and everyone is double, triple their age.”

Last year, Dana-Farber opened a Young Adult Lounge meant for patients aged 18 years or older to be able to relax and, if they wish, interact between appointments. “When you talk to these patients, they want to meet each other,” LaCasce said. “They want to share experiences.”

The Young Adults With Cancer Program at Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, opened its doors in 2019. It recently hired an interim nurse navigator, said Cathy Eng, MD, FACP, FASCO, director of the Program, which concentrates on patients aged 25-45 years.

“The face of cancer has changed,” Eng said.

She advises other oncologists to talk to their young adult patients as much as possible. “Really talk to them as an individual and see what other needs they have,” she said. “Even if they don’t tell you the first time, ask them the second time, ask them the third time.”

Christopher Cann, MD, executive director of the Young Adult Cancer Program at Fox Chase Cancer Center in Philadelphia, did his fellowship under Eng. He joined Fox Chase in 2023, and the Young Adult Cancer Program started accepting patients around the end of last year, zeroing in on patients aged 18-39 years.

Following the implementation of a new best practice advisory that pops up in the medical records system, he said, oncofertility referrals increased by 400% within 6 months.

“My hope is that if every institution throughout the country can have a young adult program, even something small like this can provide a large impact for patients,” Cann said.

The University of North Carolina (UNC) AYA Cancer Program, part of the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, formed in 2015. It has expanded into a team of about 12 including a nurse practitioner, fertility counselor, and psychologist, said Jacob Stein, MD, MPH, the program’s AYA oncology liaison. UNC sees about 400 AYA patients with cancer annually, and the program interacts with slightly more than 100 of them, according to Stein.

“Our program has taken a very different approach, to target services, contact, and engagement with AYAs who we perceive to be at the highest need, either clinically or socially, for support,” he said.

Stein was the lead author on research presented last year at the ASCO Quality Care Symposium in San Francisco finding that patients engaged in the program were more likely to participate in clinical trials and received higher rates of fertility preservation and palliative care than AYA patients at UNC without program contact.

Andrew Smitherman, MD, MS, medical director of the UNC AYA Cancer Center Program, said the AYA field has grown impressively since a progress review group was started in 2005, which was backed by the National Cancer Institute and LIVESTRONG Young Adult Alliance. The group developed recommendations to address AYA oncology nationwide, in hopes of acting as a catalyst for future initiatives. Clearly, others caring for patients with cancer heard the message.

“If a colleague comes to me and says, ‘Where do I start, how do I make this change at my institution,’ I usually lead with changing the culture,” Smitherman said. “Educating hospital leadership about the importance of this population, educating colleagues, finding partners. And then start thinking about ways to make structural changes, like creating space. That’s worked really well for us.”

DuVall, Sung, Roth, LaCasce, Eng, Cann, Stein, and Smitherman declared no conflicts of interest.

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

Adam DuVall, MD, MPH, is a rare medical oncologist who trained in both adult and pediatric hematology/oncology.

This distinction, which DuVall said he shares with only a handful of oncologists in the world, matches his role at University of Chicago (UChicago) Medicine, Chicago. Since joining UChicago in 2020, DuVall has helped expand its Adolescent and Young Adult (AYA) Oncology Program, which aims to provide comprehensive, one-stop care and support for patients with cancer aged from 15 to 39 years.

Started in 2012, the program is one of the oldest in a growing array of initiatives nationwide that seek to address the specific psychosocial and other support needs of patients with cancer who fall into the gap between young children and the older patients who more typically have cancer. Along with DuVall and other oncologists, UChicago’s AYA Program offers dedicated nurse practitioners, social workers, psychologists, a physical therapist, and a program administrator. A community health worker, who does home visits, helps patients coordinate travel, works with their insurance, and generally navigates the medical system, DuVall added.

The program receives about 1500-2000 visits a year, according to DuVall. What the young adult population with cancer has in common that distinguishes it from other age cohorts, he said, are its members’ particular psychosocial needs. “Going through adolescence and young adulthood without cancer, there’s plenty of things that are hard,” DuVall observed. “Put cancer on top of that, and it impacts every aspect of life.”

‘Millennials Have Higher Risk’

The proliferation of AYA programs comes as more and more studies have been published recently showing that young adults are increasingly getting cancer.

According to American Cancer Society research published in December in The Lancet Oncology, incidence rates of colorectal cancer (CRC) among young adults aged 25-49 years rose in the decade through 2017 in more than half of the 50 countries and territories examined. For the past 5 years studied, the incidence rate of early-onset CRC was highest in Australia, Puerto Rico, New Zealand, the United States, and South Korea. At the same time, the study found, rates among older adults in all of those places except South Korea were stable or declining.

Hyuna Sung, PhD, the study’s lead author, said, “Research has shown that Gen X and millennials have higher risk of multiple types of cancer compared to the older generations.”

Some of the cancers found to be increasing among younger adults are linked to “excess body obesity,” Sung said, including not only CRC but also cancers of the uterine corpus, gallbladder, kidney, pancreas, breast, and stomach cardia, as well as myeloma. Early onset of cancers not linked to obesity, such as testicular cancer and small intestinal cancer, has also been shown to be on the rise, Sung noted.

As cancer rates among young adults have risen, nonprofits have stepped in to help medical institutions open programs geared to their needs. Teen Cancer America, founded by members of rock band The Who, has partnered with 64 hospitals in 36 cities to develop AYA-focused programs, funding 85 hospital positions, according to a spokesperson. The Los Angeles–based nonprofit has also provided free consultation to 130 hospitals without formally providing a grant, the spokesperson said.

A map on Teen Cancer America’s website illustrates the nationwide spread of AYA programs, from UCLA Santa Monica Medical Center to Memorial Sloan Kettering Cancer Center in New York City, with more in between.

‘Setting Them Up for a Life of Meaning’

Michael Roth, MD, co-director of the AYA Program at the University of Texas MD Anderson Cancer Center in Houston, likes to say, “If you’ve seen one AYA Program, you’ve seen one AYA Program.”

In other words, offerings vary. “Most centers do not have comprehensive AYA programs,” Roth said, noting that at many sites the AYA Program might consist of oncofertility support. “That said, programs are doing the best they can, knowing that the AYA population is growing exponentially globally.”

Almost 90,000 AYA patients are diagnosed with cancer each year, and 85% will be at least 5-year survivors, Roth said. There are more than 2 million survivors of AYA cancer, he added, and if the median age of diagnosis is 30, they can live five decades beyond their cancer treatment. “Their life matters,” Roth said. “It matters during treatment. Their life after cancer matters.”

The AYA Program at MD Anderson began in 2017, and it sees more than 2000 AYAs diagnosed with cancer every year, according to Roth. The program is designed to complement the care that patients with cancer aged from 15 to 39 years or older may already be receiving from their primary treatment teams. New patients see a medical provider, a social worker, and a vocational counselor for discussions about their needs and concerns, and they have access to a nutritionist and genetic counselor.

The program offers psychosocial and supportive care for patients who may be facing challenges with school, work, relationships, having young children, and mental health, Roth said. Along with assessments and counseling around fertility risks and genetic predisposition, MD Anderson also provides patients in the program with a long-term survivorship plan.

“It’s not just increasing cures,” Roth observed. “We’re also setting them up for a life of meaning and happiness and productivity and health.”

Almost 40% of visits to the program are conducted virtually, according to Roth. “Our goal is to meet the patients where they are,” he said. “We want to be convenient, not be a burden.”

‘The Face of Cancer Has Changed’

Patients with AYA cancer diagnoses may be finishing up school or starting a job, developing their body image and sexual identity, or caring for young children or older parents.

“They feel incredibly isolated,” said Ann LaCasce, MD, MMSc, co-director of the Center for Adolescent and Young Adult Oncology at Dana-Farber Cancer Institute in Boston. “They go into the cancer center or their community practice, and everyone is double, triple their age.”

Last year, Dana-Farber opened a Young Adult Lounge meant for patients aged 18 years or older to be able to relax and, if they wish, interact between appointments. “When you talk to these patients, they want to meet each other,” LaCasce said. “They want to share experiences.”

The Young Adults With Cancer Program at Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, opened its doors in 2019. It recently hired an interim nurse navigator, said Cathy Eng, MD, FACP, FASCO, director of the Program, which concentrates on patients aged 25-45 years.

“The face of cancer has changed,” Eng said.

She advises other oncologists to talk to their young adult patients as much as possible. “Really talk to them as an individual and see what other needs they have,” she said. “Even if they don’t tell you the first time, ask them the second time, ask them the third time.”

Christopher Cann, MD, executive director of the Young Adult Cancer Program at Fox Chase Cancer Center in Philadelphia, did his fellowship under Eng. He joined Fox Chase in 2023, and the Young Adult Cancer Program started accepting patients around the end of last year, zeroing in on patients aged 18-39 years.

Following the implementation of a new best practice advisory that pops up in the medical records system, he said, oncofertility referrals increased by 400% within 6 months.

“My hope is that if every institution throughout the country can have a young adult program, even something small like this can provide a large impact for patients,” Cann said.

The University of North Carolina (UNC) AYA Cancer Program, part of the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, formed in 2015. It has expanded into a team of about 12 including a nurse practitioner, fertility counselor, and psychologist, said Jacob Stein, MD, MPH, the program’s AYA oncology liaison. UNC sees about 400 AYA patients with cancer annually, and the program interacts with slightly more than 100 of them, according to Stein.

“Our program has taken a very different approach, to target services, contact, and engagement with AYAs who we perceive to be at the highest need, either clinically or socially, for support,” he said.

Stein was the lead author on research presented last year at the ASCO Quality Care Symposium in San Francisco finding that patients engaged in the program were more likely to participate in clinical trials and received higher rates of fertility preservation and palliative care than AYA patients at UNC without program contact.

Andrew Smitherman, MD, MS, medical director of the UNC AYA Cancer Center Program, said the AYA field has grown impressively since a progress review group was started in 2005, which was backed by the National Cancer Institute and LIVESTRONG Young Adult Alliance. The group developed recommendations to address AYA oncology nationwide, in hopes of acting as a catalyst for future initiatives. Clearly, others caring for patients with cancer heard the message.

“If a colleague comes to me and says, ‘Where do I start, how do I make this change at my institution,’ I usually lead with changing the culture,” Smitherman said. “Educating hospital leadership about the importance of this population, educating colleagues, finding partners. And then start thinking about ways to make structural changes, like creating space. That’s worked really well for us.”

DuVall, Sung, Roth, LaCasce, Eng, Cann, Stein, and Smitherman declared no conflicts of interest.

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

Adam DuVall, MD, MPH, is a rare medical oncologist who trained in both adult and pediatric hematology/oncology.

This distinction, which DuVall said he shares with only a handful of oncologists in the world, matches his role at University of Chicago (UChicago) Medicine, Chicago. Since joining UChicago in 2020, DuVall has helped expand its Adolescent and Young Adult (AYA) Oncology Program, which aims to provide comprehensive, one-stop care and support for patients with cancer aged from 15 to 39 years.

Started in 2012, the program is one of the oldest in a growing array of initiatives nationwide that seek to address the specific psychosocial and other support needs of patients with cancer who fall into the gap between young children and the older patients who more typically have cancer. Along with DuVall and other oncologists, UChicago’s AYA Program offers dedicated nurse practitioners, social workers, psychologists, a physical therapist, and a program administrator. A community health worker, who does home visits, helps patients coordinate travel, works with their insurance, and generally navigates the medical system, DuVall added.

The program receives about 1500-2000 visits a year, according to DuVall. What the young adult population with cancer has in common that distinguishes it from other age cohorts, he said, are its members’ particular psychosocial needs. “Going through adolescence and young adulthood without cancer, there’s plenty of things that are hard,” DuVall observed. “Put cancer on top of that, and it impacts every aspect of life.”

‘Millennials Have Higher Risk’

The proliferation of AYA programs comes as more and more studies have been published recently showing that young adults are increasingly getting cancer.

According to American Cancer Society research published in December in The Lancet Oncology, incidence rates of colorectal cancer (CRC) among young adults aged 25-49 years rose in the decade through 2017 in more than half of the 50 countries and territories examined. For the past 5 years studied, the incidence rate of early-onset CRC was highest in Australia, Puerto Rico, New Zealand, the United States, and South Korea. At the same time, the study found, rates among older adults in all of those places except South Korea were stable or declining.

Hyuna Sung, PhD, the study’s lead author, said, “Research has shown that Gen X and millennials have higher risk of multiple types of cancer compared to the older generations.”

Some of the cancers found to be increasing among younger adults are linked to “excess body obesity,” Sung said, including not only CRC but also cancers of the uterine corpus, gallbladder, kidney, pancreas, breast, and stomach cardia, as well as myeloma. Early onset of cancers not linked to obesity, such as testicular cancer and small intestinal cancer, has also been shown to be on the rise, Sung noted.

As cancer rates among young adults have risen, nonprofits have stepped in to help medical institutions open programs geared to their needs. Teen Cancer America, founded by members of rock band The Who, has partnered with 64 hospitals in 36 cities to develop AYA-focused programs, funding 85 hospital positions, according to a spokesperson. The Los Angeles–based nonprofit has also provided free consultation to 130 hospitals without formally providing a grant, the spokesperson said.

A map on Teen Cancer America’s website illustrates the nationwide spread of AYA programs, from UCLA Santa Monica Medical Center to Memorial Sloan Kettering Cancer Center in New York City, with more in between.

‘Setting Them Up for a Life of Meaning’

Michael Roth, MD, co-director of the AYA Program at the University of Texas MD Anderson Cancer Center in Houston, likes to say, “If you’ve seen one AYA Program, you’ve seen one AYA Program.”

In other words, offerings vary. “Most centers do not have comprehensive AYA programs,” Roth said, noting that at many sites the AYA Program might consist of oncofertility support. “That said, programs are doing the best they can, knowing that the AYA population is growing exponentially globally.”

Almost 90,000 AYA patients are diagnosed with cancer each year, and 85% will be at least 5-year survivors, Roth said. There are more than 2 million survivors of AYA cancer, he added, and if the median age of diagnosis is 30, they can live five decades beyond their cancer treatment. “Their life matters,” Roth said. “It matters during treatment. Their life after cancer matters.”

The AYA Program at MD Anderson began in 2017, and it sees more than 2000 AYAs diagnosed with cancer every year, according to Roth. The program is designed to complement the care that patients with cancer aged from 15 to 39 years or older may already be receiving from their primary treatment teams. New patients see a medical provider, a social worker, and a vocational counselor for discussions about their needs and concerns, and they have access to a nutritionist and genetic counselor.

The program offers psychosocial and supportive care for patients who may be facing challenges with school, work, relationships, having young children, and mental health, Roth said. Along with assessments and counseling around fertility risks and genetic predisposition, MD Anderson also provides patients in the program with a long-term survivorship plan.

“It’s not just increasing cures,” Roth observed. “We’re also setting them up for a life of meaning and happiness and productivity and health.”

Almost 40% of visits to the program are conducted virtually, according to Roth. “Our goal is to meet the patients where they are,” he said. “We want to be convenient, not be a burden.”

‘The Face of Cancer Has Changed’

Patients with AYA cancer diagnoses may be finishing up school or starting a job, developing their body image and sexual identity, or caring for young children or older parents.

“They feel incredibly isolated,” said Ann LaCasce, MD, MMSc, co-director of the Center for Adolescent and Young Adult Oncology at Dana-Farber Cancer Institute in Boston. “They go into the cancer center or their community practice, and everyone is double, triple their age.”

Last year, Dana-Farber opened a Young Adult Lounge meant for patients aged 18 years or older to be able to relax and, if they wish, interact between appointments. “When you talk to these patients, they want to meet each other,” LaCasce said. “They want to share experiences.”

The Young Adults With Cancer Program at Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, opened its doors in 2019. It recently hired an interim nurse navigator, said Cathy Eng, MD, FACP, FASCO, director of the Program, which concentrates on patients aged 25-45 years.

“The face of cancer has changed,” Eng said.

She advises other oncologists to talk to their young adult patients as much as possible. “Really talk to them as an individual and see what other needs they have,” she said. “Even if they don’t tell you the first time, ask them the second time, ask them the third time.”

Christopher Cann, MD, executive director of the Young Adult Cancer Program at Fox Chase Cancer Center in Philadelphia, did his fellowship under Eng. He joined Fox Chase in 2023, and the Young Adult Cancer Program started accepting patients around the end of last year, zeroing in on patients aged 18-39 years.

Following the implementation of a new best practice advisory that pops up in the medical records system, he said, oncofertility referrals increased by 400% within 6 months.

“My hope is that if every institution throughout the country can have a young adult program, even something small like this can provide a large impact for patients,” Cann said.

The University of North Carolina (UNC) AYA Cancer Program, part of the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, formed in 2015. It has expanded into a team of about 12 including a nurse practitioner, fertility counselor, and psychologist, said Jacob Stein, MD, MPH, the program’s AYA oncology liaison. UNC sees about 400 AYA patients with cancer annually, and the program interacts with slightly more than 100 of them, according to Stein.

“Our program has taken a very different approach, to target services, contact, and engagement with AYAs who we perceive to be at the highest need, either clinically or socially, for support,” he said.

Stein was the lead author on research presented last year at the ASCO Quality Care Symposium in San Francisco finding that patients engaged in the program were more likely to participate in clinical trials and received higher rates of fertility preservation and palliative care than AYA patients at UNC without program contact.

Andrew Smitherman, MD, MS, medical director of the UNC AYA Cancer Center Program, said the AYA field has grown impressively since a progress review group was started in 2005, which was backed by the National Cancer Institute and LIVESTRONG Young Adult Alliance. The group developed recommendations to address AYA oncology nationwide, in hopes of acting as a catalyst for future initiatives. Clearly, others caring for patients with cancer heard the message.

“If a colleague comes to me and says, ‘Where do I start, how do I make this change at my institution,’ I usually lead with changing the culture,” Smitherman said. “Educating hospital leadership about the importance of this population, educating colleagues, finding partners. And then start thinking about ways to make structural changes, like creating space. That’s worked really well for us.”

DuVall, Sung, Roth, LaCasce, Eng, Cann, Stein, and Smitherman declared no conflicts of interest.

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

The US Food and Drug Administration (FDA) has approved nivolumab (Opdivo, Bristol Myers Squibb) with ipilimumab (Yervoy, Bristol Myers Squibb) as a first-line treatment for adults with unresectable or metastatic hepatocellular carcinoma (HCC). 

The decision, which follows the FDA’s 2020 accelerated approval in the second-line setting for advanced HCC and adds to the list of other indications for the combination therapy, was based on efficacy demonstrated in the randomized, open-label CHECKMATE-9DW trial. The trial enrolled 668 patients with unresectable or metastatic HCC and no prior systemic therapy for advanced disease, according to the FDA approval notice. 

Median overall survival, the primary outcome measure, was 23.7 months in those randomized to receive nivolumab + ipilimumab, compared with 20.6 months in those randomized to receive investigators’ choice of lenvatinib or sorafenib (hazard ratio, 0.79). The overall response rate was 36.1% vs 13.2% in the arms, respectively.

Those in the treatment arm received 1 mg/kg intravenous (IV) nivolumab with 3 mg/kg IV ipilimumab every 3 weeks for up to four doses, followed by single-agent IV nivolumab at 480 mg every 4 weeks. Those in the control arm received either 8 or 12 mg lenvatinib daily or 400 mg sorafenib twice daily until disease progression or unacceptable toxicity, according to early results from the trial, which were presented at the 2024 American Society of Clinical Oncology meeting. 

Adverse reactions occurring in more than 20% of patients included rash, pruritus, fatigue, and diarrhea.

The recommended nivolumab dose for this indication is 1 mg/kg with 3 mg/kg ipilimumab given intravenously every 3 weeks for up to four doses, followed by 240 mg nivolumab every 2 weeks or 480 mg nivolumab every 4 weeks. Full prescribing information will be available at Drugs@FDA.

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

The US Food and Drug Administration (FDA) has approved nivolumab (Opdivo, Bristol Myers Squibb) with ipilimumab (Yervoy, Bristol Myers Squibb) as a first-line treatment for adults with unresectable or metastatic hepatocellular carcinoma (HCC). 

The decision, which follows the FDA’s 2020 accelerated approval in the second-line setting for advanced HCC and adds to the list of other indications for the combination therapy, was based on efficacy demonstrated in the randomized, open-label CHECKMATE-9DW trial. The trial enrolled 668 patients with unresectable or metastatic HCC and no prior systemic therapy for advanced disease, according to the FDA approval notice. 

Median overall survival, the primary outcome measure, was 23.7 months in those randomized to receive nivolumab + ipilimumab, compared with 20.6 months in those randomized to receive investigators’ choice of lenvatinib or sorafenib (hazard ratio, 0.79). The overall response rate was 36.1% vs 13.2% in the arms, respectively.

Those in the treatment arm received 1 mg/kg intravenous (IV) nivolumab with 3 mg/kg IV ipilimumab every 3 weeks for up to four doses, followed by single-agent IV nivolumab at 480 mg every 4 weeks. Those in the control arm received either 8 or 12 mg lenvatinib daily or 400 mg sorafenib twice daily until disease progression or unacceptable toxicity, according to early results from the trial, which were presented at the 2024 American Society of Clinical Oncology meeting. 

Adverse reactions occurring in more than 20% of patients included rash, pruritus, fatigue, and diarrhea.

The recommended nivolumab dose for this indication is 1 mg/kg with 3 mg/kg ipilimumab given intravenously every 3 weeks for up to four doses, followed by 240 mg nivolumab every 2 weeks or 480 mg nivolumab every 4 weeks. Full prescribing information will be available at Drugs@FDA.

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

The US Food and Drug Administration (FDA) has approved nivolumab (Opdivo, Bristol Myers Squibb) with ipilimumab (Yervoy, Bristol Myers Squibb) as a first-line treatment for adults with unresectable or metastatic hepatocellular carcinoma (HCC). 

The decision, which follows the FDA’s 2020 accelerated approval in the second-line setting for advanced HCC and adds to the list of other indications for the combination therapy, was based on efficacy demonstrated in the randomized, open-label CHECKMATE-9DW trial. The trial enrolled 668 patients with unresectable or metastatic HCC and no prior systemic therapy for advanced disease, according to the FDA approval notice. 

Median overall survival, the primary outcome measure, was 23.7 months in those randomized to receive nivolumab + ipilimumab, compared with 20.6 months in those randomized to receive investigators’ choice of lenvatinib or sorafenib (hazard ratio, 0.79). The overall response rate was 36.1% vs 13.2% in the arms, respectively.

Those in the treatment arm received 1 mg/kg intravenous (IV) nivolumab with 3 mg/kg IV ipilimumab every 3 weeks for up to four doses, followed by single-agent IV nivolumab at 480 mg every 4 weeks. Those in the control arm received either 8 or 12 mg lenvatinib daily or 400 mg sorafenib twice daily until disease progression or unacceptable toxicity, according to early results from the trial, which were presented at the 2024 American Society of Clinical Oncology meeting. 

Adverse reactions occurring in more than 20% of patients included rash, pruritus, fatigue, and diarrhea.

The recommended nivolumab dose for this indication is 1 mg/kg with 3 mg/kg ipilimumab given intravenously every 3 weeks for up to four doses, followed by 240 mg nivolumab every 2 weeks or 480 mg nivolumab every 4 weeks. Full prescribing information will be available at Drugs@FDA.

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

One patient, a 39-year-old woman, went to a dermatologist seeking care for fluid-filled blisters over the backs of her hands and arms. Another patient, a 56-year-old man, sought care from his general practitioner owing to fatigue.

Their presentations were quite different, but the two patients shared one thing in common: iron overload. Both ended up in the care of hematologists who diagnosed their conditions as porphyria cutanea tarda (PCT) and hemochromatosis, respectively.

A pair of hematologists discussed the treatment of these disorders at the American Society of Hematology (ASH) 2024 Annual Meeting and in reports in Hematology: American Society of Hematology Education Program. Here’s a look at the guidance they provided.

 

Porphyria Cutanea Tarda: Skin Trouble

Testing revealed that the female patient had a highly elevated porphyrin levels: Her urine uroporphyrin was 3959  nmol/L (normal, < 30 nmol/L) and plasma uroporphyrin was 2.0 µg/dL (normal, < 1.0  µg/dL). Her serum ferritin level was also high, at 420 ng/mL (normal, < 200 ng/mL).

Rebecca Karp Leaf, MD, of Massachusetts General Hospital and Harvard Medical School, diagnosed her with PCT, a disorder of heme biosynthesis that often presents with skin manifestations.

As co-founder and co-director of the Boston hospital’s Porphyria Center, Karp Leaf is a leading expert in PCT, a rare disease that affects 5-10 people per 100,000. In addition to speaking at the ASH meeting in December, she described PCT in a December 2024 article in Hematology: American Society of Hematology Education Program. 

PCT is caused by inhibition of an enzyme in heme biosynthesis and leads to accumulation of porphyrins in the liver and plasma, Karp Leaf said. Through a complex process, excess of iron leads to inhibition of the enzyme, which leads to a buildup of toxic porphyrins, she said. The condition causes painless, blistering lesions on sun-exposed skin, scarring, skin fragility, dark urine, and liver disease. 

PCT most commonly occurs in middle age after the age of 40 and affects men more than women. “It’s the only porphyria that can occur absent a genetic variant,” she said, and 75% of cases have no genetic component. 

 

Options for Treatment Include Antivirals and Phlebotomy

Risk factors for PCT include alcohol use, smoking, exogenous estrogen, hepatitis, and HIV mutations. 

In regard to treatment, “modification of risk factors can be variably helpful: alcohol and smoking cessation, stopping exogenous estrogen, sun-protective clothing, and steroid-containing creams for lesions,” Karp Leaf said. “Most patients typically require further therapy to reduce liver porphyrins.”

Urine and plasma tests can help with diagnosis, she said. In patients with hepatitis C (HCV), “direct-acting antivirals can actually lead to resolution of PCT without any other therapy. We suspect that with effective antiviral treatment for HCV, the incidence of PCT will really go down.”

Therapeutic phlebotomy — blood removal — is another option. “It’s one of my favorite therapies because you don’t have to give somebody a drug. You can just take out iron,” Karp Leaf said. “Typically, we’ll start with venesection of 450 ccs of whole blood every 2 weeks, We target a ferritin level of 20 [ng/mL] but permit it up to 50 [ng/mL], or a little bit higher.”

The treatment leads to resolution of blisters in about 2-3 months, she said, and normalization of porphyrins by 13 months. Patients typically require about 6-8 treatments, she said. 

Another option is iron chelation, iron removal via medicine, “but it’s expensive, has side effects, and is really not recommended if other treatments are available,” she said. 

 

Hydroxychloroquine Can Be Helpful Too

Low-dose hydroxychloroquine can also be effective at 100 mg twice a week, “much lower than what we use in autoimmune disease,” Karp Leaf said. “We suspect that it’s taken up by the hepatic lysosomes and causes release of porphyrins. It causes clinical remission in about 6 months.”

However, higher doses can lead to liver injury, and the drug’s use is limited in end-stage kidney disease since porphyrins are excreted in the urine. These patients are especially difficult to treat, she said.

In the case of the 39-year-old patient, Karp Leaf recommended that the woman reduce her alcohol intake and begin using a copper intrauterine device for contraception instead of a combined oral contraceptive pill, which allowed her to undergo phlebotomy.

“She needed about eight sessions of therapeutic phlebotomy to achieve a ferritin of 30 [ng/mL], and her lesions resolved in 6 months,” Karp Leaf said. “Her plasma porphyrins resolved by 12 months. Her liver biochemistries were a bit elevated, and they subsequently normalized.”

Karp Leaf said she sees the patient about once a year. 

 

Hemochromatosis: It’s (Probably) a Family Affair

In an adjoining presentation at ASH and in a December 2024 article in Hematology: American Society of Hematology Education Program, hematologist Domenico Girelli, MD, PhD, with the University of Verona, Italy, told colleagues about the 56-year-old male patient with fatigue. He also had a mildly enlarged liver, hyperferritinemia (890  µg/L vs normal value < 300 µg/L) and a mildly increased alanine aminotransferase level (46 U/L vs normal value < 40 U/L).

The patient was diagnosed with hemochromatosis, a genetic disorder caused by mutations that leads to increased transferrin saturation, Girelli said. 

“By definition, hemochromatosis is characterized by the absence of signs of a primary red blood cell disorder — different from other disorders like transfusion iron overload or iron-loading anemias,” he said. 

It’s also important to consider other possible causes of hyperferritinemia, because most cases of the symptom aren’t related to iron overload, he said. “A careful clinical history and a few laboratory parameters including transferrin saturation are generally sufficient for the differential diagnosis.”

As Girelli noted, “hemochromatosis can have a wide clinical spectrum ranging from mild to severe forms, which are strongly influenced by the co-presence of risk factors like alcohol [use], blood transfusion, and genetic factors captured by polygenic risk score.”

 

In Many Cases, Hemochromatosis Can Be Successfully Treated

According to Girelli, it’s important to understand the disease stage, because this information can predict the probability of advanced liver fibrosis, which can be a sign of a worse prognosis.

“The strongest clinical predictors of advanced liver fibrosis are ferritin higher than 1000 [µg/L] and the presence of arthropathy [joint disease],” he said. “If both are absent and the patient is asymptomatic, there is no need for further investigation. If both are present, further investigation — including cardiac MRI and full endocrine profile — are indicated. Liver biopsy may be indicated only in uncertain cases.”

Fortunately, “most patients are diagnosed in preclinical or early stage, and their prognosis is excellent, with a normal life expectancy,” he said 

Phlebotomy remains the standard of care for hemochromatosis in uncomplicated cases. “It is safe, cheap, well-tolerated, and significantly reduces mortality and morbidity, especially when it is started before the development of cirrhosis,” he said. 

 

Family Members Should Be Tested for Genetic Traits

It’s important to advise patients prior to phlebotomy to avoid undercooked seafood and wound contact with sea water because of the risk for sepsis due to the pathogen Vibrio vulnificus, Girelli said. 

And it’s a good idea to test family members to see if they share a genetic risk for hemochromatosis, he said. The 56-year-old patient’s brother turned out to also have genetic risk, and his iron levels were very high. He had recently been diagnosed with seronegative arthritis that could be classified as secondary to hemochromatosis.

For management, Girelli said, patients should minimize or avoid alcohol consumption, eat a healthy diet, and avoid vitamin C and iron supplements even in multivitamin compounds. Patients should be encouraged to exercise and maintain an ideal weight. 

The 56-year-old patient fared well, reaching a ferritin target of 50 mg/mL after multiple phlebotomy procedures that removed nearly 5 g of iron.

The patient tolerated the treatment and his fatigue resolved, Girelli said. “The maintenance treatment consisted of 3 phlebotomies per year. The patient remained asymptomatic and was eventually enrolled as a regular blood donor.”

Karp Leaf disclosed relationships with Alnylam, Recordati, and Disc Medicine. She is a member of the Porphyrias Consortium, part of the Rare Diseases Clinical Research Network, funded by the National Institutes of Health and led by the National Center for Advancing Translational Sciences (NCATS). The consortium is funded by NCATS and the National Institute of Diabetes and Digestive and Kidney Diseases. Girelli had no disclosures.

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

One patient, a 39-year-old woman, went to a dermatologist seeking care for fluid-filled blisters over the backs of her hands and arms. Another patient, a 56-year-old man, sought care from his general practitioner owing to fatigue.

Their presentations were quite different, but the two patients shared one thing in common: iron overload. Both ended up in the care of hematologists who diagnosed their conditions as porphyria cutanea tarda (PCT) and hemochromatosis, respectively.

A pair of hematologists discussed the treatment of these disorders at the American Society of Hematology (ASH) 2024 Annual Meeting and in reports in Hematology: American Society of Hematology Education Program. Here’s a look at the guidance they provided.

 

Porphyria Cutanea Tarda: Skin Trouble

Testing revealed that the female patient had a highly elevated porphyrin levels: Her urine uroporphyrin was 3959  nmol/L (normal, < 30 nmol/L) and plasma uroporphyrin was 2.0 µg/dL (normal, < 1.0  µg/dL). Her serum ferritin level was also high, at 420 ng/mL (normal, < 200 ng/mL).

Rebecca Karp Leaf, MD, of Massachusetts General Hospital and Harvard Medical School, diagnosed her with PCT, a disorder of heme biosynthesis that often presents with skin manifestations.

As co-founder and co-director of the Boston hospital’s Porphyria Center, Karp Leaf is a leading expert in PCT, a rare disease that affects 5-10 people per 100,000. In addition to speaking at the ASH meeting in December, she described PCT in a December 2024 article in Hematology: American Society of Hematology Education Program. 

PCT is caused by inhibition of an enzyme in heme biosynthesis and leads to accumulation of porphyrins in the liver and plasma, Karp Leaf said. Through a complex process, excess of iron leads to inhibition of the enzyme, which leads to a buildup of toxic porphyrins, she said. The condition causes painless, blistering lesions on sun-exposed skin, scarring, skin fragility, dark urine, and liver disease. 

PCT most commonly occurs in middle age after the age of 40 and affects men more than women. “It’s the only porphyria that can occur absent a genetic variant,” she said, and 75% of cases have no genetic component. 

 

Options for Treatment Include Antivirals and Phlebotomy

Risk factors for PCT include alcohol use, smoking, exogenous estrogen, hepatitis, and HIV mutations. 

In regard to treatment, “modification of risk factors can be variably helpful: alcohol and smoking cessation, stopping exogenous estrogen, sun-protective clothing, and steroid-containing creams for lesions,” Karp Leaf said. “Most patients typically require further therapy to reduce liver porphyrins.”

Urine and plasma tests can help with diagnosis, she said. In patients with hepatitis C (HCV), “direct-acting antivirals can actually lead to resolution of PCT without any other therapy. We suspect that with effective antiviral treatment for HCV, the incidence of PCT will really go down.”

Therapeutic phlebotomy — blood removal — is another option. “It’s one of my favorite therapies because you don’t have to give somebody a drug. You can just take out iron,” Karp Leaf said. “Typically, we’ll start with venesection of 450 ccs of whole blood every 2 weeks, We target a ferritin level of 20 [ng/mL] but permit it up to 50 [ng/mL], or a little bit higher.”

The treatment leads to resolution of blisters in about 2-3 months, she said, and normalization of porphyrins by 13 months. Patients typically require about 6-8 treatments, she said. 

Another option is iron chelation, iron removal via medicine, “but it’s expensive, has side effects, and is really not recommended if other treatments are available,” she said. 

 

Hydroxychloroquine Can Be Helpful Too

Low-dose hydroxychloroquine can also be effective at 100 mg twice a week, “much lower than what we use in autoimmune disease,” Karp Leaf said. “We suspect that it’s taken up by the hepatic lysosomes and causes release of porphyrins. It causes clinical remission in about 6 months.”

However, higher doses can lead to liver injury, and the drug’s use is limited in end-stage kidney disease since porphyrins are excreted in the urine. These patients are especially difficult to treat, she said.

In the case of the 39-year-old patient, Karp Leaf recommended that the woman reduce her alcohol intake and begin using a copper intrauterine device for contraception instead of a combined oral contraceptive pill, which allowed her to undergo phlebotomy.

“She needed about eight sessions of therapeutic phlebotomy to achieve a ferritin of 30 [ng/mL], and her lesions resolved in 6 months,” Karp Leaf said. “Her plasma porphyrins resolved by 12 months. Her liver biochemistries were a bit elevated, and they subsequently normalized.”

Karp Leaf said she sees the patient about once a year. 

 

Hemochromatosis: It’s (Probably) a Family Affair

In an adjoining presentation at ASH and in a December 2024 article in Hematology: American Society of Hematology Education Program, hematologist Domenico Girelli, MD, PhD, with the University of Verona, Italy, told colleagues about the 56-year-old male patient with fatigue. He also had a mildly enlarged liver, hyperferritinemia (890  µg/L vs normal value < 300 µg/L) and a mildly increased alanine aminotransferase level (46 U/L vs normal value < 40 U/L).

The patient was diagnosed with hemochromatosis, a genetic disorder caused by mutations that leads to increased transferrin saturation, Girelli said. 

“By definition, hemochromatosis is characterized by the absence of signs of a primary red blood cell disorder — different from other disorders like transfusion iron overload or iron-loading anemias,” he said. 

It’s also important to consider other possible causes of hyperferritinemia, because most cases of the symptom aren’t related to iron overload, he said. “A careful clinical history and a few laboratory parameters including transferrin saturation are generally sufficient for the differential diagnosis.”

As Girelli noted, “hemochromatosis can have a wide clinical spectrum ranging from mild to severe forms, which are strongly influenced by the co-presence of risk factors like alcohol [use], blood transfusion, and genetic factors captured by polygenic risk score.”

 

In Many Cases, Hemochromatosis Can Be Successfully Treated

According to Girelli, it’s important to understand the disease stage, because this information can predict the probability of advanced liver fibrosis, which can be a sign of a worse prognosis.

“The strongest clinical predictors of advanced liver fibrosis are ferritin higher than 1000 [µg/L] and the presence of arthropathy [joint disease],” he said. “If both are absent and the patient is asymptomatic, there is no need for further investigation. If both are present, further investigation — including cardiac MRI and full endocrine profile — are indicated. Liver biopsy may be indicated only in uncertain cases.”

Fortunately, “most patients are diagnosed in preclinical or early stage, and their prognosis is excellent, with a normal life expectancy,” he said 

Phlebotomy remains the standard of care for hemochromatosis in uncomplicated cases. “It is safe, cheap, well-tolerated, and significantly reduces mortality and morbidity, especially when it is started before the development of cirrhosis,” he said. 

 

Family Members Should Be Tested for Genetic Traits

It’s important to advise patients prior to phlebotomy to avoid undercooked seafood and wound contact with sea water because of the risk for sepsis due to the pathogen Vibrio vulnificus, Girelli said. 

And it’s a good idea to test family members to see if they share a genetic risk for hemochromatosis, he said. The 56-year-old patient’s brother turned out to also have genetic risk, and his iron levels were very high. He had recently been diagnosed with seronegative arthritis that could be classified as secondary to hemochromatosis.

For management, Girelli said, patients should minimize or avoid alcohol consumption, eat a healthy diet, and avoid vitamin C and iron supplements even in multivitamin compounds. Patients should be encouraged to exercise and maintain an ideal weight. 

The 56-year-old patient fared well, reaching a ferritin target of 50 mg/mL after multiple phlebotomy procedures that removed nearly 5 g of iron.

The patient tolerated the treatment and his fatigue resolved, Girelli said. “The maintenance treatment consisted of 3 phlebotomies per year. The patient remained asymptomatic and was eventually enrolled as a regular blood donor.”

Karp Leaf disclosed relationships with Alnylam, Recordati, and Disc Medicine. She is a member of the Porphyrias Consortium, part of the Rare Diseases Clinical Research Network, funded by the National Institutes of Health and led by the National Center for Advancing Translational Sciences (NCATS). The consortium is funded by NCATS and the National Institute of Diabetes and Digestive and Kidney Diseases. Girelli had no disclosures.

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

One patient, a 39-year-old woman, went to a dermatologist seeking care for fluid-filled blisters over the backs of her hands and arms. Another patient, a 56-year-old man, sought care from his general practitioner owing to fatigue.

Their presentations were quite different, but the two patients shared one thing in common: iron overload. Both ended up in the care of hematologists who diagnosed their conditions as porphyria cutanea tarda (PCT) and hemochromatosis, respectively.

A pair of hematologists discussed the treatment of these disorders at the American Society of Hematology (ASH) 2024 Annual Meeting and in reports in Hematology: American Society of Hematology Education Program. Here’s a look at the guidance they provided.

 

Porphyria Cutanea Tarda: Skin Trouble

Testing revealed that the female patient had a highly elevated porphyrin levels: Her urine uroporphyrin was 3959  nmol/L (normal, < 30 nmol/L) and plasma uroporphyrin was 2.0 µg/dL (normal, < 1.0  µg/dL). Her serum ferritin level was also high, at 420 ng/mL (normal, < 200 ng/mL).

Rebecca Karp Leaf, MD, of Massachusetts General Hospital and Harvard Medical School, diagnosed her with PCT, a disorder of heme biosynthesis that often presents with skin manifestations.

As co-founder and co-director of the Boston hospital’s Porphyria Center, Karp Leaf is a leading expert in PCT, a rare disease that affects 5-10 people per 100,000. In addition to speaking at the ASH meeting in December, she described PCT in a December 2024 article in Hematology: American Society of Hematology Education Program. 

PCT is caused by inhibition of an enzyme in heme biosynthesis and leads to accumulation of porphyrins in the liver and plasma, Karp Leaf said. Through a complex process, excess of iron leads to inhibition of the enzyme, which leads to a buildup of toxic porphyrins, she said. The condition causes painless, blistering lesions on sun-exposed skin, scarring, skin fragility, dark urine, and liver disease. 

PCT most commonly occurs in middle age after the age of 40 and affects men more than women. “It’s the only porphyria that can occur absent a genetic variant,” she said, and 75% of cases have no genetic component. 

 

Options for Treatment Include Antivirals and Phlebotomy

Risk factors for PCT include alcohol use, smoking, exogenous estrogen, hepatitis, and HIV mutations. 

In regard to treatment, “modification of risk factors can be variably helpful: alcohol and smoking cessation, stopping exogenous estrogen, sun-protective clothing, and steroid-containing creams for lesions,” Karp Leaf said. “Most patients typically require further therapy to reduce liver porphyrins.”

Urine and plasma tests can help with diagnosis, she said. In patients with hepatitis C (HCV), “direct-acting antivirals can actually lead to resolution of PCT without any other therapy. We suspect that with effective antiviral treatment for HCV, the incidence of PCT will really go down.”

Therapeutic phlebotomy — blood removal — is another option. “It’s one of my favorite therapies because you don’t have to give somebody a drug. You can just take out iron,” Karp Leaf said. “Typically, we’ll start with venesection of 450 ccs of whole blood every 2 weeks, We target a ferritin level of 20 [ng/mL] but permit it up to 50 [ng/mL], or a little bit higher.”

The treatment leads to resolution of blisters in about 2-3 months, she said, and normalization of porphyrins by 13 months. Patients typically require about 6-8 treatments, she said. 

Another option is iron chelation, iron removal via medicine, “but it’s expensive, has side effects, and is really not recommended if other treatments are available,” she said. 

 

Hydroxychloroquine Can Be Helpful Too

Low-dose hydroxychloroquine can also be effective at 100 mg twice a week, “much lower than what we use in autoimmune disease,” Karp Leaf said. “We suspect that it’s taken up by the hepatic lysosomes and causes release of porphyrins. It causes clinical remission in about 6 months.”

However, higher doses can lead to liver injury, and the drug’s use is limited in end-stage kidney disease since porphyrins are excreted in the urine. These patients are especially difficult to treat, she said.

In the case of the 39-year-old patient, Karp Leaf recommended that the woman reduce her alcohol intake and begin using a copper intrauterine device for contraception instead of a combined oral contraceptive pill, which allowed her to undergo phlebotomy.

“She needed about eight sessions of therapeutic phlebotomy to achieve a ferritin of 30 [ng/mL], and her lesions resolved in 6 months,” Karp Leaf said. “Her plasma porphyrins resolved by 12 months. Her liver biochemistries were a bit elevated, and they subsequently normalized.”

Karp Leaf said she sees the patient about once a year. 

 

Hemochromatosis: It’s (Probably) a Family Affair

In an adjoining presentation at ASH and in a December 2024 article in Hematology: American Society of Hematology Education Program, hematologist Domenico Girelli, MD, PhD, with the University of Verona, Italy, told colleagues about the 56-year-old male patient with fatigue. He also had a mildly enlarged liver, hyperferritinemia (890  µg/L vs normal value < 300 µg/L) and a mildly increased alanine aminotransferase level (46 U/L vs normal value < 40 U/L).

The patient was diagnosed with hemochromatosis, a genetic disorder caused by mutations that leads to increased transferrin saturation, Girelli said. 

“By definition, hemochromatosis is characterized by the absence of signs of a primary red blood cell disorder — different from other disorders like transfusion iron overload or iron-loading anemias,” he said. 

It’s also important to consider other possible causes of hyperferritinemia, because most cases of the symptom aren’t related to iron overload, he said. “A careful clinical history and a few laboratory parameters including transferrin saturation are generally sufficient for the differential diagnosis.”

As Girelli noted, “hemochromatosis can have a wide clinical spectrum ranging from mild to severe forms, which are strongly influenced by the co-presence of risk factors like alcohol [use], blood transfusion, and genetic factors captured by polygenic risk score.”

 

In Many Cases, Hemochromatosis Can Be Successfully Treated

According to Girelli, it’s important to understand the disease stage, because this information can predict the probability of advanced liver fibrosis, which can be a sign of a worse prognosis.

“The strongest clinical predictors of advanced liver fibrosis are ferritin higher than 1000 [µg/L] and the presence of arthropathy [joint disease],” he said. “If both are absent and the patient is asymptomatic, there is no need for further investigation. If both are present, further investigation — including cardiac MRI and full endocrine profile — are indicated. Liver biopsy may be indicated only in uncertain cases.”

Fortunately, “most patients are diagnosed in preclinical or early stage, and their prognosis is excellent, with a normal life expectancy,” he said 

Phlebotomy remains the standard of care for hemochromatosis in uncomplicated cases. “It is safe, cheap, well-tolerated, and significantly reduces mortality and morbidity, especially when it is started before the development of cirrhosis,” he said. 

 

Family Members Should Be Tested for Genetic Traits

It’s important to advise patients prior to phlebotomy to avoid undercooked seafood and wound contact with sea water because of the risk for sepsis due to the pathogen Vibrio vulnificus, Girelli said. 

And it’s a good idea to test family members to see if they share a genetic risk for hemochromatosis, he said. The 56-year-old patient’s brother turned out to also have genetic risk, and his iron levels were very high. He had recently been diagnosed with seronegative arthritis that could be classified as secondary to hemochromatosis.

For management, Girelli said, patients should minimize or avoid alcohol consumption, eat a healthy diet, and avoid vitamin C and iron supplements even in multivitamin compounds. Patients should be encouraged to exercise and maintain an ideal weight. 

The 56-year-old patient fared well, reaching a ferritin target of 50 mg/mL after multiple phlebotomy procedures that removed nearly 5 g of iron.

The patient tolerated the treatment and his fatigue resolved, Girelli said. “The maintenance treatment consisted of 3 phlebotomies per year. The patient remained asymptomatic and was eventually enrolled as a regular blood donor.”

Karp Leaf disclosed relationships with Alnylam, Recordati, and Disc Medicine. She is a member of the Porphyrias Consortium, part of the Rare Diseases Clinical Research Network, funded by the National Institutes of Health and led by the National Center for Advancing Translational Sciences (NCATS). The consortium is funded by NCATS and the National Institute of Diabetes and Digestive and Kidney Diseases. Girelli had no disclosures.

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

A noninvasive clinicopathologic and gene expression profiling (CP-GEP)–based tool, the Merlin assay, shows promise for identifying recurrence risks in patients with early-stage melanoma who do not undergo sentinel lymph node biopsy (SNLB).

This was the conclusion of a retrospective analysis of a large cohort of patients with stage I/II disease, reported by Teresa Amaral, MD, PhD, at the 11th World Congress of Melanoma and 21st European Association of Dermato-Oncology Congress 2025.

Of 930 patients included in the study, the assay identified 879 as having a low risk for recurrence and 51 as having high risk for recurrence. The overall 5-year recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and melanoma-specific survival (MSS) rates were 90.9%, 96.9%, and 97.5%, respectively.

The corresponding rates among those stratified by the assay as having low vs high recurrence risk, respectively, were 94.6% and 26.6% for RFS (hazard ratio [HR], 25.08), 98.6% vs 62.1% for DMFS (HR, 35.39), and 99.4% vs 61.7% for MSS (HR, 71.05), said Amaral, during her presentation at the meeting.

Of 16 melanoma-specific deaths, 12 were stratified as high risk for recurrence by the CP-GEP assay, said Amaral, head of the Skin Cancer Clinical Trials Center at the University of Tübingen, Tübingen, Germany, and first author of the study.

Study participants had stages IA-IIC melanoma, 41% were women, and median age was 64 years. Median melanoma thickness was 0.5 mm, and 94% were not ulcerated. 

No systemic treatment options currently exist for patients with this early-stage disease, the author said.

The CP-GEP model, initially developed by the Mayo Clinic and SkylineDx BV to predict the positivity of SNLB, has been validated in multiple studies.

Amaral and her colleagues previously demonstrated the ability of the CP-GEP model to stratify patients with stages I-II disease as having low or high risk for recurrence — including in a small number of patients without SNLB. Those findings are confirmed in this larger population of patients who did not undergo SNLB, she said.

SkylineDx announced the findings in a press release stating the results validate the prognostic power of the Merlin assay for “identifying tumors at high risk for relapse that would otherwise be missed by traditional clinical and pathological evaluation.”

SNLB is the gold standard for nodal assessment for staging cutaneous melanoma. More than 80% of patients who undergo SNLB are negative for nodal metastases, but most patients who relapse or die from their melanoma are initially stratified by SNLB as having low-risk early-stage disease, Amaral explained. This suggests “SNLB is not enough,” she noted.

The findings suggest that CP-GEP has the potential to risk stratify patients with early-stage melanoma that did not undergo SLNB and help select those who can forgo SLNB, she said.

Without another means of assessing risk, patients considered low risk based on SNLB are closely followed, the author explained.

“If we could identify the very low-risk patient and then allocate the resources to the very high-risk patients who really need a more detailed and more tailored approach…we would be doing a favor to our patients,” the author concluded.

Amaral disclosed personal financial relationships with Delcath, Philogen, Bristol Myers Squibb, NeraCare, Novartis, Pierre Fabre, CeCaVa, and MedTrix.

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

A noninvasive clinicopathologic and gene expression profiling (CP-GEP)–based tool, the Merlin assay, shows promise for identifying recurrence risks in patients with early-stage melanoma who do not undergo sentinel lymph node biopsy (SNLB).

This was the conclusion of a retrospective analysis of a large cohort of patients with stage I/II disease, reported by Teresa Amaral, MD, PhD, at the 11th World Congress of Melanoma and 21st European Association of Dermato-Oncology Congress 2025.

Of 930 patients included in the study, the assay identified 879 as having a low risk for recurrence and 51 as having high risk for recurrence. The overall 5-year recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and melanoma-specific survival (MSS) rates were 90.9%, 96.9%, and 97.5%, respectively.

The corresponding rates among those stratified by the assay as having low vs high recurrence risk, respectively, were 94.6% and 26.6% for RFS (hazard ratio [HR], 25.08), 98.6% vs 62.1% for DMFS (HR, 35.39), and 99.4% vs 61.7% for MSS (HR, 71.05), said Amaral, during her presentation at the meeting.

Of 16 melanoma-specific deaths, 12 were stratified as high risk for recurrence by the CP-GEP assay, said Amaral, head of the Skin Cancer Clinical Trials Center at the University of Tübingen, Tübingen, Germany, and first author of the study.

Study participants had stages IA-IIC melanoma, 41% were women, and median age was 64 years. Median melanoma thickness was 0.5 mm, and 94% were not ulcerated. 

No systemic treatment options currently exist for patients with this early-stage disease, the author said.

The CP-GEP model, initially developed by the Mayo Clinic and SkylineDx BV to predict the positivity of SNLB, has been validated in multiple studies.

Amaral and her colleagues previously demonstrated the ability of the CP-GEP model to stratify patients with stages I-II disease as having low or high risk for recurrence — including in a small number of patients without SNLB. Those findings are confirmed in this larger population of patients who did not undergo SNLB, she said.

SkylineDx announced the findings in a press release stating the results validate the prognostic power of the Merlin assay for “identifying tumors at high risk for relapse that would otherwise be missed by traditional clinical and pathological evaluation.”

SNLB is the gold standard for nodal assessment for staging cutaneous melanoma. More than 80% of patients who undergo SNLB are negative for nodal metastases, but most patients who relapse or die from their melanoma are initially stratified by SNLB as having low-risk early-stage disease, Amaral explained. This suggests “SNLB is not enough,” she noted.

The findings suggest that CP-GEP has the potential to risk stratify patients with early-stage melanoma that did not undergo SLNB and help select those who can forgo SLNB, she said.

Without another means of assessing risk, patients considered low risk based on SNLB are closely followed, the author explained.

“If we could identify the very low-risk patient and then allocate the resources to the very high-risk patients who really need a more detailed and more tailored approach…we would be doing a favor to our patients,” the author concluded.

Amaral disclosed personal financial relationships with Delcath, Philogen, Bristol Myers Squibb, NeraCare, Novartis, Pierre Fabre, CeCaVa, and MedTrix.

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

A noninvasive clinicopathologic and gene expression profiling (CP-GEP)–based tool, the Merlin assay, shows promise for identifying recurrence risks in patients with early-stage melanoma who do not undergo sentinel lymph node biopsy (SNLB).

This was the conclusion of a retrospective analysis of a large cohort of patients with stage I/II disease, reported by Teresa Amaral, MD, PhD, at the 11th World Congress of Melanoma and 21st European Association of Dermato-Oncology Congress 2025.

Of 930 patients included in the study, the assay identified 879 as having a low risk for recurrence and 51 as having high risk for recurrence. The overall 5-year recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and melanoma-specific survival (MSS) rates were 90.9%, 96.9%, and 97.5%, respectively.

The corresponding rates among those stratified by the assay as having low vs high recurrence risk, respectively, were 94.6% and 26.6% for RFS (hazard ratio [HR], 25.08), 98.6% vs 62.1% for DMFS (HR, 35.39), and 99.4% vs 61.7% for MSS (HR, 71.05), said Amaral, during her presentation at the meeting.

Of 16 melanoma-specific deaths, 12 were stratified as high risk for recurrence by the CP-GEP assay, said Amaral, head of the Skin Cancer Clinical Trials Center at the University of Tübingen, Tübingen, Germany, and first author of the study.

Study participants had stages IA-IIC melanoma, 41% were women, and median age was 64 years. Median melanoma thickness was 0.5 mm, and 94% were not ulcerated. 

No systemic treatment options currently exist for patients with this early-stage disease, the author said.

The CP-GEP model, initially developed by the Mayo Clinic and SkylineDx BV to predict the positivity of SNLB, has been validated in multiple studies.

Amaral and her colleagues previously demonstrated the ability of the CP-GEP model to stratify patients with stages I-II disease as having low or high risk for recurrence — including in a small number of patients without SNLB. Those findings are confirmed in this larger population of patients who did not undergo SNLB, she said.

SkylineDx announced the findings in a press release stating the results validate the prognostic power of the Merlin assay for “identifying tumors at high risk for relapse that would otherwise be missed by traditional clinical and pathological evaluation.”

SNLB is the gold standard for nodal assessment for staging cutaneous melanoma. More than 80% of patients who undergo SNLB are negative for nodal metastases, but most patients who relapse or die from their melanoma are initially stratified by SNLB as having low-risk early-stage disease, Amaral explained. This suggests “SNLB is not enough,” she noted.

The findings suggest that CP-GEP has the potential to risk stratify patients with early-stage melanoma that did not undergo SLNB and help select those who can forgo SLNB, she said.

Without another means of assessing risk, patients considered low risk based on SNLB are closely followed, the author explained.

“If we could identify the very low-risk patient and then allocate the resources to the very high-risk patients who really need a more detailed and more tailored approach…we would be doing a favor to our patients,” the author concluded.

Amaral disclosed personal financial relationships with Delcath, Philogen, Bristol Myers Squibb, NeraCare, Novartis, Pierre Fabre, CeCaVa, and MedTrix.

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