AVAHO

To date, men undergoing screening through the measurement of prostate-specific antigen (PSA) levels have had a significant reduction in neoplastic mortality. Because of its low specificity, however, this practice often leads to frequent, unnecessary, invasive biopsies and the diagnosis of low-grade, indolent cancer. While guided biopsies with multiparametric MRI can improve the diagnosis of grade 2 prostate cancers, widespread implementation remains challenging. The use of noninvasive biomarkers to stratify the risk for prostate cancer may be a more practical option.

The National Comprehensive Cancer Network proposes a test consisting of six blood and urine biomarkers for all grades of prostate cancer, and it outperforms PSA testing. However, current practice focuses on detecting high-grade cancers. It has been hypothesized that increasing the number of biomarkers by including molecules specifically expressed in aggressive high-grade prostate cancers could improve test accuracy. Based on the identification of new genes that are overexpressed in high-grade cancers, a polymerase chain reaction (PCR) technique targeting 54 candidate markers was used to develop an optimal 18-gene test that could be used before imaging (with MRI) and biopsy and to assess whether the latter procedures are warranted.
 

Development Cohort

In the development cohort (n = 815; median age, 63 years), quantitative PCR (qPCR) analysis of the 54 candidate genes was performed on urine samples that had been prospectively collected before biopsy following a digital rectal examination. Patients with previously diagnosed prostate cancer, abnormal MRI results, and those who had already undergone a prostate biopsy were excluded. Participants’ PSA levels ranged from 3 to 10 ng/mL (median interquartile range [IQR], 5.6 [4.6-7.2] ng/mL). Valid qPCR results were obtained from 761 participants (93.4%). Subsequently, prostate biopsy revealed grade 2 or higher cancer in 293 participants (38.5%).

Thus, a urine test called MyProstateScore 2.0 (MPSA) was developed, with two formulations: MPSA2 and MPSA2+, depending on whether a prostate volume was considered. The final MPSA2 development model included clinical data and 17 of the most informative markers, including nine specific to cancer, which were associated with the KLK3 reference gene.
 

Validation and Analyses

The external validation cohort (n = 813) consisted of participants in the NCI EDRN PCA3 Evaluation trial. Valid qPCR results were obtained from 743 participants, of whom 151 (20.3%) were found to have high-grade prostate cancer.

The median MPS2 score was higher in patients with grade 2 or higher prostate cancer (0.44; IQR, 0.23-0.69) than in those with noncontributory biopsies (0.08; IQR, 0.03-0.19; P < .001) or grade 1 cancer (0.25; IQR, 0.09-0.48; P < .01).

Comparative analyses included PSA, the Prostate Cancer Prevention Trial risk calculator, the Prostate Health Index (PHI), and various previous genetic models. Decision curve analyses quantified the benefit of each biomarker studied. The 151 participants with high-grade prostate cancer had operating curve values ranging from 0.60 for PSA alone to 0.77 for PHI and 0.76 for a two-gene multiplex model. The MPSA model had values of 0.81 and 0.82 for MPSA2+. For a required sensitivity of 95%, the MPS2 model could reduce the rate of unnecessary initial biopsies in the population by 35%-42%, with an impact of 15%-30% for other tests. Among the subgroups analyzed, MPS2 models showed negative predictive values of 95%-99% for grade 2 or higher prostate cancers and 99% for grade 3 or higher tumors.
 

MPS2 and Competitors

Existing biomarkers have reduced selectivity in detecting high-grade prostate tumors. This lower performance has led to the development of a new urine test including, for the first time, markers specifically overexpressed in high-grade prostate cancer. This new MPS2 test has a sensitivity of 95% for high-grade prostate cancer and a specificity ranging from 35% to 51%, depending on the subgroups. For clinicians, widespread use of MPS2 could greatly reduce the number of unnecessary biopsies while maintaining a high detection rate of grade 2 or higher prostate cancer.

Among patients who have had a negative first biopsy, MPS2 would have a sensitivity of 94.4% and a specificity of 51%, which is much higher than other tests like prostate cancer antigen 3 gene, three-gene model, and MPS. In addition, in patients with grade 1 prostate cancer, urinary markers for high-grade cancer could indicate the existence of a more aggressive tumor requiring increased monitoring.

This study has limitations, however. The ethnic diversity of its population was limited. A few Black men were included, for example. Second, a systematic biopsy was used as the reference, which can increase negative predictive value and decrease positive predictive value. Classification errors may have occurred. Therefore, further studies are needed to confirm these initial results and the long-term positive impact of using MPS2.

In conclusion, an 18-gene urine test seems to be more relevant for diagnosing high-grade prostate cancer than existing tests. It could prevent additional imaging or biopsy examinations in 35%-41% of patients. Therefore, the use of such tests in patients with high PSA levels could reduce the potential risks associated with prostate cancer screening while preserving its long-term benefits.

This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

To date, men undergoing screening through the measurement of prostate-specific antigen (PSA) levels have had a significant reduction in neoplastic mortality. Because of its low specificity, however, this practice often leads to frequent, unnecessary, invasive biopsies and the diagnosis of low-grade, indolent cancer. While guided biopsies with multiparametric MRI can improve the diagnosis of grade 2 prostate cancers, widespread implementation remains challenging. The use of noninvasive biomarkers to stratify the risk for prostate cancer may be a more practical option.

The National Comprehensive Cancer Network proposes a test consisting of six blood and urine biomarkers for all grades of prostate cancer, and it outperforms PSA testing. However, current practice focuses on detecting high-grade cancers. It has been hypothesized that increasing the number of biomarkers by including molecules specifically expressed in aggressive high-grade prostate cancers could improve test accuracy. Based on the identification of new genes that are overexpressed in high-grade cancers, a polymerase chain reaction (PCR) technique targeting 54 candidate markers was used to develop an optimal 18-gene test that could be used before imaging (with MRI) and biopsy and to assess whether the latter procedures are warranted.
 

Development Cohort

In the development cohort (n = 815; median age, 63 years), quantitative PCR (qPCR) analysis of the 54 candidate genes was performed on urine samples that had been prospectively collected before biopsy following a digital rectal examination. Patients with previously diagnosed prostate cancer, abnormal MRI results, and those who had already undergone a prostate biopsy were excluded. Participants’ PSA levels ranged from 3 to 10 ng/mL (median interquartile range [IQR], 5.6 [4.6-7.2] ng/mL). Valid qPCR results were obtained from 761 participants (93.4%). Subsequently, prostate biopsy revealed grade 2 or higher cancer in 293 participants (38.5%).

Thus, a urine test called MyProstateScore 2.0 (MPSA) was developed, with two formulations: MPSA2 and MPSA2+, depending on whether a prostate volume was considered. The final MPSA2 development model included clinical data and 17 of the most informative markers, including nine specific to cancer, which were associated with the KLK3 reference gene.
 

Validation and Analyses

The external validation cohort (n = 813) consisted of participants in the NCI EDRN PCA3 Evaluation trial. Valid qPCR results were obtained from 743 participants, of whom 151 (20.3%) were found to have high-grade prostate cancer.

The median MPS2 score was higher in patients with grade 2 or higher prostate cancer (0.44; IQR, 0.23-0.69) than in those with noncontributory biopsies (0.08; IQR, 0.03-0.19; P < .001) or grade 1 cancer (0.25; IQR, 0.09-0.48; P < .01).

Comparative analyses included PSA, the Prostate Cancer Prevention Trial risk calculator, the Prostate Health Index (PHI), and various previous genetic models. Decision curve analyses quantified the benefit of each biomarker studied. The 151 participants with high-grade prostate cancer had operating curve values ranging from 0.60 for PSA alone to 0.77 for PHI and 0.76 for a two-gene multiplex model. The MPSA model had values of 0.81 and 0.82 for MPSA2+. For a required sensitivity of 95%, the MPS2 model could reduce the rate of unnecessary initial biopsies in the population by 35%-42%, with an impact of 15%-30% for other tests. Among the subgroups analyzed, MPS2 models showed negative predictive values of 95%-99% for grade 2 or higher prostate cancers and 99% for grade 3 or higher tumors.
 

MPS2 and Competitors

Existing biomarkers have reduced selectivity in detecting high-grade prostate tumors. This lower performance has led to the development of a new urine test including, for the first time, markers specifically overexpressed in high-grade prostate cancer. This new MPS2 test has a sensitivity of 95% for high-grade prostate cancer and a specificity ranging from 35% to 51%, depending on the subgroups. For clinicians, widespread use of MPS2 could greatly reduce the number of unnecessary biopsies while maintaining a high detection rate of grade 2 or higher prostate cancer.

Among patients who have had a negative first biopsy, MPS2 would have a sensitivity of 94.4% and a specificity of 51%, which is much higher than other tests like prostate cancer antigen 3 gene, three-gene model, and MPS. In addition, in patients with grade 1 prostate cancer, urinary markers for high-grade cancer could indicate the existence of a more aggressive tumor requiring increased monitoring.

This study has limitations, however. The ethnic diversity of its population was limited. A few Black men were included, for example. Second, a systematic biopsy was used as the reference, which can increase negative predictive value and decrease positive predictive value. Classification errors may have occurred. Therefore, further studies are needed to confirm these initial results and the long-term positive impact of using MPS2.

In conclusion, an 18-gene urine test seems to be more relevant for diagnosing high-grade prostate cancer than existing tests. It could prevent additional imaging or biopsy examinations in 35%-41% of patients. Therefore, the use of such tests in patients with high PSA levels could reduce the potential risks associated with prostate cancer screening while preserving its long-term benefits.

This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

To date, men undergoing screening through the measurement of prostate-specific antigen (PSA) levels have had a significant reduction in neoplastic mortality. Because of its low specificity, however, this practice often leads to frequent, unnecessary, invasive biopsies and the diagnosis of low-grade, indolent cancer. While guided biopsies with multiparametric MRI can improve the diagnosis of grade 2 prostate cancers, widespread implementation remains challenging. The use of noninvasive biomarkers to stratify the risk for prostate cancer may be a more practical option.

The National Comprehensive Cancer Network proposes a test consisting of six blood and urine biomarkers for all grades of prostate cancer, and it outperforms PSA testing. However, current practice focuses on detecting high-grade cancers. It has been hypothesized that increasing the number of biomarkers by including molecules specifically expressed in aggressive high-grade prostate cancers could improve test accuracy. Based on the identification of new genes that are overexpressed in high-grade cancers, a polymerase chain reaction (PCR) technique targeting 54 candidate markers was used to develop an optimal 18-gene test that could be used before imaging (with MRI) and biopsy and to assess whether the latter procedures are warranted.
 

Development Cohort

In the development cohort (n = 815; median age, 63 years), quantitative PCR (qPCR) analysis of the 54 candidate genes was performed on urine samples that had been prospectively collected before biopsy following a digital rectal examination. Patients with previously diagnosed prostate cancer, abnormal MRI results, and those who had already undergone a prostate biopsy were excluded. Participants’ PSA levels ranged from 3 to 10 ng/mL (median interquartile range [IQR], 5.6 [4.6-7.2] ng/mL). Valid qPCR results were obtained from 761 participants (93.4%). Subsequently, prostate biopsy revealed grade 2 or higher cancer in 293 participants (38.5%).

Thus, a urine test called MyProstateScore 2.0 (MPSA) was developed, with two formulations: MPSA2 and MPSA2+, depending on whether a prostate volume was considered. The final MPSA2 development model included clinical data and 17 of the most informative markers, including nine specific to cancer, which were associated with the KLK3 reference gene.
 

Validation and Analyses

The external validation cohort (n = 813) consisted of participants in the NCI EDRN PCA3 Evaluation trial. Valid qPCR results were obtained from 743 participants, of whom 151 (20.3%) were found to have high-grade prostate cancer.

The median MPS2 score was higher in patients with grade 2 or higher prostate cancer (0.44; IQR, 0.23-0.69) than in those with noncontributory biopsies (0.08; IQR, 0.03-0.19; P < .001) or grade 1 cancer (0.25; IQR, 0.09-0.48; P < .01).

Comparative analyses included PSA, the Prostate Cancer Prevention Trial risk calculator, the Prostate Health Index (PHI), and various previous genetic models. Decision curve analyses quantified the benefit of each biomarker studied. The 151 participants with high-grade prostate cancer had operating curve values ranging from 0.60 for PSA alone to 0.77 for PHI and 0.76 for a two-gene multiplex model. The MPSA model had values of 0.81 and 0.82 for MPSA2+. For a required sensitivity of 95%, the MPS2 model could reduce the rate of unnecessary initial biopsies in the population by 35%-42%, with an impact of 15%-30% for other tests. Among the subgroups analyzed, MPS2 models showed negative predictive values of 95%-99% for grade 2 or higher prostate cancers and 99% for grade 3 or higher tumors.
 

MPS2 and Competitors

Existing biomarkers have reduced selectivity in detecting high-grade prostate tumors. This lower performance has led to the development of a new urine test including, for the first time, markers specifically overexpressed in high-grade prostate cancer. This new MPS2 test has a sensitivity of 95% for high-grade prostate cancer and a specificity ranging from 35% to 51%, depending on the subgroups. For clinicians, widespread use of MPS2 could greatly reduce the number of unnecessary biopsies while maintaining a high detection rate of grade 2 or higher prostate cancer.

Among patients who have had a negative first biopsy, MPS2 would have a sensitivity of 94.4% and a specificity of 51%, which is much higher than other tests like prostate cancer antigen 3 gene, three-gene model, and MPS. In addition, in patients with grade 1 prostate cancer, urinary markers for high-grade cancer could indicate the existence of a more aggressive tumor requiring increased monitoring.

This study has limitations, however. The ethnic diversity of its population was limited. A few Black men were included, for example. Second, a systematic biopsy was used as the reference, which can increase negative predictive value and decrease positive predictive value. Classification errors may have occurred. Therefore, further studies are needed to confirm these initial results and the long-term positive impact of using MPS2.

In conclusion, an 18-gene urine test seems to be more relevant for diagnosing high-grade prostate cancer than existing tests. It could prevent additional imaging or biopsy examinations in 35%-41% of patients. Therefore, the use of such tests in patients with high PSA levels could reduce the potential risks associated with prostate cancer screening while preserving its long-term benefits.

This story was translated from JIM, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

It sounds like a gimmick. Drink a couple glasses of wine and feel only half as intoxicated as you normally would — and sustain less damage to your liver and other organs.

But that’s the promise of a new gel, developed by researchers in Switzerland, that changes how the body processes alcohol. The gel has been tested in mice so far, but the researchers hope to make it available to people soon. The goal: To protect people from alcohol-related accidents and chronic disease — responsible for more than three million annual deaths worldwide.

“It is a global, urgent issue,” said study coauthor Raffaele Mezzenga, PhD, a professor at ETH Zürich, Switzerland.

The advance builds on a decades-long quest among scientists to reduce the toxicity of alcohol, said Che-Hong Chen, PhD, a molecular biologist at Stanford School of Medicine, Stanford, California, who was not involved in the study. Some probiotic-based products aim to help process alcohol’s toxic byproduct acetaldehyde in the gut, but their effects seem inconsistent from one person to another, Dr. Chen said. Intravenous infusions of natural enzyme complexes, such as those that mimic liver cells to speed up alcohol metabolism, can actually produce some acetaldehyde, mitigating their detoxifying effects.

“Our method has the potential to fill the gap of most of the approaches being explored,” Dr. Mezzenga said. “We hope and plan to move to clinical studies as soon as possible.” 

Usually, the liver processes alcohol, causing the release of toxic acetaldehyde followed by less harmful acetic acid. Acetaldehyde can cause DNA damage, oxidative stress, and vascular inflammation. Too much acetaldehyde can increase the risk for cancer.

But the gel catalyzes the breakdown of alcohol in the digestive tract, converting about half of it into acetic acid. Only the remaining 45% enters the bloodstream and becomes acetaldehyde.

“The concentration of acetaldehyde will be decreased by a factor of more than two and so will the ‘intoxicating’ effect of the alcohol,” said Dr. Mezzenga.

Ideally, someone would ingest the gel immediately before or when consuming alcohol. It’s designed to continue working for several hours.

Some of the mice received one serving of alcohol, while others were served regularly for 10 days. The gel slashed their blood alcohol level by 40% after half an hour and by up to 56% after 5 hours compared with a control group given alcohol but not the gel. Mice that consumed the gel also had less liver and intestinal damage.

“The results, both the short-term behavior of the mice and in the long term for the preservation of organs, were way beyond our expectation,” said Dr. Mezzenga.

Casual drinkers could benefit from the gel. However, the gel could also lead people to consume more alcohol than they would normally to feel intoxicated, Dr. Chen said.
 

Bypassing a Problematic Pathway

A liver enzyme called alcohol dehydrogenase (ADH) converts alcohol to acetaldehyde before a second enzyme called aldehyde dehydrogenase (ALDH2) helps process acetaldehyde into acetic acid. But with the gel, alcohol transforms directly to acetic acid in the digestive tract.

“This chemical reaction seems to bypass the known biological pathway of alcohol metabolism. That’s new to me,” said Dr. Chen, a senior research scientist at Stanford and country director at the Center for Asian Health Research and Education Center. The processing of alcohol before it passes through the mucous membrane of the digestive tract is “another novel aspect,”Dr. Chen said.

To make the gel, the researchers boil whey proteins — also found in milk — to produce stringy fibrils. Next, they add salt and water to cause the fibrils to crosslink, forming a gel. The gel gets infused with iron atoms, which catalyze the conversion of alcohol into acetic acid. That conversion relies on hydrogen peroxide, the byproduct of a reaction between gold and glucose, both of which are also added to the gel.

A previous version of the technology used iron nanoparticles, which needed to be “digested down to ionic form by the acidic pH in the stomach,” said Dr. Mezzenga. That process took too long, giving alcohol more time to cross into the bloodstream. By “decorating” the protein fibrils with single iron atoms, the researchers were able to “increase their catalytic efficiency,” he added.
 

What’s Next?

With animal studies completed, human clinical studies are next. How soon that could happen will depend on ethical clearance and financial support, the researchers said.

An “interesting next step,” said Dr. Chen, would be to give the gel to mice with a genetic mutation in ALDH2. The mutation makes it harder to process acetaldehyde, often causing facial redness. Prevalent among East Asian populations, the mutation affects about 560 million people and has been linked to Alzheimer’s disease. Dr. Chen’s lab found a chemical compound that can increase the activity of ADH2, which is expected to begin phase 2 clinical trials this year.
 

A version of this article appeared on Medscape.com.

It sounds like a gimmick. Drink a couple glasses of wine and feel only half as intoxicated as you normally would — and sustain less damage to your liver and other organs.

But that’s the promise of a new gel, developed by researchers in Switzerland, that changes how the body processes alcohol. The gel has been tested in mice so far, but the researchers hope to make it available to people soon. The goal: To protect people from alcohol-related accidents and chronic disease — responsible for more than three million annual deaths worldwide.

“It is a global, urgent issue,” said study coauthor Raffaele Mezzenga, PhD, a professor at ETH Zürich, Switzerland.

The advance builds on a decades-long quest among scientists to reduce the toxicity of alcohol, said Che-Hong Chen, PhD, a molecular biologist at Stanford School of Medicine, Stanford, California, who was not involved in the study. Some probiotic-based products aim to help process alcohol’s toxic byproduct acetaldehyde in the gut, but their effects seem inconsistent from one person to another, Dr. Chen said. Intravenous infusions of natural enzyme complexes, such as those that mimic liver cells to speed up alcohol metabolism, can actually produce some acetaldehyde, mitigating their detoxifying effects.

“Our method has the potential to fill the gap of most of the approaches being explored,” Dr. Mezzenga said. “We hope and plan to move to clinical studies as soon as possible.” 

Usually, the liver processes alcohol, causing the release of toxic acetaldehyde followed by less harmful acetic acid. Acetaldehyde can cause DNA damage, oxidative stress, and vascular inflammation. Too much acetaldehyde can increase the risk for cancer.

But the gel catalyzes the breakdown of alcohol in the digestive tract, converting about half of it into acetic acid. Only the remaining 45% enters the bloodstream and becomes acetaldehyde.

“The concentration of acetaldehyde will be decreased by a factor of more than two and so will the ‘intoxicating’ effect of the alcohol,” said Dr. Mezzenga.

Ideally, someone would ingest the gel immediately before or when consuming alcohol. It’s designed to continue working for several hours.

Some of the mice received one serving of alcohol, while others were served regularly for 10 days. The gel slashed their blood alcohol level by 40% after half an hour and by up to 56% after 5 hours compared with a control group given alcohol but not the gel. Mice that consumed the gel also had less liver and intestinal damage.

“The results, both the short-term behavior of the mice and in the long term for the preservation of organs, were way beyond our expectation,” said Dr. Mezzenga.

Casual drinkers could benefit from the gel. However, the gel could also lead people to consume more alcohol than they would normally to feel intoxicated, Dr. Chen said.
 

Bypassing a Problematic Pathway

A liver enzyme called alcohol dehydrogenase (ADH) converts alcohol to acetaldehyde before a second enzyme called aldehyde dehydrogenase (ALDH2) helps process acetaldehyde into acetic acid. But with the gel, alcohol transforms directly to acetic acid in the digestive tract.

“This chemical reaction seems to bypass the known biological pathway of alcohol metabolism. That’s new to me,” said Dr. Chen, a senior research scientist at Stanford and country director at the Center for Asian Health Research and Education Center. The processing of alcohol before it passes through the mucous membrane of the digestive tract is “another novel aspect,”Dr. Chen said.

To make the gel, the researchers boil whey proteins — also found in milk — to produce stringy fibrils. Next, they add salt and water to cause the fibrils to crosslink, forming a gel. The gel gets infused with iron atoms, which catalyze the conversion of alcohol into acetic acid. That conversion relies on hydrogen peroxide, the byproduct of a reaction between gold and glucose, both of which are also added to the gel.

A previous version of the technology used iron nanoparticles, which needed to be “digested down to ionic form by the acidic pH in the stomach,” said Dr. Mezzenga. That process took too long, giving alcohol more time to cross into the bloodstream. By “decorating” the protein fibrils with single iron atoms, the researchers were able to “increase their catalytic efficiency,” he added.
 

What’s Next?

With animal studies completed, human clinical studies are next. How soon that could happen will depend on ethical clearance and financial support, the researchers said.

An “interesting next step,” said Dr. Chen, would be to give the gel to mice with a genetic mutation in ALDH2. The mutation makes it harder to process acetaldehyde, often causing facial redness. Prevalent among East Asian populations, the mutation affects about 560 million people and has been linked to Alzheimer’s disease. Dr. Chen’s lab found a chemical compound that can increase the activity of ADH2, which is expected to begin phase 2 clinical trials this year.
 

A version of this article appeared on Medscape.com.

It sounds like a gimmick. Drink a couple glasses of wine and feel only half as intoxicated as you normally would — and sustain less damage to your liver and other organs.

But that’s the promise of a new gel, developed by researchers in Switzerland, that changes how the body processes alcohol. The gel has been tested in mice so far, but the researchers hope to make it available to people soon. The goal: To protect people from alcohol-related accidents and chronic disease — responsible for more than three million annual deaths worldwide.

“It is a global, urgent issue,” said study coauthor Raffaele Mezzenga, PhD, a professor at ETH Zürich, Switzerland.

The advance builds on a decades-long quest among scientists to reduce the toxicity of alcohol, said Che-Hong Chen, PhD, a molecular biologist at Stanford School of Medicine, Stanford, California, who was not involved in the study. Some probiotic-based products aim to help process alcohol’s toxic byproduct acetaldehyde in the gut, but their effects seem inconsistent from one person to another, Dr. Chen said. Intravenous infusions of natural enzyme complexes, such as those that mimic liver cells to speed up alcohol metabolism, can actually produce some acetaldehyde, mitigating their detoxifying effects.

“Our method has the potential to fill the gap of most of the approaches being explored,” Dr. Mezzenga said. “We hope and plan to move to clinical studies as soon as possible.” 

Usually, the liver processes alcohol, causing the release of toxic acetaldehyde followed by less harmful acetic acid. Acetaldehyde can cause DNA damage, oxidative stress, and vascular inflammation. Too much acetaldehyde can increase the risk for cancer.

But the gel catalyzes the breakdown of alcohol in the digestive tract, converting about half of it into acetic acid. Only the remaining 45% enters the bloodstream and becomes acetaldehyde.

“The concentration of acetaldehyde will be decreased by a factor of more than two and so will the ‘intoxicating’ effect of the alcohol,” said Dr. Mezzenga.

Ideally, someone would ingest the gel immediately before or when consuming alcohol. It’s designed to continue working for several hours.

Some of the mice received one serving of alcohol, while others were served regularly for 10 days. The gel slashed their blood alcohol level by 40% after half an hour and by up to 56% after 5 hours compared with a control group given alcohol but not the gel. Mice that consumed the gel also had less liver and intestinal damage.

“The results, both the short-term behavior of the mice and in the long term for the preservation of organs, were way beyond our expectation,” said Dr. Mezzenga.

Casual drinkers could benefit from the gel. However, the gel could also lead people to consume more alcohol than they would normally to feel intoxicated, Dr. Chen said.
 

Bypassing a Problematic Pathway

A liver enzyme called alcohol dehydrogenase (ADH) converts alcohol to acetaldehyde before a second enzyme called aldehyde dehydrogenase (ALDH2) helps process acetaldehyde into acetic acid. But with the gel, alcohol transforms directly to acetic acid in the digestive tract.

“This chemical reaction seems to bypass the known biological pathway of alcohol metabolism. That’s new to me,” said Dr. Chen, a senior research scientist at Stanford and country director at the Center for Asian Health Research and Education Center. The processing of alcohol before it passes through the mucous membrane of the digestive tract is “another novel aspect,”Dr. Chen said.

To make the gel, the researchers boil whey proteins — also found in milk — to produce stringy fibrils. Next, they add salt and water to cause the fibrils to crosslink, forming a gel. The gel gets infused with iron atoms, which catalyze the conversion of alcohol into acetic acid. That conversion relies on hydrogen peroxide, the byproduct of a reaction between gold and glucose, both of which are also added to the gel.

A previous version of the technology used iron nanoparticles, which needed to be “digested down to ionic form by the acidic pH in the stomach,” said Dr. Mezzenga. That process took too long, giving alcohol more time to cross into the bloodstream. By “decorating” the protein fibrils with single iron atoms, the researchers were able to “increase their catalytic efficiency,” he added.
 

What’s Next?

With animal studies completed, human clinical studies are next. How soon that could happen will depend on ethical clearance and financial support, the researchers said.

An “interesting next step,” said Dr. Chen, would be to give the gel to mice with a genetic mutation in ALDH2. The mutation makes it harder to process acetaldehyde, often causing facial redness. Prevalent among East Asian populations, the mutation affects about 560 million people and has been linked to Alzheimer’s disease. Dr. Chen’s lab found a chemical compound that can increase the activity of ADH2, which is expected to begin phase 2 clinical trials this year.
 

A version of this article appeared on Medscape.com.

Lung cancer screening with low-dose CT (LDCT) can effectively evaluate a high-risk population for undiagnosed chronic obstructive pulmonary disease (COPD) and airflow obstruction, based on data from a new study of approximately 2000 individuals.

Previous research suggests that approximately 70%-90% of individuals with COPD are undiagnosed, especially low-income and minority populations who may be less likely to undergo screening, said Michaela A. Seigo, DO, of Temple University Hospital, Philadelphia, in a study presented at the American Thoracic Society (ATS) 2024 International Conference.

Although the current guidance from the United States Preventive Services Task Force (USPSTF) recommends against universal COPD screening in asymptomatic adults, the use of LDCT may be an option for evaluating a high-risk population, the researchers noted.

The researchers reviewed data from 2083 adults enrolled in the Temple Healthy Chest Initiative, an urban health system-wide lung cancer screening program, combined with the detection of symptoms and comorbidities.
 

Baseline LDCT for Identification of Comorbidities

Study participants underwent baseline LDCT between October 2021 and October 2022. The images were reviewed by radiologists for pulmonary comorbidities including emphysema, airway disease, bronchiectasis, and interstitial lung disease. In addition, 604 participants (29%) completed a symptom survey, and 624 (30%) underwent spirometry. The mean age of the participants was 65.8 years and 63.9 years for those with and without a history of COPD, respectively.

Approximately half of the participants in both groups were female.

Overall, 66 of 181 (36.5%) individuals previously undiagnosed with COPD had spirometry consistent with airflow obstruction (forced expiratory volume in 1 second/forced vital capacity, < 70%). Individuals with previously undiagnosed COPD were more likely to be younger, male, current smokers, and identified as Hispanic or other race (not Black, White, Hispanic, or Asian/Native American/Pacific Islander).

Individuals without a reported history of COPD had fewer pulmonary comorbidities on LDCT and lower rates of respiratory symptoms than those with COPD. However, nearly 25% of individuals with no reported history of COPD said that breathing issues affected their “ability to do things,” Ms. Seigo said, and a majority of those with no COPD diagnosis exhibited airway disease (76.2% compared with 84% of diagnosed patients with COPD). In addition, 88.1% reported ever experiencing dyspnea and 72.6% reported experiencing cough; both symptoms are compatible with a clinical diagnosis of COPD, the researchers noted.

“We detected pulmonary comorbidities at higher rates than previously published,” Ms. Seigo said in an interview. The increase likely reflects the patient population at Temple, which includes a relatively high percentage of city-dwelling, lower-income individuals, as well as more racial-ethnic minorities and persons of color, she said.

However, “these findings will help clinicians target the most at-risk populations for previously undiagnosed COPD,” Ms. Seigo said.

Looking ahead, Ms. Seigo said she sees a dominant role for artificial intelligence (AI) in COPD screening. “At-risk populations will get LDCT scans, and AI will identify pulmonary and extra-pulmonary comorbidities that may need to be addressed,” she said.

A combination of symptom detection plus strategic and more widely available access to screening offers “a huge opportunity to intervene earlier and potentially save lives,” she told this news organization.
 

Lung Cancer Screening May Promote Earlier COPD Intervention

The current study examines the prevalence of undiagnosed COPD, especially among low-income and minority populations, in an asymptomatic high-risk group. “By integrating lung cancer CT screening with the detection of pulmonary comorbidities on LDCT and respiratory symptoms, the current study aimed to identify individuals with undiagnosed COPD,” said Dharani K. Narendra, MD, of Baylor College of Medicine, Houston, in an interview.

“The study highlighted the feasibility and potential benefits of coupling lung cancer screening tests with COPD detection, which is noteworthy, and hits two targets with one arrow — early detection of lung cancer and COPD — in high-risk groups, Dr. Narendra said.

“Although the USPSTF recommends against screening for COPD in asymptomatic patients, abnormal pulmonary comorbidities observed on CT chest scans could serve as a gateway for clinicians to screen for COPD,” said Dr. Narendra. “This approach allows for early diagnosis, education on smoking cessation, and timely treatment of COPD, potentially preventing lung function deterioration and reducing the risk of exacerbations,” she noted.

The finding that one third of previously undiagnosed and asymptomatic patients with COPD showed significant rates of airflow obstruction on spirometry is consistent with previous research, Dr. Narendra told this news organization.

“Interestingly, in questions about specific symptoms, undiagnosed COPD patients reported higher rates of dyspnea, more cough, and breathing difficulties affecting their daily activities, at 16.1%, 27.4%, and 24.5%, respectively, highlighting a lower perception of symptoms,” she said.

“Barriers to lung cancer screening in urban, high-risk communities include limited healthcare facility access, insufficient awareness of screening programs, financial constraints, and cultural or language barriers,” said Dr. Narendra.

Potential strategies to overcome these barriers include improving access through additional screening centers and providing transportation, implementing community-based education and outreach programs to increase awareness about the benefits of lung cancer screening and early COPD detection, and providing financial assistance in the form of free screening options and collaboration with insurers to cover screening expenses, she said.

“Healthcare providers must recognize the dual benefits of lung cancer screening programs, including the opportunity to screen for undiagnosed COPD,” Dr. Narendra emphasized. “This integrated approach is crucial in identifying high-risk individuals who could benefit from early intervention and effective management of COPD. Clinicians should actively support implementing comprehensive screening programs incorporating assessments for pulmonary comorbidities through LDCT and screening questionnaires for COPD symptoms,” she said.

“Further research is needed to evaluate long-term mortality outcomes and identify best practices to determine the most effective methods and cost-effectiveness for implementing and sustaining combined screening programs in various urban settings,” Dr. Narendra told this news organization.

Other areas to address in future studies include investigating specific barriers to screening among different high-risk groups and tailoring interventions to improve screening uptake and adherence, Narendra said. “By addressing these research gaps, health care providers can optimize screening programs and enhance the overall health of urban, high-risk populations,” she added.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Narendra serves on the editorial board of CHEST Physician.

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

Lung cancer screening with low-dose CT (LDCT) can effectively evaluate a high-risk population for undiagnosed chronic obstructive pulmonary disease (COPD) and airflow obstruction, based on data from a new study of approximately 2000 individuals.

Previous research suggests that approximately 70%-90% of individuals with COPD are undiagnosed, especially low-income and minority populations who may be less likely to undergo screening, said Michaela A. Seigo, DO, of Temple University Hospital, Philadelphia, in a study presented at the American Thoracic Society (ATS) 2024 International Conference.

Although the current guidance from the United States Preventive Services Task Force (USPSTF) recommends against universal COPD screening in asymptomatic adults, the use of LDCT may be an option for evaluating a high-risk population, the researchers noted.

The researchers reviewed data from 2083 adults enrolled in the Temple Healthy Chest Initiative, an urban health system-wide lung cancer screening program, combined with the detection of symptoms and comorbidities.
 

Baseline LDCT for Identification of Comorbidities

Study participants underwent baseline LDCT between October 2021 and October 2022. The images were reviewed by radiologists for pulmonary comorbidities including emphysema, airway disease, bronchiectasis, and interstitial lung disease. In addition, 604 participants (29%) completed a symptom survey, and 624 (30%) underwent spirometry. The mean age of the participants was 65.8 years and 63.9 years for those with and without a history of COPD, respectively.

Approximately half of the participants in both groups were female.

Overall, 66 of 181 (36.5%) individuals previously undiagnosed with COPD had spirometry consistent with airflow obstruction (forced expiratory volume in 1 second/forced vital capacity, < 70%). Individuals with previously undiagnosed COPD were more likely to be younger, male, current smokers, and identified as Hispanic or other race (not Black, White, Hispanic, or Asian/Native American/Pacific Islander).

Individuals without a reported history of COPD had fewer pulmonary comorbidities on LDCT and lower rates of respiratory symptoms than those with COPD. However, nearly 25% of individuals with no reported history of COPD said that breathing issues affected their “ability to do things,” Ms. Seigo said, and a majority of those with no COPD diagnosis exhibited airway disease (76.2% compared with 84% of diagnosed patients with COPD). In addition, 88.1% reported ever experiencing dyspnea and 72.6% reported experiencing cough; both symptoms are compatible with a clinical diagnosis of COPD, the researchers noted.

“We detected pulmonary comorbidities at higher rates than previously published,” Ms. Seigo said in an interview. The increase likely reflects the patient population at Temple, which includes a relatively high percentage of city-dwelling, lower-income individuals, as well as more racial-ethnic minorities and persons of color, she said.

However, “these findings will help clinicians target the most at-risk populations for previously undiagnosed COPD,” Ms. Seigo said.

Looking ahead, Ms. Seigo said she sees a dominant role for artificial intelligence (AI) in COPD screening. “At-risk populations will get LDCT scans, and AI will identify pulmonary and extra-pulmonary comorbidities that may need to be addressed,” she said.

A combination of symptom detection plus strategic and more widely available access to screening offers “a huge opportunity to intervene earlier and potentially save lives,” she told this news organization.
 

Lung Cancer Screening May Promote Earlier COPD Intervention

The current study examines the prevalence of undiagnosed COPD, especially among low-income and minority populations, in an asymptomatic high-risk group. “By integrating lung cancer CT screening with the detection of pulmonary comorbidities on LDCT and respiratory symptoms, the current study aimed to identify individuals with undiagnosed COPD,” said Dharani K. Narendra, MD, of Baylor College of Medicine, Houston, in an interview.

“The study highlighted the feasibility and potential benefits of coupling lung cancer screening tests with COPD detection, which is noteworthy, and hits two targets with one arrow — early detection of lung cancer and COPD — in high-risk groups, Dr. Narendra said.

“Although the USPSTF recommends against screening for COPD in asymptomatic patients, abnormal pulmonary comorbidities observed on CT chest scans could serve as a gateway for clinicians to screen for COPD,” said Dr. Narendra. “This approach allows for early diagnosis, education on smoking cessation, and timely treatment of COPD, potentially preventing lung function deterioration and reducing the risk of exacerbations,” she noted.

The finding that one third of previously undiagnosed and asymptomatic patients with COPD showed significant rates of airflow obstruction on spirometry is consistent with previous research, Dr. Narendra told this news organization.

“Interestingly, in questions about specific symptoms, undiagnosed COPD patients reported higher rates of dyspnea, more cough, and breathing difficulties affecting their daily activities, at 16.1%, 27.4%, and 24.5%, respectively, highlighting a lower perception of symptoms,” she said.

“Barriers to lung cancer screening in urban, high-risk communities include limited healthcare facility access, insufficient awareness of screening programs, financial constraints, and cultural or language barriers,” said Dr. Narendra.

Potential strategies to overcome these barriers include improving access through additional screening centers and providing transportation, implementing community-based education and outreach programs to increase awareness about the benefits of lung cancer screening and early COPD detection, and providing financial assistance in the form of free screening options and collaboration with insurers to cover screening expenses, she said.

“Healthcare providers must recognize the dual benefits of lung cancer screening programs, including the opportunity to screen for undiagnosed COPD,” Dr. Narendra emphasized. “This integrated approach is crucial in identifying high-risk individuals who could benefit from early intervention and effective management of COPD. Clinicians should actively support implementing comprehensive screening programs incorporating assessments for pulmonary comorbidities through LDCT and screening questionnaires for COPD symptoms,” she said.

“Further research is needed to evaluate long-term mortality outcomes and identify best practices to determine the most effective methods and cost-effectiveness for implementing and sustaining combined screening programs in various urban settings,” Dr. Narendra told this news organization.

Other areas to address in future studies include investigating specific barriers to screening among different high-risk groups and tailoring interventions to improve screening uptake and adherence, Narendra said. “By addressing these research gaps, health care providers can optimize screening programs and enhance the overall health of urban, high-risk populations,” she added.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Narendra serves on the editorial board of CHEST Physician.

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

Lung cancer screening with low-dose CT (LDCT) can effectively evaluate a high-risk population for undiagnosed chronic obstructive pulmonary disease (COPD) and airflow obstruction, based on data from a new study of approximately 2000 individuals.

Previous research suggests that approximately 70%-90% of individuals with COPD are undiagnosed, especially low-income and minority populations who may be less likely to undergo screening, said Michaela A. Seigo, DO, of Temple University Hospital, Philadelphia, in a study presented at the American Thoracic Society (ATS) 2024 International Conference.

Although the current guidance from the United States Preventive Services Task Force (USPSTF) recommends against universal COPD screening in asymptomatic adults, the use of LDCT may be an option for evaluating a high-risk population, the researchers noted.

The researchers reviewed data from 2083 adults enrolled in the Temple Healthy Chest Initiative, an urban health system-wide lung cancer screening program, combined with the detection of symptoms and comorbidities.
 

Baseline LDCT for Identification of Comorbidities

Study participants underwent baseline LDCT between October 2021 and October 2022. The images were reviewed by radiologists for pulmonary comorbidities including emphysema, airway disease, bronchiectasis, and interstitial lung disease. In addition, 604 participants (29%) completed a symptom survey, and 624 (30%) underwent spirometry. The mean age of the participants was 65.8 years and 63.9 years for those with and without a history of COPD, respectively.

Approximately half of the participants in both groups were female.

Overall, 66 of 181 (36.5%) individuals previously undiagnosed with COPD had spirometry consistent with airflow obstruction (forced expiratory volume in 1 second/forced vital capacity, < 70%). Individuals with previously undiagnosed COPD were more likely to be younger, male, current smokers, and identified as Hispanic or other race (not Black, White, Hispanic, or Asian/Native American/Pacific Islander).

Individuals without a reported history of COPD had fewer pulmonary comorbidities on LDCT and lower rates of respiratory symptoms than those with COPD. However, nearly 25% of individuals with no reported history of COPD said that breathing issues affected their “ability to do things,” Ms. Seigo said, and a majority of those with no COPD diagnosis exhibited airway disease (76.2% compared with 84% of diagnosed patients with COPD). In addition, 88.1% reported ever experiencing dyspnea and 72.6% reported experiencing cough; both symptoms are compatible with a clinical diagnosis of COPD, the researchers noted.

“We detected pulmonary comorbidities at higher rates than previously published,” Ms. Seigo said in an interview. The increase likely reflects the patient population at Temple, which includes a relatively high percentage of city-dwelling, lower-income individuals, as well as more racial-ethnic minorities and persons of color, she said.

However, “these findings will help clinicians target the most at-risk populations for previously undiagnosed COPD,” Ms. Seigo said.

Looking ahead, Ms. Seigo said she sees a dominant role for artificial intelligence (AI) in COPD screening. “At-risk populations will get LDCT scans, and AI will identify pulmonary and extra-pulmonary comorbidities that may need to be addressed,” she said.

A combination of symptom detection plus strategic and more widely available access to screening offers “a huge opportunity to intervene earlier and potentially save lives,” she told this news organization.
 

Lung Cancer Screening May Promote Earlier COPD Intervention

The current study examines the prevalence of undiagnosed COPD, especially among low-income and minority populations, in an asymptomatic high-risk group. “By integrating lung cancer CT screening with the detection of pulmonary comorbidities on LDCT and respiratory symptoms, the current study aimed to identify individuals with undiagnosed COPD,” said Dharani K. Narendra, MD, of Baylor College of Medicine, Houston, in an interview.

“The study highlighted the feasibility and potential benefits of coupling lung cancer screening tests with COPD detection, which is noteworthy, and hits two targets with one arrow — early detection of lung cancer and COPD — in high-risk groups, Dr. Narendra said.

“Although the USPSTF recommends against screening for COPD in asymptomatic patients, abnormal pulmonary comorbidities observed on CT chest scans could serve as a gateway for clinicians to screen for COPD,” said Dr. Narendra. “This approach allows for early diagnosis, education on smoking cessation, and timely treatment of COPD, potentially preventing lung function deterioration and reducing the risk of exacerbations,” she noted.

The finding that one third of previously undiagnosed and asymptomatic patients with COPD showed significant rates of airflow obstruction on spirometry is consistent with previous research, Dr. Narendra told this news organization.

“Interestingly, in questions about specific symptoms, undiagnosed COPD patients reported higher rates of dyspnea, more cough, and breathing difficulties affecting their daily activities, at 16.1%, 27.4%, and 24.5%, respectively, highlighting a lower perception of symptoms,” she said.

“Barriers to lung cancer screening in urban, high-risk communities include limited healthcare facility access, insufficient awareness of screening programs, financial constraints, and cultural or language barriers,” said Dr. Narendra.

Potential strategies to overcome these barriers include improving access through additional screening centers and providing transportation, implementing community-based education and outreach programs to increase awareness about the benefits of lung cancer screening and early COPD detection, and providing financial assistance in the form of free screening options and collaboration with insurers to cover screening expenses, she said.

“Healthcare providers must recognize the dual benefits of lung cancer screening programs, including the opportunity to screen for undiagnosed COPD,” Dr. Narendra emphasized. “This integrated approach is crucial in identifying high-risk individuals who could benefit from early intervention and effective management of COPD. Clinicians should actively support implementing comprehensive screening programs incorporating assessments for pulmonary comorbidities through LDCT and screening questionnaires for COPD symptoms,” she said.

“Further research is needed to evaluate long-term mortality outcomes and identify best practices to determine the most effective methods and cost-effectiveness for implementing and sustaining combined screening programs in various urban settings,” Dr. Narendra told this news organization.

Other areas to address in future studies include investigating specific barriers to screening among different high-risk groups and tailoring interventions to improve screening uptake and adherence, Narendra said. “By addressing these research gaps, health care providers can optimize screening programs and enhance the overall health of urban, high-risk populations,” she added.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Narendra serves on the editorial board of CHEST Physician.

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

Most younger women diagnosed with nonmetastatic breast cancer will succeed if they attempt to become pregnant after treatment, according to new research.

The findings, presented May 23 in advance of the annual meeting of the American Society of Clinical Oncology (ASCO) represent the most comprehensive look to date at fertility outcomes following treatment for women diagnosed with breast cancer before age 40 (Abstract 1518).

Kimia Sorouri, MD, a research fellow at the Dana-Farber Cancer Center in Boston, Massachusetts, and her colleagues, looked at data from the Young Women’s Breast Cancer study, a multicenter longitudinal cohort study, for 1213 U.S. and Canadian women (74% non-Hispanic white) who were diagnosed with stages 0-III breast cancer between 2006 and 2016. None of the included patients had metastatic disease, prior hysterectomy, or prior oophorectomy at diagnosis.

During a median 11 years of follow up, 197 of the women reported attempting pregnancy. Of these, 73% reported becoming pregnant, and 65% delivered a live infant a median 4 years after cancer diagnosis. The median age at diagnosis was 32 years, and 28% opted for egg or embryo freezing to preserve fertility. Importantly, 68% received chemotherapy, which can impair fertility, with only a small percentage undergoing ovarian suppression during chemotherapy treatment.

Key predictors of pregnancy or live birth in this study were “financial comfort,” a self-reported measure defined as having money left over to spend after bills are paid (odds ratio [OR], 2.04; 95% CI 1.01-4.12; P = .047); younger age at the time of diagnosis; and undergoing fertility preservation interventions at diagnosis (OR, 2.78; 95% CI 1.29-6.00; P = .009). Chemotherapy and other treatment factors were not seen to be associated with pregnancy or birth outcomes.

“Current research that informs our understanding of the impact of breast cancer treatment on pregnancy and live birth rates is fairly limited,” Dr. Sorouri said during an online press conference announcing the findings. Quality data on fertility outcomes has been limited to studies in certain subgroups, such as women with estrogen receptor–positive breast cancers, she noted, while other studies “have short-term follow-up and critically lack prospective assessment of attempt at conception.”

The new findings show, Dr. Sorouri said, “that in this modern cohort with a heightened awareness of fertility, access to fertility preservation can help to mitigate a portion of the damage from chemotherapy and other agents. Importantly, this highlights the need for increased accessibility of fertility preservation services for women newly diagnosed with breast cancer who are interested in a future pregnancy.”

Commenting on Dr. Sorouri and colleagues’ findings, Julie Gralow, MD, a breast cancer researcher and ASCO’s chief medical officer, stressed that, while younger age at diagnosis and financial comfort were two factors outside the scope of clinical oncology practice, “we can impact fertility preservation prior to treatment.”

She called it “critical” that every patient be informed of the impact of a breast cancer diagnosis and treatment on future fertility, and that all young patients interested in future fertility be offered fertility preservation prior to beginning treatment.

Ann Partridge, MD, of Dana-Farber, said in an interview that the findings reflected a decades’ long change in approach. “Twenty years ago when we first started this cohort, people would tell women ‘you can’t get pregnant. It’s too dangerous. You won’t be able to.’ And some indeed aren’t able to, but the majority who are attempting are succeeding, especially if they preserve their eggs or embryos. So even if chemo puts you into menopause or made you subfertile, if you’ve preserved eggs or embryos, we now can mitigate that distressing effect that many cancer patients have suffered from historically. That’s the good news here.”

Nonetheless, Dr. Partridge, an oncologist and the last author of the study, noted, the results reflected success only for women actively attempting pregnancy. “Remember, we’re not including the people who didn’t attempt. There may be some who went into menopause who never banked eggs or embryos, and may never have tried because they went to a doctor who told them they’re not fertile.” Further, she said, not all insurances cover in vitro fertilization for women who have had breast cancer.

The fact that financial comfort was correlated with reproductive success, Dr. Partridge said, speaks to broader issues about access. “It may not be all about insurers. It may be to have the ability, to have the time, the education and the wherewithal to do this right — and about being with doctors who talk about it.”

Dr. Sorouri and colleagues’ study was sponsored by the Breast Cancer Research Foundation and Susan G. Komen. Several co-authors disclosed receiving speaking and/or consulting fees from pharmaceutical companies, and one reported being an employee of GlaxoSmithKline. Dr. Sorouri reported no industry funding, while Dr. Partridge reported research funding from Novartis.

Most younger women diagnosed with nonmetastatic breast cancer will succeed if they attempt to become pregnant after treatment, according to new research.

The findings, presented May 23 in advance of the annual meeting of the American Society of Clinical Oncology (ASCO) represent the most comprehensive look to date at fertility outcomes following treatment for women diagnosed with breast cancer before age 40 (Abstract 1518).

Kimia Sorouri, MD, a research fellow at the Dana-Farber Cancer Center in Boston, Massachusetts, and her colleagues, looked at data from the Young Women’s Breast Cancer study, a multicenter longitudinal cohort study, for 1213 U.S. and Canadian women (74% non-Hispanic white) who were diagnosed with stages 0-III breast cancer between 2006 and 2016. None of the included patients had metastatic disease, prior hysterectomy, or prior oophorectomy at diagnosis.

During a median 11 years of follow up, 197 of the women reported attempting pregnancy. Of these, 73% reported becoming pregnant, and 65% delivered a live infant a median 4 years after cancer diagnosis. The median age at diagnosis was 32 years, and 28% opted for egg or embryo freezing to preserve fertility. Importantly, 68% received chemotherapy, which can impair fertility, with only a small percentage undergoing ovarian suppression during chemotherapy treatment.

Key predictors of pregnancy or live birth in this study were “financial comfort,” a self-reported measure defined as having money left over to spend after bills are paid (odds ratio [OR], 2.04; 95% CI 1.01-4.12; P = .047); younger age at the time of diagnosis; and undergoing fertility preservation interventions at diagnosis (OR, 2.78; 95% CI 1.29-6.00; P = .009). Chemotherapy and other treatment factors were not seen to be associated with pregnancy or birth outcomes.

“Current research that informs our understanding of the impact of breast cancer treatment on pregnancy and live birth rates is fairly limited,” Dr. Sorouri said during an online press conference announcing the findings. Quality data on fertility outcomes has been limited to studies in certain subgroups, such as women with estrogen receptor–positive breast cancers, she noted, while other studies “have short-term follow-up and critically lack prospective assessment of attempt at conception.”

The new findings show, Dr. Sorouri said, “that in this modern cohort with a heightened awareness of fertility, access to fertility preservation can help to mitigate a portion of the damage from chemotherapy and other agents. Importantly, this highlights the need for increased accessibility of fertility preservation services for women newly diagnosed with breast cancer who are interested in a future pregnancy.”

Commenting on Dr. Sorouri and colleagues’ findings, Julie Gralow, MD, a breast cancer researcher and ASCO’s chief medical officer, stressed that, while younger age at diagnosis and financial comfort were two factors outside the scope of clinical oncology practice, “we can impact fertility preservation prior to treatment.”

She called it “critical” that every patient be informed of the impact of a breast cancer diagnosis and treatment on future fertility, and that all young patients interested in future fertility be offered fertility preservation prior to beginning treatment.

Ann Partridge, MD, of Dana-Farber, said in an interview that the findings reflected a decades’ long change in approach. “Twenty years ago when we first started this cohort, people would tell women ‘you can’t get pregnant. It’s too dangerous. You won’t be able to.’ And some indeed aren’t able to, but the majority who are attempting are succeeding, especially if they preserve their eggs or embryos. So even if chemo puts you into menopause or made you subfertile, if you’ve preserved eggs or embryos, we now can mitigate that distressing effect that many cancer patients have suffered from historically. That’s the good news here.”

Nonetheless, Dr. Partridge, an oncologist and the last author of the study, noted, the results reflected success only for women actively attempting pregnancy. “Remember, we’re not including the people who didn’t attempt. There may be some who went into menopause who never banked eggs or embryos, and may never have tried because they went to a doctor who told them they’re not fertile.” Further, she said, not all insurances cover in vitro fertilization for women who have had breast cancer.

The fact that financial comfort was correlated with reproductive success, Dr. Partridge said, speaks to broader issues about access. “It may not be all about insurers. It may be to have the ability, to have the time, the education and the wherewithal to do this right — and about being with doctors who talk about it.”

Dr. Sorouri and colleagues’ study was sponsored by the Breast Cancer Research Foundation and Susan G. Komen. Several co-authors disclosed receiving speaking and/or consulting fees from pharmaceutical companies, and one reported being an employee of GlaxoSmithKline. Dr. Sorouri reported no industry funding, while Dr. Partridge reported research funding from Novartis.

Most younger women diagnosed with nonmetastatic breast cancer will succeed if they attempt to become pregnant after treatment, according to new research.

The findings, presented May 23 in advance of the annual meeting of the American Society of Clinical Oncology (ASCO) represent the most comprehensive look to date at fertility outcomes following treatment for women diagnosed with breast cancer before age 40 (Abstract 1518).

Kimia Sorouri, MD, a research fellow at the Dana-Farber Cancer Center in Boston, Massachusetts, and her colleagues, looked at data from the Young Women’s Breast Cancer study, a multicenter longitudinal cohort study, for 1213 U.S. and Canadian women (74% non-Hispanic white) who were diagnosed with stages 0-III breast cancer between 2006 and 2016. None of the included patients had metastatic disease, prior hysterectomy, or prior oophorectomy at diagnosis.

During a median 11 years of follow up, 197 of the women reported attempting pregnancy. Of these, 73% reported becoming pregnant, and 65% delivered a live infant a median 4 years after cancer diagnosis. The median age at diagnosis was 32 years, and 28% opted for egg or embryo freezing to preserve fertility. Importantly, 68% received chemotherapy, which can impair fertility, with only a small percentage undergoing ovarian suppression during chemotherapy treatment.

Key predictors of pregnancy or live birth in this study were “financial comfort,” a self-reported measure defined as having money left over to spend after bills are paid (odds ratio [OR], 2.04; 95% CI 1.01-4.12; P = .047); younger age at the time of diagnosis; and undergoing fertility preservation interventions at diagnosis (OR, 2.78; 95% CI 1.29-6.00; P = .009). Chemotherapy and other treatment factors were not seen to be associated with pregnancy or birth outcomes.

“Current research that informs our understanding of the impact of breast cancer treatment on pregnancy and live birth rates is fairly limited,” Dr. Sorouri said during an online press conference announcing the findings. Quality data on fertility outcomes has been limited to studies in certain subgroups, such as women with estrogen receptor–positive breast cancers, she noted, while other studies “have short-term follow-up and critically lack prospective assessment of attempt at conception.”

The new findings show, Dr. Sorouri said, “that in this modern cohort with a heightened awareness of fertility, access to fertility preservation can help to mitigate a portion of the damage from chemotherapy and other agents. Importantly, this highlights the need for increased accessibility of fertility preservation services for women newly diagnosed with breast cancer who are interested in a future pregnancy.”

Commenting on Dr. Sorouri and colleagues’ findings, Julie Gralow, MD, a breast cancer researcher and ASCO’s chief medical officer, stressed that, while younger age at diagnosis and financial comfort were two factors outside the scope of clinical oncology practice, “we can impact fertility preservation prior to treatment.”

She called it “critical” that every patient be informed of the impact of a breast cancer diagnosis and treatment on future fertility, and that all young patients interested in future fertility be offered fertility preservation prior to beginning treatment.

Ann Partridge, MD, of Dana-Farber, said in an interview that the findings reflected a decades’ long change in approach. “Twenty years ago when we first started this cohort, people would tell women ‘you can’t get pregnant. It’s too dangerous. You won’t be able to.’ And some indeed aren’t able to, but the majority who are attempting are succeeding, especially if they preserve their eggs or embryos. So even if chemo puts you into menopause or made you subfertile, if you’ve preserved eggs or embryos, we now can mitigate that distressing effect that many cancer patients have suffered from historically. That’s the good news here.”

Nonetheless, Dr. Partridge, an oncologist and the last author of the study, noted, the results reflected success only for women actively attempting pregnancy. “Remember, we’re not including the people who didn’t attempt. There may be some who went into menopause who never banked eggs or embryos, and may never have tried because they went to a doctor who told them they’re not fertile.” Further, she said, not all insurances cover in vitro fertilization for women who have had breast cancer.

The fact that financial comfort was correlated with reproductive success, Dr. Partridge said, speaks to broader issues about access. “It may not be all about insurers. It may be to have the ability, to have the time, the education and the wherewithal to do this right — and about being with doctors who talk about it.”

Dr. Sorouri and colleagues’ study was sponsored by the Breast Cancer Research Foundation and Susan G. Komen. Several co-authors disclosed receiving speaking and/or consulting fees from pharmaceutical companies, and one reported being an employee of GlaxoSmithKline. Dr. Sorouri reported no industry funding, while Dr. Partridge reported research funding from Novartis.

TOPLINE:

Vaginal estrogen therapy does not increase the risk for recurrence in women with hormone receptor (HR)–negative breast cancer or in those with HR–positive tumors concurrently treated with tamoxifen but should be avoided in aromatase inhibitor users, a French study suggested.

METHODOLOGY:

• Survivors of breast cancer often experience genitourinary symptoms due to declining estrogen levels. Vaginal estrogen therapies, including estriol and promestriene (3-propyl ethyl, 17B-methyl estradiol), can prevent these symptoms, but the effect on breast cancer outcomes remains uncertain.
• Researchers used French insurance claims data to emulate a target trial assessing the effect of initiating vaginal estrogen therapy — any molecule, promestriene, or estriol — on disease-free survival in survivors of breast cancer.
• Patients included in the study had a median age of 54 years; 85% were HR-positive, and 15% were HR–negative. The researchers conducted subgroup analyses based on HR status and endocrine therapy regimen.

TAKEAWAY:

• Among 134,942 unique patients, 1739 started vaginal estrogen therapy — 56%, promestriene; 34%, estriol; and 10%, both. 
• Initiation of vaginal estrogen therapy led to a modest decrease in disease-free survival in patients with HR–positive tumors (−2.1 percentage point at 5 years), particularly in those concurrently treated with an aromatase inhibitor (−3.0 percentage points).
• No decrease in disease-free survival was observed in patients with HR–negative tumors or in those treated with tamoxifen.
• In aromatase inhibitor users, starting estriol led to a “more severe and premature” decrease in disease-free survival (−4.2 percentage point after 3 years) compared with initiating promestriene (1.0 percentage point difference at 3 years).

IN PRACTICE:

“This study addresses a very important survivorship issue — sexual dysfunction in cancer patients — which is associated with anxiety and depression and should be considered a crucial component of survivorship care,” said study discussant Matteo Lambertini, MD, PhD, with University of Genova, Genova, Italy.

Our results suggest that using vaginal estrogen therapy “is safe in individuals with HR-negative tumors and in those concurrently treated with tamoxifen,” said study presenter Elise Dumas, PhD, with Institut Curie, Paris, France. For breast cancer survivors treated with aromatase inhibitors, vaginal estrogen therapy should be avoided as much as possible, but promestriene is preferred over estriol in this subgroup of patients.

SOURCE:

The research (Abstract 268MO) was presented at the European Society for Medical Oncology Breast Cancer 2024 Annual Congress on May 17, 2024.

LIMITATIONS:

No limitations were discussed in the presentation.

DISCLOSURES:

Funding was provided by Monoprix and the French National Cancer Institute. Dumas declared no conflicts of interest. Lambertini has financial relationships with various pharmaceutical companies including Roche, Novartis, AstraZeneca, Lilly, Exact Sciences, Pfizer, and others.

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

TOPLINE:

Vaginal estrogen therapy does not increase the risk for recurrence in women with hormone receptor (HR)–negative breast cancer or in those with HR–positive tumors concurrently treated with tamoxifen but should be avoided in aromatase inhibitor users, a French study suggested.

METHODOLOGY:

• Survivors of breast cancer often experience genitourinary symptoms due to declining estrogen levels. Vaginal estrogen therapies, including estriol and promestriene (3-propyl ethyl, 17B-methyl estradiol), can prevent these symptoms, but the effect on breast cancer outcomes remains uncertain.
• Researchers used French insurance claims data to emulate a target trial assessing the effect of initiating vaginal estrogen therapy — any molecule, promestriene, or estriol — on disease-free survival in survivors of breast cancer.
• Patients included in the study had a median age of 54 years; 85% were HR-positive, and 15% were HR–negative. The researchers conducted subgroup analyses based on HR status and endocrine therapy regimen.

TAKEAWAY:

• Among 134,942 unique patients, 1739 started vaginal estrogen therapy — 56%, promestriene; 34%, estriol; and 10%, both. 
• Initiation of vaginal estrogen therapy led to a modest decrease in disease-free survival in patients with HR–positive tumors (−2.1 percentage point at 5 years), particularly in those concurrently treated with an aromatase inhibitor (−3.0 percentage points).
• No decrease in disease-free survival was observed in patients with HR–negative tumors or in those treated with tamoxifen.
• In aromatase inhibitor users, starting estriol led to a “more severe and premature” decrease in disease-free survival (−4.2 percentage point after 3 years) compared with initiating promestriene (1.0 percentage point difference at 3 years).

IN PRACTICE:

“This study addresses a very important survivorship issue — sexual dysfunction in cancer patients — which is associated with anxiety and depression and should be considered a crucial component of survivorship care,” said study discussant Matteo Lambertini, MD, PhD, with University of Genova, Genova, Italy.

Our results suggest that using vaginal estrogen therapy “is safe in individuals with HR-negative tumors and in those concurrently treated with tamoxifen,” said study presenter Elise Dumas, PhD, with Institut Curie, Paris, France. For breast cancer survivors treated with aromatase inhibitors, vaginal estrogen therapy should be avoided as much as possible, but promestriene is preferred over estriol in this subgroup of patients.

SOURCE:

The research (Abstract 268MO) was presented at the European Society for Medical Oncology Breast Cancer 2024 Annual Congress on May 17, 2024.

LIMITATIONS:

No limitations were discussed in the presentation.

DISCLOSURES:

Funding was provided by Monoprix and the French National Cancer Institute. Dumas declared no conflicts of interest. Lambertini has financial relationships with various pharmaceutical companies including Roche, Novartis, AstraZeneca, Lilly, Exact Sciences, Pfizer, and others.

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

TOPLINE:

Vaginal estrogen therapy does not increase the risk for recurrence in women with hormone receptor (HR)–negative breast cancer or in those with HR–positive tumors concurrently treated with tamoxifen but should be avoided in aromatase inhibitor users, a French study suggested.

METHODOLOGY:

• Survivors of breast cancer often experience genitourinary symptoms due to declining estrogen levels. Vaginal estrogen therapies, including estriol and promestriene (3-propyl ethyl, 17B-methyl estradiol), can prevent these symptoms, but the effect on breast cancer outcomes remains uncertain.
• Researchers used French insurance claims data to emulate a target trial assessing the effect of initiating vaginal estrogen therapy — any molecule, promestriene, or estriol — on disease-free survival in survivors of breast cancer.
• Patients included in the study had a median age of 54 years; 85% were HR-positive, and 15% were HR–negative. The researchers conducted subgroup analyses based on HR status and endocrine therapy regimen.

TAKEAWAY:

• Among 134,942 unique patients, 1739 started vaginal estrogen therapy — 56%, promestriene; 34%, estriol; and 10%, both. 
• Initiation of vaginal estrogen therapy led to a modest decrease in disease-free survival in patients with HR–positive tumors (−2.1 percentage point at 5 years), particularly in those concurrently treated with an aromatase inhibitor (−3.0 percentage points).
• No decrease in disease-free survival was observed in patients with HR–negative tumors or in those treated with tamoxifen.
• In aromatase inhibitor users, starting estriol led to a “more severe and premature” decrease in disease-free survival (−4.2 percentage point after 3 years) compared with initiating promestriene (1.0 percentage point difference at 3 years).

IN PRACTICE:

“This study addresses a very important survivorship issue — sexual dysfunction in cancer patients — which is associated with anxiety and depression and should be considered a crucial component of survivorship care,” said study discussant Matteo Lambertini, MD, PhD, with University of Genova, Genova, Italy.

Our results suggest that using vaginal estrogen therapy “is safe in individuals with HR-negative tumors and in those concurrently treated with tamoxifen,” said study presenter Elise Dumas, PhD, with Institut Curie, Paris, France. For breast cancer survivors treated with aromatase inhibitors, vaginal estrogen therapy should be avoided as much as possible, but promestriene is preferred over estriol in this subgroup of patients.

SOURCE:

The research (Abstract 268MO) was presented at the European Society for Medical Oncology Breast Cancer 2024 Annual Congress on May 17, 2024.

LIMITATIONS:

No limitations were discussed in the presentation.

DISCLOSURES:

Funding was provided by Monoprix and the French National Cancer Institute. Dumas declared no conflicts of interest. Lambertini has financial relationships with various pharmaceutical companies including Roche, Novartis, AstraZeneca, Lilly, Exact Sciences, Pfizer, and others.

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

In February, the US Food and Drug Administration (FDA) approved irinotecan liposome (Onivyde) as part of a new regimen for first-line metastatic pancreatic adenocarcinoma called NALIRIFOX.

The main difference between NALIRIFOX and a standard go-to regimen for the indication, modified FOLFIRINOX, is that liposomal irinotecan — irinotecan encased in a lipid nanoparticle — is used instead of free irinotecan.

Trial data suggested a better overall response rate, a slight progression-free survival advantage, and potentially fewer adverse events with the liposomal formulation.

The substitution, however, raises the cost of treatment substantially. According to one estimate, a single cycle of FOLFIRINOX costs about $500 at a body surface area of 2 m², while the equivalent single cycle of NALIRIFOX costs $7800 — over 15-fold more expensive.

While some oncologists have called the NALIRIFOX regimen a potential new standard first-line treatment for metastatic pancreatic adenocarcinoma, others have expressed serious doubts about whether the potential benefits are worth the extra cost.

“I can’t really see a single scenario where I would recommend NALIRIFOX over FOLFIRINOX” Ignacio Garrido-Laguna, MD, PhD, a gastrointestinal oncologist and pancreatic cancer researcher at the University of Utah, Salt Lake City, told this news organization. “Most of us in the academic setting have the same take on this.”
 

No Head-to-Head Comparison

Uncertainty surrounding the benefits of NALIRIFOX is largely driven by the fact that NALIRIFOX wasn’t compared with FOLFIRINOX in the phase 3 trial that won liposomal irinotecan approval.

Instead, the 770-patient NAPOLI 3 trial compared NALIRIFOX — which also includes oxaliplatin, fluorouracil, and leucovorin — with a two-drug regimen, nab-paclitaxel and gemcitabine. In the trial, overall survival and other outcomes were moderately better with NALIRIFOX.

Oncologists have said that the true value of the trial is that it conclusively demonstrates that a four-drug regimen is superior to a two-drug regimen for patients who can tolerate the more intensive therapy.

Eileen M. O’Reilly, MD, the senior investigator on NAPOLI 3, made this point when she presented the phase 3 results at the 2023 ASCO annual meeting.

The trial “answers the question of four drugs versus two” for first-line metastatic pancreatic cancer but “does not address the question of NALIRIFOX versus FOLFIRINOX,” said Dr. O’Reilly, a pancreatic and hepatobiliary oncologist and researcher at Memorial Sloan Kettering Cancer Center in New York City.

Comparing them directly in the study “probably wouldn’t have been in the interest of the sponsor,” said Dr. O’Reilly.

With no head-to-head comparison, oncologists have been comparing NAPOLI 3 results with those from PRODIGE 4, the 2011 trial that won FOLFIRINOX its place as a first-line regimen.

When comparing the trials, median overall survival was exactly the same for the two regimens — 11.1 months. FOLFIRINOX was associated with a slightly higher 1-year survival rate — 48.4% with FOLFIRINOX vs 45.6% with NALIRIFOX.

However, Dr. O’Reilly and her colleagues also highlighted comparisons between the two trials that favored NAPOLI 3.

NAPOLI 3 had no age limit, while PRODIGE subjects were no older than 75 years. Median progression-free survival was 1 month longer among patients receiving NALIRIFOX — 7.4 months vs 6.4 months in PRODIGE — and overall response rates were higher as well — 41.8% in NAPOLI 3 vs 31.6%. Patients receiving NALIRIFOX also had lower rates of grade 3/4 neutropenia (23.8% vs 45.7%, respectively) and peripheral sensory neuropathy (3.5% vs 9.0%, respectively).

The authors explained that the lower rate of neuropathy could be because NALIRIFOX uses a lower dose of oxaliplatin (FOLFIRINOX), at 60 mg/m² instead of 85 mg/m².
 

Is It Worth It?

During a presentation of the phase 3 findings last year, study author Zev A. Wainberg, MD, of the University of California, Los Angeles, said the NALIRIFOX regimen can be considered the new reference regimen for first-line treatment of metastatic pancreatic adenocarcinoma.

The study discussant, Laura Goff, MD, MSCI, of Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, agreed that the results support the NALIRIFOX regimen as “the new standard for fit patients.”

However, other oncologists remain skeptical about the benefits of the new regimen over FOLFIRINOX for patients with metastatic pancreatic adenocarcinoma.

In a recent editorial, Dr. Garrido-Laguna and University of Utah gastrointestinal oncologist Christopher Nevala-Plagemann, MD, compared the evidence for both regimens.

The experts pointed out that overall response rates were assessed by investigators in NAPOLI 3 and not by an independent review committee, as in PRODIGE 4, and might have been overestimated.

Although the lack of an age limit was touted as a benefit of NAPOLI 3, Dr. Garrido-Laguna and Dr. Nevala-Plagemann doubt whether enough patients over 75 years old participated to draw any meaningful conclusions about using NALIRIFOX in older, frailer patients. If anything, patients in PRODIGE 4 might have been less fit because, among other things, the trial allowed patients with serum albumins < 3 g/dL.

On the adverse event front, the authors highlighted the higher incidences of grade 3 or worse diarrhea with NALIRIFOX (20% vs 12.7%) and questioned if there truly is less neutropenia with NALIRIFOX because high-risk patients in NAPOLI 3 were treated with granulocyte colony-stimulating factor to prevent it. The pair also questioned whether the differences in neuropathy rates between the two trials were big enough to be clinically meaningful.

Insights from a recent meta-analysis may further clarify some of the lingering questions about the efficacy of NALIRIFOX vs FOLFIRINOX.

In the analysis, the team found no meaningful difference in overall and progression-free survival between the two regimens. Differences in rates of peripheral neuropathy and diarrhea were not statistically significant, but NALIRIFOX did carry a statistically significant advantage in lower rates of febrile neutropenia, thrombocytopenia, and vomiting.

The team concluded that “NALIRIFOX and FOLFIRINOX may provide equal efficacy as first-line treatment of metastatic pancreatic cancer, but with different toxicity profiles,” and called for careful patient selection when choosing between the two regimens as well as consideration of financial toxicity.

Dr. Garrido-Laguna had a different take. With the current data, NALIRIFOX does not seem to “add anything substantially different to what we already” have with FOLFIRINOX, he told this news organization. Given that, “we can’t really justify NALIRIFOX over FOLFIRINOX without more of a head-to-head comparison.”

The higher cost of NALIRIFOX, in particular, remains a major drawback.

“We think it would be an economic disservice to our healthcare systems if we used NALIRIFOX instead of FOLFIRINOX for these patients on the basis of [NAPOLI 3] data,” Bishal Gyawali, MD, PhD, and Christopher Booth, MD, gastrointestinal oncologists at Queen’s University in Kingston, Ontario, Canada, said in a recent essay.

Dr. Garrido-Laguna and Dr. Nevala-Plagemann reiterated this concern.

Overall, “NALIRIFOX does not seem to raise the bar but rather exposes patients and healthcare systems to financial toxicities,” Dr. Garrido-Laguna and Dr. Nevala-Plagemann wrote in their review.

NAPOLI 3 was funded by Ipsen and PRODIGE 4 was funded by the government of France. No funding source was reported for the meta-analysis. NAPOLI 3 investigators included Ipsen employees. Dr. O’Reilly disclosed grants or contracts from Ipsen and many other companies. Dr. Garrido-Laguna reported institutional research funding from Bristol Myers Squibb, Novartis, Pfizer, and other companies, but not Ipsen. Dr. Nevala-Plagemann is an advisor for Seagen and reported institutional research funding from Theriva. Dr. Gyawali is a consultant for Vivio Health; Dr. Booth had no disclosures. Two meta-analysis authors reported grants or personal fees from Ipsen as well as ties to other companies.

A version of this article appeared on Medscape.com.

In February, the US Food and Drug Administration (FDA) approved irinotecan liposome (Onivyde) as part of a new regimen for first-line metastatic pancreatic adenocarcinoma called NALIRIFOX.

The main difference between NALIRIFOX and a standard go-to regimen for the indication, modified FOLFIRINOX, is that liposomal irinotecan — irinotecan encased in a lipid nanoparticle — is used instead of free irinotecan.

Trial data suggested a better overall response rate, a slight progression-free survival advantage, and potentially fewer adverse events with the liposomal formulation.

The substitution, however, raises the cost of treatment substantially. According to one estimate, a single cycle of FOLFIRINOX costs about $500 at a body surface area of 2 m², while the equivalent single cycle of NALIRIFOX costs $7800 — over 15-fold more expensive.

While some oncologists have called the NALIRIFOX regimen a potential new standard first-line treatment for metastatic pancreatic adenocarcinoma, others have expressed serious doubts about whether the potential benefits are worth the extra cost.

“I can’t really see a single scenario where I would recommend NALIRIFOX over FOLFIRINOX” Ignacio Garrido-Laguna, MD, PhD, a gastrointestinal oncologist and pancreatic cancer researcher at the University of Utah, Salt Lake City, told this news organization. “Most of us in the academic setting have the same take on this.”
 

No Head-to-Head Comparison

Uncertainty surrounding the benefits of NALIRIFOX is largely driven by the fact that NALIRIFOX wasn’t compared with FOLFIRINOX in the phase 3 trial that won liposomal irinotecan approval.

Instead, the 770-patient NAPOLI 3 trial compared NALIRIFOX — which also includes oxaliplatin, fluorouracil, and leucovorin — with a two-drug regimen, nab-paclitaxel and gemcitabine. In the trial, overall survival and other outcomes were moderately better with NALIRIFOX.

Oncologists have said that the true value of the trial is that it conclusively demonstrates that a four-drug regimen is superior to a two-drug regimen for patients who can tolerate the more intensive therapy.

Eileen M. O’Reilly, MD, the senior investigator on NAPOLI 3, made this point when she presented the phase 3 results at the 2023 ASCO annual meeting.

The trial “answers the question of four drugs versus two” for first-line metastatic pancreatic cancer but “does not address the question of NALIRIFOX versus FOLFIRINOX,” said Dr. O’Reilly, a pancreatic and hepatobiliary oncologist and researcher at Memorial Sloan Kettering Cancer Center in New York City.

Comparing them directly in the study “probably wouldn’t have been in the interest of the sponsor,” said Dr. O’Reilly.

With no head-to-head comparison, oncologists have been comparing NAPOLI 3 results with those from PRODIGE 4, the 2011 trial that won FOLFIRINOX its place as a first-line regimen.

When comparing the trials, median overall survival was exactly the same for the two regimens — 11.1 months. FOLFIRINOX was associated with a slightly higher 1-year survival rate — 48.4% with FOLFIRINOX vs 45.6% with NALIRIFOX.

However, Dr. O’Reilly and her colleagues also highlighted comparisons between the two trials that favored NAPOLI 3.

NAPOLI 3 had no age limit, while PRODIGE subjects were no older than 75 years. Median progression-free survival was 1 month longer among patients receiving NALIRIFOX — 7.4 months vs 6.4 months in PRODIGE — and overall response rates were higher as well — 41.8% in NAPOLI 3 vs 31.6%. Patients receiving NALIRIFOX also had lower rates of grade 3/4 neutropenia (23.8% vs 45.7%, respectively) and peripheral sensory neuropathy (3.5% vs 9.0%, respectively).

The authors explained that the lower rate of neuropathy could be because NALIRIFOX uses a lower dose of oxaliplatin (FOLFIRINOX), at 60 mg/m² instead of 85 mg/m².
 

Is It Worth It?

During a presentation of the phase 3 findings last year, study author Zev A. Wainberg, MD, of the University of California, Los Angeles, said the NALIRIFOX regimen can be considered the new reference regimen for first-line treatment of metastatic pancreatic adenocarcinoma.

The study discussant, Laura Goff, MD, MSCI, of Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, agreed that the results support the NALIRIFOX regimen as “the new standard for fit patients.”

However, other oncologists remain skeptical about the benefits of the new regimen over FOLFIRINOX for patients with metastatic pancreatic adenocarcinoma.

In a recent editorial, Dr. Garrido-Laguna and University of Utah gastrointestinal oncologist Christopher Nevala-Plagemann, MD, compared the evidence for both regimens.

The experts pointed out that overall response rates were assessed by investigators in NAPOLI 3 and not by an independent review committee, as in PRODIGE 4, and might have been overestimated.

Although the lack of an age limit was touted as a benefit of NAPOLI 3, Dr. Garrido-Laguna and Dr. Nevala-Plagemann doubt whether enough patients over 75 years old participated to draw any meaningful conclusions about using NALIRIFOX in older, frailer patients. If anything, patients in PRODIGE 4 might have been less fit because, among other things, the trial allowed patients with serum albumins < 3 g/dL.

On the adverse event front, the authors highlighted the higher incidences of grade 3 or worse diarrhea with NALIRIFOX (20% vs 12.7%) and questioned if there truly is less neutropenia with NALIRIFOX because high-risk patients in NAPOLI 3 were treated with granulocyte colony-stimulating factor to prevent it. The pair also questioned whether the differences in neuropathy rates between the two trials were big enough to be clinically meaningful.

Insights from a recent meta-analysis may further clarify some of the lingering questions about the efficacy of NALIRIFOX vs FOLFIRINOX.

In the analysis, the team found no meaningful difference in overall and progression-free survival between the two regimens. Differences in rates of peripheral neuropathy and diarrhea were not statistically significant, but NALIRIFOX did carry a statistically significant advantage in lower rates of febrile neutropenia, thrombocytopenia, and vomiting.

The team concluded that “NALIRIFOX and FOLFIRINOX may provide equal efficacy as first-line treatment of metastatic pancreatic cancer, but with different toxicity profiles,” and called for careful patient selection when choosing between the two regimens as well as consideration of financial toxicity.

Dr. Garrido-Laguna had a different take. With the current data, NALIRIFOX does not seem to “add anything substantially different to what we already” have with FOLFIRINOX, he told this news organization. Given that, “we can’t really justify NALIRIFOX over FOLFIRINOX without more of a head-to-head comparison.”

The higher cost of NALIRIFOX, in particular, remains a major drawback.

“We think it would be an economic disservice to our healthcare systems if we used NALIRIFOX instead of FOLFIRINOX for these patients on the basis of [NAPOLI 3] data,” Bishal Gyawali, MD, PhD, and Christopher Booth, MD, gastrointestinal oncologists at Queen’s University in Kingston, Ontario, Canada, said in a recent essay.

Dr. Garrido-Laguna and Dr. Nevala-Plagemann reiterated this concern.

Overall, “NALIRIFOX does not seem to raise the bar but rather exposes patients and healthcare systems to financial toxicities,” Dr. Garrido-Laguna and Dr. Nevala-Plagemann wrote in their review.

NAPOLI 3 was funded by Ipsen and PRODIGE 4 was funded by the government of France. No funding source was reported for the meta-analysis. NAPOLI 3 investigators included Ipsen employees. Dr. O’Reilly disclosed grants or contracts from Ipsen and many other companies. Dr. Garrido-Laguna reported institutional research funding from Bristol Myers Squibb, Novartis, Pfizer, and other companies, but not Ipsen. Dr. Nevala-Plagemann is an advisor for Seagen and reported institutional research funding from Theriva. Dr. Gyawali is a consultant for Vivio Health; Dr. Booth had no disclosures. Two meta-analysis authors reported grants or personal fees from Ipsen as well as ties to other companies.

A version of this article appeared on Medscape.com.

In February, the US Food and Drug Administration (FDA) approved irinotecan liposome (Onivyde) as part of a new regimen for first-line metastatic pancreatic adenocarcinoma called NALIRIFOX.

The main difference between NALIRIFOX and a standard go-to regimen for the indication, modified FOLFIRINOX, is that liposomal irinotecan — irinotecan encased in a lipid nanoparticle — is used instead of free irinotecan.

Trial data suggested a better overall response rate, a slight progression-free survival advantage, and potentially fewer adverse events with the liposomal formulation.

The substitution, however, raises the cost of treatment substantially. According to one estimate, a single cycle of FOLFIRINOX costs about $500 at a body surface area of 2 m², while the equivalent single cycle of NALIRIFOX costs $7800 — over 15-fold more expensive.

While some oncologists have called the NALIRIFOX regimen a potential new standard first-line treatment for metastatic pancreatic adenocarcinoma, others have expressed serious doubts about whether the potential benefits are worth the extra cost.

“I can’t really see a single scenario where I would recommend NALIRIFOX over FOLFIRINOX” Ignacio Garrido-Laguna, MD, PhD, a gastrointestinal oncologist and pancreatic cancer researcher at the University of Utah, Salt Lake City, told this news organization. “Most of us in the academic setting have the same take on this.”
 

No Head-to-Head Comparison

Uncertainty surrounding the benefits of NALIRIFOX is largely driven by the fact that NALIRIFOX wasn’t compared with FOLFIRINOX in the phase 3 trial that won liposomal irinotecan approval.

Instead, the 770-patient NAPOLI 3 trial compared NALIRIFOX — which also includes oxaliplatin, fluorouracil, and leucovorin — with a two-drug regimen, nab-paclitaxel and gemcitabine. In the trial, overall survival and other outcomes were moderately better with NALIRIFOX.

Oncologists have said that the true value of the trial is that it conclusively demonstrates that a four-drug regimen is superior to a two-drug regimen for patients who can tolerate the more intensive therapy.

Eileen M. O’Reilly, MD, the senior investigator on NAPOLI 3, made this point when she presented the phase 3 results at the 2023 ASCO annual meeting.

The trial “answers the question of four drugs versus two” for first-line metastatic pancreatic cancer but “does not address the question of NALIRIFOX versus FOLFIRINOX,” said Dr. O’Reilly, a pancreatic and hepatobiliary oncologist and researcher at Memorial Sloan Kettering Cancer Center in New York City.

Comparing them directly in the study “probably wouldn’t have been in the interest of the sponsor,” said Dr. O’Reilly.

With no head-to-head comparison, oncologists have been comparing NAPOLI 3 results with those from PRODIGE 4, the 2011 trial that won FOLFIRINOX its place as a first-line regimen.

When comparing the trials, median overall survival was exactly the same for the two regimens — 11.1 months. FOLFIRINOX was associated with a slightly higher 1-year survival rate — 48.4% with FOLFIRINOX vs 45.6% with NALIRIFOX.

However, Dr. O’Reilly and her colleagues also highlighted comparisons between the two trials that favored NAPOLI 3.

NAPOLI 3 had no age limit, while PRODIGE subjects were no older than 75 years. Median progression-free survival was 1 month longer among patients receiving NALIRIFOX — 7.4 months vs 6.4 months in PRODIGE — and overall response rates were higher as well — 41.8% in NAPOLI 3 vs 31.6%. Patients receiving NALIRIFOX also had lower rates of grade 3/4 neutropenia (23.8% vs 45.7%, respectively) and peripheral sensory neuropathy (3.5% vs 9.0%, respectively).

The authors explained that the lower rate of neuropathy could be because NALIRIFOX uses a lower dose of oxaliplatin (FOLFIRINOX), at 60 mg/m² instead of 85 mg/m².
 

Is It Worth It?

During a presentation of the phase 3 findings last year, study author Zev A. Wainberg, MD, of the University of California, Los Angeles, said the NALIRIFOX regimen can be considered the new reference regimen for first-line treatment of metastatic pancreatic adenocarcinoma.

The study discussant, Laura Goff, MD, MSCI, of Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, agreed that the results support the NALIRIFOX regimen as “the new standard for fit patients.”

However, other oncologists remain skeptical about the benefits of the new regimen over FOLFIRINOX for patients with metastatic pancreatic adenocarcinoma.

In a recent editorial, Dr. Garrido-Laguna and University of Utah gastrointestinal oncologist Christopher Nevala-Plagemann, MD, compared the evidence for both regimens.

The experts pointed out that overall response rates were assessed by investigators in NAPOLI 3 and not by an independent review committee, as in PRODIGE 4, and might have been overestimated.

Although the lack of an age limit was touted as a benefit of NAPOLI 3, Dr. Garrido-Laguna and Dr. Nevala-Plagemann doubt whether enough patients over 75 years old participated to draw any meaningful conclusions about using NALIRIFOX in older, frailer patients. If anything, patients in PRODIGE 4 might have been less fit because, among other things, the trial allowed patients with serum albumins < 3 g/dL.

On the adverse event front, the authors highlighted the higher incidences of grade 3 or worse diarrhea with NALIRIFOX (20% vs 12.7%) and questioned if there truly is less neutropenia with NALIRIFOX because high-risk patients in NAPOLI 3 were treated with granulocyte colony-stimulating factor to prevent it. The pair also questioned whether the differences in neuropathy rates between the two trials were big enough to be clinically meaningful.

Insights from a recent meta-analysis may further clarify some of the lingering questions about the efficacy of NALIRIFOX vs FOLFIRINOX.

In the analysis, the team found no meaningful difference in overall and progression-free survival between the two regimens. Differences in rates of peripheral neuropathy and diarrhea were not statistically significant, but NALIRIFOX did carry a statistically significant advantage in lower rates of febrile neutropenia, thrombocytopenia, and vomiting.

The team concluded that “NALIRIFOX and FOLFIRINOX may provide equal efficacy as first-line treatment of metastatic pancreatic cancer, but with different toxicity profiles,” and called for careful patient selection when choosing between the two regimens as well as consideration of financial toxicity.

Dr. Garrido-Laguna had a different take. With the current data, NALIRIFOX does not seem to “add anything substantially different to what we already” have with FOLFIRINOX, he told this news organization. Given that, “we can’t really justify NALIRIFOX over FOLFIRINOX without more of a head-to-head comparison.”

The higher cost of NALIRIFOX, in particular, remains a major drawback.

“We think it would be an economic disservice to our healthcare systems if we used NALIRIFOX instead of FOLFIRINOX for these patients on the basis of [NAPOLI 3] data,” Bishal Gyawali, MD, PhD, and Christopher Booth, MD, gastrointestinal oncologists at Queen’s University in Kingston, Ontario, Canada, said in a recent essay.

Dr. Garrido-Laguna and Dr. Nevala-Plagemann reiterated this concern.

Overall, “NALIRIFOX does not seem to raise the bar but rather exposes patients and healthcare systems to financial toxicities,” Dr. Garrido-Laguna and Dr. Nevala-Plagemann wrote in their review.

NAPOLI 3 was funded by Ipsen and PRODIGE 4 was funded by the government of France. No funding source was reported for the meta-analysis. NAPOLI 3 investigators included Ipsen employees. Dr. O’Reilly disclosed grants or contracts from Ipsen and many other companies. Dr. Garrido-Laguna reported institutional research funding from Bristol Myers Squibb, Novartis, Pfizer, and other companies, but not Ipsen. Dr. Nevala-Plagemann is an advisor for Seagen and reported institutional research funding from Theriva. Dr. Gyawali is a consultant for Vivio Health; Dr. Booth had no disclosures. Two meta-analysis authors reported grants or personal fees from Ipsen as well as ties to other companies.

A version of this article appeared on Medscape.com.

The next frontier in cancer detection could be the humble urine test.

Emerging science suggests that the body’s “liquid gold” could be particularly useful for liquid biopsies, offering a convenient, pain-free, and cost-effective way to spot otherwise hard-to-detect cancers.

“The search for cancer biomarkers that can be detected in urine could provide an enormous step forward to decrease cancer patient mortality,” said Kenneth R. Shroyer, MD, PhD, a pathologist at Stony Brook University, Stony Brook, New York, who studies cancer biomarkers.

Physicians have long known that urine can reveal a lot about our health — that’s why urinalysis has been part of medicine for 6000 years. Urine tests can detect diabetes, pregnancy, drug use, and urinary or kidney conditions.

But other conditions leave clues in urine, too, and cancer may be one of the most promising. “Urine testing could detect biomarkers of early-stage cancers, not only from local but also distant sites,” Dr. Shroyer said. It could also help flag recurrence in cancer survivors who have undergone treatment.

Granted, cancer biomarkers in urine are not nearly as widely studied as those in the blood, Dr. Shroyer noted. But a new wave of urine tests suggests research is gaining pace.

“The recent availability of high-throughput screening technologies has enabled researchers to investigate cancer from a top-down, comprehensive approach,” said Pak Kin Wong, PhD, professor of mechanical engineering, biomedical engineering, and surgery at The Pennsylvania State University. “We are starting to understand the rich information that can be obtained from urine.”

Urine is mostly water (about 95%) and urea, a metabolic byproduct that imparts that signature yellow color (about 2%). The other 3% is a mix of waste products, minerals, and other compounds the kidneys removed from the blood. Even in trace amounts, these substances say a lot.

Among them are “exfoliated cancer cells, cell-free DNA, hormones, and the urine microbiota — the collection of microbes in our urinary tract system,” Dr. Wong said.

“It is highly promising to be one of the major biological fluids used for screening, diagnosis, prognosis, and monitoring treatment efficiency in the era of precision medicine,” Dr. Wong said.

How Urine Testing Could Reveal Cancer

Still, as exciting as the prospect is, there’s a lot to consider in the hunt for cancer biomarkers in urine. These biomarkers must be able to pass through the renal nephrons (filtering units), remain stable in urine, and have high-level sensitivity, Dr. Shroyer said. They should also have high specificity for cancer vs benign conditions and be expressed at early stages, before the primary tumor has spread.

“At this stage, few circulating biomarkers have been found that are both sensitive and specific for early-stage disease,” said Dr. Shroyer.

But there are a few promising examples under investigation in humans:

Prostate cancer. Researchers at the University of Michigan have developed a urine test that detects high-grade prostate cancer more accurately than existing tests, including PHI, SelectMDx, 4Kscore, EPI, MPS, and IsoPSA.

The MyProstateScore 2.0 (MPS2) test, which looks for 18 genes associated with high-grade tumors, could reduce unnecessary biopsies in men with elevated prostate-specific antigen levels, according to a paper published in JAMA Oncology.

It makes sense. The prostate gland secretes fluid that becomes part of the semen, traces of which enter urine. After a digital rectal exam, even more prostate fluid enters the urine. If a patient has prostate cancer, genetic material from the cancer cells will infiltrate the urine.

In the MPS2 test, researchers used polymerase chain reaction (PCR) testing in urine. “The technology used for COVID PCR is essentially the same as the PCR used to detect transcripts associated with high-grade prostate cancer in urine,” said study author Arul Chinnaiyan, MD, PhD, director of the Michigan Center for Translational Pathology at the University of Michigan, Ann Arbor. “In the case of the MPS2 test, we are doing PCR on 18 genes simultaneously on urine samples.”

A statistical model uses levels of that genetic material to predict the risk for high-grade disease, helping doctors decide what to do next. At 95% sensitivity, the MPS2 model could eliminate 35%-45% of unnecessary biopsies, compared with 15%-30% for the other tests, and reduce repeat biopsies by 46%-51%, compared with 9%-21% for the other tests.

Head and neck cancer. In a paper published in JCI Insight, researchers described a test that finds ultra-short fragments of DNA in urine to enable early detection of head and neck cancers caused by human papillomavirus.

“Our data show that a relatively small volume of urine (30-60 mL) gives overall detection results comparable to a tube of blood,” said study author Muneesh Tewari, MD, PhD, professor of hematology and oncology at the University of Michigan .

A larger volume of urine could potentially “make cancer detection even more sensitive than blood,” Dr. Tewari said, “allowing cancers to be detected at the earliest stages when they are more curable.”

The team used a technique called droplet digital PCR to detect DNA fragments that are “ultra-short” (less than 50 base pairs long) and usually missed by conventional PCR testing. This transrenal cell-free tumor DNA, which travels from the tumor into the bloodstream, is broken down small enough to pass through the kidneys and into the urine. But the fragments are still long enough to carry information about the tumor’s genetic signature.

This test could spot cancer before a tumor grows big enough — about a centimeter wide and carrying a billion cells — to spot on a CT scan or other imaging test. “When we are instead detecting fragments of DNA released from a tumor,” said Dr. Tewari, “our testing methods are very sensitive and can detect DNA in urine that came from just 5-10 cells in a tumor that died and released their DNA into the blood, which then made its way into the urine.”

Pancreatic cancer. Pancreatic ductal adenocarcinoma is one of the deadliest cancers, largely because it is diagnosed so late. A urine panel now in clinical trials could help doctors diagnose the cancer before it has spread so more people can have the tumor surgically removed, improving prognosis.

Using enzyme-linked immunosorbent assay test, a common lab method that detects antibodies and other proteins, the team measured expression levels for three genes (LYVE1, REG1B, and TFF1) in urine samples collected from people up to 5 years before they were diagnosed with pancreatic cancer. The researchers combined this result with patients’ urinary creatinine levels, a common component of existing urinalysis, and their age to develop a risk score.

This score performed similarly to an existing blood test, CA19-9, in predicting patients’ risk for pancreatic cancer up to 1 year before diagnosis. When combined with CA19-9, the urinary panel helped spot cancer up to 2 years before diagnosis.

According to a paper in the International Journal of Cancer, “the urine panel and affiliated PancRISK are currently being validated in a prospective clinical study (UroPanc).” If all goes well, they could be implemented in clinical practice in a few years as a “noninvasive stratification tool” to identify patients for further testing, speeding up diagnosis, and saving lives.

Limitations and Promises

Each cancer type is different, and more research is needed to map out which substances in urine predict which cancers and to develop tests for mass adoption. “There are medical and technological hurdles to the large-scale implementation of urine analysis for complex diseases such as cancer,” said Dr. Wong.

One possibility: Scientists and clinicians could collaborate and use artificial intelligence techniques to combine urine test results with other data.

“It is likely that future diagnostics may combine urine with other biological samples such as feces and saliva, among others,” said Dr. Wong. “This is especially true when novel data science and machine learning techniques can integrate comprehensive data from patients that span genetic, proteomic, metabolic, microbiomic, and even behavioral data to evaluate a patient’s condition.”

One thing that excites Dr. Tewari about urine-based cancer testing: “We think it could be especially impactful for patients living in rural areas or other areas with less access to healthcare services,” he said.
 

A version of this article appeared on Medscape.com.

The next frontier in cancer detection could be the humble urine test.

Emerging science suggests that the body’s “liquid gold” could be particularly useful for liquid biopsies, offering a convenient, pain-free, and cost-effective way to spot otherwise hard-to-detect cancers.

“The search for cancer biomarkers that can be detected in urine could provide an enormous step forward to decrease cancer patient mortality,” said Kenneth R. Shroyer, MD, PhD, a pathologist at Stony Brook University, Stony Brook, New York, who studies cancer biomarkers.

Physicians have long known that urine can reveal a lot about our health — that’s why urinalysis has been part of medicine for 6000 years. Urine tests can detect diabetes, pregnancy, drug use, and urinary or kidney conditions.

But other conditions leave clues in urine, too, and cancer may be one of the most promising. “Urine testing could detect biomarkers of early-stage cancers, not only from local but also distant sites,” Dr. Shroyer said. It could also help flag recurrence in cancer survivors who have undergone treatment.

Granted, cancer biomarkers in urine are not nearly as widely studied as those in the blood, Dr. Shroyer noted. But a new wave of urine tests suggests research is gaining pace.

“The recent availability of high-throughput screening technologies has enabled researchers to investigate cancer from a top-down, comprehensive approach,” said Pak Kin Wong, PhD, professor of mechanical engineering, biomedical engineering, and surgery at The Pennsylvania State University. “We are starting to understand the rich information that can be obtained from urine.”

Urine is mostly water (about 95%) and urea, a metabolic byproduct that imparts that signature yellow color (about 2%). The other 3% is a mix of waste products, minerals, and other compounds the kidneys removed from the blood. Even in trace amounts, these substances say a lot.

Among them are “exfoliated cancer cells, cell-free DNA, hormones, and the urine microbiota — the collection of microbes in our urinary tract system,” Dr. Wong said.

“It is highly promising to be one of the major biological fluids used for screening, diagnosis, prognosis, and monitoring treatment efficiency in the era of precision medicine,” Dr. Wong said.

How Urine Testing Could Reveal Cancer

Still, as exciting as the prospect is, there’s a lot to consider in the hunt for cancer biomarkers in urine. These biomarkers must be able to pass through the renal nephrons (filtering units), remain stable in urine, and have high-level sensitivity, Dr. Shroyer said. They should also have high specificity for cancer vs benign conditions and be expressed at early stages, before the primary tumor has spread.

“At this stage, few circulating biomarkers have been found that are both sensitive and specific for early-stage disease,” said Dr. Shroyer.

But there are a few promising examples under investigation in humans:

Prostate cancer. Researchers at the University of Michigan have developed a urine test that detects high-grade prostate cancer more accurately than existing tests, including PHI, SelectMDx, 4Kscore, EPI, MPS, and IsoPSA.

The MyProstateScore 2.0 (MPS2) test, which looks for 18 genes associated with high-grade tumors, could reduce unnecessary biopsies in men with elevated prostate-specific antigen levels, according to a paper published in JAMA Oncology.

It makes sense. The prostate gland secretes fluid that becomes part of the semen, traces of which enter urine. After a digital rectal exam, even more prostate fluid enters the urine. If a patient has prostate cancer, genetic material from the cancer cells will infiltrate the urine.

In the MPS2 test, researchers used polymerase chain reaction (PCR) testing in urine. “The technology used for COVID PCR is essentially the same as the PCR used to detect transcripts associated with high-grade prostate cancer in urine,” said study author Arul Chinnaiyan, MD, PhD, director of the Michigan Center for Translational Pathology at the University of Michigan, Ann Arbor. “In the case of the MPS2 test, we are doing PCR on 18 genes simultaneously on urine samples.”

A statistical model uses levels of that genetic material to predict the risk for high-grade disease, helping doctors decide what to do next. At 95% sensitivity, the MPS2 model could eliminate 35%-45% of unnecessary biopsies, compared with 15%-30% for the other tests, and reduce repeat biopsies by 46%-51%, compared with 9%-21% for the other tests.

Head and neck cancer. In a paper published in JCI Insight, researchers described a test that finds ultra-short fragments of DNA in urine to enable early detection of head and neck cancers caused by human papillomavirus.

“Our data show that a relatively small volume of urine (30-60 mL) gives overall detection results comparable to a tube of blood,” said study author Muneesh Tewari, MD, PhD, professor of hematology and oncology at the University of Michigan .

A larger volume of urine could potentially “make cancer detection even more sensitive than blood,” Dr. Tewari said, “allowing cancers to be detected at the earliest stages when they are more curable.”

The team used a technique called droplet digital PCR to detect DNA fragments that are “ultra-short” (less than 50 base pairs long) and usually missed by conventional PCR testing. This transrenal cell-free tumor DNA, which travels from the tumor into the bloodstream, is broken down small enough to pass through the kidneys and into the urine. But the fragments are still long enough to carry information about the tumor’s genetic signature.

This test could spot cancer before a tumor grows big enough — about a centimeter wide and carrying a billion cells — to spot on a CT scan or other imaging test. “When we are instead detecting fragments of DNA released from a tumor,” said Dr. Tewari, “our testing methods are very sensitive and can detect DNA in urine that came from just 5-10 cells in a tumor that died and released their DNA into the blood, which then made its way into the urine.”

Pancreatic cancer. Pancreatic ductal adenocarcinoma is one of the deadliest cancers, largely because it is diagnosed so late. A urine panel now in clinical trials could help doctors diagnose the cancer before it has spread so more people can have the tumor surgically removed, improving prognosis.

Using enzyme-linked immunosorbent assay test, a common lab method that detects antibodies and other proteins, the team measured expression levels for three genes (LYVE1, REG1B, and TFF1) in urine samples collected from people up to 5 years before they were diagnosed with pancreatic cancer. The researchers combined this result with patients’ urinary creatinine levels, a common component of existing urinalysis, and their age to develop a risk score.

This score performed similarly to an existing blood test, CA19-9, in predicting patients’ risk for pancreatic cancer up to 1 year before diagnosis. When combined with CA19-9, the urinary panel helped spot cancer up to 2 years before diagnosis.

According to a paper in the International Journal of Cancer, “the urine panel and affiliated PancRISK are currently being validated in a prospective clinical study (UroPanc).” If all goes well, they could be implemented in clinical practice in a few years as a “noninvasive stratification tool” to identify patients for further testing, speeding up diagnosis, and saving lives.

Limitations and Promises

Each cancer type is different, and more research is needed to map out which substances in urine predict which cancers and to develop tests for mass adoption. “There are medical and technological hurdles to the large-scale implementation of urine analysis for complex diseases such as cancer,” said Dr. Wong.

One possibility: Scientists and clinicians could collaborate and use artificial intelligence techniques to combine urine test results with other data.

“It is likely that future diagnostics may combine urine with other biological samples such as feces and saliva, among others,” said Dr. Wong. “This is especially true when novel data science and machine learning techniques can integrate comprehensive data from patients that span genetic, proteomic, metabolic, microbiomic, and even behavioral data to evaluate a patient’s condition.”

One thing that excites Dr. Tewari about urine-based cancer testing: “We think it could be especially impactful for patients living in rural areas or other areas with less access to healthcare services,” he said.
 

A version of this article appeared on Medscape.com.

The next frontier in cancer detection could be the humble urine test.

Emerging science suggests that the body’s “liquid gold” could be particularly useful for liquid biopsies, offering a convenient, pain-free, and cost-effective way to spot otherwise hard-to-detect cancers.

“The search for cancer biomarkers that can be detected in urine could provide an enormous step forward to decrease cancer patient mortality,” said Kenneth R. Shroyer, MD, PhD, a pathologist at Stony Brook University, Stony Brook, New York, who studies cancer biomarkers.

Physicians have long known that urine can reveal a lot about our health — that’s why urinalysis has been part of medicine for 6000 years. Urine tests can detect diabetes, pregnancy, drug use, and urinary or kidney conditions.

But other conditions leave clues in urine, too, and cancer may be one of the most promising. “Urine testing could detect biomarkers of early-stage cancers, not only from local but also distant sites,” Dr. Shroyer said. It could also help flag recurrence in cancer survivors who have undergone treatment.

Granted, cancer biomarkers in urine are not nearly as widely studied as those in the blood, Dr. Shroyer noted. But a new wave of urine tests suggests research is gaining pace.

“The recent availability of high-throughput screening technologies has enabled researchers to investigate cancer from a top-down, comprehensive approach,” said Pak Kin Wong, PhD, professor of mechanical engineering, biomedical engineering, and surgery at The Pennsylvania State University. “We are starting to understand the rich information that can be obtained from urine.”

Urine is mostly water (about 95%) and urea, a metabolic byproduct that imparts that signature yellow color (about 2%). The other 3% is a mix of waste products, minerals, and other compounds the kidneys removed from the blood. Even in trace amounts, these substances say a lot.

Among them are “exfoliated cancer cells, cell-free DNA, hormones, and the urine microbiota — the collection of microbes in our urinary tract system,” Dr. Wong said.

“It is highly promising to be one of the major biological fluids used for screening, diagnosis, prognosis, and monitoring treatment efficiency in the era of precision medicine,” Dr. Wong said.

How Urine Testing Could Reveal Cancer

Still, as exciting as the prospect is, there’s a lot to consider in the hunt for cancer biomarkers in urine. These biomarkers must be able to pass through the renal nephrons (filtering units), remain stable in urine, and have high-level sensitivity, Dr. Shroyer said. They should also have high specificity for cancer vs benign conditions and be expressed at early stages, before the primary tumor has spread.

“At this stage, few circulating biomarkers have been found that are both sensitive and specific for early-stage disease,” said Dr. Shroyer.

But there are a few promising examples under investigation in humans:

Prostate cancer. Researchers at the University of Michigan have developed a urine test that detects high-grade prostate cancer more accurately than existing tests, including PHI, SelectMDx, 4Kscore, EPI, MPS, and IsoPSA.

The MyProstateScore 2.0 (MPS2) test, which looks for 18 genes associated with high-grade tumors, could reduce unnecessary biopsies in men with elevated prostate-specific antigen levels, according to a paper published in JAMA Oncology.

It makes sense. The prostate gland secretes fluid that becomes part of the semen, traces of which enter urine. After a digital rectal exam, even more prostate fluid enters the urine. If a patient has prostate cancer, genetic material from the cancer cells will infiltrate the urine.

In the MPS2 test, researchers used polymerase chain reaction (PCR) testing in urine. “The technology used for COVID PCR is essentially the same as the PCR used to detect transcripts associated with high-grade prostate cancer in urine,” said study author Arul Chinnaiyan, MD, PhD, director of the Michigan Center for Translational Pathology at the University of Michigan, Ann Arbor. “In the case of the MPS2 test, we are doing PCR on 18 genes simultaneously on urine samples.”

A statistical model uses levels of that genetic material to predict the risk for high-grade disease, helping doctors decide what to do next. At 95% sensitivity, the MPS2 model could eliminate 35%-45% of unnecessary biopsies, compared with 15%-30% for the other tests, and reduce repeat biopsies by 46%-51%, compared with 9%-21% for the other tests.

Head and neck cancer. In a paper published in JCI Insight, researchers described a test that finds ultra-short fragments of DNA in urine to enable early detection of head and neck cancers caused by human papillomavirus.

“Our data show that a relatively small volume of urine (30-60 mL) gives overall detection results comparable to a tube of blood,” said study author Muneesh Tewari, MD, PhD, professor of hematology and oncology at the University of Michigan .

A larger volume of urine could potentially “make cancer detection even more sensitive than blood,” Dr. Tewari said, “allowing cancers to be detected at the earliest stages when they are more curable.”

The team used a technique called droplet digital PCR to detect DNA fragments that are “ultra-short” (less than 50 base pairs long) and usually missed by conventional PCR testing. This transrenal cell-free tumor DNA, which travels from the tumor into the bloodstream, is broken down small enough to pass through the kidneys and into the urine. But the fragments are still long enough to carry information about the tumor’s genetic signature.

This test could spot cancer before a tumor grows big enough — about a centimeter wide and carrying a billion cells — to spot on a CT scan or other imaging test. “When we are instead detecting fragments of DNA released from a tumor,” said Dr. Tewari, “our testing methods are very sensitive and can detect DNA in urine that came from just 5-10 cells in a tumor that died and released their DNA into the blood, which then made its way into the urine.”

Pancreatic cancer. Pancreatic ductal adenocarcinoma is one of the deadliest cancers, largely because it is diagnosed so late. A urine panel now in clinical trials could help doctors diagnose the cancer before it has spread so more people can have the tumor surgically removed, improving prognosis.

Using enzyme-linked immunosorbent assay test, a common lab method that detects antibodies and other proteins, the team measured expression levels for three genes (LYVE1, REG1B, and TFF1) in urine samples collected from people up to 5 years before they were diagnosed with pancreatic cancer. The researchers combined this result with patients’ urinary creatinine levels, a common component of existing urinalysis, and their age to develop a risk score.

This score performed similarly to an existing blood test, CA19-9, in predicting patients’ risk for pancreatic cancer up to 1 year before diagnosis. When combined with CA19-9, the urinary panel helped spot cancer up to 2 years before diagnosis.

According to a paper in the International Journal of Cancer, “the urine panel and affiliated PancRISK are currently being validated in a prospective clinical study (UroPanc).” If all goes well, they could be implemented in clinical practice in a few years as a “noninvasive stratification tool” to identify patients for further testing, speeding up diagnosis, and saving lives.

Limitations and Promises

Each cancer type is different, and more research is needed to map out which substances in urine predict which cancers and to develop tests for mass adoption. “There are medical and technological hurdles to the large-scale implementation of urine analysis for complex diseases such as cancer,” said Dr. Wong.

One possibility: Scientists and clinicians could collaborate and use artificial intelligence techniques to combine urine test results with other data.

“It is likely that future diagnostics may combine urine with other biological samples such as feces and saliva, among others,” said Dr. Wong. “This is especially true when novel data science and machine learning techniques can integrate comprehensive data from patients that span genetic, proteomic, metabolic, microbiomic, and even behavioral data to evaluate a patient’s condition.”

One thing that excites Dr. Tewari about urine-based cancer testing: “We think it could be especially impactful for patients living in rural areas or other areas with less access to healthcare services,” he said.
 

A version of this article appeared on Medscape.com.

Breast cancer mortality was significantly lower among patients who used statins than in those who did not use these cholesterol-lowering drugs, a new study finds.

Previous research examining the association between cholesterol and breast cancer metabolism suggests that cholesterol-lowering medications such as statins may improve outcomes in breast cancer patients, Sixten Harborg, a medical student and PhD student at Aarhus University, Denmark, said in a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

In addition, cardiovascular-related death is the second most common cause of death for breast cancer survivors, and given the survival rates in early breast cancer, there is a demand for cardioprotective initiatives and maintenance of cardioprotective drugs after diagnosis, he said in an interview.
 

What Is Known About Statins and Breast Cancer?

Statins are the most common drugs used to lower cholesterol and may deprive tumor cells of the cholesterol needed for cell membrane synthesis, Mr. Harborg said in his presentation.

Data from a randomized trial published in the Journal of Clinical Oncology in 2017 showed significantly improved disease-free survival, breast cancer–free interval, and distant recurrence–free interval in early stage breast cancer patients randomized to cholesterol-lowering medication vs. those who did not receive cholesterol-lowering medication.

The 2017 study prompted the creation of the MASTER study, a randomized, multicenter, double-blind, placebo-controlled trial comparing standard adjuvant therapy plus placebo to standard adjuvant therapy plus atorvastatin in patients with early breast cancer (NCT04601116), Mr. Harborg said. The MASTER trial is currently recruiting patients in Denmark.
 

How Was the Current Study Designed?

To provide preliminary analysis, Mr. Harborg and colleagues used an emulation trial design based on electronic health care data from 110,160 females with a diagnosis of stage I, II, or III breast cancer who were part of the Danish Breast Cancer Group, a national clinical registry in Denmark, between 2000 and 2020.

As defined in the European Journal of Epidemiology in 2017, target trial emulation involves application of randomized trial designs to observational data with the goal of improving the quality of observational epidemiology when a comparator trial is not yet available.

The researchers created a cohort of patients based on electronic health care data to simulate a target trial of the use of atorvastatin after breast cancer diagnosis. Patients were randomized to one of two treatment strategies: starting to use statins within 36 months of diagnosis, or not using statins. The primary outcome was death from breast cancer. The follow-up for the MASTER study starts with inclusion and ends with death, emigration from Denmark, end of clinical follow-up, or 10 years of follow-up (whichever comes first); the follow-up was the same in the current study.

The researchers calculated hazard ratios (HR) of breast cancer mortality in statin users vs. non–statin users and used a technique known as inverse-probability of censoring-weighting (IPCW) to estimate the effects of statin use based on prognostic factors.
 

What Did the Results Show?

The results favored statin use for improved survival in early breast cancer patients, Mr. Harborg said. Overall, the hazard ratio for breast cancer mortality was 0.96 in statin users compared with non–statin users, and was similar in both a Cox regression analysis (HR 0.81), and in a 10-year landmark analysis (HR 0.86).

The difference in mortality between statin and non–statin users was even stronger in patients who were receiving adjuvant chemotherapy (HR 0.94, 0.64, and 0.76 on the IPCW, Cox, and landmark analyses, respectively).

The results were in line with previous reports of statins’ effect on breast cancer survival, Mr. Harborg said in an interview.

“We believe the results encourage the continuous effort of the currently enrolling MASTER trial,” he said.

The results also suggest that deprescribing statins at the time of breast cancer diagnosis is not recommended, and that statin treatment can safely be prescribed to breast cancer patients with increased cardiovascular disease risk and/or dyslipidemia, Mr. Harborg said in the interview.
 

What Is the Takeaway Message for Clinical Practice?

“The clinical takeaway from our study is that statin use is associated with reduced risk of dying from breast cancer, but that it is not possible to determine the true effect of statins on breast cancer survival without a randomized, placebo-controlled trial,” Mr. Harborg told this publication. “Statins are inexpensive and well-tolerated drugs and may have a beneficial effect in terms of survival for breast cancer patients. However, with the current level of evidence [because the MASTER study is ongoing], we still cannot recommend that oncologists prescribe statins to prevent mortality from breast cancer,” he said.

What Are the Next Steps for Research?

The findings were limited by the study design, and real-world data are needed, Dr. Harborg said. Other limitations include the presence of residual bias, and the use of data based on prescription codes, but these were not considered to have an effect on the main conclusion of the study, Mr. Harborg said in the interview.

However, the results suggest that the addition of statins may improve outcomes for early breast cancer patients, especially when used with chemotherapy, and support the value of the ongoing MASTER study, he concluded.

Ultimately, the MASTER study will provide a more definitive answer to the question of whether statins should be added to the adjuvant treatment regimen of breast cancer to improve breast cancer outcomes, he said.
 

What Do Clinicians Think of the Study?

The current study is timely and highlights the need for phase 3 trials to examine the potential of statin use for breast cancer outcomes, Malinda T. West, MD, a medical oncologist and breast oncologist at the University of Wisconsin Carbone Cancer Center, Madison, said in an interview.

Questions for future research include whether statins can be used in combination with adjuvant abemaciclib if indicated, or how to best sequence these agents, said Dr. West, who was not involved in the study. Other questions raised by the current study include whether other cholesterol-lowering agents have a potential adjuvant benefit in reducing breast cancer recurrent and/or mortality, and whether the addition of statins would benefit subgroups such as HER2+ and triple negative breast cancer, she said.

“I was not surprised to see another study reporting benefit with statins and reduced risk of breast cancer recurrence and/or mortality, but I think the larger question is defining the subgroups who benefit the most, and identifying predictors for benefit or resistance,” Dr. West said in an interview.

Previous studies have shown that cholesterol elevation, specifically LDL levels, can be linked to increased tumor growth in breast cancer, so the lower mortality risk associated with lipid-lowering therapies in the current study was consistent, Peyton L. Reves, MD, a hematology/oncology fellow, also at the University of Wisconsin, said in an interview. In practice, data from the current study and previous research could be especially useful for patients with elevated LDL levels, said Dr. Reves, who was not involved in the study.

“These results could impact clinical practice in many ways, including leading to routine cholesterol monitoring in breast cancer patients on adjuvant therapy as well as the addition of lipid-lowering therapy with statins in these patients,” Dr. Reves said.

The findings showing particular benefit for patients on adjuvant chemotherapy highlight the need for more research on this specific population and the effect of statins on overall breast cancer mortality, to explore the extent to which the results of the current study were driven by the benefit seen in patients receiving adjuvant chemotherapy, Dr. Reves said.

The study was supported by Director Michael Hermann Nielsen’s Memorial Grant, Manufacturer Einar Willumsen’s Memorial Grant, Astrid Thaysen’s Grant for Medical Basic Research, Eva and Henry Fraenkel’s Memorial Fund, and the Novo Nordisk Foundation.

The researchers had no financial conflicts to disclose. Dr. West and Dr. Reves had no financial conflicts to disclose.

Breast cancer mortality was significantly lower among patients who used statins than in those who did not use these cholesterol-lowering drugs, a new study finds.

Previous research examining the association between cholesterol and breast cancer metabolism suggests that cholesterol-lowering medications such as statins may improve outcomes in breast cancer patients, Sixten Harborg, a medical student and PhD student at Aarhus University, Denmark, said in a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

In addition, cardiovascular-related death is the second most common cause of death for breast cancer survivors, and given the survival rates in early breast cancer, there is a demand for cardioprotective initiatives and maintenance of cardioprotective drugs after diagnosis, he said in an interview.
 

What Is Known About Statins and Breast Cancer?

Statins are the most common drugs used to lower cholesterol and may deprive tumor cells of the cholesterol needed for cell membrane synthesis, Mr. Harborg said in his presentation.

Data from a randomized trial published in the Journal of Clinical Oncology in 2017 showed significantly improved disease-free survival, breast cancer–free interval, and distant recurrence–free interval in early stage breast cancer patients randomized to cholesterol-lowering medication vs. those who did not receive cholesterol-lowering medication.

The 2017 study prompted the creation of the MASTER study, a randomized, multicenter, double-blind, placebo-controlled trial comparing standard adjuvant therapy plus placebo to standard adjuvant therapy plus atorvastatin in patients with early breast cancer (NCT04601116), Mr. Harborg said. The MASTER trial is currently recruiting patients in Denmark.
 

How Was the Current Study Designed?

To provide preliminary analysis, Mr. Harborg and colleagues used an emulation trial design based on electronic health care data from 110,160 females with a diagnosis of stage I, II, or III breast cancer who were part of the Danish Breast Cancer Group, a national clinical registry in Denmark, between 2000 and 2020.

As defined in the European Journal of Epidemiology in 2017, target trial emulation involves application of randomized trial designs to observational data with the goal of improving the quality of observational epidemiology when a comparator trial is not yet available.

The researchers created a cohort of patients based on electronic health care data to simulate a target trial of the use of atorvastatin after breast cancer diagnosis. Patients were randomized to one of two treatment strategies: starting to use statins within 36 months of diagnosis, or not using statins. The primary outcome was death from breast cancer. The follow-up for the MASTER study starts with inclusion and ends with death, emigration from Denmark, end of clinical follow-up, or 10 years of follow-up (whichever comes first); the follow-up was the same in the current study.

The researchers calculated hazard ratios (HR) of breast cancer mortality in statin users vs. non–statin users and used a technique known as inverse-probability of censoring-weighting (IPCW) to estimate the effects of statin use based on prognostic factors.
 

What Did the Results Show?

The results favored statin use for improved survival in early breast cancer patients, Mr. Harborg said. Overall, the hazard ratio for breast cancer mortality was 0.96 in statin users compared with non–statin users, and was similar in both a Cox regression analysis (HR 0.81), and in a 10-year landmark analysis (HR 0.86).

The difference in mortality between statin and non–statin users was even stronger in patients who were receiving adjuvant chemotherapy (HR 0.94, 0.64, and 0.76 on the IPCW, Cox, and landmark analyses, respectively).

The results were in line with previous reports of statins’ effect on breast cancer survival, Mr. Harborg said in an interview.

“We believe the results encourage the continuous effort of the currently enrolling MASTER trial,” he said.

The results also suggest that deprescribing statins at the time of breast cancer diagnosis is not recommended, and that statin treatment can safely be prescribed to breast cancer patients with increased cardiovascular disease risk and/or dyslipidemia, Mr. Harborg said in the interview.
 

What Is the Takeaway Message for Clinical Practice?

“The clinical takeaway from our study is that statin use is associated with reduced risk of dying from breast cancer, but that it is not possible to determine the true effect of statins on breast cancer survival without a randomized, placebo-controlled trial,” Mr. Harborg told this publication. “Statins are inexpensive and well-tolerated drugs and may have a beneficial effect in terms of survival for breast cancer patients. However, with the current level of evidence [because the MASTER study is ongoing], we still cannot recommend that oncologists prescribe statins to prevent mortality from breast cancer,” he said.

What Are the Next Steps for Research?

The findings were limited by the study design, and real-world data are needed, Dr. Harborg said. Other limitations include the presence of residual bias, and the use of data based on prescription codes, but these were not considered to have an effect on the main conclusion of the study, Mr. Harborg said in the interview.

However, the results suggest that the addition of statins may improve outcomes for early breast cancer patients, especially when used with chemotherapy, and support the value of the ongoing MASTER study, he concluded.

Ultimately, the MASTER study will provide a more definitive answer to the question of whether statins should be added to the adjuvant treatment regimen of breast cancer to improve breast cancer outcomes, he said.
 

What Do Clinicians Think of the Study?

The current study is timely and highlights the need for phase 3 trials to examine the potential of statin use for breast cancer outcomes, Malinda T. West, MD, a medical oncologist and breast oncologist at the University of Wisconsin Carbone Cancer Center, Madison, said in an interview.

Questions for future research include whether statins can be used in combination with adjuvant abemaciclib if indicated, or how to best sequence these agents, said Dr. West, who was not involved in the study. Other questions raised by the current study include whether other cholesterol-lowering agents have a potential adjuvant benefit in reducing breast cancer recurrent and/or mortality, and whether the addition of statins would benefit subgroups such as HER2+ and triple negative breast cancer, she said.

“I was not surprised to see another study reporting benefit with statins and reduced risk of breast cancer recurrence and/or mortality, but I think the larger question is defining the subgroups who benefit the most, and identifying predictors for benefit or resistance,” Dr. West said in an interview.

Previous studies have shown that cholesterol elevation, specifically LDL levels, can be linked to increased tumor growth in breast cancer, so the lower mortality risk associated with lipid-lowering therapies in the current study was consistent, Peyton L. Reves, MD, a hematology/oncology fellow, also at the University of Wisconsin, said in an interview. In practice, data from the current study and previous research could be especially useful for patients with elevated LDL levels, said Dr. Reves, who was not involved in the study.

“These results could impact clinical practice in many ways, including leading to routine cholesterol monitoring in breast cancer patients on adjuvant therapy as well as the addition of lipid-lowering therapy with statins in these patients,” Dr. Reves said.

The findings showing particular benefit for patients on adjuvant chemotherapy highlight the need for more research on this specific population and the effect of statins on overall breast cancer mortality, to explore the extent to which the results of the current study were driven by the benefit seen in patients receiving adjuvant chemotherapy, Dr. Reves said.

The study was supported by Director Michael Hermann Nielsen’s Memorial Grant, Manufacturer Einar Willumsen’s Memorial Grant, Astrid Thaysen’s Grant for Medical Basic Research, Eva and Henry Fraenkel’s Memorial Fund, and the Novo Nordisk Foundation.

The researchers had no financial conflicts to disclose. Dr. West and Dr. Reves had no financial conflicts to disclose.

Breast cancer mortality was significantly lower among patients who used statins than in those who did not use these cholesterol-lowering drugs, a new study finds.

Previous research examining the association between cholesterol and breast cancer metabolism suggests that cholesterol-lowering medications such as statins may improve outcomes in breast cancer patients, Sixten Harborg, a medical student and PhD student at Aarhus University, Denmark, said in a presentation at the European Society for Medical Oncology (ESMO) Breast Cancer annual congress.

In addition, cardiovascular-related death is the second most common cause of death for breast cancer survivors, and given the survival rates in early breast cancer, there is a demand for cardioprotective initiatives and maintenance of cardioprotective drugs after diagnosis, he said in an interview.
 

What Is Known About Statins and Breast Cancer?

Statins are the most common drugs used to lower cholesterol and may deprive tumor cells of the cholesterol needed for cell membrane synthesis, Mr. Harborg said in his presentation.

Data from a randomized trial published in the Journal of Clinical Oncology in 2017 showed significantly improved disease-free survival, breast cancer–free interval, and distant recurrence–free interval in early stage breast cancer patients randomized to cholesterol-lowering medication vs. those who did not receive cholesterol-lowering medication.

The 2017 study prompted the creation of the MASTER study, a randomized, multicenter, double-blind, placebo-controlled trial comparing standard adjuvant therapy plus placebo to standard adjuvant therapy plus atorvastatin in patients with early breast cancer (NCT04601116), Mr. Harborg said. The MASTER trial is currently recruiting patients in Denmark.
 

How Was the Current Study Designed?

To provide preliminary analysis, Mr. Harborg and colleagues used an emulation trial design based on electronic health care data from 110,160 females with a diagnosis of stage I, II, or III breast cancer who were part of the Danish Breast Cancer Group, a national clinical registry in Denmark, between 2000 and 2020.

As defined in the European Journal of Epidemiology in 2017, target trial emulation involves application of randomized trial designs to observational data with the goal of improving the quality of observational epidemiology when a comparator trial is not yet available.

The researchers created a cohort of patients based on electronic health care data to simulate a target trial of the use of atorvastatin after breast cancer diagnosis. Patients were randomized to one of two treatment strategies: starting to use statins within 36 months of diagnosis, or not using statins. The primary outcome was death from breast cancer. The follow-up for the MASTER study starts with inclusion and ends with death, emigration from Denmark, end of clinical follow-up, or 10 years of follow-up (whichever comes first); the follow-up was the same in the current study.

The researchers calculated hazard ratios (HR) of breast cancer mortality in statin users vs. non–statin users and used a technique known as inverse-probability of censoring-weighting (IPCW) to estimate the effects of statin use based on prognostic factors.
 

What Did the Results Show?

The results favored statin use for improved survival in early breast cancer patients, Mr. Harborg said. Overall, the hazard ratio for breast cancer mortality was 0.96 in statin users compared with non–statin users, and was similar in both a Cox regression analysis (HR 0.81), and in a 10-year landmark analysis (HR 0.86).

The difference in mortality between statin and non–statin users was even stronger in patients who were receiving adjuvant chemotherapy (HR 0.94, 0.64, and 0.76 on the IPCW, Cox, and landmark analyses, respectively).

The results were in line with previous reports of statins’ effect on breast cancer survival, Mr. Harborg said in an interview.

“We believe the results encourage the continuous effort of the currently enrolling MASTER trial,” he said.

The results also suggest that deprescribing statins at the time of breast cancer diagnosis is not recommended, and that statin treatment can safely be prescribed to breast cancer patients with increased cardiovascular disease risk and/or dyslipidemia, Mr. Harborg said in the interview.
 

What Is the Takeaway Message for Clinical Practice?

“The clinical takeaway from our study is that statin use is associated with reduced risk of dying from breast cancer, but that it is not possible to determine the true effect of statins on breast cancer survival without a randomized, placebo-controlled trial,” Mr. Harborg told this publication. “Statins are inexpensive and well-tolerated drugs and may have a beneficial effect in terms of survival for breast cancer patients. However, with the current level of evidence [because the MASTER study is ongoing], we still cannot recommend that oncologists prescribe statins to prevent mortality from breast cancer,” he said.

What Are the Next Steps for Research?

The findings were limited by the study design, and real-world data are needed, Dr. Harborg said. Other limitations include the presence of residual bias, and the use of data based on prescription codes, but these were not considered to have an effect on the main conclusion of the study, Mr. Harborg said in the interview.

However, the results suggest that the addition of statins may improve outcomes for early breast cancer patients, especially when used with chemotherapy, and support the value of the ongoing MASTER study, he concluded.

Ultimately, the MASTER study will provide a more definitive answer to the question of whether statins should be added to the adjuvant treatment regimen of breast cancer to improve breast cancer outcomes, he said.
 

What Do Clinicians Think of the Study?

The current study is timely and highlights the need for phase 3 trials to examine the potential of statin use for breast cancer outcomes, Malinda T. West, MD, a medical oncologist and breast oncologist at the University of Wisconsin Carbone Cancer Center, Madison, said in an interview.

Questions for future research include whether statins can be used in combination with adjuvant abemaciclib if indicated, or how to best sequence these agents, said Dr. West, who was not involved in the study. Other questions raised by the current study include whether other cholesterol-lowering agents have a potential adjuvant benefit in reducing breast cancer recurrent and/or mortality, and whether the addition of statins would benefit subgroups such as HER2+ and triple negative breast cancer, she said.

“I was not surprised to see another study reporting benefit with statins and reduced risk of breast cancer recurrence and/or mortality, but I think the larger question is defining the subgroups who benefit the most, and identifying predictors for benefit or resistance,” Dr. West said in an interview.

Previous studies have shown that cholesterol elevation, specifically LDL levels, can be linked to increased tumor growth in breast cancer, so the lower mortality risk associated with lipid-lowering therapies in the current study was consistent, Peyton L. Reves, MD, a hematology/oncology fellow, also at the University of Wisconsin, said in an interview. In practice, data from the current study and previous research could be especially useful for patients with elevated LDL levels, said Dr. Reves, who was not involved in the study.

“These results could impact clinical practice in many ways, including leading to routine cholesterol monitoring in breast cancer patients on adjuvant therapy as well as the addition of lipid-lowering therapy with statins in these patients,” Dr. Reves said.

The findings showing particular benefit for patients on adjuvant chemotherapy highlight the need for more research on this specific population and the effect of statins on overall breast cancer mortality, to explore the extent to which the results of the current study were driven by the benefit seen in patients receiving adjuvant chemotherapy, Dr. Reves said.

The study was supported by Director Michael Hermann Nielsen’s Memorial Grant, Manufacturer Einar Willumsen’s Memorial Grant, Astrid Thaysen’s Grant for Medical Basic Research, Eva and Henry Fraenkel’s Memorial Fund, and the Novo Nordisk Foundation.

The researchers had no financial conflicts to disclose. Dr. West and Dr. Reves had no financial conflicts to disclose.

A California jury has awarded $14 million to a former University of California, Los Angeles (UCLA) oncologist who claimed she was paid thousands less than her male colleagues and wrongfully terminated after her complaints of gender-based harassment and intimidation were ignored by program leadership.

The decision comes after a lengthy 8-year legal battle in which an appellate judge reversed a previous jury decision in her favor.

Lauren Pinter-Brown, MD, a hematologic oncologist, was hired in 2005 by the University of California, Los Angeles School of Medicine — now called UCLA’s David Geffen School of Medicine. As the school’s lymphoma program director, she conducted clinical research alongside other oncology doctors, including Sven de Vos, MD.

She claimed that her professional relationship with Dr. de Vos became contentious after he demonstrated “oppositional” and “disrespectful” behavior at team meetings, such as talking over her and turning his chair so Dr. Pinter-Brown faced his back. Court documents indicated that Dr. de Vos refused to use Dr. Pinter-Brown’s title in front of colleagues despite doing so for male counterparts.

Dr. Pinter-Brown argued that she was treated as the “butt of a joke” by Dr. de Vos and other male colleagues. In 2016, she sued Dr. de Vos, the university, and its governing body, the Board of Regents, for wrongful termination.

She was awarded a $13 million verdict in 2018. However, the California Court of Appeals overturned it in 2020 after concluding that several mistakes during the court proceedings impeded the school’s right to a fair and impartial trial. The case was retried, culminating in the even higher award of $14 million issued on May 9.

“Two juries have come to virtually identical findings showing multiple problems at UCLA involving gender discrimination,” Dr. Pinter-Brown’s attorney, Carney R. Shegerian, JD, told this news organization.

A spokesperson from UCLA’s David Geffen School of Medicine said administrators are carefully reviewing the new decision.

The spokesperson told this news organization that the medical school and its health system remain “deeply committed to maintaining a workplace free from discrimination, intimidation, retaliation, or harassment of any kind” and fostering a “respectful and inclusive environment ... in research, medical education, and patient care.”
 

Gender Pay Disparities Persist in Medicine

The gender pay gap in medicine is well documented. The 2024 Medscape Physician Compensation Report found that male doctors earn about 29% more than their female counterparts, with the disparity growing larger among specialists. In addition, a recent JAMA Health Forum study found that male physicians earned 21%-24% more per hour than female physicians.

Dr. Pinter-Brown, who now works at the University of California, Irvine, alleged that she was paid $200,000 less annually, on average, than her male colleagues.

That’s not surprising, says Martha Gulati, MD, professor and director of preventive cardiology at Cedars-Sinai Smidt Heart Institute, Los Angeles. She coauthored a commentary about gender disparities in JAMA Network Open. Dr. Gulati told this news organization that even a “small” pay disparity of $100,000 annually adds up.

“Let’s say the [male physician] invests it at 3% and adds to it yearly. Even without a raise, in 20 years, that is approximately $3 million,” Dr. Gulati explained. “Once you find out you are paid less than your male colleagues, you are upset. Your sense of value and self-worth disappears.”

Eileen Barrett, MD, MPH, president-elect of the American Medical Women’s Association, said that gender discrimination is likely more prevalent than research indicates. She told this news organization that self-doubt and fear of retaliation keep many from exposing the mistreatment.

Although more women are entering medicine, too few rise to the highest positions, Dr. Barrett said.

“Unfortunately, many are pulled and pushed into specialties and subspecialties that have lower compensation and are not promoted to leadership, so just having numbers isn’t enough to achieve equity,” Dr. Barrett said.

Dr. Pinter-Brown claimed she was repeatedly harassed and intimidated by Dr. de Vos from 2008 to 2015. Despite voicing concerns multiple times about the discriminatory behavior, the only resolutions offered by the male-dominated program leadership were for her to separate from the group and conduct lymphoma research independently or to avoid interacting with Dr. de Vos, court records said.

Even the school’s male Title IX officer, Jan Tillisch, MD, who handled gender-based discrimination complaints, reportedly made sexist comments. When Dr. Pinter-Brown sought his help, he allegedly told her that she had a reputation as an “angry woman” and “diva,” court records showed.

According to court documents, Dr. Pinter-Brown endured nitpicking and research audits as retaliation for speaking out, temporarily suspending her research privileges. She said she was subsequently removed from the director position and replaced by Dr. de Vos.

Female physicians who report discriminatory behavior often have unfavorable outcomes and risk future career prospects, Dr. Gulati said.

To shift this dynamic, she said institutions must increase transparency and practices that support female doctors receiving “equal pay for equal work.”
 

A version of this article appeared on Medscape.com.

A California jury has awarded $14 million to a former University of California, Los Angeles (UCLA) oncologist who claimed she was paid thousands less than her male colleagues and wrongfully terminated after her complaints of gender-based harassment and intimidation were ignored by program leadership.

The decision comes after a lengthy 8-year legal battle in which an appellate judge reversed a previous jury decision in her favor.

Lauren Pinter-Brown, MD, a hematologic oncologist, was hired in 2005 by the University of California, Los Angeles School of Medicine — now called UCLA’s David Geffen School of Medicine. As the school’s lymphoma program director, she conducted clinical research alongside other oncology doctors, including Sven de Vos, MD.

She claimed that her professional relationship with Dr. de Vos became contentious after he demonstrated “oppositional” and “disrespectful” behavior at team meetings, such as talking over her and turning his chair so Dr. Pinter-Brown faced his back. Court documents indicated that Dr. de Vos refused to use Dr. Pinter-Brown’s title in front of colleagues despite doing so for male counterparts.

Dr. Pinter-Brown argued that she was treated as the “butt of a joke” by Dr. de Vos and other male colleagues. In 2016, she sued Dr. de Vos, the university, and its governing body, the Board of Regents, for wrongful termination.

She was awarded a $13 million verdict in 2018. However, the California Court of Appeals overturned it in 2020 after concluding that several mistakes during the court proceedings impeded the school’s right to a fair and impartial trial. The case was retried, culminating in the even higher award of $14 million issued on May 9.

“Two juries have come to virtually identical findings showing multiple problems at UCLA involving gender discrimination,” Dr. Pinter-Brown’s attorney, Carney R. Shegerian, JD, told this news organization.

A spokesperson from UCLA’s David Geffen School of Medicine said administrators are carefully reviewing the new decision.

The spokesperson told this news organization that the medical school and its health system remain “deeply committed to maintaining a workplace free from discrimination, intimidation, retaliation, or harassment of any kind” and fostering a “respectful and inclusive environment ... in research, medical education, and patient care.”
 

Gender Pay Disparities Persist in Medicine

The gender pay gap in medicine is well documented. The 2024 Medscape Physician Compensation Report found that male doctors earn about 29% more than their female counterparts, with the disparity growing larger among specialists. In addition, a recent JAMA Health Forum study found that male physicians earned 21%-24% more per hour than female physicians.

Dr. Pinter-Brown, who now works at the University of California, Irvine, alleged that she was paid $200,000 less annually, on average, than her male colleagues.

That’s not surprising, says Martha Gulati, MD, professor and director of preventive cardiology at Cedars-Sinai Smidt Heart Institute, Los Angeles. She coauthored a commentary about gender disparities in JAMA Network Open. Dr. Gulati told this news organization that even a “small” pay disparity of $100,000 annually adds up.

“Let’s say the [male physician] invests it at 3% and adds to it yearly. Even without a raise, in 20 years, that is approximately $3 million,” Dr. Gulati explained. “Once you find out you are paid less than your male colleagues, you are upset. Your sense of value and self-worth disappears.”

Eileen Barrett, MD, MPH, president-elect of the American Medical Women’s Association, said that gender discrimination is likely more prevalent than research indicates. She told this news organization that self-doubt and fear of retaliation keep many from exposing the mistreatment.

Although more women are entering medicine, too few rise to the highest positions, Dr. Barrett said.

“Unfortunately, many are pulled and pushed into specialties and subspecialties that have lower compensation and are not promoted to leadership, so just having numbers isn’t enough to achieve equity,” Dr. Barrett said.

Dr. Pinter-Brown claimed she was repeatedly harassed and intimidated by Dr. de Vos from 2008 to 2015. Despite voicing concerns multiple times about the discriminatory behavior, the only resolutions offered by the male-dominated program leadership were for her to separate from the group and conduct lymphoma research independently or to avoid interacting with Dr. de Vos, court records said.

Even the school’s male Title IX officer, Jan Tillisch, MD, who handled gender-based discrimination complaints, reportedly made sexist comments. When Dr. Pinter-Brown sought his help, he allegedly told her that she had a reputation as an “angry woman” and “diva,” court records showed.

According to court documents, Dr. Pinter-Brown endured nitpicking and research audits as retaliation for speaking out, temporarily suspending her research privileges. She said she was subsequently removed from the director position and replaced by Dr. de Vos.

Female physicians who report discriminatory behavior often have unfavorable outcomes and risk future career prospects, Dr. Gulati said.

To shift this dynamic, she said institutions must increase transparency and practices that support female doctors receiving “equal pay for equal work.”
 

A version of this article appeared on Medscape.com.

A California jury has awarded $14 million to a former University of California, Los Angeles (UCLA) oncologist who claimed she was paid thousands less than her male colleagues and wrongfully terminated after her complaints of gender-based harassment and intimidation were ignored by program leadership.

The decision comes after a lengthy 8-year legal battle in which an appellate judge reversed a previous jury decision in her favor.

Lauren Pinter-Brown, MD, a hematologic oncologist, was hired in 2005 by the University of California, Los Angeles School of Medicine — now called UCLA’s David Geffen School of Medicine. As the school’s lymphoma program director, she conducted clinical research alongside other oncology doctors, including Sven de Vos, MD.

She claimed that her professional relationship with Dr. de Vos became contentious after he demonstrated “oppositional” and “disrespectful” behavior at team meetings, such as talking over her and turning his chair so Dr. Pinter-Brown faced his back. Court documents indicated that Dr. de Vos refused to use Dr. Pinter-Brown’s title in front of colleagues despite doing so for male counterparts.

Dr. Pinter-Brown argued that she was treated as the “butt of a joke” by Dr. de Vos and other male colleagues. In 2016, she sued Dr. de Vos, the university, and its governing body, the Board of Regents, for wrongful termination.

She was awarded a $13 million verdict in 2018. However, the California Court of Appeals overturned it in 2020 after concluding that several mistakes during the court proceedings impeded the school’s right to a fair and impartial trial. The case was retried, culminating in the even higher award of $14 million issued on May 9.

“Two juries have come to virtually identical findings showing multiple problems at UCLA involving gender discrimination,” Dr. Pinter-Brown’s attorney, Carney R. Shegerian, JD, told this news organization.

A spokesperson from UCLA’s David Geffen School of Medicine said administrators are carefully reviewing the new decision.

The spokesperson told this news organization that the medical school and its health system remain “deeply committed to maintaining a workplace free from discrimination, intimidation, retaliation, or harassment of any kind” and fostering a “respectful and inclusive environment ... in research, medical education, and patient care.”
 

Gender Pay Disparities Persist in Medicine

The gender pay gap in medicine is well documented. The 2024 Medscape Physician Compensation Report found that male doctors earn about 29% more than their female counterparts, with the disparity growing larger among specialists. In addition, a recent JAMA Health Forum study found that male physicians earned 21%-24% more per hour than female physicians.

Dr. Pinter-Brown, who now works at the University of California, Irvine, alleged that she was paid $200,000 less annually, on average, than her male colleagues.

That’s not surprising, says Martha Gulati, MD, professor and director of preventive cardiology at Cedars-Sinai Smidt Heart Institute, Los Angeles. She coauthored a commentary about gender disparities in JAMA Network Open. Dr. Gulati told this news organization that even a “small” pay disparity of $100,000 annually adds up.

“Let’s say the [male physician] invests it at 3% and adds to it yearly. Even without a raise, in 20 years, that is approximately $3 million,” Dr. Gulati explained. “Once you find out you are paid less than your male colleagues, you are upset. Your sense of value and self-worth disappears.”

Eileen Barrett, MD, MPH, president-elect of the American Medical Women’s Association, said that gender discrimination is likely more prevalent than research indicates. She told this news organization that self-doubt and fear of retaliation keep many from exposing the mistreatment.

Although more women are entering medicine, too few rise to the highest positions, Dr. Barrett said.

“Unfortunately, many are pulled and pushed into specialties and subspecialties that have lower compensation and are not promoted to leadership, so just having numbers isn’t enough to achieve equity,” Dr. Barrett said.

Dr. Pinter-Brown claimed she was repeatedly harassed and intimidated by Dr. de Vos from 2008 to 2015. Despite voicing concerns multiple times about the discriminatory behavior, the only resolutions offered by the male-dominated program leadership were for her to separate from the group and conduct lymphoma research independently or to avoid interacting with Dr. de Vos, court records said.

Even the school’s male Title IX officer, Jan Tillisch, MD, who handled gender-based discrimination complaints, reportedly made sexist comments. When Dr. Pinter-Brown sought his help, he allegedly told her that she had a reputation as an “angry woman” and “diva,” court records showed.

According to court documents, Dr. Pinter-Brown endured nitpicking and research audits as retaliation for speaking out, temporarily suspending her research privileges. She said she was subsequently removed from the director position and replaced by Dr. de Vos.

Female physicians who report discriminatory behavior often have unfavorable outcomes and risk future career prospects, Dr. Gulati said.

To shift this dynamic, she said institutions must increase transparency and practices that support female doctors receiving “equal pay for equal work.”
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved ColoSense (Geneoscopy, Inc), a multitarget stool RNA (mt-sRNA) test for colorectal cancer (CRC) screening in adults aged 45 years or older who are at average risk for CRC.

ColoSense, which had breakthrough device designation by the FDA, detects colorectal neoplasia–associated RNA markers and the presence of occult hemoglobin in human stool. 

A positive ColoSense test result may indicate the presence of CRC, advanced adenomas, or serrated precancerous lesions and should be followed by a colonoscopy, the company said in a news release. 

The FDA approval was based on results of the CRC-PREVENT trial, which evaluated the ColoSense mt-sRNA test in a diverse group of adults undergoing colonoscopy. 

Olivier Le Moal/Getty Images

The mt-sRNA test results were compared with the colonoscopy results.

Among all average-risk individuals, the sensitivity of the mt-sRNA test was 93% for CRC, 100% for early (stage I) CRC, and 45% for advanced adenomas. In a subgroup of those aged 45-49 years, the sensitivity was 100% for CRC and 44% for advanced adenomas.

The trial results were presented last year at the American College of Gastroenterology annual meeting and simultaneously published in JAMA .

CRC is the second deadliest cancer in the United States, and adherence rates to recommended colonoscopies as a screening modality have remained consistently low at roughly 60%. 

Cases of CRC are also rising among people younger than age 50 years, leading the United States Preventive Services Task Force to recommend initiation of CRC screening at age 45 years.

“The growing number of adults diagnosed with colorectal cancer underscores the urgent need for innovative approaches in screening. It’s essential to eliminate obstacles and broaden the availability of screening methods for healthcare providers and patients,” Anjee Davis, president of Fight CRC, said in the news release. 

“We hope that introducing new FDA-approved diagnostic tools, including stool-based tests like ColoSense, will help to advance access and increase screening rates, ultimately reducing the impact of late-stage colorectal cancer diagnoses,” Ms. Davis said. 

The company plans to make ColoSense available in the United States later this year or early in 2025.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved ColoSense (Geneoscopy, Inc), a multitarget stool RNA (mt-sRNA) test for colorectal cancer (CRC) screening in adults aged 45 years or older who are at average risk for CRC.

ColoSense, which had breakthrough device designation by the FDA, detects colorectal neoplasia–associated RNA markers and the presence of occult hemoglobin in human stool. 

A positive ColoSense test result may indicate the presence of CRC, advanced adenomas, or serrated precancerous lesions and should be followed by a colonoscopy, the company said in a news release. 

The FDA approval was based on results of the CRC-PREVENT trial, which evaluated the ColoSense mt-sRNA test in a diverse group of adults undergoing colonoscopy. 

Olivier Le Moal/Getty Images

The mt-sRNA test results were compared with the colonoscopy results.

Among all average-risk individuals, the sensitivity of the mt-sRNA test was 93% for CRC, 100% for early (stage I) CRC, and 45% for advanced adenomas. In a subgroup of those aged 45-49 years, the sensitivity was 100% for CRC and 44% for advanced adenomas.

The trial results were presented last year at the American College of Gastroenterology annual meeting and simultaneously published in JAMA .

CRC is the second deadliest cancer in the United States, and adherence rates to recommended colonoscopies as a screening modality have remained consistently low at roughly 60%. 

Cases of CRC are also rising among people younger than age 50 years, leading the United States Preventive Services Task Force to recommend initiation of CRC screening at age 45 years.

“The growing number of adults diagnosed with colorectal cancer underscores the urgent need for innovative approaches in screening. It’s essential to eliminate obstacles and broaden the availability of screening methods for healthcare providers and patients,” Anjee Davis, president of Fight CRC, said in the news release. 

“We hope that introducing new FDA-approved diagnostic tools, including stool-based tests like ColoSense, will help to advance access and increase screening rates, ultimately reducing the impact of late-stage colorectal cancer diagnoses,” Ms. Davis said. 

The company plans to make ColoSense available in the United States later this year or early in 2025.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved ColoSense (Geneoscopy, Inc), a multitarget stool RNA (mt-sRNA) test for colorectal cancer (CRC) screening in adults aged 45 years or older who are at average risk for CRC.

ColoSense, which had breakthrough device designation by the FDA, detects colorectal neoplasia–associated RNA markers and the presence of occult hemoglobin in human stool. 

A positive ColoSense test result may indicate the presence of CRC, advanced adenomas, or serrated precancerous lesions and should be followed by a colonoscopy, the company said in a news release. 

The FDA approval was based on results of the CRC-PREVENT trial, which evaluated the ColoSense mt-sRNA test in a diverse group of adults undergoing colonoscopy. 

Olivier Le Moal/Getty Images

The mt-sRNA test results were compared with the colonoscopy results.

Among all average-risk individuals, the sensitivity of the mt-sRNA test was 93% for CRC, 100% for early (stage I) CRC, and 45% for advanced adenomas. In a subgroup of those aged 45-49 years, the sensitivity was 100% for CRC and 44% for advanced adenomas.

The trial results were presented last year at the American College of Gastroenterology annual meeting and simultaneously published in JAMA .

CRC is the second deadliest cancer in the United States, and adherence rates to recommended colonoscopies as a screening modality have remained consistently low at roughly 60%. 

Cases of CRC are also rising among people younger than age 50 years, leading the United States Preventive Services Task Force to recommend initiation of CRC screening at age 45 years.

“The growing number of adults diagnosed with colorectal cancer underscores the urgent need for innovative approaches in screening. It’s essential to eliminate obstacles and broaden the availability of screening methods for healthcare providers and patients,” Anjee Davis, president of Fight CRC, said in the news release. 

“We hope that introducing new FDA-approved diagnostic tools, including stool-based tests like ColoSense, will help to advance access and increase screening rates, ultimately reducing the impact of late-stage colorectal cancer diagnoses,” Ms. Davis said. 

The company plans to make ColoSense available in the United States later this year or early in 2025.

A version of this article appeared on Medscape.com.