Patient & Survivor Care

The advent of new immune checkpoint inhibitor combinations for urothelial carcinoma has yielded dramatic changes in patient care, according to Thomas W. Flaig, MD, vice chancellor for research at the University of Colorado Anschutz Medical Campus, Aurora.

Combination therapies involving enfortumab and nivolumab are demonstrating success in recent studies and have been incorporated into the latest guidelines, Dr. Flaig said in a presentation at the National Comprehensive Cancer Network (NCCN) annual conference.
 

What's New in The Updated Guidelines?

Advances in the treatment options for metastatic urothelial carcinoma in the last decade have been dramatic, with ongoing developments and new emerging treatment options, Dr. Flaig told the audience of his session.

This has led to the identification of new and effective immune checkpoint inhibitor combinations. Consequently, immune checkpoint inhibitors are currently included in all preferred/other recommended first-line treatment regimens, he said.

“Enfortumab vedotin plus pembrolizumab is now the sole preferred first-line regimen for locally advanced or metastatic disease.” Based on the recent research, the mindset regarding cisplatin-eligible patient selection may be changing, he added.

“We have used cisplatin eligibility as a key factor in determining first-line therapy for years, and that paradigm is now shifting with the emergence of enfortumab plus pembrolizumab, a new non–cisplatin containing regimen” Dr. Flaig noted.

Although the optimal choice for second- or third-line therapy after immune checkpoint inhibitors is not well-defined, options include platinum regimens, antibody-drug conjugate, and erdafitinib in eligible patients, he said.
 

Other Current Strategies for Localized Bladder Cancer Management

The incidence of bladder cancer has been stable for decades, with minimal therapeutic developments until the approval of immune checkpoint inhibitors in the last decade, Dr. Flaig said.

Bladder cancer is more common in older adults, with an average onset age of 73 years, and most patients (75%) are male, he said. Comorbid disease is common in these patients, and many have a history of smoking, Dr. Flaig added.

The traditional medical approach to treating bladder cancer has been based on combination therapies including cisplatin. This has also reflected the approach used in the treatment of lung cancer, historically, Dr. Flaig said.

Cisplatin, while effective, is a challenging therapy to administer and is not an option for all bladder cancer patients because of potential adverse effects, he noted. Antibody drug conjugates and immune checkpoint inhibitors are new alternatives for some who are not able to receive cisplatin.

What are the New Options for Treating Metastatic Urothelial Bladder Cancer?

The approval of antibody drug conjugates offers new treatment with a “specific target and therapeutic payload,” said Dr. Flaig in his presentation. Two antibody drug conjugates, enfortumab vedotin and sacituzumab govitecan, have been approved by the US Food and Drug Administration (FDA), he said. Enforumab vedotin was approved by the FDA in 2021 for adults with locally advanced or metastatic urothelial cancer for subsequent line therapy in select patients. In a 2021 study published in The New England Journal of Medicine, the primary outcome of overall response rate was significantly greater in patients with advanced urothelial carcinoma who were treated with enfortumab vedotin than in those treated with standard chemotherapy (overall response rate [ORR] 40.6% vs 17.9%, respectively).

Side effects associated with enfortumab vedotin “are intrinsic to the payload toxicity and the target distribution. Ideally, the target would be present on all of the cancer cells and none of the normal tissue,” said Dr. Flaig. With enfortumab, specific toxicities included neuropathy, skin reactions, and blood glucose elevation/diabetic ketoacidosis, he said.

A second agent, sacituzumab govitecan, was approved by the FDA for metastatic urothelial cancer patients in 2021, based on data from the TROPHY-U-O1 phase 2 open-label study of 113 individuals. In that study, the ORR was 27% at a median follow-up of 9.1 months. Adverse events included neutropenia, leukopenia, and diarrhea.
 

What Do the Latest Studies of Combination Therapy Show?

Immune checkpoint inhibitor combinations are significantly changing the landscape of bladder cancer treatment, Dr. Flaig explained.

A recent phase 3 study published in 2024 in The New England Journal of Medicine comparing enfortumab vedotin plus pembrolizumab to platinum-based combination chemotherapy showed an overall response rate of 67.7% vs 44.4% in favor of enfortumab/pembrolizumab, said Dr. Flaig. In addition, the risk of disease progression or death was approximately 55% lower in the enfortumab vedotin-pembrolizumab group vs the chemotherapy group (hazard ratio [HR], 0.45; P less than .001) and the median progression-free survival was approximately doubled (12.5 months vs 6.3 months).

Dr. Flaig described this study as “very notable”because “the enfortumab plus pembrolizumab arm was clearly more effective than the long-standing chemotherapy arm, now becoming the preferred, first-line treatment in the NCCN guidelines. Based on preliminary results of the study, this combination was approved by the FDA in 2023 for locally advanced or metastatic urothelial cancer patients regardless of their eligibility for cisplatin.

Another promising combination, nivolumab plus gemcitabine-cisplatin, was associated with significantly longer overall and progression-free survival in patients with previously untreated unresectable or metastatic urothelial carcinoma, Dr. Flaig said. The therapy was approved by the FDA in March 2024 for first-line therapy.

In a study of 608 patients published in The New England Journal of Medicine, median overall survival was 21.7 months for the nivolumab group vs 18.9 months for the gemcitabine-cisplatin alone group. The overall response rates were 57.6% in the nivolumab group vs 43.1% in the gemcitabine-cisplatin–alone group, and complete response rates were 21.7% and 11.8%, respectively. Serious adverse events (grade 3 or higher) were similar between the groups (61.8% and 51.7%, respectively).
 

What About Targeted Therapy?

Erdafitinib, a tyrosine kinase inhibitor of FGFR1–4, was approved by the FDA in January 2024 for adults with locally advanced or metastatic urothelial carcinoma who had susceptible FGFR3 genetic alterations, said Dr. Flaig, during his presentation. The limitation of this treatment to only those patients with an FGFR3 mutation is a recent update in its use, he noted.

“Up to 20% of patients with advanced urothelial carcinoma have FGFR alterations,” he said. In an open-label phase 2 study of 99 individuals with unresectable or metastatic urothelial carcinoma, past chemotherapy, and FGFR alterations, confirmed response to erdafitinib was 40% with a median overall survival of 13.8 months.

Dr. Flaig disclosed grant/research support from Agensys; Astellas Pharma US; AstraZeneca Pharmaceuticals LP; Bristol Myers Squibb; Genentech, Inc.; Janssen Pharmaceutica Products, LP; Merck & Co.; Sanofi-Aventis U.S.; and SeaGen. He also disclosed equity interest/stock options and intellectual property rights in Aurora Oncology, and serving as a consultant or scientific advisor for Janssen Pharmaceutica Product, LP, and Criterium, Inc.

The advent of new immune checkpoint inhibitor combinations for urothelial carcinoma has yielded dramatic changes in patient care, according to Thomas W. Flaig, MD, vice chancellor for research at the University of Colorado Anschutz Medical Campus, Aurora.

Combination therapies involving enfortumab and nivolumab are demonstrating success in recent studies and have been incorporated into the latest guidelines, Dr. Flaig said in a presentation at the National Comprehensive Cancer Network (NCCN) annual conference.
 

What's New in The Updated Guidelines?

Advances in the treatment options for metastatic urothelial carcinoma in the last decade have been dramatic, with ongoing developments and new emerging treatment options, Dr. Flaig told the audience of his session.

This has led to the identification of new and effective immune checkpoint inhibitor combinations. Consequently, immune checkpoint inhibitors are currently included in all preferred/other recommended first-line treatment regimens, he said.

“Enfortumab vedotin plus pembrolizumab is now the sole preferred first-line regimen for locally advanced or metastatic disease.” Based on the recent research, the mindset regarding cisplatin-eligible patient selection may be changing, he added.

“We have used cisplatin eligibility as a key factor in determining first-line therapy for years, and that paradigm is now shifting with the emergence of enfortumab plus pembrolizumab, a new non–cisplatin containing regimen” Dr. Flaig noted.

Although the optimal choice for second- or third-line therapy after immune checkpoint inhibitors is not well-defined, options include platinum regimens, antibody-drug conjugate, and erdafitinib in eligible patients, he said.
 

Other Current Strategies for Localized Bladder Cancer Management

The incidence of bladder cancer has been stable for decades, with minimal therapeutic developments until the approval of immune checkpoint inhibitors in the last decade, Dr. Flaig said.

Bladder cancer is more common in older adults, with an average onset age of 73 years, and most patients (75%) are male, he said. Comorbid disease is common in these patients, and many have a history of smoking, Dr. Flaig added.

The traditional medical approach to treating bladder cancer has been based on combination therapies including cisplatin. This has also reflected the approach used in the treatment of lung cancer, historically, Dr. Flaig said.

Cisplatin, while effective, is a challenging therapy to administer and is not an option for all bladder cancer patients because of potential adverse effects, he noted. Antibody drug conjugates and immune checkpoint inhibitors are new alternatives for some who are not able to receive cisplatin.

What are the New Options for Treating Metastatic Urothelial Bladder Cancer?

The approval of antibody drug conjugates offers new treatment with a “specific target and therapeutic payload,” said Dr. Flaig in his presentation. Two antibody drug conjugates, enfortumab vedotin and sacituzumab govitecan, have been approved by the US Food and Drug Administration (FDA), he said. Enforumab vedotin was approved by the FDA in 2021 for adults with locally advanced or metastatic urothelial cancer for subsequent line therapy in select patients. In a 2021 study published in The New England Journal of Medicine, the primary outcome of overall response rate was significantly greater in patients with advanced urothelial carcinoma who were treated with enfortumab vedotin than in those treated with standard chemotherapy (overall response rate [ORR] 40.6% vs 17.9%, respectively).

Side effects associated with enfortumab vedotin “are intrinsic to the payload toxicity and the target distribution. Ideally, the target would be present on all of the cancer cells and none of the normal tissue,” said Dr. Flaig. With enfortumab, specific toxicities included neuropathy, skin reactions, and blood glucose elevation/diabetic ketoacidosis, he said.

A second agent, sacituzumab govitecan, was approved by the FDA for metastatic urothelial cancer patients in 2021, based on data from the TROPHY-U-O1 phase 2 open-label study of 113 individuals. In that study, the ORR was 27% at a median follow-up of 9.1 months. Adverse events included neutropenia, leukopenia, and diarrhea.
 

What Do the Latest Studies of Combination Therapy Show?

Immune checkpoint inhibitor combinations are significantly changing the landscape of bladder cancer treatment, Dr. Flaig explained.

A recent phase 3 study published in 2024 in The New England Journal of Medicine comparing enfortumab vedotin plus pembrolizumab to platinum-based combination chemotherapy showed an overall response rate of 67.7% vs 44.4% in favor of enfortumab/pembrolizumab, said Dr. Flaig. In addition, the risk of disease progression or death was approximately 55% lower in the enfortumab vedotin-pembrolizumab group vs the chemotherapy group (hazard ratio [HR], 0.45; P less than .001) and the median progression-free survival was approximately doubled (12.5 months vs 6.3 months).

Dr. Flaig described this study as “very notable”because “the enfortumab plus pembrolizumab arm was clearly more effective than the long-standing chemotherapy arm, now becoming the preferred, first-line treatment in the NCCN guidelines. Based on preliminary results of the study, this combination was approved by the FDA in 2023 for locally advanced or metastatic urothelial cancer patients regardless of their eligibility for cisplatin.

Another promising combination, nivolumab plus gemcitabine-cisplatin, was associated with significantly longer overall and progression-free survival in patients with previously untreated unresectable or metastatic urothelial carcinoma, Dr. Flaig said. The therapy was approved by the FDA in March 2024 for first-line therapy.

In a study of 608 patients published in The New England Journal of Medicine, median overall survival was 21.7 months for the nivolumab group vs 18.9 months for the gemcitabine-cisplatin alone group. The overall response rates were 57.6% in the nivolumab group vs 43.1% in the gemcitabine-cisplatin–alone group, and complete response rates were 21.7% and 11.8%, respectively. Serious adverse events (grade 3 or higher) were similar between the groups (61.8% and 51.7%, respectively).
 

What About Targeted Therapy?

Erdafitinib, a tyrosine kinase inhibitor of FGFR1–4, was approved by the FDA in January 2024 for adults with locally advanced or metastatic urothelial carcinoma who had susceptible FGFR3 genetic alterations, said Dr. Flaig, during his presentation. The limitation of this treatment to only those patients with an FGFR3 mutation is a recent update in its use, he noted.

“Up to 20% of patients with advanced urothelial carcinoma have FGFR alterations,” he said. In an open-label phase 2 study of 99 individuals with unresectable or metastatic urothelial carcinoma, past chemotherapy, and FGFR alterations, confirmed response to erdafitinib was 40% with a median overall survival of 13.8 months.

Dr. Flaig disclosed grant/research support from Agensys; Astellas Pharma US; AstraZeneca Pharmaceuticals LP; Bristol Myers Squibb; Genentech, Inc.; Janssen Pharmaceutica Products, LP; Merck & Co.; Sanofi-Aventis U.S.; and SeaGen. He also disclosed equity interest/stock options and intellectual property rights in Aurora Oncology, and serving as a consultant or scientific advisor for Janssen Pharmaceutica Product, LP, and Criterium, Inc.

The advent of new immune checkpoint inhibitor combinations for urothelial carcinoma has yielded dramatic changes in patient care, according to Thomas W. Flaig, MD, vice chancellor for research at the University of Colorado Anschutz Medical Campus, Aurora.

Combination therapies involving enfortumab and nivolumab are demonstrating success in recent studies and have been incorporated into the latest guidelines, Dr. Flaig said in a presentation at the National Comprehensive Cancer Network (NCCN) annual conference.
 

What's New in The Updated Guidelines?

Advances in the treatment options for metastatic urothelial carcinoma in the last decade have been dramatic, with ongoing developments and new emerging treatment options, Dr. Flaig told the audience of his session.

This has led to the identification of new and effective immune checkpoint inhibitor combinations. Consequently, immune checkpoint inhibitors are currently included in all preferred/other recommended first-line treatment regimens, he said.

“Enfortumab vedotin plus pembrolizumab is now the sole preferred first-line regimen for locally advanced or metastatic disease.” Based on the recent research, the mindset regarding cisplatin-eligible patient selection may be changing, he added.

“We have used cisplatin eligibility as a key factor in determining first-line therapy for years, and that paradigm is now shifting with the emergence of enfortumab plus pembrolizumab, a new non–cisplatin containing regimen” Dr. Flaig noted.

Although the optimal choice for second- or third-line therapy after immune checkpoint inhibitors is not well-defined, options include platinum regimens, antibody-drug conjugate, and erdafitinib in eligible patients, he said.
 

Other Current Strategies for Localized Bladder Cancer Management

The incidence of bladder cancer has been stable for decades, with minimal therapeutic developments until the approval of immune checkpoint inhibitors in the last decade, Dr. Flaig said.

Bladder cancer is more common in older adults, with an average onset age of 73 years, and most patients (75%) are male, he said. Comorbid disease is common in these patients, and many have a history of smoking, Dr. Flaig added.

The traditional medical approach to treating bladder cancer has been based on combination therapies including cisplatin. This has also reflected the approach used in the treatment of lung cancer, historically, Dr. Flaig said.

Cisplatin, while effective, is a challenging therapy to administer and is not an option for all bladder cancer patients because of potential adverse effects, he noted. Antibody drug conjugates and immune checkpoint inhibitors are new alternatives for some who are not able to receive cisplatin.

What are the New Options for Treating Metastatic Urothelial Bladder Cancer?

The approval of antibody drug conjugates offers new treatment with a “specific target and therapeutic payload,” said Dr. Flaig in his presentation. Two antibody drug conjugates, enfortumab vedotin and sacituzumab govitecan, have been approved by the US Food and Drug Administration (FDA), he said. Enforumab vedotin was approved by the FDA in 2021 for adults with locally advanced or metastatic urothelial cancer for subsequent line therapy in select patients. In a 2021 study published in The New England Journal of Medicine, the primary outcome of overall response rate was significantly greater in patients with advanced urothelial carcinoma who were treated with enfortumab vedotin than in those treated with standard chemotherapy (overall response rate [ORR] 40.6% vs 17.9%, respectively).

Side effects associated with enfortumab vedotin “are intrinsic to the payload toxicity and the target distribution. Ideally, the target would be present on all of the cancer cells and none of the normal tissue,” said Dr. Flaig. With enfortumab, specific toxicities included neuropathy, skin reactions, and blood glucose elevation/diabetic ketoacidosis, he said.

A second agent, sacituzumab govitecan, was approved by the FDA for metastatic urothelial cancer patients in 2021, based on data from the TROPHY-U-O1 phase 2 open-label study of 113 individuals. In that study, the ORR was 27% at a median follow-up of 9.1 months. Adverse events included neutropenia, leukopenia, and diarrhea.
 

What Do the Latest Studies of Combination Therapy Show?

Immune checkpoint inhibitor combinations are significantly changing the landscape of bladder cancer treatment, Dr. Flaig explained.

A recent phase 3 study published in 2024 in The New England Journal of Medicine comparing enfortumab vedotin plus pembrolizumab to platinum-based combination chemotherapy showed an overall response rate of 67.7% vs 44.4% in favor of enfortumab/pembrolizumab, said Dr. Flaig. In addition, the risk of disease progression or death was approximately 55% lower in the enfortumab vedotin-pembrolizumab group vs the chemotherapy group (hazard ratio [HR], 0.45; P less than .001) and the median progression-free survival was approximately doubled (12.5 months vs 6.3 months).

Dr. Flaig described this study as “very notable”because “the enfortumab plus pembrolizumab arm was clearly more effective than the long-standing chemotherapy arm, now becoming the preferred, first-line treatment in the NCCN guidelines. Based on preliminary results of the study, this combination was approved by the FDA in 2023 for locally advanced or metastatic urothelial cancer patients regardless of their eligibility for cisplatin.

Another promising combination, nivolumab plus gemcitabine-cisplatin, was associated with significantly longer overall and progression-free survival in patients with previously untreated unresectable or metastatic urothelial carcinoma, Dr. Flaig said. The therapy was approved by the FDA in March 2024 for first-line therapy.

In a study of 608 patients published in The New England Journal of Medicine, median overall survival was 21.7 months for the nivolumab group vs 18.9 months for the gemcitabine-cisplatin alone group. The overall response rates were 57.6% in the nivolumab group vs 43.1% in the gemcitabine-cisplatin–alone group, and complete response rates were 21.7% and 11.8%, respectively. Serious adverse events (grade 3 or higher) were similar between the groups (61.8% and 51.7%, respectively).
 

What About Targeted Therapy?

Erdafitinib, a tyrosine kinase inhibitor of FGFR1–4, was approved by the FDA in January 2024 for adults with locally advanced or metastatic urothelial carcinoma who had susceptible FGFR3 genetic alterations, said Dr. Flaig, during his presentation. The limitation of this treatment to only those patients with an FGFR3 mutation is a recent update in its use, he noted.

“Up to 20% of patients with advanced urothelial carcinoma have FGFR alterations,” he said. In an open-label phase 2 study of 99 individuals with unresectable or metastatic urothelial carcinoma, past chemotherapy, and FGFR alterations, confirmed response to erdafitinib was 40% with a median overall survival of 13.8 months.

Dr. Flaig disclosed grant/research support from Agensys; Astellas Pharma US; AstraZeneca Pharmaceuticals LP; Bristol Myers Squibb; Genentech, Inc.; Janssen Pharmaceutica Products, LP; Merck & Co.; Sanofi-Aventis U.S.; and SeaGen. He also disclosed equity interest/stock options and intellectual property rights in Aurora Oncology, and serving as a consultant or scientific advisor for Janssen Pharmaceutica Product, LP, and Criterium, Inc.

Medicare reimbursement for common breast cancer surgeries decreased significantly over the past two decades, and the resulting shortage of funds could affect quality of care and access to services, especially for vulnerable patient populations.

These were findings of new research presented by Terry P. Gao, MD, at the American Society of Breast Surgeons annual meeting.

Medicare reimbursements often set a benchmark that is followed by private insurers, and the impact of changes on various breast surgeries have not been examined, Dr. Gao, a research resident at Temple University Hospital, Philadelphia, said during a press briefing in advance of the meeting.

“This study is important because it is the first to analyze trends in Medicare reimbursement for breast cancer surgery over a long period,” Dr. Gao said during an interview. The findings highlight a critical issue that could impact access to quality care, especially for vulnerable populations, she said.
 

How Were the Data Analyzed?

Dr. Gao and colleagues reviewed percent changes in reimbursement procedures over a 20-year period and compared them to changes in the consumer price index (CPI) to show the real-life impact of inflation.

The study examined reimbursements based on the Medicare Physician Fee Schedule Look-Up Tool from 2003 to 2023 for 10 procedures. The procedures were core needle biopsy, open incisional breast biopsy, open excisional breast biopsy, lumpectomy, lumpectomy with axillary lymph node dissection (ALND), simple mastectomy, radical mastectomy, modified radical mastectomy, biopsy/removal of lymph nodes, and sentinel lymph node biopsy.
 

What Does the New Study Show?

“Reimbursements did not keep pace with the price of goods and services,” Dr. Gao said during the press briefing.

After the researchers corrected data for inflation, the overall mean Medicare reimbursement for breast cancer surgeries decreased by approximately 21%, based in part on the 69% increase in the CPI over the study period, Dr. Gao said. The greatest change was in core needle biopsy, for which reimbursement decreased by 36%.

After inflation adjustment, reimbursement increases were seen for only two procedures, lumpectomy and simple mastectomy, of 0.37% and 3.58%, respectively, but these do not represent meaningful gains, Dr. Gao said.

The researchers also used a model to estimate the real-life impact of decreased reimbursement on clinicians. They subtracted the actual 2023 compensation from expected 2023 compensation based on inflation for a breast cancer case incidence of 297,790 patients who underwent axillary surgery, breast lumpectomy, or simple mastectomy. The calculated potential real-world compensation loss for that year was $107,604,444.
 

What are the Clinical Implications? 

The current study is the first to put specific numbers on the trend in declining breast cancer payments, and the findings should encourage physicians to advocate for equitable policies, Dr. Gao noted during the briefing.

The substantial decrease in inflation-adjusted reimbursement rates was significant, she said during the interview. Although the decrease reflects similar trends seen in other specialties, the magnitude is a potential cause for concern, she said.

Declining reimbursements could disproportionately hurt safety-net hospitals serving vulnerable populations by limiting their ability to invest in better care and potentially worsening existing racial disparities, Dr. Gao told this publication. “Additionally, surgeons may opt out of Medicare networks due to low rates, leading to access issues and longer wait times. Finally, these trends could discourage future generations from specializing in breast cancer surgery.”

The study findings should be considered in the context of the complex and rapidly changing clinical landscape in which breast cancer care is evolving, Mediget Teshome, MD, chief of breast surgery at UCLA Health, said during an interview.

“Surgery remains a critically important aspect to curative treatment,” Dr. Teshome said.

Surgical decision-making tailored to each patient’s goals involves coordination from a multidisciplinary team as well as skill and attention from surgeons, she added.

“This degree of specialization and nuance is not always captured in reimbursement models for breast surgery,” Dr. Teshome emphasized. The policy implications of any changes in Medicare reimbursement will be important given the American Cancer Society reports breast cancer as the most commonly diagnosed cancer in women in the United States, and as the second leading cause of cancer death in US women, she noted.
 

What Additional Research Is Needed?

Research is needed to understand how declining reimbursements affect patients’ access to care, treatment choices, and long-term outcomes, Dr. Gao said in the interview. Future studies also are needed to examine provider overhead costs, staffing structures, and profit margins to offer a more comprehensive understanding of financial sustainability.

Dr. Gao and Dr. Teshome had no financial conflicts to disclose.

Medicare reimbursement for common breast cancer surgeries decreased significantly over the past two decades, and the resulting shortage of funds could affect quality of care and access to services, especially for vulnerable patient populations.

These were findings of new research presented by Terry P. Gao, MD, at the American Society of Breast Surgeons annual meeting.

Medicare reimbursements often set a benchmark that is followed by private insurers, and the impact of changes on various breast surgeries have not been examined, Dr. Gao, a research resident at Temple University Hospital, Philadelphia, said during a press briefing in advance of the meeting.

“This study is important because it is the first to analyze trends in Medicare reimbursement for breast cancer surgery over a long period,” Dr. Gao said during an interview. The findings highlight a critical issue that could impact access to quality care, especially for vulnerable populations, she said.
 

How Were the Data Analyzed?

Dr. Gao and colleagues reviewed percent changes in reimbursement procedures over a 20-year period and compared them to changes in the consumer price index (CPI) to show the real-life impact of inflation.

The study examined reimbursements based on the Medicare Physician Fee Schedule Look-Up Tool from 2003 to 2023 for 10 procedures. The procedures were core needle biopsy, open incisional breast biopsy, open excisional breast biopsy, lumpectomy, lumpectomy with axillary lymph node dissection (ALND), simple mastectomy, radical mastectomy, modified radical mastectomy, biopsy/removal of lymph nodes, and sentinel lymph node biopsy.
 

What Does the New Study Show?

“Reimbursements did not keep pace with the price of goods and services,” Dr. Gao said during the press briefing.

After the researchers corrected data for inflation, the overall mean Medicare reimbursement for breast cancer surgeries decreased by approximately 21%, based in part on the 69% increase in the CPI over the study period, Dr. Gao said. The greatest change was in core needle biopsy, for which reimbursement decreased by 36%.

After inflation adjustment, reimbursement increases were seen for only two procedures, lumpectomy and simple mastectomy, of 0.37% and 3.58%, respectively, but these do not represent meaningful gains, Dr. Gao said.

The researchers also used a model to estimate the real-life impact of decreased reimbursement on clinicians. They subtracted the actual 2023 compensation from expected 2023 compensation based on inflation for a breast cancer case incidence of 297,790 patients who underwent axillary surgery, breast lumpectomy, or simple mastectomy. The calculated potential real-world compensation loss for that year was $107,604,444.
 

What are the Clinical Implications? 

The current study is the first to put specific numbers on the trend in declining breast cancer payments, and the findings should encourage physicians to advocate for equitable policies, Dr. Gao noted during the briefing.

The substantial decrease in inflation-adjusted reimbursement rates was significant, she said during the interview. Although the decrease reflects similar trends seen in other specialties, the magnitude is a potential cause for concern, she said.

Declining reimbursements could disproportionately hurt safety-net hospitals serving vulnerable populations by limiting their ability to invest in better care and potentially worsening existing racial disparities, Dr. Gao told this publication. “Additionally, surgeons may opt out of Medicare networks due to low rates, leading to access issues and longer wait times. Finally, these trends could discourage future generations from specializing in breast cancer surgery.”

The study findings should be considered in the context of the complex and rapidly changing clinical landscape in which breast cancer care is evolving, Mediget Teshome, MD, chief of breast surgery at UCLA Health, said during an interview.

“Surgery remains a critically important aspect to curative treatment,” Dr. Teshome said.

Surgical decision-making tailored to each patient’s goals involves coordination from a multidisciplinary team as well as skill and attention from surgeons, she added.

“This degree of specialization and nuance is not always captured in reimbursement models for breast surgery,” Dr. Teshome emphasized. The policy implications of any changes in Medicare reimbursement will be important given the American Cancer Society reports breast cancer as the most commonly diagnosed cancer in women in the United States, and as the second leading cause of cancer death in US women, she noted.
 

What Additional Research Is Needed?

Research is needed to understand how declining reimbursements affect patients’ access to care, treatment choices, and long-term outcomes, Dr. Gao said in the interview. Future studies also are needed to examine provider overhead costs, staffing structures, and profit margins to offer a more comprehensive understanding of financial sustainability.

Dr. Gao and Dr. Teshome had no financial conflicts to disclose.

Medicare reimbursement for common breast cancer surgeries decreased significantly over the past two decades, and the resulting shortage of funds could affect quality of care and access to services, especially for vulnerable patient populations.

These were findings of new research presented by Terry P. Gao, MD, at the American Society of Breast Surgeons annual meeting.

Medicare reimbursements often set a benchmark that is followed by private insurers, and the impact of changes on various breast surgeries have not been examined, Dr. Gao, a research resident at Temple University Hospital, Philadelphia, said during a press briefing in advance of the meeting.

“This study is important because it is the first to analyze trends in Medicare reimbursement for breast cancer surgery over a long period,” Dr. Gao said during an interview. The findings highlight a critical issue that could impact access to quality care, especially for vulnerable populations, she said.
 

How Were the Data Analyzed?

Dr. Gao and colleagues reviewed percent changes in reimbursement procedures over a 20-year period and compared them to changes in the consumer price index (CPI) to show the real-life impact of inflation.

The study examined reimbursements based on the Medicare Physician Fee Schedule Look-Up Tool from 2003 to 2023 for 10 procedures. The procedures were core needle biopsy, open incisional breast biopsy, open excisional breast biopsy, lumpectomy, lumpectomy with axillary lymph node dissection (ALND), simple mastectomy, radical mastectomy, modified radical mastectomy, biopsy/removal of lymph nodes, and sentinel lymph node biopsy.
 

What Does the New Study Show?

“Reimbursements did not keep pace with the price of goods and services,” Dr. Gao said during the press briefing.

After the researchers corrected data for inflation, the overall mean Medicare reimbursement for breast cancer surgeries decreased by approximately 21%, based in part on the 69% increase in the CPI over the study period, Dr. Gao said. The greatest change was in core needle biopsy, for which reimbursement decreased by 36%.

After inflation adjustment, reimbursement increases were seen for only two procedures, lumpectomy and simple mastectomy, of 0.37% and 3.58%, respectively, but these do not represent meaningful gains, Dr. Gao said.

The researchers also used a model to estimate the real-life impact of decreased reimbursement on clinicians. They subtracted the actual 2023 compensation from expected 2023 compensation based on inflation for a breast cancer case incidence of 297,790 patients who underwent axillary surgery, breast lumpectomy, or simple mastectomy. The calculated potential real-world compensation loss for that year was $107,604,444.
 

What are the Clinical Implications? 

The current study is the first to put specific numbers on the trend in declining breast cancer payments, and the findings should encourage physicians to advocate for equitable policies, Dr. Gao noted during the briefing.

The substantial decrease in inflation-adjusted reimbursement rates was significant, she said during the interview. Although the decrease reflects similar trends seen in other specialties, the magnitude is a potential cause for concern, she said.

Declining reimbursements could disproportionately hurt safety-net hospitals serving vulnerable populations by limiting their ability to invest in better care and potentially worsening existing racial disparities, Dr. Gao told this publication. “Additionally, surgeons may opt out of Medicare networks due to low rates, leading to access issues and longer wait times. Finally, these trends could discourage future generations from specializing in breast cancer surgery.”

The study findings should be considered in the context of the complex and rapidly changing clinical landscape in which breast cancer care is evolving, Mediget Teshome, MD, chief of breast surgery at UCLA Health, said during an interview.

“Surgery remains a critically important aspect to curative treatment,” Dr. Teshome said.

Surgical decision-making tailored to each patient’s goals involves coordination from a multidisciplinary team as well as skill and attention from surgeons, she added.

“This degree of specialization and nuance is not always captured in reimbursement models for breast surgery,” Dr. Teshome emphasized. The policy implications of any changes in Medicare reimbursement will be important given the American Cancer Society reports breast cancer as the most commonly diagnosed cancer in women in the United States, and as the second leading cause of cancer death in US women, she noted.
 

What Additional Research Is Needed?

Research is needed to understand how declining reimbursements affect patients’ access to care, treatment choices, and long-term outcomes, Dr. Gao said in the interview. Future studies also are needed to examine provider overhead costs, staffing structures, and profit margins to offer a more comprehensive understanding of financial sustainability.

Dr. Gao and Dr. Teshome had no financial conflicts to disclose.

Early data suggested that several new multicancer early detection (MCED) tests in development show promise for identifying cancers that lack routine screening options.

Analyses presented during a session at the American Association for Cancer Research annual meeting, revealed that three new MCED tests — CanScan, MERCURY, and OncoSeek — could detect a range of cancers and recognize the tissue of origin with high accuracy. One — OncoSeek — could also provide an affordable cancer screening option for individuals living in lower-income countries.

The need for these noninvasive liquid biopsy tests that can accurately identify multiple cancer types with a single blood draw, especially cancers without routine screening strategies, is pressing. “We know that the current cancer standard of care screening will identify less than 50% of all cancers, while more than 50% of all cancer deaths occur in types of cancer with no recommended screening,” said co-moderator Marie E. Wood, MD, of the University of Colorado Anschutz Medical Campus, in Aurora, Colorado.

That being said, “the clinical utility of multicancer detection tests has not been established and we’re concerned about issues of overdiagnosis and overtreatment,” she noted.

The Early Data 

One new MCED test called CanScan, developed by Geneseeq Technology, uses plasma cell-free DNA fragment patterns to detect cancer signals as well as identify the tissue of origin across 13 cancer types.

Overall, the CanScan test covers cancer types that contribute to two thirds of new cancer cases and 74% of morality globally, said presenter Shanshan Yang, of Geneseeq Research Institute, in Nanjing, China.

However, only five of these cancer types have screening recommendations issued by the US Preventive Services Task Force (USPSTF), Dr. Yang added.

The interim data comes from an ongoing large-scale prospective study evaluating the MCED test in a cohort of asymptomatic individuals between ages 45 and 75 years with an average risk for cancer and no cancer-related symptoms on enrollment.

Patients at baseline had their blood collected for the CanScan test and subsequently received annual routine physical exams once a year for 3 consecutive years, with an additional 2 years of follow-up. 

The analysis included 3724 participants with analyzable samples at the data cutoff in September 2023. Among the 3724 participants, 29 had confirmed cancer diagnoses. Among these cases, 14 patients had their cancer confirmed through USPSTF recommended screening and 15 were detected through outside of standard USPSTF screening, such as a thyroid ultrasound, Dr. Yang explained.

Almost 90% of the cancers (26 of 29) were detected in the stage I or II, and eight (27.5%) were not one of the test’s 13 targeted cancer types.

The CanScan test had a sensitivity of 55.2%, identifying 16 of 29 of the patients with cancer, including 10 of 21 individuals with stage I (47.6%), and two of three with stage II (66.7%). 

The test had a high specificity of 97.9%, meaning out of 100 people screened, only two had false negative findings.

Among the 15 patients who had their cancer detected outside of USPSTF screening recommendations, eight (53.3%) were found using a CanScan test, including patients with liver and endometrial cancers.

Compared with a positive predictive value of (PPV) of 1.6% with screening or physical exam methods alone, the CanScan test had a PPV of 17.4%, Dr. Yang reported. 

“The MCED test holds significant potential for early cancer screening in asymptomatic populations,” Dr. Yang and colleagues concluded.

Another new MCED test called MERCURY, also developed by Geneseeq Technology and presented during the session, used a similar method to detect cancer signals and predict the tissue of origin across 13 cancer types.

The researchers initially validated the test using 3076 patients with cancer and 3477 healthy controls with a target specificity of 99%. In this group, researchers reported a sensitivity of 0.865 and a specificity of 0.989.

The team then performed an independent validation analysis with 1465 participants, 732 with cancer and 733 with no cancer, and confirmed a high sensitivity and specificity of 0.874 and 0.978, respectively. The sensitivity increased incrementally by cancer stage — 0.768 for stage I, 0.840 for stage II, 0.923 for stage III, and 0.971 for stage IV.

The test identified the tissue of origin with high accuracy, the researchers noted, but cautioned that the test needs “to be further validated in a prospective cohort study.”

MCED in Low-Income Settings

The session also featured findings on a new affordable MCED test called OncoSeek, which could provide greater access to cancer testing in low- and middle-income countries.

The OncoSeek algorithm identifies the presence of cancer using seven protein tumor markers alongside clinical information, such as gender and age. Like other tests, the test also predicts the possible tissue of origin.

The test can be run on clinical protein assay instruments that are already widely available, such as Roche cobas analyzer, Mao Mao, MD, PhD, the founder and CEO of SeekIn, of Shenzhen, China, told this news organization.

This “feature makes the test accessible worldwide, even in low- and middle-income countries,” he said. “These instruments are fully-automated and part of today’s clinical practice. Therefore, the test does not require additional infrastructure building and lab personal training.”

Another notable advantage: the OncoSeek test only costs about $20, compared with other MCED tests, which can cost anywhere from $200 to $1000.

To validate the technology in a large, diverse cohort, Dr. Mao and colleagues enrolled approximately 10,000 participants, including 2003 cancer cases and 7888 non-cancer cases.

Peripheral blood was collected from each participant and analyzed using a panel of the seven protein tumor markers — AFP, CA125, CA15-3, CA19-9, CA72-4, CEA, and CYFRA 21-1.

To reduce the risk for false positive findings, the team designed the OncoSeek algorithm to achieve a specificity of 93%. Dr. Mao and colleagues found a sensitivity of 51.7%, resulting in an overall accuracy of 84.6%.

The performance was consistent in additional validation cohorts in Brazil, China, and the United States, with sensitivities ranging from 39.0% to 77.6% for detecting nine common cancer types, including breast, colorectal, liver, lung, lymphoma, esophagus, ovary, pancreas, and stomach. The sensitivity for pancreatic cancer was at the high end of 77.6%.

The test could predict the tissue of origin in about two thirds of cases. 

Given its low cost, OncoSeek represents an affordable and accessible option for cancer screening, the authors concluded. 

Overall, “I think MCEDs have the potential to enhance cancer screening,” Dr. Wood told this news organization.

Still, questions remain about the optimal use of these tests, such as whether they are best for average-risk or higher risk populations, and how to integrate them into standard screening, she said. 

Dr. Wood also cautioned that the studies presented in the session represent early data, and it is likely that the numbers, such as sensitivity and specificity, will change with further prospective analyses.

And ultimately, these tests should complement, not replace, standard screening. “A negative testing should not be taken as a sign to avoid standard screening,” Dr. Wood said.

Dr. Yang is an employee of Geneseeq Technology, Inc., and Dr. Mao is an employee of SeekIn. Dr. Wood had no disclosures to report.

A version of this article appeared on Medscape.com.

Early data suggested that several new multicancer early detection (MCED) tests in development show promise for identifying cancers that lack routine screening options.

Analyses presented during a session at the American Association for Cancer Research annual meeting, revealed that three new MCED tests — CanScan, MERCURY, and OncoSeek — could detect a range of cancers and recognize the tissue of origin with high accuracy. One — OncoSeek — could also provide an affordable cancer screening option for individuals living in lower-income countries.

The need for these noninvasive liquid biopsy tests that can accurately identify multiple cancer types with a single blood draw, especially cancers without routine screening strategies, is pressing. “We know that the current cancer standard of care screening will identify less than 50% of all cancers, while more than 50% of all cancer deaths occur in types of cancer with no recommended screening,” said co-moderator Marie E. Wood, MD, of the University of Colorado Anschutz Medical Campus, in Aurora, Colorado.

That being said, “the clinical utility of multicancer detection tests has not been established and we’re concerned about issues of overdiagnosis and overtreatment,” she noted.

The Early Data 

One new MCED test called CanScan, developed by Geneseeq Technology, uses plasma cell-free DNA fragment patterns to detect cancer signals as well as identify the tissue of origin across 13 cancer types.

Overall, the CanScan test covers cancer types that contribute to two thirds of new cancer cases and 74% of morality globally, said presenter Shanshan Yang, of Geneseeq Research Institute, in Nanjing, China.

However, only five of these cancer types have screening recommendations issued by the US Preventive Services Task Force (USPSTF), Dr. Yang added.

The interim data comes from an ongoing large-scale prospective study evaluating the MCED test in a cohort of asymptomatic individuals between ages 45 and 75 years with an average risk for cancer and no cancer-related symptoms on enrollment.

Patients at baseline had their blood collected for the CanScan test and subsequently received annual routine physical exams once a year for 3 consecutive years, with an additional 2 years of follow-up. 

The analysis included 3724 participants with analyzable samples at the data cutoff in September 2023. Among the 3724 participants, 29 had confirmed cancer diagnoses. Among these cases, 14 patients had their cancer confirmed through USPSTF recommended screening and 15 were detected through outside of standard USPSTF screening, such as a thyroid ultrasound, Dr. Yang explained.

Almost 90% of the cancers (26 of 29) were detected in the stage I or II, and eight (27.5%) were not one of the test’s 13 targeted cancer types.

The CanScan test had a sensitivity of 55.2%, identifying 16 of 29 of the patients with cancer, including 10 of 21 individuals with stage I (47.6%), and two of three with stage II (66.7%). 

The test had a high specificity of 97.9%, meaning out of 100 people screened, only two had false negative findings.

Among the 15 patients who had their cancer detected outside of USPSTF screening recommendations, eight (53.3%) were found using a CanScan test, including patients with liver and endometrial cancers.

Compared with a positive predictive value of (PPV) of 1.6% with screening or physical exam methods alone, the CanScan test had a PPV of 17.4%, Dr. Yang reported. 

“The MCED test holds significant potential for early cancer screening in asymptomatic populations,” Dr. Yang and colleagues concluded.

Another new MCED test called MERCURY, also developed by Geneseeq Technology and presented during the session, used a similar method to detect cancer signals and predict the tissue of origin across 13 cancer types.

The researchers initially validated the test using 3076 patients with cancer and 3477 healthy controls with a target specificity of 99%. In this group, researchers reported a sensitivity of 0.865 and a specificity of 0.989.

The team then performed an independent validation analysis with 1465 participants, 732 with cancer and 733 with no cancer, and confirmed a high sensitivity and specificity of 0.874 and 0.978, respectively. The sensitivity increased incrementally by cancer stage — 0.768 for stage I, 0.840 for stage II, 0.923 for stage III, and 0.971 for stage IV.

The test identified the tissue of origin with high accuracy, the researchers noted, but cautioned that the test needs “to be further validated in a prospective cohort study.”

MCED in Low-Income Settings

The session also featured findings on a new affordable MCED test called OncoSeek, which could provide greater access to cancer testing in low- and middle-income countries.

The OncoSeek algorithm identifies the presence of cancer using seven protein tumor markers alongside clinical information, such as gender and age. Like other tests, the test also predicts the possible tissue of origin.

The test can be run on clinical protein assay instruments that are already widely available, such as Roche cobas analyzer, Mao Mao, MD, PhD, the founder and CEO of SeekIn, of Shenzhen, China, told this news organization.

This “feature makes the test accessible worldwide, even in low- and middle-income countries,” he said. “These instruments are fully-automated and part of today’s clinical practice. Therefore, the test does not require additional infrastructure building and lab personal training.”

Another notable advantage: the OncoSeek test only costs about $20, compared with other MCED tests, which can cost anywhere from $200 to $1000.

To validate the technology in a large, diverse cohort, Dr. Mao and colleagues enrolled approximately 10,000 participants, including 2003 cancer cases and 7888 non-cancer cases.

Peripheral blood was collected from each participant and analyzed using a panel of the seven protein tumor markers — AFP, CA125, CA15-3, CA19-9, CA72-4, CEA, and CYFRA 21-1.

To reduce the risk for false positive findings, the team designed the OncoSeek algorithm to achieve a specificity of 93%. Dr. Mao and colleagues found a sensitivity of 51.7%, resulting in an overall accuracy of 84.6%.

The performance was consistent in additional validation cohorts in Brazil, China, and the United States, with sensitivities ranging from 39.0% to 77.6% for detecting nine common cancer types, including breast, colorectal, liver, lung, lymphoma, esophagus, ovary, pancreas, and stomach. The sensitivity for pancreatic cancer was at the high end of 77.6%.

The test could predict the tissue of origin in about two thirds of cases. 

Given its low cost, OncoSeek represents an affordable and accessible option for cancer screening, the authors concluded. 

Overall, “I think MCEDs have the potential to enhance cancer screening,” Dr. Wood told this news organization.

Still, questions remain about the optimal use of these tests, such as whether they are best for average-risk or higher risk populations, and how to integrate them into standard screening, she said. 

Dr. Wood also cautioned that the studies presented in the session represent early data, and it is likely that the numbers, such as sensitivity and specificity, will change with further prospective analyses.

And ultimately, these tests should complement, not replace, standard screening. “A negative testing should not be taken as a sign to avoid standard screening,” Dr. Wood said.

Dr. Yang is an employee of Geneseeq Technology, Inc., and Dr. Mao is an employee of SeekIn. Dr. Wood had no disclosures to report.

A version of this article appeared on Medscape.com.

Early data suggested that several new multicancer early detection (MCED) tests in development show promise for identifying cancers that lack routine screening options.

Analyses presented during a session at the American Association for Cancer Research annual meeting, revealed that three new MCED tests — CanScan, MERCURY, and OncoSeek — could detect a range of cancers and recognize the tissue of origin with high accuracy. One — OncoSeek — could also provide an affordable cancer screening option for individuals living in lower-income countries.

The need for these noninvasive liquid biopsy tests that can accurately identify multiple cancer types with a single blood draw, especially cancers without routine screening strategies, is pressing. “We know that the current cancer standard of care screening will identify less than 50% of all cancers, while more than 50% of all cancer deaths occur in types of cancer with no recommended screening,” said co-moderator Marie E. Wood, MD, of the University of Colorado Anschutz Medical Campus, in Aurora, Colorado.

That being said, “the clinical utility of multicancer detection tests has not been established and we’re concerned about issues of overdiagnosis and overtreatment,” she noted.

The Early Data 

One new MCED test called CanScan, developed by Geneseeq Technology, uses plasma cell-free DNA fragment patterns to detect cancer signals as well as identify the tissue of origin across 13 cancer types.

Overall, the CanScan test covers cancer types that contribute to two thirds of new cancer cases and 74% of morality globally, said presenter Shanshan Yang, of Geneseeq Research Institute, in Nanjing, China.

However, only five of these cancer types have screening recommendations issued by the US Preventive Services Task Force (USPSTF), Dr. Yang added.

The interim data comes from an ongoing large-scale prospective study evaluating the MCED test in a cohort of asymptomatic individuals between ages 45 and 75 years with an average risk for cancer and no cancer-related symptoms on enrollment.

Patients at baseline had their blood collected for the CanScan test and subsequently received annual routine physical exams once a year for 3 consecutive years, with an additional 2 years of follow-up. 

The analysis included 3724 participants with analyzable samples at the data cutoff in September 2023. Among the 3724 participants, 29 had confirmed cancer diagnoses. Among these cases, 14 patients had their cancer confirmed through USPSTF recommended screening and 15 were detected through outside of standard USPSTF screening, such as a thyroid ultrasound, Dr. Yang explained.

Almost 90% of the cancers (26 of 29) were detected in the stage I or II, and eight (27.5%) were not one of the test’s 13 targeted cancer types.

The CanScan test had a sensitivity of 55.2%, identifying 16 of 29 of the patients with cancer, including 10 of 21 individuals with stage I (47.6%), and two of three with stage II (66.7%). 

The test had a high specificity of 97.9%, meaning out of 100 people screened, only two had false negative findings.

Among the 15 patients who had their cancer detected outside of USPSTF screening recommendations, eight (53.3%) were found using a CanScan test, including patients with liver and endometrial cancers.

Compared with a positive predictive value of (PPV) of 1.6% with screening or physical exam methods alone, the CanScan test had a PPV of 17.4%, Dr. Yang reported. 

“The MCED test holds significant potential for early cancer screening in asymptomatic populations,” Dr. Yang and colleagues concluded.

Another new MCED test called MERCURY, also developed by Geneseeq Technology and presented during the session, used a similar method to detect cancer signals and predict the tissue of origin across 13 cancer types.

The researchers initially validated the test using 3076 patients with cancer and 3477 healthy controls with a target specificity of 99%. In this group, researchers reported a sensitivity of 0.865 and a specificity of 0.989.

The team then performed an independent validation analysis with 1465 participants, 732 with cancer and 733 with no cancer, and confirmed a high sensitivity and specificity of 0.874 and 0.978, respectively. The sensitivity increased incrementally by cancer stage — 0.768 for stage I, 0.840 for stage II, 0.923 for stage III, and 0.971 for stage IV.

The test identified the tissue of origin with high accuracy, the researchers noted, but cautioned that the test needs “to be further validated in a prospective cohort study.”

MCED in Low-Income Settings

The session also featured findings on a new affordable MCED test called OncoSeek, which could provide greater access to cancer testing in low- and middle-income countries.

The OncoSeek algorithm identifies the presence of cancer using seven protein tumor markers alongside clinical information, such as gender and age. Like other tests, the test also predicts the possible tissue of origin.

The test can be run on clinical protein assay instruments that are already widely available, such as Roche cobas analyzer, Mao Mao, MD, PhD, the founder and CEO of SeekIn, of Shenzhen, China, told this news organization.

This “feature makes the test accessible worldwide, even in low- and middle-income countries,” he said. “These instruments are fully-automated and part of today’s clinical practice. Therefore, the test does not require additional infrastructure building and lab personal training.”

Another notable advantage: the OncoSeek test only costs about $20, compared with other MCED tests, which can cost anywhere from $200 to $1000.

To validate the technology in a large, diverse cohort, Dr. Mao and colleagues enrolled approximately 10,000 participants, including 2003 cancer cases and 7888 non-cancer cases.

Peripheral blood was collected from each participant and analyzed using a panel of the seven protein tumor markers — AFP, CA125, CA15-3, CA19-9, CA72-4, CEA, and CYFRA 21-1.

To reduce the risk for false positive findings, the team designed the OncoSeek algorithm to achieve a specificity of 93%. Dr. Mao and colleagues found a sensitivity of 51.7%, resulting in an overall accuracy of 84.6%.

The performance was consistent in additional validation cohorts in Brazil, China, and the United States, with sensitivities ranging from 39.0% to 77.6% for detecting nine common cancer types, including breast, colorectal, liver, lung, lymphoma, esophagus, ovary, pancreas, and stomach. The sensitivity for pancreatic cancer was at the high end of 77.6%.

The test could predict the tissue of origin in about two thirds of cases. 

Given its low cost, OncoSeek represents an affordable and accessible option for cancer screening, the authors concluded. 

Overall, “I think MCEDs have the potential to enhance cancer screening,” Dr. Wood told this news organization.

Still, questions remain about the optimal use of these tests, such as whether they are best for average-risk or higher risk populations, and how to integrate them into standard screening, she said. 

Dr. Wood also cautioned that the studies presented in the session represent early data, and it is likely that the numbers, such as sensitivity and specificity, will change with further prospective analyses.

And ultimately, these tests should complement, not replace, standard screening. “A negative testing should not be taken as a sign to avoid standard screening,” Dr. Wood said.

Dr. Yang is an employee of Geneseeq Technology, Inc., and Dr. Mao is an employee of SeekIn. Dr. Wood had no disclosures to report.

A version of this article appeared on Medscape.com.

SAN DIEGO — A new blood test that combines cell-free DNA fragmentomes and protein biomarkers to screen for ovarian cancer shows promising results, according to an initial analysis. 

The test, under development by Delfi Diagnostics, “looks very sensitive for detecting ovarian cancer early,” said company founder and board member Victor E. Velculescu, MD, PhD, codirector of Cancer Genetics and Epigenetics at Johns Hopkins University, Baltimore. 

The assay uses machine learning to integrate cell-free DNA fragment patterns with concentrations of two ovarian cancer biomarkers — CA125 and HE4 — to detect tumors. 

While fragmentation patterns are organized in healthy people, they are chaotic in cancer and reveal both its presence and location, said Velculescu who presented the findings at the American Association for Cancer Research annual meeting.

The researchers tested the assay in 134 women with ovarian cancer, 204 women without cancer, and 203 women with benign adnexal masses. The approach identified 69% of stage 1 cancers, 76% of stage 2, 85% of stage 3, and 100% of stage 4 at a specificity of over 99% and an area under the curve (AUC) of 0.97.

The test identified 91% of high-grade serous ovarian cancers — the most common type of ovarian cancer.

The AUC for distinguishing benign masses from cancer was 0.87, with 60% of ovarian cancers detected at a specificity of 95%. 

“In the preoperative setting where lower specificity is acceptable, this approach may improve management of adnexal masses,” the investigators said in their abstract.

Dr. Velculescu cautioned that the report “is an initial analysis” and that his team is working on validating the finding on a larger scale in both average and high-risk women.

If validated, the test “could enable population-wide ovarian cancer screening,” he added.

Delfi recently launched a lung cancer screening blood test — FirstLook Lung— that also uses a “fragmentomics” approach to detect tumors. The company is hopeful it will reach the market with a similar test for ovarian cancer, but it’s not a certainty. 

With lung cancer, we know screening helps. For ovarian cancer, however, it’s unclear whether this will help or not, said Dr. Velculescu. But based on the study findings, but “we are now optimistic that this could make an impact. We have more work to do.” 

This presentation was one of many at the meeting about liquid biopsies using DNA, RNA, and proteins to detect cancer, including a new assay for pancreatic cancer, another cancer that like ovarian cancer is difficult to detect in the early stages. 

“This is the future,” said study moderator Roy S. Herbst, MD, PhD, chief of medical oncology at Yale University in New Haven, Connecticut. 

He called liquid biopsy “a great advance” in many oncology settings, including cancer screening because finding tumors early offers the best chance at cure. 

However, one of the main concerns about rolling out liquid biopsies for wide-scale cancer screening is the possibility that a test will come back positive, but no tumor will be seen on diagnostic imaging, said Herbst. It won’t be clear if the test was a false positive or if the patient has a brewing tumor that can’t be located and treated, a difficult situation for both patients and doctors. 

What to do in that situation is “a policy question that the entire country is asking now as liquid biopsies are moving forward,” he said. We are going to have to come together to figure it out and learn how to use these tests.

The work was funded by Delfi Diagnostics, the National Institutes of Health, and others. Dr. Velculescu, in addition to founding Delfi, holds patents on the technology. Dr. Herbst is a consultant, researcher, and/or holds stock in many companies, including AstraZeneca, Pfizer, and Checkpoint Therapeutics. 
 

A version of this article appeared on Medscape.com .

SAN DIEGO — A new blood test that combines cell-free DNA fragmentomes and protein biomarkers to screen for ovarian cancer shows promising results, according to an initial analysis. 

The test, under development by Delfi Diagnostics, “looks very sensitive for detecting ovarian cancer early,” said company founder and board member Victor E. Velculescu, MD, PhD, codirector of Cancer Genetics and Epigenetics at Johns Hopkins University, Baltimore. 

The assay uses machine learning to integrate cell-free DNA fragment patterns with concentrations of two ovarian cancer biomarkers — CA125 and HE4 — to detect tumors. 

While fragmentation patterns are organized in healthy people, they are chaotic in cancer and reveal both its presence and location, said Velculescu who presented the findings at the American Association for Cancer Research annual meeting.

The researchers tested the assay in 134 women with ovarian cancer, 204 women without cancer, and 203 women with benign adnexal masses. The approach identified 69% of stage 1 cancers, 76% of stage 2, 85% of stage 3, and 100% of stage 4 at a specificity of over 99% and an area under the curve (AUC) of 0.97.

The test identified 91% of high-grade serous ovarian cancers — the most common type of ovarian cancer.

The AUC for distinguishing benign masses from cancer was 0.87, with 60% of ovarian cancers detected at a specificity of 95%. 

“In the preoperative setting where lower specificity is acceptable, this approach may improve management of adnexal masses,” the investigators said in their abstract.

Dr. Velculescu cautioned that the report “is an initial analysis” and that his team is working on validating the finding on a larger scale in both average and high-risk women.

If validated, the test “could enable population-wide ovarian cancer screening,” he added.

Delfi recently launched a lung cancer screening blood test — FirstLook Lung— that also uses a “fragmentomics” approach to detect tumors. The company is hopeful it will reach the market with a similar test for ovarian cancer, but it’s not a certainty. 

With lung cancer, we know screening helps. For ovarian cancer, however, it’s unclear whether this will help or not, said Dr. Velculescu. But based on the study findings, but “we are now optimistic that this could make an impact. We have more work to do.” 

This presentation was one of many at the meeting about liquid biopsies using DNA, RNA, and proteins to detect cancer, including a new assay for pancreatic cancer, another cancer that like ovarian cancer is difficult to detect in the early stages. 

“This is the future,” said study moderator Roy S. Herbst, MD, PhD, chief of medical oncology at Yale University in New Haven, Connecticut. 

He called liquid biopsy “a great advance” in many oncology settings, including cancer screening because finding tumors early offers the best chance at cure. 

However, one of the main concerns about rolling out liquid biopsies for wide-scale cancer screening is the possibility that a test will come back positive, but no tumor will be seen on diagnostic imaging, said Herbst. It won’t be clear if the test was a false positive or if the patient has a brewing tumor that can’t be located and treated, a difficult situation for both patients and doctors. 

What to do in that situation is “a policy question that the entire country is asking now as liquid biopsies are moving forward,” he said. We are going to have to come together to figure it out and learn how to use these tests.

The work was funded by Delfi Diagnostics, the National Institutes of Health, and others. Dr. Velculescu, in addition to founding Delfi, holds patents on the technology. Dr. Herbst is a consultant, researcher, and/or holds stock in many companies, including AstraZeneca, Pfizer, and Checkpoint Therapeutics. 
 

A version of this article appeared on Medscape.com .

SAN DIEGO — A new blood test that combines cell-free DNA fragmentomes and protein biomarkers to screen for ovarian cancer shows promising results, according to an initial analysis. 

The test, under development by Delfi Diagnostics, “looks very sensitive for detecting ovarian cancer early,” said company founder and board member Victor E. Velculescu, MD, PhD, codirector of Cancer Genetics and Epigenetics at Johns Hopkins University, Baltimore. 

The assay uses machine learning to integrate cell-free DNA fragment patterns with concentrations of two ovarian cancer biomarkers — CA125 and HE4 — to detect tumors. 

While fragmentation patterns are organized in healthy people, they are chaotic in cancer and reveal both its presence and location, said Velculescu who presented the findings at the American Association for Cancer Research annual meeting.

The researchers tested the assay in 134 women with ovarian cancer, 204 women without cancer, and 203 women with benign adnexal masses. The approach identified 69% of stage 1 cancers, 76% of stage 2, 85% of stage 3, and 100% of stage 4 at a specificity of over 99% and an area under the curve (AUC) of 0.97.

The test identified 91% of high-grade serous ovarian cancers — the most common type of ovarian cancer.

The AUC for distinguishing benign masses from cancer was 0.87, with 60% of ovarian cancers detected at a specificity of 95%. 

“In the preoperative setting where lower specificity is acceptable, this approach may improve management of adnexal masses,” the investigators said in their abstract.

Dr. Velculescu cautioned that the report “is an initial analysis” and that his team is working on validating the finding on a larger scale in both average and high-risk women.

If validated, the test “could enable population-wide ovarian cancer screening,” he added.

Delfi recently launched a lung cancer screening blood test — FirstLook Lung— that also uses a “fragmentomics” approach to detect tumors. The company is hopeful it will reach the market with a similar test for ovarian cancer, but it’s not a certainty. 

With lung cancer, we know screening helps. For ovarian cancer, however, it’s unclear whether this will help or not, said Dr. Velculescu. But based on the study findings, but “we are now optimistic that this could make an impact. We have more work to do.” 

This presentation was one of many at the meeting about liquid biopsies using DNA, RNA, and proteins to detect cancer, including a new assay for pancreatic cancer, another cancer that like ovarian cancer is difficult to detect in the early stages. 

“This is the future,” said study moderator Roy S. Herbst, MD, PhD, chief of medical oncology at Yale University in New Haven, Connecticut. 

He called liquid biopsy “a great advance” in many oncology settings, including cancer screening because finding tumors early offers the best chance at cure. 

However, one of the main concerns about rolling out liquid biopsies for wide-scale cancer screening is the possibility that a test will come back positive, but no tumor will be seen on diagnostic imaging, said Herbst. It won’t be clear if the test was a false positive or if the patient has a brewing tumor that can’t be located and treated, a difficult situation for both patients and doctors. 

What to do in that situation is “a policy question that the entire country is asking now as liquid biopsies are moving forward,” he said. We are going to have to come together to figure it out and learn how to use these tests.

The work was funded by Delfi Diagnostics, the National Institutes of Health, and others. Dr. Velculescu, in addition to founding Delfi, holds patents on the technology. Dr. Herbst is a consultant, researcher, and/or holds stock in many companies, including AstraZeneca, Pfizer, and Checkpoint Therapeutics. 
 

A version of this article appeared on Medscape.com .

TOPLINE:

A recent survey highlighted ethical concerns US oncologists have about using artificial intelligence (AI) to help make cancer treatment decisions and revealed some contradictory views about how best to integrate these tools into practice. Most respondents, for instance, said patients should not be expected to understand how AI tools work, but many also felt patients could make treatment decisions based on AI-generated recommendations. Most oncologists also felt responsible for protecting patients from biased AI, but few were confident that they could do so.

METHODOLOGY:

• The US Food and Drug Administration (FDA) has  for use in various medical specialties over the past few decades, and increasingly, AI tools are being integrated into cancer care.
• However, the uptake of these tools in oncology has raised ethical questions and concerns, including challenges with AI bias, error, or misuse, as well as issues explaining how an AI model reached a result.
• In the current study, researchers asked 204 oncologists from 37 states for their views on the ethical implications of using AI for cancer care.
• Among the survey respondents, 64% were men and 63% were non-Hispanic White; 29% were from academic practices, 47% had received some education on AI use in healthcare, and 45% were familiar with clinical decision models.
• The researchers assessed respondents’ answers to various questions, including whether to provide informed consent for AI use and how oncologists would approach a scenario where the AI model and the oncologist recommended a different treatment regimen.

TAKEAWAY:

• Overall, 81% of oncologists supported having patient consent to use an AI model during treatment decisions, and 85% felt that oncologists needed to be able to explain an AI-based clinical decision model to use it in the clinic; however, only 23% felt that patients also needed to be able to explain an AI model.
• When an AI decision model recommended a different treatment regimen than the treating oncologist, the most common response (36.8%) was to present both options to the patient and let the patient decide. Oncologists from academic settings were about 2.5 times more likely than those from other settings to let the patient decide. About 34% of respondents said they would present both options but recommend the oncologist’s regimen, whereas about 22% said they would present both but recommend the AI’s regimen. A small percentage would only present the oncologist’s regimen (5%) or the AI’s regimen (about 2.5%).
• About three of four respondents (76.5%) agreed that oncologists should protect patients from biased AI tools; however, only about one of four (27.9%) felt confident they could identify biased AI models.
• Most oncologists (91%) felt that AI developers were responsible for the medico-legal problems associated with AI use; less than half (47%) said oncologists or hospitals (43%) shared this responsibility.

IN PRACTICE:

“Together, these data characterize barriers that may impede the ethical adoption of AI into cancer care. The findings suggest that the implementation of AI in oncology must include rigorous assessments of its effect on care decisions, as well as decisional responsibility when problems related to AI use arise,” the authors concluded.

SOURCE:

The study, with first author Andrew Hantel, MD, from Dana-Farber Cancer Institute, Boston, was published last month in JAMA Network Open.

LIMITATIONS:

The study had a moderate sample size and response rate, although demographics of participating oncologists appear to be nationally representative. The cross-sectional study design limited the generalizability of the findings over time as AI is integrated into cancer care.

DISCLOSURES:

The study was funded by the National Cancer Institute, the Dana-Farber McGraw/Patterson Research Fund, and the Mark Foundation Emerging Leader Award. Dr. Hantel reported receiving personal fees from AbbVie, AstraZeneca, the American Journal of Managed Care, Genentech, and GSK.

A version of this article appeared on Medscape.com.

TOPLINE:

A recent survey highlighted ethical concerns US oncologists have about using artificial intelligence (AI) to help make cancer treatment decisions and revealed some contradictory views about how best to integrate these tools into practice. Most respondents, for instance, said patients should not be expected to understand how AI tools work, but many also felt patients could make treatment decisions based on AI-generated recommendations. Most oncologists also felt responsible for protecting patients from biased AI, but few were confident that they could do so.

METHODOLOGY:

• The US Food and Drug Administration (FDA) has  for use in various medical specialties over the past few decades, and increasingly, AI tools are being integrated into cancer care.
• However, the uptake of these tools in oncology has raised ethical questions and concerns, including challenges with AI bias, error, or misuse, as well as issues explaining how an AI model reached a result.
• In the current study, researchers asked 204 oncologists from 37 states for their views on the ethical implications of using AI for cancer care.
• Among the survey respondents, 64% were men and 63% were non-Hispanic White; 29% were from academic practices, 47% had received some education on AI use in healthcare, and 45% were familiar with clinical decision models.
• The researchers assessed respondents’ answers to various questions, including whether to provide informed consent for AI use and how oncologists would approach a scenario where the AI model and the oncologist recommended a different treatment regimen.

TAKEAWAY:

• Overall, 81% of oncologists supported having patient consent to use an AI model during treatment decisions, and 85% felt that oncologists needed to be able to explain an AI-based clinical decision model to use it in the clinic; however, only 23% felt that patients also needed to be able to explain an AI model.
• When an AI decision model recommended a different treatment regimen than the treating oncologist, the most common response (36.8%) was to present both options to the patient and let the patient decide. Oncologists from academic settings were about 2.5 times more likely than those from other settings to let the patient decide. About 34% of respondents said they would present both options but recommend the oncologist’s regimen, whereas about 22% said they would present both but recommend the AI’s regimen. A small percentage would only present the oncologist’s regimen (5%) or the AI’s regimen (about 2.5%).
• About three of four respondents (76.5%) agreed that oncologists should protect patients from biased AI tools; however, only about one of four (27.9%) felt confident they could identify biased AI models.
• Most oncologists (91%) felt that AI developers were responsible for the medico-legal problems associated with AI use; less than half (47%) said oncologists or hospitals (43%) shared this responsibility.

IN PRACTICE:

“Together, these data characterize barriers that may impede the ethical adoption of AI into cancer care. The findings suggest that the implementation of AI in oncology must include rigorous assessments of its effect on care decisions, as well as decisional responsibility when problems related to AI use arise,” the authors concluded.

SOURCE:

The study, with first author Andrew Hantel, MD, from Dana-Farber Cancer Institute, Boston, was published last month in JAMA Network Open.

LIMITATIONS:

The study had a moderate sample size and response rate, although demographics of participating oncologists appear to be nationally representative. The cross-sectional study design limited the generalizability of the findings over time as AI is integrated into cancer care.

DISCLOSURES:

The study was funded by the National Cancer Institute, the Dana-Farber McGraw/Patterson Research Fund, and the Mark Foundation Emerging Leader Award. Dr. Hantel reported receiving personal fees from AbbVie, AstraZeneca, the American Journal of Managed Care, Genentech, and GSK.

A version of this article appeared on Medscape.com.

TOPLINE:

A recent survey highlighted ethical concerns US oncologists have about using artificial intelligence (AI) to help make cancer treatment decisions and revealed some contradictory views about how best to integrate these tools into practice. Most respondents, for instance, said patients should not be expected to understand how AI tools work, but many also felt patients could make treatment decisions based on AI-generated recommendations. Most oncologists also felt responsible for protecting patients from biased AI, but few were confident that they could do so.

METHODOLOGY:

• The US Food and Drug Administration (FDA) has  for use in various medical specialties over the past few decades, and increasingly, AI tools are being integrated into cancer care.
• However, the uptake of these tools in oncology has raised ethical questions and concerns, including challenges with AI bias, error, or misuse, as well as issues explaining how an AI model reached a result.
• In the current study, researchers asked 204 oncologists from 37 states for their views on the ethical implications of using AI for cancer care.
• Among the survey respondents, 64% were men and 63% were non-Hispanic White; 29% were from academic practices, 47% had received some education on AI use in healthcare, and 45% were familiar with clinical decision models.
• The researchers assessed respondents’ answers to various questions, including whether to provide informed consent for AI use and how oncologists would approach a scenario where the AI model and the oncologist recommended a different treatment regimen.

TAKEAWAY:

• Overall, 81% of oncologists supported having patient consent to use an AI model during treatment decisions, and 85% felt that oncologists needed to be able to explain an AI-based clinical decision model to use it in the clinic; however, only 23% felt that patients also needed to be able to explain an AI model.
• When an AI decision model recommended a different treatment regimen than the treating oncologist, the most common response (36.8%) was to present both options to the patient and let the patient decide. Oncologists from academic settings were about 2.5 times more likely than those from other settings to let the patient decide. About 34% of respondents said they would present both options but recommend the oncologist’s regimen, whereas about 22% said they would present both but recommend the AI’s regimen. A small percentage would only present the oncologist’s regimen (5%) or the AI’s regimen (about 2.5%).
• About three of four respondents (76.5%) agreed that oncologists should protect patients from biased AI tools; however, only about one of four (27.9%) felt confident they could identify biased AI models.
• Most oncologists (91%) felt that AI developers were responsible for the medico-legal problems associated with AI use; less than half (47%) said oncologists or hospitals (43%) shared this responsibility.

IN PRACTICE:

“Together, these data characterize barriers that may impede the ethical adoption of AI into cancer care. The findings suggest that the implementation of AI in oncology must include rigorous assessments of its effect on care decisions, as well as decisional responsibility when problems related to AI use arise,” the authors concluded.

SOURCE:

The study, with first author Andrew Hantel, MD, from Dana-Farber Cancer Institute, Boston, was published last month in JAMA Network Open.

LIMITATIONS:

The study had a moderate sample size and response rate, although demographics of participating oncologists appear to be nationally representative. The cross-sectional study design limited the generalizability of the findings over time as AI is integrated into cancer care.

DISCLOSURES:

The study was funded by the National Cancer Institute, the Dana-Farber McGraw/Patterson Research Fund, and the Mark Foundation Emerging Leader Award. Dr. Hantel reported receiving personal fees from AbbVie, AstraZeneca, the American Journal of Managed Care, Genentech, and GSK.

A version of this article appeared on Medscape.com.

TOPLINE:

No significant association was found between the use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and thyroid cancer over nearly 4 years.

METHODOLOGY:

• A cohort study using data from nationwide registers in Denmark, Norway, and Sweden between 2007 and 2021 included 145,410 patients who initiated GLP-1 RAs and 291,667 propensity score-matched patients initiating dipeptidyl peptidase 4 (DPP4) inhibitors as active comparators.
• Additional analysis included 111,744 who initiated GLP-1 RAs and 148,179 patients initiating sodium-glucose cotransporter 2 (SGLT2) inhibitors.
• Overall, mean follow-up time was 3.9 years, with 25% followed for more than 6 years.

TAKEAWAY:

• The most common individual GLP-1 RAs were liraglutide (57.3%) and semaglutide (32.9%).
• During follow-up, there were 76 incident thyroid cancer cases among GLP-1 RA users and 184 cases in DPP4 inhibitor users, giving incidence rates per 10,000 of 1.33 and 1.46, respectively, a nonsignificant difference (hazard ratio [HR], 0.93; 95% CI, 0.66-1.31).
• Papillary thyroid cancer was the most common thyroid cancer subtype, followed by follicular and medullary, with no significant increases in risk with GLP-1 RAs by cancer type, although the numbers were small.
• In the SGLT2 inhibitor comparison, there was also no significantly increased thyroid cancer risk for GLP-1 RAs (HR, 1.16; 95% CI, 0.65-2.05).

IN PRACTICE:

“Given the upper limit of the confidence interval, the findings are incompatible with more than a 31% increased relative risk of thyroid cancer. In absolute terms, this translates to no more than 0.36 excess cases per 10 000 person-years, a figure that should be interpreted against the background incidence of 1.46 per 10,000 person-years among the comparator group in the study populations.”

SOURCE:

This study was conducted by Björn Pasternak, MD, PhD, of the Karolinska Institutet, Stockholm, and colleagues. It was published online on April 10, 2024, in The BMJ.

LIMITATIONS:

Relatively short follow-up for cancer risk. Risk by individual GLP-1 RA not analyzed. Small event numbers. Observational, with potential for residual confounding and time-release bias.

DISCLOSURES:

The study was supported by grants from the Swedish Cancer Society and the Swedish Research Council. Dr. Pasternak was supported by a consolidator investigator grant from Karolinska Institutet. Some of the coauthors had industry disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

No significant association was found between the use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and thyroid cancer over nearly 4 years.

METHODOLOGY:

• A cohort study using data from nationwide registers in Denmark, Norway, and Sweden between 2007 and 2021 included 145,410 patients who initiated GLP-1 RAs and 291,667 propensity score-matched patients initiating dipeptidyl peptidase 4 (DPP4) inhibitors as active comparators.
• Additional analysis included 111,744 who initiated GLP-1 RAs and 148,179 patients initiating sodium-glucose cotransporter 2 (SGLT2) inhibitors.
• Overall, mean follow-up time was 3.9 years, with 25% followed for more than 6 years.

TAKEAWAY:

• The most common individual GLP-1 RAs were liraglutide (57.3%) and semaglutide (32.9%).
• During follow-up, there were 76 incident thyroid cancer cases among GLP-1 RA users and 184 cases in DPP4 inhibitor users, giving incidence rates per 10,000 of 1.33 and 1.46, respectively, a nonsignificant difference (hazard ratio [HR], 0.93; 95% CI, 0.66-1.31).
• Papillary thyroid cancer was the most common thyroid cancer subtype, followed by follicular and medullary, with no significant increases in risk with GLP-1 RAs by cancer type, although the numbers were small.
• In the SGLT2 inhibitor comparison, there was also no significantly increased thyroid cancer risk for GLP-1 RAs (HR, 1.16; 95% CI, 0.65-2.05).

IN PRACTICE:

“Given the upper limit of the confidence interval, the findings are incompatible with more than a 31% increased relative risk of thyroid cancer. In absolute terms, this translates to no more than 0.36 excess cases per 10 000 person-years, a figure that should be interpreted against the background incidence of 1.46 per 10,000 person-years among the comparator group in the study populations.”

SOURCE:

This study was conducted by Björn Pasternak, MD, PhD, of the Karolinska Institutet, Stockholm, and colleagues. It was published online on April 10, 2024, in The BMJ.

LIMITATIONS:

Relatively short follow-up for cancer risk. Risk by individual GLP-1 RA not analyzed. Small event numbers. Observational, with potential for residual confounding and time-release bias.

DISCLOSURES:

The study was supported by grants from the Swedish Cancer Society and the Swedish Research Council. Dr. Pasternak was supported by a consolidator investigator grant from Karolinska Institutet. Some of the coauthors had industry disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

No significant association was found between the use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and thyroid cancer over nearly 4 years.

METHODOLOGY:

• A cohort study using data from nationwide registers in Denmark, Norway, and Sweden between 2007 and 2021 included 145,410 patients who initiated GLP-1 RAs and 291,667 propensity score-matched patients initiating dipeptidyl peptidase 4 (DPP4) inhibitors as active comparators.
• Additional analysis included 111,744 who initiated GLP-1 RAs and 148,179 patients initiating sodium-glucose cotransporter 2 (SGLT2) inhibitors.
• Overall, mean follow-up time was 3.9 years, with 25% followed for more than 6 years.

TAKEAWAY:

• The most common individual GLP-1 RAs were liraglutide (57.3%) and semaglutide (32.9%).
• During follow-up, there were 76 incident thyroid cancer cases among GLP-1 RA users and 184 cases in DPP4 inhibitor users, giving incidence rates per 10,000 of 1.33 and 1.46, respectively, a nonsignificant difference (hazard ratio [HR], 0.93; 95% CI, 0.66-1.31).
• Papillary thyroid cancer was the most common thyroid cancer subtype, followed by follicular and medullary, with no significant increases in risk with GLP-1 RAs by cancer type, although the numbers were small.
• In the SGLT2 inhibitor comparison, there was also no significantly increased thyroid cancer risk for GLP-1 RAs (HR, 1.16; 95% CI, 0.65-2.05).

IN PRACTICE:

“Given the upper limit of the confidence interval, the findings are incompatible with more than a 31% increased relative risk of thyroid cancer. In absolute terms, this translates to no more than 0.36 excess cases per 10 000 person-years, a figure that should be interpreted against the background incidence of 1.46 per 10,000 person-years among the comparator group in the study populations.”

SOURCE:

This study was conducted by Björn Pasternak, MD, PhD, of the Karolinska Institutet, Stockholm, and colleagues. It was published online on April 10, 2024, in The BMJ.

LIMITATIONS:

Relatively short follow-up for cancer risk. Risk by individual GLP-1 RA not analyzed. Small event numbers. Observational, with potential for residual confounding and time-release bias.

DISCLOSURES:

The study was supported by grants from the Swedish Cancer Society and the Swedish Research Council. Dr. Pasternak was supported by a consolidator investigator grant from Karolinska Institutet. Some of the coauthors had industry disclosures.

A version of this article appeared on Medscape.com.

Multitarget stool-based tests are showing promise for colorectal cancer (CRC) screening in average-risk individuals and could edge out the current standard fecal immunochemical test (FIT).

These new tests aren’t radical departures from the standard FIT. Like the standard test, the multitarget FIT uses antibodies to test for hemoglobin in stool samples. But these multitarget approaches take the standard FIT a step further by testing for additional DNA, RNA, or protein biomarkers associated with CRC to help improve early detection.

Currently, the US Preventive Services Task Force (USPSTF) recommends two FIT tests — standard FIT and stool FIT-DNA — as well as a third noninvasive CRC screening test, guaiac fecal occult blood test (gFOBT). gFOBT detects heme, a component of hemoglobin, through a chemical reaction.

But both standard FIT and stool FIT-DNA come with caveats. Compared to the standard test, FIT-DNA tends to be better at detecting traces of blood in the stool, and thus can uncover more instances of CRC or other advanced lesions. The flipside is that the DNA test also often leads to more false-positive findings.

In fact, the American College of Physicians does not recommend stool FIT-DNA for screening, citing issues such as cost — more than $600 per test vs about $30 for standard FIT — and the greater likelihood of false-positives compared with both standard FIT and gFOBT.

Given these trade-offs with current noninvasive screening options, developing a FIT option that can improve early detection of CRC and advanced precancerous lesions without increasing false-positives could make a big difference in outcomes. 

Three new noninvasive multitarget tests under investigation — an updated DNA-based test, Cologuard 2.0 (Exact Sciences; Madison, WI); an RNA-based test, ColoSense (Geneoscopy; St Louis, MO); and a protein-based test from CRCbioscreen (Amsterdam, the Netherlands) — may be able to do just that. 
 

Cologuard 2.0: Multitarget Stool DNA-Based Test

An updated version of the stool FIT-DNA is currently under development. Dubbed Next Generation Cologuard, or Cologuard 2.0, this multitarget test detects three novel methylated DNA markers along with fecal hemoglobin.

In a recent trial comparing Cologuard 2.0 vs standard FIT, 20,176 participants aged 40 years or older were screened with Cologuard 2.0 as well as standard FIT before they all also received a colonoscopy. The researchers compared findings with Cologuard 2.0 and standard FIT, which used a positivity cutoff ≥ 20 mcg hemoglobin/g feces. 

The researchers then assessed Cologuard 2.0’s sensitivity (a gauge of how well it detects disease that is truly present) and specificity (a measure of how well a test indicates the absence of disease when no disease is present) compared with standard FIT and the original Cologuard test.

Overall, Cologuard 2.0 demonstrated better sensitivity for CRC than did standard FIT (93.9% vs 67.3%, respectively) and for advanced precancerous lesions (43.4% vs 23.3%). The next-generation test, for instance, identified 92 of 98 participants with colonoscopy-confirmed CRC diagnoses vs 66 cases using standard FIT.

Compared with the original Cologuard, Cologuard 2.0’s sensitivity improved slightly for CRC, from 92% to 93.9%,; for advanced precancerous lesions, from 42% to 43.4%; and for high-grade dysplasia, from 69% to 75%. Specificity also improved with the latest version, from 87% to 90.6%. 

However, Cologuard 2.0’s specificity for advanced neoplasia was worse than that of standard FIT (90.6% vs 94.8%, respectively), which would increase the likelihood of false-positive findings.

Despite its lower specificity compared with standard FIT, Cologuard 2.0 has several advantages. The test can identify more people with CRC and advanced precancerous lesions than the standard test and can lead to fewer false-positives than the original Cologuard test.

Cologuard maker Exact Sciences has submitted trial data to the US Food and Drug Administration (FDA) for approval.
 

Multitarget Stool RNA-Based Test

ColoSense, an RNA-based stool test, looks for eight RNA biomarkers associated with CRC. 

The company says that RNA-based testing has an advantage over DNA biomarker assays, such as the currently marketed Cologuard test, because it isn›t subject to the age-related changes in DNA methylation that can throw off the results from DNA assays. 

Like Cologuard 2.0, Geneoscopy’s Colosense test is under review by the FDA.

The data Geneoscopy submitted to the FDA came from the CRC-PREVENT trial, which included 8920 participants who were screened with both ColoSense and standard FIT before all had a colonoscopy. The participants ranged in age from 45 to 90 years, with 22% between 45 and 50 years old, a population recently added to the USPSTF screening recommendations. 

ColoSense showed higher sensitivity than standard FIT for the presence of CRC (94% vs 78%, respectively) and advanced adenomas (46% vs 29%). In the group aged 45-50 years, the RNA-based test had a sensitivity of 100% for CRC, correctly identifying all five people with colonoscopy-confirmed CRC, and 45% for advanced adenomas.

However, ColoSense was less specific than standard FIT compared with negative colonoscopy findings (88% vs 96%, respectively) and negative findings for advanced lesions or CRC (85.5% vs 94.9%); thus, it was more likely to lead to false-positive results.

Overall, the investigators said ColoSense is comparable to Cologuard — its chief market rival — in terms of sensitivity for CRC and advanced adenomas but has higher sensitivity for colorectal neoplasia in people aged 50 years or younger.
 

Multitarget Protein-Based Test

The multitarget protein-based FIT uses antibodies to test for two additional proteins: calprotectin, an inflammatory marker associated with CRC, and serpin family F member 2, a protease inhibitor thought to be upregulated in colon cancer. 

A 2021 study of 1284 patients found that the sensitivity of the multitarget protein-based test was 42.9% for advanced neoplasias compared with 37.3% with standard FIT. Its specificity was similar to that of standard FIT, at 96.6% for advanced neoplasias. 

In a more recent report published in The Lancet Oncology, the team modeled three scenarios comparing the two FIT tests. These scenarios used different cutoff values for a test to be positive for CRC or an advanced lesion.

Overall, the analysis included stool samples from 13,187 patients aged 55-75 years who were in the Netherlands’ national CRC screening program. Stool samples were evaluated with both the multitarget test and the standard FIT, using a positivity cutoff ≥ 47 mcg hemoglobin/g feces. Colonoscopy data were available for only 1270 participants. 

In scenario 1, the multitarget test had a lower threshold for a positive test and consequently identified more precancerous lesions than the standard FIT (828 vs 354, respectively). The multitarget FIT identified a few more CRC cases: Of 29 colonoscopy-confirmed CRC cases, the multitarget FIT identified 26 vs 23 with standard FIT. 

But the multitarget FIT also had more than double the number of false-positives than the standard FIT (347 vs 161, respectively).

Perhaps the most telling comparison occurred in scenario 2, with both tests set at the same low positivity threshold to minimize false-positives.

As expected, the two tests had similar positivity rates for advanced lesions, with the multitarget test correctly identifying 22 of 29 people with CRC, one fewer than the standard test. The protein-based test identified slightly more people with advanced lesions (156 vs 136 with the standard test), leading to a higher sensitivity for advanced lesions. 

Most notably, the protein-based test resulted in fewer false-positives than did the standard test (295 vs 311, respectively) , resulting in a slightly higher specificity.

In this scenario, “a single screening round might not have the biggest impact on cancer incidence and mortality,” the authors said, but the higher detection rate would still accumulate over 20 years of testing. The authors estimated that, under this scenario, substituting the multitarget FIT for the standard test in the Netherlands’ CRC screening program could reduce CRC incidence by 5% and CRC mortality by 4%.

Gerrit Meijer, MD, PhD, a pathologist at the Netherlands Cancer Institute, and colleagues recently launched a company called CRCbioscreen to commercialize this multitarget FIT for large-scale programs. The company›s priority is to develop and validate a clinical-grade test to sell to federal governments with national screening programs, such as those throughout Europe, Australia, and Asia, Dr. Meijer told this news organization. Dr. Meijer expects this process will take about 4 years.

The test will be developed for the US market, but with no nationwide screening program in the United States, future availability will depend on interest from providers and institutions, noted Dr. Meijer, who is also chief scientific officer at CRCbioscreen.

Overall, these three new multitarget stool-based CRC screening tests could help catch more cancers and advanced precancerous lesions. And, if the tests have a high enough specificity, a negative test result could also allow people to forgo screening colonoscopy. 

Still, people with a positive FIT finding would require follow-up colonoscopy, but about 10% of patients decline colonoscopy following an abnormal FIT, Mark A. Lewis, MD, director of gastrointestinal oncology at Intermountain Health in Murray, Utah, told this news organization last year. That means that even if precancerous lesions and CRC are being caught earlier, treatment can’t be started unless people follow through with colonoscopy.

A version of this article appeared on Medscape.com.

Multitarget stool-based tests are showing promise for colorectal cancer (CRC) screening in average-risk individuals and could edge out the current standard fecal immunochemical test (FIT).

These new tests aren’t radical departures from the standard FIT. Like the standard test, the multitarget FIT uses antibodies to test for hemoglobin in stool samples. But these multitarget approaches take the standard FIT a step further by testing for additional DNA, RNA, or protein biomarkers associated with CRC to help improve early detection.

Currently, the US Preventive Services Task Force (USPSTF) recommends two FIT tests — standard FIT and stool FIT-DNA — as well as a third noninvasive CRC screening test, guaiac fecal occult blood test (gFOBT). gFOBT detects heme, a component of hemoglobin, through a chemical reaction.

But both standard FIT and stool FIT-DNA come with caveats. Compared to the standard test, FIT-DNA tends to be better at detecting traces of blood in the stool, and thus can uncover more instances of CRC or other advanced lesions. The flipside is that the DNA test also often leads to more false-positive findings.

In fact, the American College of Physicians does not recommend stool FIT-DNA for screening, citing issues such as cost — more than $600 per test vs about $30 for standard FIT — and the greater likelihood of false-positives compared with both standard FIT and gFOBT.

Given these trade-offs with current noninvasive screening options, developing a FIT option that can improve early detection of CRC and advanced precancerous lesions without increasing false-positives could make a big difference in outcomes. 

Three new noninvasive multitarget tests under investigation — an updated DNA-based test, Cologuard 2.0 (Exact Sciences; Madison, WI); an RNA-based test, ColoSense (Geneoscopy; St Louis, MO); and a protein-based test from CRCbioscreen (Amsterdam, the Netherlands) — may be able to do just that. 
 

Cologuard 2.0: Multitarget Stool DNA-Based Test

An updated version of the stool FIT-DNA is currently under development. Dubbed Next Generation Cologuard, or Cologuard 2.0, this multitarget test detects three novel methylated DNA markers along with fecal hemoglobin.

In a recent trial comparing Cologuard 2.0 vs standard FIT, 20,176 participants aged 40 years or older were screened with Cologuard 2.0 as well as standard FIT before they all also received a colonoscopy. The researchers compared findings with Cologuard 2.0 and standard FIT, which used a positivity cutoff ≥ 20 mcg hemoglobin/g feces. 

The researchers then assessed Cologuard 2.0’s sensitivity (a gauge of how well it detects disease that is truly present) and specificity (a measure of how well a test indicates the absence of disease when no disease is present) compared with standard FIT and the original Cologuard test.

Overall, Cologuard 2.0 demonstrated better sensitivity for CRC than did standard FIT (93.9% vs 67.3%, respectively) and for advanced precancerous lesions (43.4% vs 23.3%). The next-generation test, for instance, identified 92 of 98 participants with colonoscopy-confirmed CRC diagnoses vs 66 cases using standard FIT.

Compared with the original Cologuard, Cologuard 2.0’s sensitivity improved slightly for CRC, from 92% to 93.9%,; for advanced precancerous lesions, from 42% to 43.4%; and for high-grade dysplasia, from 69% to 75%. Specificity also improved with the latest version, from 87% to 90.6%. 

However, Cologuard 2.0’s specificity for advanced neoplasia was worse than that of standard FIT (90.6% vs 94.8%, respectively), which would increase the likelihood of false-positive findings.

Despite its lower specificity compared with standard FIT, Cologuard 2.0 has several advantages. The test can identify more people with CRC and advanced precancerous lesions than the standard test and can lead to fewer false-positives than the original Cologuard test.

Cologuard maker Exact Sciences has submitted trial data to the US Food and Drug Administration (FDA) for approval.
 

Multitarget Stool RNA-Based Test

ColoSense, an RNA-based stool test, looks for eight RNA biomarkers associated with CRC. 

The company says that RNA-based testing has an advantage over DNA biomarker assays, such as the currently marketed Cologuard test, because it isn›t subject to the age-related changes in DNA methylation that can throw off the results from DNA assays. 

Like Cologuard 2.0, Geneoscopy’s Colosense test is under review by the FDA.

The data Geneoscopy submitted to the FDA came from the CRC-PREVENT trial, which included 8920 participants who were screened with both ColoSense and standard FIT before all had a colonoscopy. The participants ranged in age from 45 to 90 years, with 22% between 45 and 50 years old, a population recently added to the USPSTF screening recommendations. 

ColoSense showed higher sensitivity than standard FIT for the presence of CRC (94% vs 78%, respectively) and advanced adenomas (46% vs 29%). In the group aged 45-50 years, the RNA-based test had a sensitivity of 100% for CRC, correctly identifying all five people with colonoscopy-confirmed CRC, and 45% for advanced adenomas.

However, ColoSense was less specific than standard FIT compared with negative colonoscopy findings (88% vs 96%, respectively) and negative findings for advanced lesions or CRC (85.5% vs 94.9%); thus, it was more likely to lead to false-positive results.

Overall, the investigators said ColoSense is comparable to Cologuard — its chief market rival — in terms of sensitivity for CRC and advanced adenomas but has higher sensitivity for colorectal neoplasia in people aged 50 years or younger.
 

Multitarget Protein-Based Test

The multitarget protein-based FIT uses antibodies to test for two additional proteins: calprotectin, an inflammatory marker associated with CRC, and serpin family F member 2, a protease inhibitor thought to be upregulated in colon cancer. 

A 2021 study of 1284 patients found that the sensitivity of the multitarget protein-based test was 42.9% for advanced neoplasias compared with 37.3% with standard FIT. Its specificity was similar to that of standard FIT, at 96.6% for advanced neoplasias. 

In a more recent report published in The Lancet Oncology, the team modeled three scenarios comparing the two FIT tests. These scenarios used different cutoff values for a test to be positive for CRC or an advanced lesion.

Overall, the analysis included stool samples from 13,187 patients aged 55-75 years who were in the Netherlands’ national CRC screening program. Stool samples were evaluated with both the multitarget test and the standard FIT, using a positivity cutoff ≥ 47 mcg hemoglobin/g feces. Colonoscopy data were available for only 1270 participants. 

In scenario 1, the multitarget test had a lower threshold for a positive test and consequently identified more precancerous lesions than the standard FIT (828 vs 354, respectively). The multitarget FIT identified a few more CRC cases: Of 29 colonoscopy-confirmed CRC cases, the multitarget FIT identified 26 vs 23 with standard FIT. 

But the multitarget FIT also had more than double the number of false-positives than the standard FIT (347 vs 161, respectively).

Perhaps the most telling comparison occurred in scenario 2, with both tests set at the same low positivity threshold to minimize false-positives.

As expected, the two tests had similar positivity rates for advanced lesions, with the multitarget test correctly identifying 22 of 29 people with CRC, one fewer than the standard test. The protein-based test identified slightly more people with advanced lesions (156 vs 136 with the standard test), leading to a higher sensitivity for advanced lesions. 

Most notably, the protein-based test resulted in fewer false-positives than did the standard test (295 vs 311, respectively) , resulting in a slightly higher specificity.

In this scenario, “a single screening round might not have the biggest impact on cancer incidence and mortality,” the authors said, but the higher detection rate would still accumulate over 20 years of testing. The authors estimated that, under this scenario, substituting the multitarget FIT for the standard test in the Netherlands’ CRC screening program could reduce CRC incidence by 5% and CRC mortality by 4%.

Gerrit Meijer, MD, PhD, a pathologist at the Netherlands Cancer Institute, and colleagues recently launched a company called CRCbioscreen to commercialize this multitarget FIT for large-scale programs. The company›s priority is to develop and validate a clinical-grade test to sell to federal governments with national screening programs, such as those throughout Europe, Australia, and Asia, Dr. Meijer told this news organization. Dr. Meijer expects this process will take about 4 years.

The test will be developed for the US market, but with no nationwide screening program in the United States, future availability will depend on interest from providers and institutions, noted Dr. Meijer, who is also chief scientific officer at CRCbioscreen.

Overall, these three new multitarget stool-based CRC screening tests could help catch more cancers and advanced precancerous lesions. And, if the tests have a high enough specificity, a negative test result could also allow people to forgo screening colonoscopy. 

Still, people with a positive FIT finding would require follow-up colonoscopy, but about 10% of patients decline colonoscopy following an abnormal FIT, Mark A. Lewis, MD, director of gastrointestinal oncology at Intermountain Health in Murray, Utah, told this news organization last year. That means that even if precancerous lesions and CRC are being caught earlier, treatment can’t be started unless people follow through with colonoscopy.

A version of this article appeared on Medscape.com.

Multitarget stool-based tests are showing promise for colorectal cancer (CRC) screening in average-risk individuals and could edge out the current standard fecal immunochemical test (FIT).

These new tests aren’t radical departures from the standard FIT. Like the standard test, the multitarget FIT uses antibodies to test for hemoglobin in stool samples. But these multitarget approaches take the standard FIT a step further by testing for additional DNA, RNA, or protein biomarkers associated with CRC to help improve early detection.

Currently, the US Preventive Services Task Force (USPSTF) recommends two FIT tests — standard FIT and stool FIT-DNA — as well as a third noninvasive CRC screening test, guaiac fecal occult blood test (gFOBT). gFOBT detects heme, a component of hemoglobin, through a chemical reaction.

But both standard FIT and stool FIT-DNA come with caveats. Compared to the standard test, FIT-DNA tends to be better at detecting traces of blood in the stool, and thus can uncover more instances of CRC or other advanced lesions. The flipside is that the DNA test also often leads to more false-positive findings.

In fact, the American College of Physicians does not recommend stool FIT-DNA for screening, citing issues such as cost — more than $600 per test vs about $30 for standard FIT — and the greater likelihood of false-positives compared with both standard FIT and gFOBT.

Given these trade-offs with current noninvasive screening options, developing a FIT option that can improve early detection of CRC and advanced precancerous lesions without increasing false-positives could make a big difference in outcomes. 

Three new noninvasive multitarget tests under investigation — an updated DNA-based test, Cologuard 2.0 (Exact Sciences; Madison, WI); an RNA-based test, ColoSense (Geneoscopy; St Louis, MO); and a protein-based test from CRCbioscreen (Amsterdam, the Netherlands) — may be able to do just that. 
 

Cologuard 2.0: Multitarget Stool DNA-Based Test

An updated version of the stool FIT-DNA is currently under development. Dubbed Next Generation Cologuard, or Cologuard 2.0, this multitarget test detects three novel methylated DNA markers along with fecal hemoglobin.

In a recent trial comparing Cologuard 2.0 vs standard FIT, 20,176 participants aged 40 years or older were screened with Cologuard 2.0 as well as standard FIT before they all also received a colonoscopy. The researchers compared findings with Cologuard 2.0 and standard FIT, which used a positivity cutoff ≥ 20 mcg hemoglobin/g feces. 

The researchers then assessed Cologuard 2.0’s sensitivity (a gauge of how well it detects disease that is truly present) and specificity (a measure of how well a test indicates the absence of disease when no disease is present) compared with standard FIT and the original Cologuard test.

Overall, Cologuard 2.0 demonstrated better sensitivity for CRC than did standard FIT (93.9% vs 67.3%, respectively) and for advanced precancerous lesions (43.4% vs 23.3%). The next-generation test, for instance, identified 92 of 98 participants with colonoscopy-confirmed CRC diagnoses vs 66 cases using standard FIT.

Compared with the original Cologuard, Cologuard 2.0’s sensitivity improved slightly for CRC, from 92% to 93.9%,; for advanced precancerous lesions, from 42% to 43.4%; and for high-grade dysplasia, from 69% to 75%. Specificity also improved with the latest version, from 87% to 90.6%. 

However, Cologuard 2.0’s specificity for advanced neoplasia was worse than that of standard FIT (90.6% vs 94.8%, respectively), which would increase the likelihood of false-positive findings.

Despite its lower specificity compared with standard FIT, Cologuard 2.0 has several advantages. The test can identify more people with CRC and advanced precancerous lesions than the standard test and can lead to fewer false-positives than the original Cologuard test.

Cologuard maker Exact Sciences has submitted trial data to the US Food and Drug Administration (FDA) for approval.
 

Multitarget Stool RNA-Based Test

ColoSense, an RNA-based stool test, looks for eight RNA biomarkers associated with CRC. 

The company says that RNA-based testing has an advantage over DNA biomarker assays, such as the currently marketed Cologuard test, because it isn›t subject to the age-related changes in DNA methylation that can throw off the results from DNA assays. 

Like Cologuard 2.0, Geneoscopy’s Colosense test is under review by the FDA.

The data Geneoscopy submitted to the FDA came from the CRC-PREVENT trial, which included 8920 participants who were screened with both ColoSense and standard FIT before all had a colonoscopy. The participants ranged in age from 45 to 90 years, with 22% between 45 and 50 years old, a population recently added to the USPSTF screening recommendations. 

ColoSense showed higher sensitivity than standard FIT for the presence of CRC (94% vs 78%, respectively) and advanced adenomas (46% vs 29%). In the group aged 45-50 years, the RNA-based test had a sensitivity of 100% for CRC, correctly identifying all five people with colonoscopy-confirmed CRC, and 45% for advanced adenomas.

However, ColoSense was less specific than standard FIT compared with negative colonoscopy findings (88% vs 96%, respectively) and negative findings for advanced lesions or CRC (85.5% vs 94.9%); thus, it was more likely to lead to false-positive results.

Overall, the investigators said ColoSense is comparable to Cologuard — its chief market rival — in terms of sensitivity for CRC and advanced adenomas but has higher sensitivity for colorectal neoplasia in people aged 50 years or younger.
 

Multitarget Protein-Based Test

The multitarget protein-based FIT uses antibodies to test for two additional proteins: calprotectin, an inflammatory marker associated with CRC, and serpin family F member 2, a protease inhibitor thought to be upregulated in colon cancer. 

A 2021 study of 1284 patients found that the sensitivity of the multitarget protein-based test was 42.9% for advanced neoplasias compared with 37.3% with standard FIT. Its specificity was similar to that of standard FIT, at 96.6% for advanced neoplasias. 

In a more recent report published in The Lancet Oncology, the team modeled three scenarios comparing the two FIT tests. These scenarios used different cutoff values for a test to be positive for CRC or an advanced lesion.

Overall, the analysis included stool samples from 13,187 patients aged 55-75 years who were in the Netherlands’ national CRC screening program. Stool samples were evaluated with both the multitarget test and the standard FIT, using a positivity cutoff ≥ 47 mcg hemoglobin/g feces. Colonoscopy data were available for only 1270 participants. 

In scenario 1, the multitarget test had a lower threshold for a positive test and consequently identified more precancerous lesions than the standard FIT (828 vs 354, respectively). The multitarget FIT identified a few more CRC cases: Of 29 colonoscopy-confirmed CRC cases, the multitarget FIT identified 26 vs 23 with standard FIT. 

But the multitarget FIT also had more than double the number of false-positives than the standard FIT (347 vs 161, respectively).

Perhaps the most telling comparison occurred in scenario 2, with both tests set at the same low positivity threshold to minimize false-positives.

As expected, the two tests had similar positivity rates for advanced lesions, with the multitarget test correctly identifying 22 of 29 people with CRC, one fewer than the standard test. The protein-based test identified slightly more people with advanced lesions (156 vs 136 with the standard test), leading to a higher sensitivity for advanced lesions. 

Most notably, the protein-based test resulted in fewer false-positives than did the standard test (295 vs 311, respectively) , resulting in a slightly higher specificity.

In this scenario, “a single screening round might not have the biggest impact on cancer incidence and mortality,” the authors said, but the higher detection rate would still accumulate over 20 years of testing. The authors estimated that, under this scenario, substituting the multitarget FIT for the standard test in the Netherlands’ CRC screening program could reduce CRC incidence by 5% and CRC mortality by 4%.

Gerrit Meijer, MD, PhD, a pathologist at the Netherlands Cancer Institute, and colleagues recently launched a company called CRCbioscreen to commercialize this multitarget FIT for large-scale programs. The company›s priority is to develop and validate a clinical-grade test to sell to federal governments with national screening programs, such as those throughout Europe, Australia, and Asia, Dr. Meijer told this news organization. Dr. Meijer expects this process will take about 4 years.

The test will be developed for the US market, but with no nationwide screening program in the United States, future availability will depend on interest from providers and institutions, noted Dr. Meijer, who is also chief scientific officer at CRCbioscreen.

Overall, these three new multitarget stool-based CRC screening tests could help catch more cancers and advanced precancerous lesions. And, if the tests have a high enough specificity, a negative test result could also allow people to forgo screening colonoscopy. 

Still, people with a positive FIT finding would require follow-up colonoscopy, but about 10% of patients decline colonoscopy following an abnormal FIT, Mark A. Lewis, MD, director of gastrointestinal oncology at Intermountain Health in Murray, Utah, told this news organization last year. That means that even if precancerous lesions and CRC are being caught earlier, treatment can’t be started unless people follow through with colonoscopy.

A version of this article appeared on Medscape.com.

SAN DIEGO — Monitoring a patient’s circulating tumor DNA (ctDNA) can provide valuable insights on early response to targeted therapies among patients with HER2-positive cancers.

This was the main finding of new data presented by study author Razelle Kurzrock, MD, at the American Association for Cancer Research annual meeting.

“We found that on-treatment ctDNA can detect progression before standard-of-care response assessments. These data suggest that monitoring ctDNA can provide clinicians with important prognostic information that may guide treatment decisions,” Dr. Kurzrock, professor at the Medical College of Wisconsin, Milwaukee, said during her presentation.

Christos Evangelou/MDedge News

Commenting on the clinical implications of these findings during an interview, she said the results suggest that ctDNA dynamics provide an early window into predicting response to targeted therapies in patients with HER2-altered cancers, confirming previous findings of the predictive value of ctDNA in other cancer types.

“Such monitoring may be useful in clinical trials and eventually in practice,” she added.
 

Need for new methods to predict early tumor response

Limitations of standard radiographic tumor assessments present challenges in determining clinical response, particularly for patients receiving targeted therapies.

During her talk, Dr. Kurzrock explained that although targeted therapies are effective for patients with specific molecular alterations, standard imaging assessments fail to uncover molecular-level changes within tumors, limiting the ability of clinicians to accurately assess a patient’s response to targeted therapies.

“In addition to limitations with imaging, patients and physicians want to know as soon as possible whether or not the agents are effective, especially if there are side effects,” Dr. Kurzrock during an interview. She added that monitoring early response may be especially important across tumor types, as HER2 therapies are increasingly being considered in the pan-cancer setting.

Commenting on the potential use of this method in other cancer types with HER2 alterations, Pashtoon Murtaza Kasi, MD, MS, noted that since the study relied on a tumor-informed assay, it would be applicable across diverse tumor types.

“It is less about tissue type but more about that particular patient’s tumor at that instant in time for which a unique barcode is created,” said Dr. Kasi, a medical oncologist at Weill Cornell Medicine, New York, who was not involved in the study.

In an interview, he added that the shedding and biology would affect the assay’s performance for some tissue types.
 

Design of patient-specific ctDNA assays

In this retrospective study, the researchers examined ctDNA dynamics in 58 patients with various HER2-positive tumor types, including breast, colorectal, and other solid malignancies harboring HER2 alterations. All the patients received combination HER2-targeted therapy with trastuzumab and pertuzumab in the phase 2 basket trial My Pathway (NCT02091141).

By leveraging comprehensive genomic profiling of each patient’s tumor, the researchers designed personalized ctDNA assays, tracking 2-16 tumor-specific genetic variants in the patients’ blood samples. FoundationOne Tracker was used to detect and quantify ctDNA at baseline and the third cycle of therapy (cycle 3 day 1, or C3D1).

During an interview, Dr. Kurzrock explained that FoundationOne Tracker is a personalized ctDNA monitoring assay that allows for the detection of ctDNA in plasma, enabling ongoing liquid-based monitoring and highly sensitive quantification of ctDNA levels as mean tumor molecules per milliliter of plasma.

Among the 52 patients for whom personalized ctDNA assays were successfully designed, 48 (92.3%) had ctDNA data available at baseline, with a median of 100.7 tumor molecules per milliliter of plasma. Most patients (89.6%) were deemed ctDNA-positive, with a median of 119.5 tumor molecules per milliliter of plasma.
 

Changes in ctDNA levels predict patient survival

The researchers found that patients who experienced a greater than 90% decline in ctDNA levels by the third treatment cycle had significantly longer overall survival (OS) than those with less than 90% ctDNA decline or any increase. According to data presented by Dr. Kurzrock, the median OS was not reached in the group with greater than 90% decline in on-treatment ctDNA levels, versus 9.4 months in the group with less than 90% decline or ctDNA increase (P = .007). These findings held true when the analysis was limited to the 14 patients with colorectal cancer, in which median OS was not reached in the group with greater than 90% decline in on-treatment ctDNA levels, versus 10.2 months in the group with less than 90% decline or ctDNA increase (P = 0.04).

Notably, the prognostic significance of ctDNA changes remained even among patients exhibiting radiographic stable disease, underscoring the limitations of relying solely on anatomic tumor measurements and highlighting the potential for ctDNA monitoring to complement standard clinical assessments. In the subset of patients with radiographic stable disease, those with a greater than 90% ctDNA decline had significantly longer OS than those with less ctDNA reduction (not reached versus 9.4 months; P = .01).

“When used as a complement to imaging, tissue-informed ctDNA monitoring with FoundationOne Tracker can provide more accuracy than imaging alone,” Dr. Kurzrock noted in an interview.

Dr. Kasi echoed Dr. Kurzrock’s enthusiasm regarding the clinical usefulness of these findings, saying, “Not only can you see very early on in whom the ctDNA is going down and clearing, but you can also tell apart within the group who has ‘stable disease’ as to who is deriving more benefit.”

The researchers also observed that increases in on-treatment ctDNA levels often preceded radiographic evidence of disease progression by a median of 1.3 months. These findings highlight the potential for ctDNA monitoring to complement standard clinical assessments, allowing us to detect treatment response and disease progression earlier than what is possible with imaging alone, Dr. Kurzrock explained during her talk. “This early warning signal could allow clinicians to intervene and modify treatment strategies before overt clinical deterioration,” she said.

In an interview, Dr. Kasi highlighted that this high sensitivity and specificity and the short half-life of the tumor-informed ctDNA assay make this liquid biopsy of great clinical value. “The short half-life of a few hours means that if you do an intervention to treat cancer with HER2-directed therapy, you can very quickly assess response to therapy way earlier than traditional radiographic methods.”

Dr. Kasi cautioned, however, that this assay would not capture whether new mutations or HER2 loss occurred at the time of resistance. “A repeat tissue biopsy or a next-generation sequencing-based plasma-only assay would be required for that,” he said.
 

Implementation of ctDNA monitoring in clinical trials

Dr. Kurzrock acknowledged that further research is needed to validate these results in larger, prospective cohorts before FoundationOne Tracker is adopted in the clinic. She noted, however, that this retrospective analysis, along with results from previous studies, provides a rationale for the use of ctDNA monitoring in clinical trials.

“In some centers like ours, ctDNA monitoring is already part of our standard of care since not only does it help from a physician standpoint to have a more accurate and early assessment of response, but patients also appreciate the information gained from ctDNA dynamics,” Dr. Kasi said in an interview. He explained that when radiographic findings are equivocal, ctDNA monitoring is an additional tool in their toolbox to help guide care.

He noted, however, that the cost is a challenge for implementing ctDNA monitoring as a complementary tool for real-time treatment response monitoring. “For serial monitoring, helping to reduce costs would be important in the long run,” he said in an interview. He added that obtaining sufficient tissue for testing using a tumor-informed assay can present a logistical challenge, at least for the first test. “You need sufficient tissue to make the barcode that you then follow along,” he explained.

“Developing guidelines through systematic studies about testing cadence would also be important. This would help establish whether ctDNA monitoring is helpful,” Dr. Kasi said in an interview. He explained that in some situations, biological variables affect the shedding and detection of ctDNA beyond the assay — in those cases, ctDNA monitoring may not be helpful. “Like any test, it is not meant for every patient or clinical question,” Dr. Kasi concluded.

Dr. Kurzrock and Dr. Kasi reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

SAN DIEGO — Monitoring a patient’s circulating tumor DNA (ctDNA) can provide valuable insights on early response to targeted therapies among patients with HER2-positive cancers.

This was the main finding of new data presented by study author Razelle Kurzrock, MD, at the American Association for Cancer Research annual meeting.

“We found that on-treatment ctDNA can detect progression before standard-of-care response assessments. These data suggest that monitoring ctDNA can provide clinicians with important prognostic information that may guide treatment decisions,” Dr. Kurzrock, professor at the Medical College of Wisconsin, Milwaukee, said during her presentation.

Christos Evangelou/MDedge News

Commenting on the clinical implications of these findings during an interview, she said the results suggest that ctDNA dynamics provide an early window into predicting response to targeted therapies in patients with HER2-altered cancers, confirming previous findings of the predictive value of ctDNA in other cancer types.

“Such monitoring may be useful in clinical trials and eventually in practice,” she added.
 

Need for new methods to predict early tumor response

Limitations of standard radiographic tumor assessments present challenges in determining clinical response, particularly for patients receiving targeted therapies.

During her talk, Dr. Kurzrock explained that although targeted therapies are effective for patients with specific molecular alterations, standard imaging assessments fail to uncover molecular-level changes within tumors, limiting the ability of clinicians to accurately assess a patient’s response to targeted therapies.

“In addition to limitations with imaging, patients and physicians want to know as soon as possible whether or not the agents are effective, especially if there are side effects,” Dr. Kurzrock during an interview. She added that monitoring early response may be especially important across tumor types, as HER2 therapies are increasingly being considered in the pan-cancer setting.

Commenting on the potential use of this method in other cancer types with HER2 alterations, Pashtoon Murtaza Kasi, MD, MS, noted that since the study relied on a tumor-informed assay, it would be applicable across diverse tumor types.

“It is less about tissue type but more about that particular patient’s tumor at that instant in time for which a unique barcode is created,” said Dr. Kasi, a medical oncologist at Weill Cornell Medicine, New York, who was not involved in the study.

In an interview, he added that the shedding and biology would affect the assay’s performance for some tissue types.
 

Design of patient-specific ctDNA assays

In this retrospective study, the researchers examined ctDNA dynamics in 58 patients with various HER2-positive tumor types, including breast, colorectal, and other solid malignancies harboring HER2 alterations. All the patients received combination HER2-targeted therapy with trastuzumab and pertuzumab in the phase 2 basket trial My Pathway (NCT02091141).

By leveraging comprehensive genomic profiling of each patient’s tumor, the researchers designed personalized ctDNA assays, tracking 2-16 tumor-specific genetic variants in the patients’ blood samples. FoundationOne Tracker was used to detect and quantify ctDNA at baseline and the third cycle of therapy (cycle 3 day 1, or C3D1).

During an interview, Dr. Kurzrock explained that FoundationOne Tracker is a personalized ctDNA monitoring assay that allows for the detection of ctDNA in plasma, enabling ongoing liquid-based monitoring and highly sensitive quantification of ctDNA levels as mean tumor molecules per milliliter of plasma.

Among the 52 patients for whom personalized ctDNA assays were successfully designed, 48 (92.3%) had ctDNA data available at baseline, with a median of 100.7 tumor molecules per milliliter of plasma. Most patients (89.6%) were deemed ctDNA-positive, with a median of 119.5 tumor molecules per milliliter of plasma.
 

Changes in ctDNA levels predict patient survival

The researchers found that patients who experienced a greater than 90% decline in ctDNA levels by the third treatment cycle had significantly longer overall survival (OS) than those with less than 90% ctDNA decline or any increase. According to data presented by Dr. Kurzrock, the median OS was not reached in the group with greater than 90% decline in on-treatment ctDNA levels, versus 9.4 months in the group with less than 90% decline or ctDNA increase (P = .007). These findings held true when the analysis was limited to the 14 patients with colorectal cancer, in which median OS was not reached in the group with greater than 90% decline in on-treatment ctDNA levels, versus 10.2 months in the group with less than 90% decline or ctDNA increase (P = 0.04).

Notably, the prognostic significance of ctDNA changes remained even among patients exhibiting radiographic stable disease, underscoring the limitations of relying solely on anatomic tumor measurements and highlighting the potential for ctDNA monitoring to complement standard clinical assessments. In the subset of patients with radiographic stable disease, those with a greater than 90% ctDNA decline had significantly longer OS than those with less ctDNA reduction (not reached versus 9.4 months; P = .01).

“When used as a complement to imaging, tissue-informed ctDNA monitoring with FoundationOne Tracker can provide more accuracy than imaging alone,” Dr. Kurzrock noted in an interview.

Dr. Kasi echoed Dr. Kurzrock’s enthusiasm regarding the clinical usefulness of these findings, saying, “Not only can you see very early on in whom the ctDNA is going down and clearing, but you can also tell apart within the group who has ‘stable disease’ as to who is deriving more benefit.”

The researchers also observed that increases in on-treatment ctDNA levels often preceded radiographic evidence of disease progression by a median of 1.3 months. These findings highlight the potential for ctDNA monitoring to complement standard clinical assessments, allowing us to detect treatment response and disease progression earlier than what is possible with imaging alone, Dr. Kurzrock explained during her talk. “This early warning signal could allow clinicians to intervene and modify treatment strategies before overt clinical deterioration,” she said.

In an interview, Dr. Kasi highlighted that this high sensitivity and specificity and the short half-life of the tumor-informed ctDNA assay make this liquid biopsy of great clinical value. “The short half-life of a few hours means that if you do an intervention to treat cancer with HER2-directed therapy, you can very quickly assess response to therapy way earlier than traditional radiographic methods.”

Dr. Kasi cautioned, however, that this assay would not capture whether new mutations or HER2 loss occurred at the time of resistance. “A repeat tissue biopsy or a next-generation sequencing-based plasma-only assay would be required for that,” he said.
 

Implementation of ctDNA monitoring in clinical trials

Dr. Kurzrock acknowledged that further research is needed to validate these results in larger, prospective cohorts before FoundationOne Tracker is adopted in the clinic. She noted, however, that this retrospective analysis, along with results from previous studies, provides a rationale for the use of ctDNA monitoring in clinical trials.

“In some centers like ours, ctDNA monitoring is already part of our standard of care since not only does it help from a physician standpoint to have a more accurate and early assessment of response, but patients also appreciate the information gained from ctDNA dynamics,” Dr. Kasi said in an interview. He explained that when radiographic findings are equivocal, ctDNA monitoring is an additional tool in their toolbox to help guide care.

He noted, however, that the cost is a challenge for implementing ctDNA monitoring as a complementary tool for real-time treatment response monitoring. “For serial monitoring, helping to reduce costs would be important in the long run,” he said in an interview. He added that obtaining sufficient tissue for testing using a tumor-informed assay can present a logistical challenge, at least for the first test. “You need sufficient tissue to make the barcode that you then follow along,” he explained.

“Developing guidelines through systematic studies about testing cadence would also be important. This would help establish whether ctDNA monitoring is helpful,” Dr. Kasi said in an interview. He explained that in some situations, biological variables affect the shedding and detection of ctDNA beyond the assay — in those cases, ctDNA monitoring may not be helpful. “Like any test, it is not meant for every patient or clinical question,” Dr. Kasi concluded.

Dr. Kurzrock and Dr. Kasi reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

SAN DIEGO — Monitoring a patient’s circulating tumor DNA (ctDNA) can provide valuable insights on early response to targeted therapies among patients with HER2-positive cancers.

This was the main finding of new data presented by study author Razelle Kurzrock, MD, at the American Association for Cancer Research annual meeting.

“We found that on-treatment ctDNA can detect progression before standard-of-care response assessments. These data suggest that monitoring ctDNA can provide clinicians with important prognostic information that may guide treatment decisions,” Dr. Kurzrock, professor at the Medical College of Wisconsin, Milwaukee, said during her presentation.

Christos Evangelou/MDedge News

Commenting on the clinical implications of these findings during an interview, she said the results suggest that ctDNA dynamics provide an early window into predicting response to targeted therapies in patients with HER2-altered cancers, confirming previous findings of the predictive value of ctDNA in other cancer types.

“Such monitoring may be useful in clinical trials and eventually in practice,” she added.
 

Need for new methods to predict early tumor response

Limitations of standard radiographic tumor assessments present challenges in determining clinical response, particularly for patients receiving targeted therapies.

During her talk, Dr. Kurzrock explained that although targeted therapies are effective for patients with specific molecular alterations, standard imaging assessments fail to uncover molecular-level changes within tumors, limiting the ability of clinicians to accurately assess a patient’s response to targeted therapies.

“In addition to limitations with imaging, patients and physicians want to know as soon as possible whether or not the agents are effective, especially if there are side effects,” Dr. Kurzrock during an interview. She added that monitoring early response may be especially important across tumor types, as HER2 therapies are increasingly being considered in the pan-cancer setting.

Commenting on the potential use of this method in other cancer types with HER2 alterations, Pashtoon Murtaza Kasi, MD, MS, noted that since the study relied on a tumor-informed assay, it would be applicable across diverse tumor types.

“It is less about tissue type but more about that particular patient’s tumor at that instant in time for which a unique barcode is created,” said Dr. Kasi, a medical oncologist at Weill Cornell Medicine, New York, who was not involved in the study.

In an interview, he added that the shedding and biology would affect the assay’s performance for some tissue types.
 

Design of patient-specific ctDNA assays

In this retrospective study, the researchers examined ctDNA dynamics in 58 patients with various HER2-positive tumor types, including breast, colorectal, and other solid malignancies harboring HER2 alterations. All the patients received combination HER2-targeted therapy with trastuzumab and pertuzumab in the phase 2 basket trial My Pathway (NCT02091141).

By leveraging comprehensive genomic profiling of each patient’s tumor, the researchers designed personalized ctDNA assays, tracking 2-16 tumor-specific genetic variants in the patients’ blood samples. FoundationOne Tracker was used to detect and quantify ctDNA at baseline and the third cycle of therapy (cycle 3 day 1, or C3D1).

During an interview, Dr. Kurzrock explained that FoundationOne Tracker is a personalized ctDNA monitoring assay that allows for the detection of ctDNA in plasma, enabling ongoing liquid-based monitoring and highly sensitive quantification of ctDNA levels as mean tumor molecules per milliliter of plasma.

Among the 52 patients for whom personalized ctDNA assays were successfully designed, 48 (92.3%) had ctDNA data available at baseline, with a median of 100.7 tumor molecules per milliliter of plasma. Most patients (89.6%) were deemed ctDNA-positive, with a median of 119.5 tumor molecules per milliliter of plasma.
 

Changes in ctDNA levels predict patient survival

The researchers found that patients who experienced a greater than 90% decline in ctDNA levels by the third treatment cycle had significantly longer overall survival (OS) than those with less than 90% ctDNA decline or any increase. According to data presented by Dr. Kurzrock, the median OS was not reached in the group with greater than 90% decline in on-treatment ctDNA levels, versus 9.4 months in the group with less than 90% decline or ctDNA increase (P = .007). These findings held true when the analysis was limited to the 14 patients with colorectal cancer, in which median OS was not reached in the group with greater than 90% decline in on-treatment ctDNA levels, versus 10.2 months in the group with less than 90% decline or ctDNA increase (P = 0.04).

Notably, the prognostic significance of ctDNA changes remained even among patients exhibiting radiographic stable disease, underscoring the limitations of relying solely on anatomic tumor measurements and highlighting the potential for ctDNA monitoring to complement standard clinical assessments. In the subset of patients with radiographic stable disease, those with a greater than 90% ctDNA decline had significantly longer OS than those with less ctDNA reduction (not reached versus 9.4 months; P = .01).

“When used as a complement to imaging, tissue-informed ctDNA monitoring with FoundationOne Tracker can provide more accuracy than imaging alone,” Dr. Kurzrock noted in an interview.

Dr. Kasi echoed Dr. Kurzrock’s enthusiasm regarding the clinical usefulness of these findings, saying, “Not only can you see very early on in whom the ctDNA is going down and clearing, but you can also tell apart within the group who has ‘stable disease’ as to who is deriving more benefit.”

The researchers also observed that increases in on-treatment ctDNA levels often preceded radiographic evidence of disease progression by a median of 1.3 months. These findings highlight the potential for ctDNA monitoring to complement standard clinical assessments, allowing us to detect treatment response and disease progression earlier than what is possible with imaging alone, Dr. Kurzrock explained during her talk. “This early warning signal could allow clinicians to intervene and modify treatment strategies before overt clinical deterioration,” she said.

In an interview, Dr. Kasi highlighted that this high sensitivity and specificity and the short half-life of the tumor-informed ctDNA assay make this liquid biopsy of great clinical value. “The short half-life of a few hours means that if you do an intervention to treat cancer with HER2-directed therapy, you can very quickly assess response to therapy way earlier than traditional radiographic methods.”

Dr. Kasi cautioned, however, that this assay would not capture whether new mutations or HER2 loss occurred at the time of resistance. “A repeat tissue biopsy or a next-generation sequencing-based plasma-only assay would be required for that,” he said.
 

Implementation of ctDNA monitoring in clinical trials

Dr. Kurzrock acknowledged that further research is needed to validate these results in larger, prospective cohorts before FoundationOne Tracker is adopted in the clinic. She noted, however, that this retrospective analysis, along with results from previous studies, provides a rationale for the use of ctDNA monitoring in clinical trials.

“In some centers like ours, ctDNA monitoring is already part of our standard of care since not only does it help from a physician standpoint to have a more accurate and early assessment of response, but patients also appreciate the information gained from ctDNA dynamics,” Dr. Kasi said in an interview. He explained that when radiographic findings are equivocal, ctDNA monitoring is an additional tool in their toolbox to help guide care.

He noted, however, that the cost is a challenge for implementing ctDNA monitoring as a complementary tool for real-time treatment response monitoring. “For serial monitoring, helping to reduce costs would be important in the long run,” he said in an interview. He added that obtaining sufficient tissue for testing using a tumor-informed assay can present a logistical challenge, at least for the first test. “You need sufficient tissue to make the barcode that you then follow along,” he explained.

“Developing guidelines through systematic studies about testing cadence would also be important. This would help establish whether ctDNA monitoring is helpful,” Dr. Kasi said in an interview. He explained that in some situations, biological variables affect the shedding and detection of ctDNA beyond the assay — in those cases, ctDNA monitoring may not be helpful. “Like any test, it is not meant for every patient or clinical question,” Dr. Kasi concluded.

Dr. Kurzrock and Dr. Kasi reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

SAN DIEGO — A liquid biopsy assay that combines a microRNA signature and a well-known biomarker for pancreatic cancer has demonstrated an accuracy of 97% for detecting stage I/II pancreatic ductal adenocarcinoma, the most common type of pancreatic cancer.

It is quite encouraging to know we have a blood test that could potentially find this disease early, said Ajay Goel, PhD, a molecular diagnostics specialist at City of Hope in Duarte, California, who presented the findings at the annual meeting of the American Association for Cancer Research (AACR).

Dr. Goel and colleagues developed a signature for pancreatic cancer based on microRNAs identified in the exomes shed from pancreatic cancers and cell-free DNA markers found in the blood of patients with the disease.

Their initial assay tested blood samples for this signature in a training cohort of 252 people in Japan, approximately 60% of whom had pancreatic cancer. The rest were healthy controls. The assay was then tested in validation cohorts of 400 subjects, half with pancreatic cancer and half controls, in China and South Korea.

In both the initial and validation tests, the microRNA assay had an accuracy of about 90% for stage I/II pancreatic cancer, already far better than commercially available assays.

In an additional validation cohort in the United States with 139 patients with pancreatic cancer and 193 controls at six centers across the country, the researchers found that adding carbohydrate antigen 19-9 — a well-known marker of pancreatic cancer — to the assay boosted the test’s accuracy to 97%.

The test performed the same whether the tumor was in the head or tail of the pancreas.

“We are very excited about this data,” said Dr. Goel.

The technology was recently licensed to Pharus Diagnostics for commercial development, which will likely include a prospective screening trial, he told this news organization.

Because pancreatic cancer is fairly uncommon, Dr. Goel did not anticipate the test being used for general screening but rather for screening high-risk patients such as those with newly diagnosed type 2 diabetes, a family history of pancreatic cancer, or predisposing genetic mutations.

“It should be a very inexpensive test; it doesn’t cost us much to do in the lab,” he added.

Study moderator Ryan Corcoran, MD, PhD, a gastrointestinal (GI) oncologist at Massachusetts General Hospital, Boston, saw the potential.

“As a GI oncologist, I know how lethal and hard to treat pancreatic cancer is,” he said. A test that could reliably detect pancreatic cancer early, with an acceptable false-positive rate, would be extremely useful.

“The cure rate is many, many times higher,” if we detect it before it has a chance to spread, he explained.

In the meantime, Dr. Goel said there’s more work to be done.

Almost 4,000 subjects have been enrolled in ongoing validation efforts, and efforts are underway to use the test to screen thousands of banked blood samples from the PLCO, a prospective cancer screening trial in healthy subjects.

The researchers also want to see if the test can distinguish benign pancreatic cysts from ones that turn cancerous.

The idea is to find the earliest possible signs of this disease to see if we can find it not “at the moment of clinical diagnosis, but possibly 6 months, 1 year, 2 years earlier” than with radiologic imaging, Dr. Goel said.

The work was funded by the National Cancer Institute and others. Dr. Goel is a consultant for Pharus Diagnostics and Cellomics. Dr. Corcoran is a consultant for, has grants from, and/or holds stock in numerous companies, including Pfizer, Novartis, Eli Lilly, and Revolution Medicines.

A version of this article appeared on Medscape.com.

SAN DIEGO — A liquid biopsy assay that combines a microRNA signature and a well-known biomarker for pancreatic cancer has demonstrated an accuracy of 97% for detecting stage I/II pancreatic ductal adenocarcinoma, the most common type of pancreatic cancer.

It is quite encouraging to know we have a blood test that could potentially find this disease early, said Ajay Goel, PhD, a molecular diagnostics specialist at City of Hope in Duarte, California, who presented the findings at the annual meeting of the American Association for Cancer Research (AACR).

Dr. Goel and colleagues developed a signature for pancreatic cancer based on microRNAs identified in the exomes shed from pancreatic cancers and cell-free DNA markers found in the blood of patients with the disease.

Their initial assay tested blood samples for this signature in a training cohort of 252 people in Japan, approximately 60% of whom had pancreatic cancer. The rest were healthy controls. The assay was then tested in validation cohorts of 400 subjects, half with pancreatic cancer and half controls, in China and South Korea.

In both the initial and validation tests, the microRNA assay had an accuracy of about 90% for stage I/II pancreatic cancer, already far better than commercially available assays.

In an additional validation cohort in the United States with 139 patients with pancreatic cancer and 193 controls at six centers across the country, the researchers found that adding carbohydrate antigen 19-9 — a well-known marker of pancreatic cancer — to the assay boosted the test’s accuracy to 97%.

The test performed the same whether the tumor was in the head or tail of the pancreas.

“We are very excited about this data,” said Dr. Goel.

The technology was recently licensed to Pharus Diagnostics for commercial development, which will likely include a prospective screening trial, he told this news organization.

Because pancreatic cancer is fairly uncommon, Dr. Goel did not anticipate the test being used for general screening but rather for screening high-risk patients such as those with newly diagnosed type 2 diabetes, a family history of pancreatic cancer, or predisposing genetic mutations.

“It should be a very inexpensive test; it doesn’t cost us much to do in the lab,” he added.

Study moderator Ryan Corcoran, MD, PhD, a gastrointestinal (GI) oncologist at Massachusetts General Hospital, Boston, saw the potential.

“As a GI oncologist, I know how lethal and hard to treat pancreatic cancer is,” he said. A test that could reliably detect pancreatic cancer early, with an acceptable false-positive rate, would be extremely useful.

“The cure rate is many, many times higher,” if we detect it before it has a chance to spread, he explained.

In the meantime, Dr. Goel said there’s more work to be done.

Almost 4,000 subjects have been enrolled in ongoing validation efforts, and efforts are underway to use the test to screen thousands of banked blood samples from the PLCO, a prospective cancer screening trial in healthy subjects.

The researchers also want to see if the test can distinguish benign pancreatic cysts from ones that turn cancerous.

The idea is to find the earliest possible signs of this disease to see if we can find it not “at the moment of clinical diagnosis, but possibly 6 months, 1 year, 2 years earlier” than with radiologic imaging, Dr. Goel said.

The work was funded by the National Cancer Institute and others. Dr. Goel is a consultant for Pharus Diagnostics and Cellomics. Dr. Corcoran is a consultant for, has grants from, and/or holds stock in numerous companies, including Pfizer, Novartis, Eli Lilly, and Revolution Medicines.

A version of this article appeared on Medscape.com.

SAN DIEGO — A liquid biopsy assay that combines a microRNA signature and a well-known biomarker for pancreatic cancer has demonstrated an accuracy of 97% for detecting stage I/II pancreatic ductal adenocarcinoma, the most common type of pancreatic cancer.

It is quite encouraging to know we have a blood test that could potentially find this disease early, said Ajay Goel, PhD, a molecular diagnostics specialist at City of Hope in Duarte, California, who presented the findings at the annual meeting of the American Association for Cancer Research (AACR).

Dr. Goel and colleagues developed a signature for pancreatic cancer based on microRNAs identified in the exomes shed from pancreatic cancers and cell-free DNA markers found in the blood of patients with the disease.

Their initial assay tested blood samples for this signature in a training cohort of 252 people in Japan, approximately 60% of whom had pancreatic cancer. The rest were healthy controls. The assay was then tested in validation cohorts of 400 subjects, half with pancreatic cancer and half controls, in China and South Korea.

In both the initial and validation tests, the microRNA assay had an accuracy of about 90% for stage I/II pancreatic cancer, already far better than commercially available assays.

In an additional validation cohort in the United States with 139 patients with pancreatic cancer and 193 controls at six centers across the country, the researchers found that adding carbohydrate antigen 19-9 — a well-known marker of pancreatic cancer — to the assay boosted the test’s accuracy to 97%.

The test performed the same whether the tumor was in the head or tail of the pancreas.

“We are very excited about this data,” said Dr. Goel.

The technology was recently licensed to Pharus Diagnostics for commercial development, which will likely include a prospective screening trial, he told this news organization.

Because pancreatic cancer is fairly uncommon, Dr. Goel did not anticipate the test being used for general screening but rather for screening high-risk patients such as those with newly diagnosed type 2 diabetes, a family history of pancreatic cancer, or predisposing genetic mutations.

“It should be a very inexpensive test; it doesn’t cost us much to do in the lab,” he added.

Study moderator Ryan Corcoran, MD, PhD, a gastrointestinal (GI) oncologist at Massachusetts General Hospital, Boston, saw the potential.

“As a GI oncologist, I know how lethal and hard to treat pancreatic cancer is,” he said. A test that could reliably detect pancreatic cancer early, with an acceptable false-positive rate, would be extremely useful.

“The cure rate is many, many times higher,” if we detect it before it has a chance to spread, he explained.

In the meantime, Dr. Goel said there’s more work to be done.

Almost 4,000 subjects have been enrolled in ongoing validation efforts, and efforts are underway to use the test to screen thousands of banked blood samples from the PLCO, a prospective cancer screening trial in healthy subjects.

The researchers also want to see if the test can distinguish benign pancreatic cysts from ones that turn cancerous.

The idea is to find the earliest possible signs of this disease to see if we can find it not “at the moment of clinical diagnosis, but possibly 6 months, 1 year, 2 years earlier” than with radiologic imaging, Dr. Goel said.

The work was funded by the National Cancer Institute and others. Dr. Goel is a consultant for Pharus Diagnostics and Cellomics. Dr. Corcoran is a consultant for, has grants from, and/or holds stock in numerous companies, including Pfizer, Novartis, Eli Lilly, and Revolution Medicines.

A version of this article appeared on Medscape.com.

SAN DIEGO — A novel multicancer early detection (MCED) blood test has demonstrated promising real-world results in detecting new cancers, including several cases of early-stage disease.

This was the conclusion of recent data presented by Ora Karp Gordon, MD, MS, during a session at the American Association for Cancer Research annual meeting.

The MCED test, known as Galleri, was made clinically available in the United States in April 2021. Developed by GRAIL LLC, the test analyzes cell-free DNA in the blood using targeted methylation analysis and machine learning to detect the presence of a cancer signal and determine its organ of origin or cancer signal origin. The initial screening of over 53,000 individuals with the Galleri test detected a cancer signal in 1.1% of participants.

The new real-world analysis examines the outcomes of repeat MCED testing in 5,794 individuals.

The study looked at individuals who initially received a ‘no cancer signal detected’ result and then underwent a second Galleri test. Over 80% of participants received their follow-up test 10-18 months after the first, with a median interval between blood draws of 12.9 months.

“The repeat tests detect those cancer cases that have reached the detection threshold since their last MCED test, which should be less than one year of incidence,” Dr. Gordon, professor at Saint John’s Cancer Institute, Santa Monica, California, said in an interview. “We are just now starting to see results from patients who get their second and even third round of screening.”

“Galleri is recommended to be used annually in addition to USPSTF [US Preventive Services Task Force]–recommended cancer screening tests, like mammography and colonoscopy,” she said.

This recommendation is based on a modeling study suggesting that annual screening would improve stage shift, diagnostic yield, and potentially mortality when compared to biennial screening, although biennial screening was still favorable compared with no screening, she explained.
 

Early Real-World Evidence of Repeat Testing

Among the cohort of 5,794 individuals who received repeat testing, 26 received a positive cancer signal on their second test, yielding a cancer signal detection rate of 0.45% (95% CI: 0.31%-0.66%). The cancer signal detection rate was slightly higher in men. The rate was 0.50% (95% CI: 0.32%-0.81%; 17 of 3367) in men versus 0.37% (95% CI: 0.2%-0.7%; 9 of 2427) in women.

During her presentation, Dr. Gordon highlighted that the repeat testing signal detection rate was lower than the initial 0.95% rate (95% CI: 0.87-1.0; 510 of 53,744) seen in the previous larger cohort of patients who were retested at 1 year.

She acknowledged that the lower cancer signal detection rate of repeat testing may indicate some degree of ‘early adopter’ bias, where those who return for a second test are systematically different from the general screening population. This could suggest that broader population-level screening may yield different results, she continued.
 

Shift Toward Unscreened Cancers

The top cancer types identified in the second round of testing were lymphoid, head and neck, bladder/urothelial, colorectal, and anal cancers. Clinicians were able to confirm clinical outcomes in 12 of 26 cases, in which cancer signals were detected. Of those 12 cases, 8 individuals received a cancer diagnosis and 4 did not have cancer. The remaining 14 of 26 cases in which cancer signals were detected are still under investigation.

“We found a shift away from USPSTF screen-detected cancers, like breast, lung, and prostate, and relative increase in unscreened urinary, head and neck, and lymphoid cancers, with 75% of cancers being those without any screening guidelines,” Dr. Gordon said in an interview.

She added that patients who choose to retest may have different cancer rates for several reasons, including bias toward a population that is health conscious and adhered to all recommended cancer screening.

“So the shift toward unscreened cancers is not unexpected and highlights the value of Galleri,” she said, but also acknowledged that “continued monitoring is needed to see if this translates in a persistent finding over time and tests.”
 

Shift Toward Early-Stage Cancers

Staging information was available for five cases, and Dr. Gordon highlighted in her talk that four of these confirmed cancers were stage I, including cancers of the anus, head and neck, bladder, and lymphoma. The fifth confirmed cancer with staging information was stage IV ovarian cancer.

“It is still early, and the numbers are very small, but the detection of early-stage cancers with second annual testing is very encouraging as these are the cases where MCED testing could have the greatest impact in improving outcomes through earlier treatment,” Dr. Gordon told this publication.

During an interview after the talk, Kenneth L. Kehl, MD, MPH, echoed that data must be confirmed in larger cohorts.

“The shift toward earlier stage cancers that are less detectable by standard screening methods is an interesting result, but we need to be cautious since the numbers were relatively small, and we do not have data on cancers that were diagnosed among patients whose second MCED test was also negative,” said Dr. Kehl, a medical oncologist at Dana-Farber Cancer Institute, Boston.
 

MCED Results Could Help Direct Diagnostic Workup

The test’s ability to predict the organ of origin was highly accurate, correctly identifying the cancer type in all eight confirmed cases. Among the eight cases with a confirmed cancer diagnosis, the accuracy of the first prediction was 100%, and diagnoses included invasive cancers across multiple tissues and organs, including anus, colon, head and neck, urothelial tract, ovary, and the lymphatic system.

“The fact that the site of origin for 100% of confirmed cancers was accurately predicted with GRAIL’s CSO by Galleri test confirms the promise that this can guide workup when a cancer signal is detected,” Dr. Gordon noted in the interview.
 

Looking Ahead

Dr. Kehl, who was not involved in the MCED study, noted in an interview that “further data on test characteristics beyond positive predictive value, including the sensitivity, specificity, and negative predictive value, as well as demonstration of clinical benefit — ideally in a randomized trial — will likely be required for MCED testing to become a standard public health recommendation.”

He added that challenges associated with implementing annual screening with MCED tests include the risks of both false positives and false negatives as testing becomes more widely available.

“False positives cause anxiety and lead to additional testing that may carry its own risks, and we need to understand if potentially false negative tests will be associated with less uptake of established screening strategies,” Dr. Kehl said in an interview. However, he noted that serial testing could lead to more frequent diagnoses of early-stage cancers that may be less detectable by standard methods.

Dr. Gordon reported financial relationships with GRAIL LLC and Genetic Technologies Corporation. Dr. Kehl reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

SAN DIEGO — A novel multicancer early detection (MCED) blood test has demonstrated promising real-world results in detecting new cancers, including several cases of early-stage disease.

This was the conclusion of recent data presented by Ora Karp Gordon, MD, MS, during a session at the American Association for Cancer Research annual meeting.

The MCED test, known as Galleri, was made clinically available in the United States in April 2021. Developed by GRAIL LLC, the test analyzes cell-free DNA in the blood using targeted methylation analysis and machine learning to detect the presence of a cancer signal and determine its organ of origin or cancer signal origin. The initial screening of over 53,000 individuals with the Galleri test detected a cancer signal in 1.1% of participants.

The new real-world analysis examines the outcomes of repeat MCED testing in 5,794 individuals.

The study looked at individuals who initially received a ‘no cancer signal detected’ result and then underwent a second Galleri test. Over 80% of participants received their follow-up test 10-18 months after the first, with a median interval between blood draws of 12.9 months.

“The repeat tests detect those cancer cases that have reached the detection threshold since their last MCED test, which should be less than one year of incidence,” Dr. Gordon, professor at Saint John’s Cancer Institute, Santa Monica, California, said in an interview. “We are just now starting to see results from patients who get their second and even third round of screening.”

“Galleri is recommended to be used annually in addition to USPSTF [US Preventive Services Task Force]–recommended cancer screening tests, like mammography and colonoscopy,” she said.

This recommendation is based on a modeling study suggesting that annual screening would improve stage shift, diagnostic yield, and potentially mortality when compared to biennial screening, although biennial screening was still favorable compared with no screening, she explained.
 

Early Real-World Evidence of Repeat Testing

Among the cohort of 5,794 individuals who received repeat testing, 26 received a positive cancer signal on their second test, yielding a cancer signal detection rate of 0.45% (95% CI: 0.31%-0.66%). The cancer signal detection rate was slightly higher in men. The rate was 0.50% (95% CI: 0.32%-0.81%; 17 of 3367) in men versus 0.37% (95% CI: 0.2%-0.7%; 9 of 2427) in women.

During her presentation, Dr. Gordon highlighted that the repeat testing signal detection rate was lower than the initial 0.95% rate (95% CI: 0.87-1.0; 510 of 53,744) seen in the previous larger cohort of patients who were retested at 1 year.

She acknowledged that the lower cancer signal detection rate of repeat testing may indicate some degree of ‘early adopter’ bias, where those who return for a second test are systematically different from the general screening population. This could suggest that broader population-level screening may yield different results, she continued.
 

Shift Toward Unscreened Cancers

The top cancer types identified in the second round of testing were lymphoid, head and neck, bladder/urothelial, colorectal, and anal cancers. Clinicians were able to confirm clinical outcomes in 12 of 26 cases, in which cancer signals were detected. Of those 12 cases, 8 individuals received a cancer diagnosis and 4 did not have cancer. The remaining 14 of 26 cases in which cancer signals were detected are still under investigation.

“We found a shift away from USPSTF screen-detected cancers, like breast, lung, and prostate, and relative increase in unscreened urinary, head and neck, and lymphoid cancers, with 75% of cancers being those without any screening guidelines,” Dr. Gordon said in an interview.

She added that patients who choose to retest may have different cancer rates for several reasons, including bias toward a population that is health conscious and adhered to all recommended cancer screening.

“So the shift toward unscreened cancers is not unexpected and highlights the value of Galleri,” she said, but also acknowledged that “continued monitoring is needed to see if this translates in a persistent finding over time and tests.”
 

Shift Toward Early-Stage Cancers

Staging information was available for five cases, and Dr. Gordon highlighted in her talk that four of these confirmed cancers were stage I, including cancers of the anus, head and neck, bladder, and lymphoma. The fifth confirmed cancer with staging information was stage IV ovarian cancer.

“It is still early, and the numbers are very small, but the detection of early-stage cancers with second annual testing is very encouraging as these are the cases where MCED testing could have the greatest impact in improving outcomes through earlier treatment,” Dr. Gordon told this publication.

During an interview after the talk, Kenneth L. Kehl, MD, MPH, echoed that data must be confirmed in larger cohorts.

“The shift toward earlier stage cancers that are less detectable by standard screening methods is an interesting result, but we need to be cautious since the numbers were relatively small, and we do not have data on cancers that were diagnosed among patients whose second MCED test was also negative,” said Dr. Kehl, a medical oncologist at Dana-Farber Cancer Institute, Boston.
 

MCED Results Could Help Direct Diagnostic Workup

The test’s ability to predict the organ of origin was highly accurate, correctly identifying the cancer type in all eight confirmed cases. Among the eight cases with a confirmed cancer diagnosis, the accuracy of the first prediction was 100%, and diagnoses included invasive cancers across multiple tissues and organs, including anus, colon, head and neck, urothelial tract, ovary, and the lymphatic system.

“The fact that the site of origin for 100% of confirmed cancers was accurately predicted with GRAIL’s CSO by Galleri test confirms the promise that this can guide workup when a cancer signal is detected,” Dr. Gordon noted in the interview.
 

Looking Ahead

Dr. Kehl, who was not involved in the MCED study, noted in an interview that “further data on test characteristics beyond positive predictive value, including the sensitivity, specificity, and negative predictive value, as well as demonstration of clinical benefit — ideally in a randomized trial — will likely be required for MCED testing to become a standard public health recommendation.”

He added that challenges associated with implementing annual screening with MCED tests include the risks of both false positives and false negatives as testing becomes more widely available.

“False positives cause anxiety and lead to additional testing that may carry its own risks, and we need to understand if potentially false negative tests will be associated with less uptake of established screening strategies,” Dr. Kehl said in an interview. However, he noted that serial testing could lead to more frequent diagnoses of early-stage cancers that may be less detectable by standard methods.

Dr. Gordon reported financial relationships with GRAIL LLC and Genetic Technologies Corporation. Dr. Kehl reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

SAN DIEGO — A novel multicancer early detection (MCED) blood test has demonstrated promising real-world results in detecting new cancers, including several cases of early-stage disease.

This was the conclusion of recent data presented by Ora Karp Gordon, MD, MS, during a session at the American Association for Cancer Research annual meeting.

The MCED test, known as Galleri, was made clinically available in the United States in April 2021. Developed by GRAIL LLC, the test analyzes cell-free DNA in the blood using targeted methylation analysis and machine learning to detect the presence of a cancer signal and determine its organ of origin or cancer signal origin. The initial screening of over 53,000 individuals with the Galleri test detected a cancer signal in 1.1% of participants.

The new real-world analysis examines the outcomes of repeat MCED testing in 5,794 individuals.

The study looked at individuals who initially received a ‘no cancer signal detected’ result and then underwent a second Galleri test. Over 80% of participants received their follow-up test 10-18 months after the first, with a median interval between blood draws of 12.9 months.

“The repeat tests detect those cancer cases that have reached the detection threshold since their last MCED test, which should be less than one year of incidence,” Dr. Gordon, professor at Saint John’s Cancer Institute, Santa Monica, California, said in an interview. “We are just now starting to see results from patients who get their second and even third round of screening.”

“Galleri is recommended to be used annually in addition to USPSTF [US Preventive Services Task Force]–recommended cancer screening tests, like mammography and colonoscopy,” she said.

This recommendation is based on a modeling study suggesting that annual screening would improve stage shift, diagnostic yield, and potentially mortality when compared to biennial screening, although biennial screening was still favorable compared with no screening, she explained.
 

Early Real-World Evidence of Repeat Testing

Among the cohort of 5,794 individuals who received repeat testing, 26 received a positive cancer signal on their second test, yielding a cancer signal detection rate of 0.45% (95% CI: 0.31%-0.66%). The cancer signal detection rate was slightly higher in men. The rate was 0.50% (95% CI: 0.32%-0.81%; 17 of 3367) in men versus 0.37% (95% CI: 0.2%-0.7%; 9 of 2427) in women.

During her presentation, Dr. Gordon highlighted that the repeat testing signal detection rate was lower than the initial 0.95% rate (95% CI: 0.87-1.0; 510 of 53,744) seen in the previous larger cohort of patients who were retested at 1 year.

She acknowledged that the lower cancer signal detection rate of repeat testing may indicate some degree of ‘early adopter’ bias, where those who return for a second test are systematically different from the general screening population. This could suggest that broader population-level screening may yield different results, she continued.
 

Shift Toward Unscreened Cancers

The top cancer types identified in the second round of testing were lymphoid, head and neck, bladder/urothelial, colorectal, and anal cancers. Clinicians were able to confirm clinical outcomes in 12 of 26 cases, in which cancer signals were detected. Of those 12 cases, 8 individuals received a cancer diagnosis and 4 did not have cancer. The remaining 14 of 26 cases in which cancer signals were detected are still under investigation.

“We found a shift away from USPSTF screen-detected cancers, like breast, lung, and prostate, and relative increase in unscreened urinary, head and neck, and lymphoid cancers, with 75% of cancers being those without any screening guidelines,” Dr. Gordon said in an interview.

She added that patients who choose to retest may have different cancer rates for several reasons, including bias toward a population that is health conscious and adhered to all recommended cancer screening.

“So the shift toward unscreened cancers is not unexpected and highlights the value of Galleri,” she said, but also acknowledged that “continued monitoring is needed to see if this translates in a persistent finding over time and tests.”
 

Shift Toward Early-Stage Cancers

Staging information was available for five cases, and Dr. Gordon highlighted in her talk that four of these confirmed cancers were stage I, including cancers of the anus, head and neck, bladder, and lymphoma. The fifth confirmed cancer with staging information was stage IV ovarian cancer.

“It is still early, and the numbers are very small, but the detection of early-stage cancers with second annual testing is very encouraging as these are the cases where MCED testing could have the greatest impact in improving outcomes through earlier treatment,” Dr. Gordon told this publication.

During an interview after the talk, Kenneth L. Kehl, MD, MPH, echoed that data must be confirmed in larger cohorts.

“The shift toward earlier stage cancers that are less detectable by standard screening methods is an interesting result, but we need to be cautious since the numbers were relatively small, and we do not have data on cancers that were diagnosed among patients whose second MCED test was also negative,” said Dr. Kehl, a medical oncologist at Dana-Farber Cancer Institute, Boston.
 

MCED Results Could Help Direct Diagnostic Workup

The test’s ability to predict the organ of origin was highly accurate, correctly identifying the cancer type in all eight confirmed cases. Among the eight cases with a confirmed cancer diagnosis, the accuracy of the first prediction was 100%, and diagnoses included invasive cancers across multiple tissues and organs, including anus, colon, head and neck, urothelial tract, ovary, and the lymphatic system.

“The fact that the site of origin for 100% of confirmed cancers was accurately predicted with GRAIL’s CSO by Galleri test confirms the promise that this can guide workup when a cancer signal is detected,” Dr. Gordon noted in the interview.
 

Looking Ahead

Dr. Kehl, who was not involved in the MCED study, noted in an interview that “further data on test characteristics beyond positive predictive value, including the sensitivity, specificity, and negative predictive value, as well as demonstration of clinical benefit — ideally in a randomized trial — will likely be required for MCED testing to become a standard public health recommendation.”

He added that challenges associated with implementing annual screening with MCED tests include the risks of both false positives and false negatives as testing becomes more widely available.

“False positives cause anxiety and lead to additional testing that may carry its own risks, and we need to understand if potentially false negative tests will be associated with less uptake of established screening strategies,” Dr. Kehl said in an interview. However, he noted that serial testing could lead to more frequent diagnoses of early-stage cancers that may be less detectable by standard methods.

Dr. Gordon reported financial relationships with GRAIL LLC and Genetic Technologies Corporation. Dr. Kehl reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.