Patient & Survivor Care

TOPLINE:

The vaccine Cervarix was effective in protecting women from cervical cancer when administered between ages 12 and 13 years, according to a new study published in Journal of the National Cancer Institute.

METHODOLOGY:

• Cervical cancer is the fourth most common cancer among women worldwide.
• Programs to provide Cervarix, a bivalent vaccine, began in the United Kingdom in 2007.
• After the initiation of the programs, administering the vaccine became part of routine care for girls starting at age 12 years.
• Researchers collected data in 2020 from 447,845 women born between 1988 and 1996 from the Scottish cervical cancer screening system to assess the efficacy of Cervarix in lowering rates of cervical cancer.
• They correlated the rate of cervical cancer per 100,000 person-years with data on women regarding vaccination status, age when vaccinated, and deprivation in areas like income, housing, and health.

TAKEAWAY:

• No cases of cervical cancer were found among women who were immunized at ages 12 or 13 years, no matter how many doses they received. 
• Women who were immunized between ages 14 and 18 years and received three doses had fewer instances of cervical cancer compared with unvaccinated women regardless of deprivation status (3.2 cases per 100,00 women vs 8.4 cases per 100,000). 

IN PRACTICE:

“Continued participation in screening and monitoring of outcomes is required, however, to assess the effects of changes in vaccines used and dosage schedules since the start of vaccination in Scotland in 2008 and the longevity of protection the vaccines offer.”

SOURCE:

The study was led by Timothy J. Palmer, PhD, Scottish Clinical Lead for Cervical Screening at Public Health Scotland.

LIMITATIONS:

Only 14,645 women had received just one or two doses, which may have affected the statistical analysis. 

DISCLOSURES:

The study was funded by Public Health Scotland. A coauthor reports attending an advisory board meeting for HOLOGIC and Vaccitech. Her institution received research funding or gratis support funding from Cepheid, Euroimmun, GeneFirst, SelfScreen, Hiantis, Seegene, Roche, Hologic, and Vaccitech in the past 3 years.
 

A version of this article appeared on Medscape.com.

TOPLINE:

The vaccine Cervarix was effective in protecting women from cervical cancer when administered between ages 12 and 13 years, according to a new study published in Journal of the National Cancer Institute.

METHODOLOGY:

• Cervical cancer is the fourth most common cancer among women worldwide.
• Programs to provide Cervarix, a bivalent vaccine, began in the United Kingdom in 2007.
• After the initiation of the programs, administering the vaccine became part of routine care for girls starting at age 12 years.
• Researchers collected data in 2020 from 447,845 women born between 1988 and 1996 from the Scottish cervical cancer screening system to assess the efficacy of Cervarix in lowering rates of cervical cancer.
• They correlated the rate of cervical cancer per 100,000 person-years with data on women regarding vaccination status, age when vaccinated, and deprivation in areas like income, housing, and health.

TAKEAWAY:

• No cases of cervical cancer were found among women who were immunized at ages 12 or 13 years, no matter how many doses they received. 
• Women who were immunized between ages 14 and 18 years and received three doses had fewer instances of cervical cancer compared with unvaccinated women regardless of deprivation status (3.2 cases per 100,00 women vs 8.4 cases per 100,000). 

IN PRACTICE:

“Continued participation in screening and monitoring of outcomes is required, however, to assess the effects of changes in vaccines used and dosage schedules since the start of vaccination in Scotland in 2008 and the longevity of protection the vaccines offer.”

SOURCE:

The study was led by Timothy J. Palmer, PhD, Scottish Clinical Lead for Cervical Screening at Public Health Scotland.

LIMITATIONS:

Only 14,645 women had received just one or two doses, which may have affected the statistical analysis. 

DISCLOSURES:

The study was funded by Public Health Scotland. A coauthor reports attending an advisory board meeting for HOLOGIC and Vaccitech. Her institution received research funding or gratis support funding from Cepheid, Euroimmun, GeneFirst, SelfScreen, Hiantis, Seegene, Roche, Hologic, and Vaccitech in the past 3 years.
 

A version of this article appeared on Medscape.com.

TOPLINE:

The vaccine Cervarix was effective in protecting women from cervical cancer when administered between ages 12 and 13 years, according to a new study published in Journal of the National Cancer Institute.

METHODOLOGY:

• Cervical cancer is the fourth most common cancer among women worldwide.
• Programs to provide Cervarix, a bivalent vaccine, began in the United Kingdom in 2007.
• After the initiation of the programs, administering the vaccine became part of routine care for girls starting at age 12 years.
• Researchers collected data in 2020 from 447,845 women born between 1988 and 1996 from the Scottish cervical cancer screening system to assess the efficacy of Cervarix in lowering rates of cervical cancer.
• They correlated the rate of cervical cancer per 100,000 person-years with data on women regarding vaccination status, age when vaccinated, and deprivation in areas like income, housing, and health.

TAKEAWAY:

• No cases of cervical cancer were found among women who were immunized at ages 12 or 13 years, no matter how many doses they received. 
• Women who were immunized between ages 14 and 18 years and received three doses had fewer instances of cervical cancer compared with unvaccinated women regardless of deprivation status (3.2 cases per 100,00 women vs 8.4 cases per 100,000). 

IN PRACTICE:

“Continued participation in screening and monitoring of outcomes is required, however, to assess the effects of changes in vaccines used and dosage schedules since the start of vaccination in Scotland in 2008 and the longevity of protection the vaccines offer.”

SOURCE:

The study was led by Timothy J. Palmer, PhD, Scottish Clinical Lead for Cervical Screening at Public Health Scotland.

LIMITATIONS:

Only 14,645 women had received just one or two doses, which may have affected the statistical analysis. 

DISCLOSURES:

The study was funded by Public Health Scotland. A coauthor reports attending an advisory board meeting for HOLOGIC and Vaccitech. Her institution received research funding or gratis support funding from Cepheid, Euroimmun, GeneFirst, SelfScreen, Hiantis, Seegene, Roche, Hologic, and Vaccitech in the past 3 years.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Using olaparib alone or in combination with durvalumab as a chemotherapy-free maintenance treatment can extend progression-free survival (PFS) in patients with advanced triple-negative breast cancer (TNBC).

METHODOLOGY:

• First-line standard therapy for advanced TNBC generally includes taxane- or platinum-based chemotherapy which poses challenging toxicities. Exploring chemotherapy-free maintenance strategies may provide adequate disease control and improve patient quality of life.
• The researchers evaluated 45 patients, at five sites in the Republic of Korea, the United States, and Singapore, with TNBC who had ongoing stable disease or complete/partial response from first- or second-line platinum-based chemotherapy.
• The patients were randomized 1:1 to receive olaparib 300 mg twice daily with or without durvalumab 1500 mg on day 1 every 4 weeks.
• The authors compared PFS with a historical control of continued platinum-based therapy. An improvement to 4 months with maintenance therapy was considered clinically significant.

TAKEAWAY:

• After a follow-up of 9.8 months, patients who received olaparib alone demonstrated median PFS of 4.0 months, and those who received the combination therapy had median PFS of 6.1 months.
• Clinical benefit rates, defined as stable disease for at least 24 weeks or complete/partial response, were reported in 44% of the monotherapy group and 36% of the combination therapy group.
• Sustained clinical benefit was evident irrespective of germline BRCA mutation or programmed death-ligand 1 status, although it tended to be associated with complete or partial response to prior platinum.
• Grade 3-4 adverse events were reported in nine patients (39%) in the olaparib arm and eight patients (36%) in the combination arm. No treatment-related deaths or new safety signals were observed.

IN PRACTICE:

“Maintenance regimens are rarely used in [triple-negative breast cancer] but offer the possibility of more tolerable long-term treatment avoiding some of the chemotherapy-related side effects of more aggressive regimens, as is standard in the first-line treatment of HER2-positive advanced breast cancer,” the researchers concluded.

SOURCE:

This study, led by Tira J. Tan from Duke-NUS Medical School, Singapore, was published online on January 18, 2024, in Clinical Cancer Research.

LIMITATIONS:

The main limitations were the small sample size and lack of a standard control arm. Most patients (76%) were Asian, limiting generalizability. The trial was not designed to compare olaparib monotherapy and olaparib plus durvalumab regimens.

DISCLOSURES:

AstraZeneca Pharmaceuticals LP supported this study. Several authors reported financial support from various sources.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Using olaparib alone or in combination with durvalumab as a chemotherapy-free maintenance treatment can extend progression-free survival (PFS) in patients with advanced triple-negative breast cancer (TNBC).

METHODOLOGY:

• First-line standard therapy for advanced TNBC generally includes taxane- or platinum-based chemotherapy which poses challenging toxicities. Exploring chemotherapy-free maintenance strategies may provide adequate disease control and improve patient quality of life.
• The researchers evaluated 45 patients, at five sites in the Republic of Korea, the United States, and Singapore, with TNBC who had ongoing stable disease or complete/partial response from first- or second-line platinum-based chemotherapy.
• The patients were randomized 1:1 to receive olaparib 300 mg twice daily with or without durvalumab 1500 mg on day 1 every 4 weeks.
• The authors compared PFS with a historical control of continued platinum-based therapy. An improvement to 4 months with maintenance therapy was considered clinically significant.

TAKEAWAY:

• After a follow-up of 9.8 months, patients who received olaparib alone demonstrated median PFS of 4.0 months, and those who received the combination therapy had median PFS of 6.1 months.
• Clinical benefit rates, defined as stable disease for at least 24 weeks or complete/partial response, were reported in 44% of the monotherapy group and 36% of the combination therapy group.
• Sustained clinical benefit was evident irrespective of germline BRCA mutation or programmed death-ligand 1 status, although it tended to be associated with complete or partial response to prior platinum.
• Grade 3-4 adverse events were reported in nine patients (39%) in the olaparib arm and eight patients (36%) in the combination arm. No treatment-related deaths or new safety signals were observed.

IN PRACTICE:

“Maintenance regimens are rarely used in [triple-negative breast cancer] but offer the possibility of more tolerable long-term treatment avoiding some of the chemotherapy-related side effects of more aggressive regimens, as is standard in the first-line treatment of HER2-positive advanced breast cancer,” the researchers concluded.

SOURCE:

This study, led by Tira J. Tan from Duke-NUS Medical School, Singapore, was published online on January 18, 2024, in Clinical Cancer Research.

LIMITATIONS:

The main limitations were the small sample size and lack of a standard control arm. Most patients (76%) were Asian, limiting generalizability. The trial was not designed to compare olaparib monotherapy and olaparib plus durvalumab regimens.

DISCLOSURES:

AstraZeneca Pharmaceuticals LP supported this study. Several authors reported financial support from various sources.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Using olaparib alone or in combination with durvalumab as a chemotherapy-free maintenance treatment can extend progression-free survival (PFS) in patients with advanced triple-negative breast cancer (TNBC).

METHODOLOGY:

• First-line standard therapy for advanced TNBC generally includes taxane- or platinum-based chemotherapy which poses challenging toxicities. Exploring chemotherapy-free maintenance strategies may provide adequate disease control and improve patient quality of life.
• The researchers evaluated 45 patients, at five sites in the Republic of Korea, the United States, and Singapore, with TNBC who had ongoing stable disease or complete/partial response from first- or second-line platinum-based chemotherapy.
• The patients were randomized 1:1 to receive olaparib 300 mg twice daily with or without durvalumab 1500 mg on day 1 every 4 weeks.
• The authors compared PFS with a historical control of continued platinum-based therapy. An improvement to 4 months with maintenance therapy was considered clinically significant.

TAKEAWAY:

• After a follow-up of 9.8 months, patients who received olaparib alone demonstrated median PFS of 4.0 months, and those who received the combination therapy had median PFS of 6.1 months.
• Clinical benefit rates, defined as stable disease for at least 24 weeks or complete/partial response, were reported in 44% of the monotherapy group and 36% of the combination therapy group.
• Sustained clinical benefit was evident irrespective of germline BRCA mutation or programmed death-ligand 1 status, although it tended to be associated with complete or partial response to prior platinum.
• Grade 3-4 adverse events were reported in nine patients (39%) in the olaparib arm and eight patients (36%) in the combination arm. No treatment-related deaths or new safety signals were observed.

IN PRACTICE:

“Maintenance regimens are rarely used in [triple-negative breast cancer] but offer the possibility of more tolerable long-term treatment avoiding some of the chemotherapy-related side effects of more aggressive regimens, as is standard in the first-line treatment of HER2-positive advanced breast cancer,” the researchers concluded.

SOURCE:

This study, led by Tira J. Tan from Duke-NUS Medical School, Singapore, was published online on January 18, 2024, in Clinical Cancer Research.

LIMITATIONS:

The main limitations were the small sample size and lack of a standard control arm. Most patients (76%) were Asian, limiting generalizability. The trial was not designed to compare olaparib monotherapy and olaparib plus durvalumab regimens.

DISCLOSURES:

AstraZeneca Pharmaceuticals LP supported this study. Several authors reported financial support from various sources.
 

A version of this article appeared on Medscape.com.

TOPLINE:

The sequence of systematic therapies for unresectable or metastatic pancreatic ductal adenocarcinoma may have an impact on patient survival, a new retrospective analysis suggests.

METHODOLOGY:

• Despite therapeutic advances, survival among patients with unresectable and/or metastatic pancreatic ductal adenocarcinoma has not markedly improved in recent years.
• In the current analysis, researchers evaluated whether treatment sequence could affect survival outcomes in this patient population.
• To this end , researchers conducted a single institution, retrospective analysis of patients who received different lines of treatment between January 2015 and December 2021.
• The most common first-line therapy was nab-paclitaxel plus S-1 (58%), followed by FOLFIRINOX (10%), nab-paclitaxel plus gemcitabine (8%), gemcitabine alone (7%), gemcitabine plus oxaliplatin (6%); second-line therapies, in order of frequency, included gemcitabine combination therapy (48%), nab-paclitaxel combination therapy (19%), FOLFIRINOX (10%), and gemcitabine alone (7%); third-line treatments consisted of FOLFIRINOX (31%), irinotecan or oxaliplatin combination therapy (23%), immunotherapy (19%), and gemcitabine combination therapy (10%).

TAKEAWAY:

• Overall, progression occurred in 90% of patients, and the median overall survival was 12.0 months, with only 48% of patients able to start a third-line therapy.
• The researchers focused on three common therapy sequences: nab-paclitaxel plus gemcitabine or nab-paclitaxel combination therapy as first-line and FOLFIRINOX as second-line (line A); nab-paclitaxel combination therapy to gemcitabine combination therapy to FOLFIRINOX (line B); and nab-paclitaxel combination therapy, to gemcitabine combination therapy, to oxaliplatin or irinotecan combination therapy (line C).
• Overall, the researchers observed a median overall survival of 14 months among patients receiving line A and C sequences and 18 months with line B.
• Patients receiving line B therapy demonstrated a 52% lower risk for death compared with those receiving line A treatment (hazard ratio [HR], 0.48; P = .018) and a 75% reduced risk for death compared with those on the line C sequence (HR, 0.25; P = .040).

IN PRACTICE:

“Our study provides real-world evidence for the effectiveness of different treatment sequences and underscores the [impact of] treatment sequences on survival outcome when considering the entire management in advanced pancreatic ductal adenocarcinoma,” the authors concluded.

SOURCE:

The study, led by Guanghai Dai, MD, from the Chinese People’s Liberation Army General Hospital, Beijing, was published in BMC Cancer on January 12, 2024.

LIMITATIONS:

The study was a single-center, retrospective analysis. 

DISCLOSURES:

The paper was funded by Beijing natural science foundation. The authors did not declare any relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

The sequence of systematic therapies for unresectable or metastatic pancreatic ductal adenocarcinoma may have an impact on patient survival, a new retrospective analysis suggests.

METHODOLOGY:

• Despite therapeutic advances, survival among patients with unresectable and/or metastatic pancreatic ductal adenocarcinoma has not markedly improved in recent years.
• In the current analysis, researchers evaluated whether treatment sequence could affect survival outcomes in this patient population.
• To this end , researchers conducted a single institution, retrospective analysis of patients who received different lines of treatment between January 2015 and December 2021.
• The most common first-line therapy was nab-paclitaxel plus S-1 (58%), followed by FOLFIRINOX (10%), nab-paclitaxel plus gemcitabine (8%), gemcitabine alone (7%), gemcitabine plus oxaliplatin (6%); second-line therapies, in order of frequency, included gemcitabine combination therapy (48%), nab-paclitaxel combination therapy (19%), FOLFIRINOX (10%), and gemcitabine alone (7%); third-line treatments consisted of FOLFIRINOX (31%), irinotecan or oxaliplatin combination therapy (23%), immunotherapy (19%), and gemcitabine combination therapy (10%).

TAKEAWAY:

• Overall, progression occurred in 90% of patients, and the median overall survival was 12.0 months, with only 48% of patients able to start a third-line therapy.
• The researchers focused on three common therapy sequences: nab-paclitaxel plus gemcitabine or nab-paclitaxel combination therapy as first-line and FOLFIRINOX as second-line (line A); nab-paclitaxel combination therapy to gemcitabine combination therapy to FOLFIRINOX (line B); and nab-paclitaxel combination therapy, to gemcitabine combination therapy, to oxaliplatin or irinotecan combination therapy (line C).
• Overall, the researchers observed a median overall survival of 14 months among patients receiving line A and C sequences and 18 months with line B.
• Patients receiving line B therapy demonstrated a 52% lower risk for death compared with those receiving line A treatment (hazard ratio [HR], 0.48; P = .018) and a 75% reduced risk for death compared with those on the line C sequence (HR, 0.25; P = .040).

IN PRACTICE:

“Our study provides real-world evidence for the effectiveness of different treatment sequences and underscores the [impact of] treatment sequences on survival outcome when considering the entire management in advanced pancreatic ductal adenocarcinoma,” the authors concluded.

SOURCE:

The study, led by Guanghai Dai, MD, from the Chinese People’s Liberation Army General Hospital, Beijing, was published in BMC Cancer on January 12, 2024.

LIMITATIONS:

The study was a single-center, retrospective analysis. 

DISCLOSURES:

The paper was funded by Beijing natural science foundation. The authors did not declare any relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

The sequence of systematic therapies for unresectable or metastatic pancreatic ductal adenocarcinoma may have an impact on patient survival, a new retrospective analysis suggests.

METHODOLOGY:

• Despite therapeutic advances, survival among patients with unresectable and/or metastatic pancreatic ductal adenocarcinoma has not markedly improved in recent years.
• In the current analysis, researchers evaluated whether treatment sequence could affect survival outcomes in this patient population.
• To this end , researchers conducted a single institution, retrospective analysis of patients who received different lines of treatment between January 2015 and December 2021.
• The most common first-line therapy was nab-paclitaxel plus S-1 (58%), followed by FOLFIRINOX (10%), nab-paclitaxel plus gemcitabine (8%), gemcitabine alone (7%), gemcitabine plus oxaliplatin (6%); second-line therapies, in order of frequency, included gemcitabine combination therapy (48%), nab-paclitaxel combination therapy (19%), FOLFIRINOX (10%), and gemcitabine alone (7%); third-line treatments consisted of FOLFIRINOX (31%), irinotecan or oxaliplatin combination therapy (23%), immunotherapy (19%), and gemcitabine combination therapy (10%).

TAKEAWAY:

• Overall, progression occurred in 90% of patients, and the median overall survival was 12.0 months, with only 48% of patients able to start a third-line therapy.
• The researchers focused on three common therapy sequences: nab-paclitaxel plus gemcitabine or nab-paclitaxel combination therapy as first-line and FOLFIRINOX as second-line (line A); nab-paclitaxel combination therapy to gemcitabine combination therapy to FOLFIRINOX (line B); and nab-paclitaxel combination therapy, to gemcitabine combination therapy, to oxaliplatin or irinotecan combination therapy (line C).
• Overall, the researchers observed a median overall survival of 14 months among patients receiving line A and C sequences and 18 months with line B.
• Patients receiving line B therapy demonstrated a 52% lower risk for death compared with those receiving line A treatment (hazard ratio [HR], 0.48; P = .018) and a 75% reduced risk for death compared with those on the line C sequence (HR, 0.25; P = .040).

IN PRACTICE:

“Our study provides real-world evidence for the effectiveness of different treatment sequences and underscores the [impact of] treatment sequences on survival outcome when considering the entire management in advanced pancreatic ductal adenocarcinoma,” the authors concluded.

SOURCE:

The study, led by Guanghai Dai, MD, from the Chinese People’s Liberation Army General Hospital, Beijing, was published in BMC Cancer on January 12, 2024.

LIMITATIONS:

The study was a single-center, retrospective analysis. 

DISCLOSURES:

The paper was funded by Beijing natural science foundation. The authors did not declare any relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

A two-step screening strategy in postmenopausal women demonstrated a high specificity, sensitivity, and positive predictive value for detecting ovarian and borderline cancer, with most identified as stage I or II disease, a new analysis with a 21-year follow-up found.

METHODOLOGY:

• Detecting ovarian cancer at stage I or II could significantly reduce ovarian cancer-related deaths, but only 25%-30% of patients are diagnosed at an early stage.
• In this single-arm prospective analysis, 7,856 healthy postmenopausal women received annual screening for ovarian cancer between 2011 and 2022. Screening involved an annual blood test to detect levels of cancer antigen 125 and track these levels over time.
• Investigators used the Risk of Ovarian Cancer Algorithm (ROCA) to determine whether ovarian cancer risk was normal, intermediate, or high. Those with elevated ROCA scores were referred for transvaginal sonography; those with intermediate scores received follow-up blood tests every 3 months.
• Overall, 92.3% of women were normal risk, 5.7% were intermediate, and 2% were high risk and recommended for transvaginal sonography.

TAKEAWAY:

• Most women (95.5%) referred for transvaginal ultrasound had one. Of these ultrasounds, most (90%) were negative or revealed benign findings, 5.2% required a repeat ultrasound, and 4.8% (34 patients) showed suspicious findings.
• Of 34 patients with suspicious findings and recommended for surgery, 15 had ovarian cancer and two had borderline tumors, indicating a positive predictive value of 50% (17 of 34 patients) for ovarian cancer. Of these 17 patients, 12 (70.6%) had stage I or II disease.
• Following abnormal ROCA results, seven other women were diagnosed with endometrial tumors (six of which were stage I), indicating a positive predictive value of 74% (25 of 34) for any cancer.
• The specificity for elevated risk ROCA prompting ultrasound was 98%, and the specificity of the ROCA and ultrasound prompting surgery was 99.8%. The sensitivity for detecting ovarian and borderline cancer was 74% (17 of 23).

IN PRACTICE:

“Remarkably, 70% of ovarian cancers detected by the ROCA” were early stage,” the authors concluded. Although the trial was not powered to detect reduced mortality, the high specificity, positive predictive value, and shift to identifying earlier-stage cancers “support further development of this strategy,” the investigators said.

LIMITATIONS:

This trial was not powered to detect mortality benefit. Six ovarian cancers and borderline tumors were missed. Only 80% of ovarian cancers express cancer antigen 125, potentially limiting the sensitivity of the algorithm.

SOURCE:

This study, led by Chae Young Han from the University of Texas MD Anderson Cancer Center, Houston, was published online on January 12 in the Journal of Clinical Oncology.

DISCLOSURES:

This study was supported by funds from the NCI Early Detection Research Network, the MD Anderson Ovarian SPOREs, the National Cancer Institute, the Department of Health and Human Services, and others. The authors reported receiving research funding, grants, consulting, and personal fees from various companies, including Curio Science, Fujirebio Diagnostics, GlaxoSmithKline, AstraZeneca, and Genentech.

A version of this article appeared on Medscape.com.

TOPLINE:

A two-step screening strategy in postmenopausal women demonstrated a high specificity, sensitivity, and positive predictive value for detecting ovarian and borderline cancer, with most identified as stage I or II disease, a new analysis with a 21-year follow-up found.

METHODOLOGY:

• Detecting ovarian cancer at stage I or II could significantly reduce ovarian cancer-related deaths, but only 25%-30% of patients are diagnosed at an early stage.
• In this single-arm prospective analysis, 7,856 healthy postmenopausal women received annual screening for ovarian cancer between 2011 and 2022. Screening involved an annual blood test to detect levels of cancer antigen 125 and track these levels over time.
• Investigators used the Risk of Ovarian Cancer Algorithm (ROCA) to determine whether ovarian cancer risk was normal, intermediate, or high. Those with elevated ROCA scores were referred for transvaginal sonography; those with intermediate scores received follow-up blood tests every 3 months.
• Overall, 92.3% of women were normal risk, 5.7% were intermediate, and 2% were high risk and recommended for transvaginal sonography.

TAKEAWAY:

• Most women (95.5%) referred for transvaginal ultrasound had one. Of these ultrasounds, most (90%) were negative or revealed benign findings, 5.2% required a repeat ultrasound, and 4.8% (34 patients) showed suspicious findings.
• Of 34 patients with suspicious findings and recommended for surgery, 15 had ovarian cancer and two had borderline tumors, indicating a positive predictive value of 50% (17 of 34 patients) for ovarian cancer. Of these 17 patients, 12 (70.6%) had stage I or II disease.
• Following abnormal ROCA results, seven other women were diagnosed with endometrial tumors (six of which were stage I), indicating a positive predictive value of 74% (25 of 34) for any cancer.
• The specificity for elevated risk ROCA prompting ultrasound was 98%, and the specificity of the ROCA and ultrasound prompting surgery was 99.8%. The sensitivity for detecting ovarian and borderline cancer was 74% (17 of 23).

IN PRACTICE:

“Remarkably, 70% of ovarian cancers detected by the ROCA” were early stage,” the authors concluded. Although the trial was not powered to detect reduced mortality, the high specificity, positive predictive value, and shift to identifying earlier-stage cancers “support further development of this strategy,” the investigators said.

LIMITATIONS:

This trial was not powered to detect mortality benefit. Six ovarian cancers and borderline tumors were missed. Only 80% of ovarian cancers express cancer antigen 125, potentially limiting the sensitivity of the algorithm.

SOURCE:

This study, led by Chae Young Han from the University of Texas MD Anderson Cancer Center, Houston, was published online on January 12 in the Journal of Clinical Oncology.

DISCLOSURES:

This study was supported by funds from the NCI Early Detection Research Network, the MD Anderson Ovarian SPOREs, the National Cancer Institute, the Department of Health and Human Services, and others. The authors reported receiving research funding, grants, consulting, and personal fees from various companies, including Curio Science, Fujirebio Diagnostics, GlaxoSmithKline, AstraZeneca, and Genentech.

A version of this article appeared on Medscape.com.

TOPLINE:

A two-step screening strategy in postmenopausal women demonstrated a high specificity, sensitivity, and positive predictive value for detecting ovarian and borderline cancer, with most identified as stage I or II disease, a new analysis with a 21-year follow-up found.

METHODOLOGY:

• Detecting ovarian cancer at stage I or II could significantly reduce ovarian cancer-related deaths, but only 25%-30% of patients are diagnosed at an early stage.
• In this single-arm prospective analysis, 7,856 healthy postmenopausal women received annual screening for ovarian cancer between 2011 and 2022. Screening involved an annual blood test to detect levels of cancer antigen 125 and track these levels over time.
• Investigators used the Risk of Ovarian Cancer Algorithm (ROCA) to determine whether ovarian cancer risk was normal, intermediate, or high. Those with elevated ROCA scores were referred for transvaginal sonography; those with intermediate scores received follow-up blood tests every 3 months.
• Overall, 92.3% of women were normal risk, 5.7% were intermediate, and 2% were high risk and recommended for transvaginal sonography.

TAKEAWAY:

• Most women (95.5%) referred for transvaginal ultrasound had one. Of these ultrasounds, most (90%) were negative or revealed benign findings, 5.2% required a repeat ultrasound, and 4.8% (34 patients) showed suspicious findings.
• Of 34 patients with suspicious findings and recommended for surgery, 15 had ovarian cancer and two had borderline tumors, indicating a positive predictive value of 50% (17 of 34 patients) for ovarian cancer. Of these 17 patients, 12 (70.6%) had stage I or II disease.
• Following abnormal ROCA results, seven other women were diagnosed with endometrial tumors (six of which were stage I), indicating a positive predictive value of 74% (25 of 34) for any cancer.
• The specificity for elevated risk ROCA prompting ultrasound was 98%, and the specificity of the ROCA and ultrasound prompting surgery was 99.8%. The sensitivity for detecting ovarian and borderline cancer was 74% (17 of 23).

IN PRACTICE:

“Remarkably, 70% of ovarian cancers detected by the ROCA” were early stage,” the authors concluded. Although the trial was not powered to detect reduced mortality, the high specificity, positive predictive value, and shift to identifying earlier-stage cancers “support further development of this strategy,” the investigators said.

LIMITATIONS:

This trial was not powered to detect mortality benefit. Six ovarian cancers and borderline tumors were missed. Only 80% of ovarian cancers express cancer antigen 125, potentially limiting the sensitivity of the algorithm.

SOURCE:

This study, led by Chae Young Han from the University of Texas MD Anderson Cancer Center, Houston, was published online on January 12 in the Journal of Clinical Oncology.

DISCLOSURES:

This study was supported by funds from the NCI Early Detection Research Network, the MD Anderson Ovarian SPOREs, the National Cancer Institute, the Department of Health and Human Services, and others. The authors reported receiving research funding, grants, consulting, and personal fees from various companies, including Curio Science, Fujirebio Diagnostics, GlaxoSmithKline, AstraZeneca, and Genentech.

A version of this article appeared on Medscape.com.

For patients with high-risk prostate cancer, treatment with long-term androgen deprivation therapy (ADT) and high-dose radiation was associated with significantly better progression-free, cancer-specific, and overall survival compared with ADT and standard-dose radiation.
The investigators also found that the patients taking long-term ADT and high-dose radiation did not experience additional late urinary tract or gastrointestinal toxicities. Christophe Hennequin, MD, PhD, reported these and other findings of the Radiation Therapy in Treating Patients Receiving Hormone Therapy for Prostate Cancer (GETUG-AFU 18) trial, at the 2024 American Society for Clinical Oncology (ASCO) Genitourinary Cancers Symposium.  
Among 505 patients randomly assigned to be treated with radiation therapy (RT) at either the standard 70 Gy dose or a high, 80 Gy dose followed by 3 years of adjuvant  ADT, the 10-year progression-free survival (PFS) rate was 83.6% for patients who had received the 80 Gy dose, vs. 72.2% for patients who had received the 70 Gy dose. This translated into a hazard ratio (HR) for biochemical or clinical progression of 0.56 (P = .0005). 
This PFS advantage for high-dose radiation was also reflected by an overall survival (OS) advantage, with 10-year OS rates of 77% vs. 65.9%, respectively, translating into a 39% reduction in risk of death (HR 0.61, P = .0039) for patients who had received the higher radiation dose, reported Dr. Hennequin, of the Hospital Saint Louis in Paris, France. 
"We have now Level 1 evidence that high-dose RT with long-term ADT must be the standard of care in high-risk prostate cancer patients," he said at the meeting. 
Dr. Hennequin noted that significantly more patients assigned to high-dose RT were treated with intensity modulated radiation therapy (IMRT) rather than conventional beam radiation, and emphasized that the superior results seen with the higher dose is likely due to the use of IMRT. 

Prior evidence 

Dr. Hennequin pointed to a meta-analysis published in The Lancet in 2022 which showed that among nearly 11,000 patients with a median follow-up of 11.4 years the addition of ADT to RT significantly improved metastasis-free survival, and that longer ADT reduced the risk of metastases by 16% compared with standard schedule ADT. 
He also cited the DART 01/05 trial results, which were published in 2022 in The Lancet: Oncology, which found a clinically relevant benefit for 24 months vs. 4 months of adjuvant ADT following a minimum of 76 Gy radiation in patients with high-risk disease, but not among patients with intermediate-risk disease.   
The GETUG-AFU 18 trial was designed to address the question of whether 80 Gy of radiation could improve outcomes compared with 70 Gy in patients treated with long-term ADT. 

Study details and results 

The investigators enrolled men with high-risk prostate cancer defined as either a prostate-specific antigen (PSA) level 20 ng/ml or greater, Gleason score 8 or higher, or clinical stage T3 or T4 disease, and after stratification by treatment center and lymph node resection randomly assigned them to receive either 70 Gy or 80 Gy RT followed by 3 years of ADT. 
Approximately two-thirds of the patients in each study arm had one risk factor and about one-fourth had two risk factors. The remaining patients had all three high-risk defining factors.  
Approximately 16.5% of patients in each arm had undergone lymph node dissection.  
The median ADT duration was 33.4 months. In all, 82.9% of patients underwent pelvic lymph node radiation; lymph node radiation was not performed in those patients who had negative node dissection results. 
Significantly more patients assigned to the 80 Gy dose were treated with IMRT (80.6% vs. 58.6%, P < .001).   
The cancer-specific survival rate was also higher for the group receiving the 80 Gy dose, with a 10 year rate of 95.6% vs. 90% for patients treated with 70 Gy. This difference translated into a HR of 0.48 (P = .0090).  
 

Comparable safety 

The safety analysis, which included 248 patients who received 80 Gy and 251 who received 70 Gy, showed that the incidence rates of both late genitourinary and gastrointestinal toxicities were low and comparable between the groups. Grade 3 or greater late genitourinary toxicities were seen in 2.0% of patients treated with 80 Gy and 3.2% of those treated with 70 Gy. In both arms, only 1.6% of patients had grade 3 or greater later GI toxicities.  
There were also no differences between the study arms in patient-reported quality of life measures related to either bowel or urinary symptoms. 
Invited discussant Neha Vapiwala, MD, FACR, from Penn Medicine in Philadelphia commented that the results of the GETUG-AFU 18 trial suggest that "if you had even lower-dose systemic therapy that the radiation control at the local level - local-regional level in this case - can in fact contribute to the prevention of distant metastases and can contribute to cancer-specific survival." 
She said that with the efficacy results and the comparable toxicity and quality of life measures, dose-escalated radiation therapy and long-term ADT appear to offer a synergistic benefit. 
The results are "practice-affirming for many, perhaps practice-changing for some if you're not already offering this," she said. 

For patients with high-risk prostate cancer, treatment with long-term androgen deprivation therapy (ADT) and high-dose radiation was associated with significantly better progression-free, cancer-specific, and overall survival compared with ADT and standard-dose radiation.
The investigators also found that the patients taking long-term ADT and high-dose radiation did not experience additional late urinary tract or gastrointestinal toxicities. Christophe Hennequin, MD, PhD, reported these and other findings of the Radiation Therapy in Treating Patients Receiving Hormone Therapy for Prostate Cancer (GETUG-AFU 18) trial, at the 2024 American Society for Clinical Oncology (ASCO) Genitourinary Cancers Symposium.  
Among 505 patients randomly assigned to be treated with radiation therapy (RT) at either the standard 70 Gy dose or a high, 80 Gy dose followed by 3 years of adjuvant  ADT, the 10-year progression-free survival (PFS) rate was 83.6% for patients who had received the 80 Gy dose, vs. 72.2% for patients who had received the 70 Gy dose. This translated into a hazard ratio (HR) for biochemical or clinical progression of 0.56 (P = .0005). 
This PFS advantage for high-dose radiation was also reflected by an overall survival (OS) advantage, with 10-year OS rates of 77% vs. 65.9%, respectively, translating into a 39% reduction in risk of death (HR 0.61, P = .0039) for patients who had received the higher radiation dose, reported Dr. Hennequin, of the Hospital Saint Louis in Paris, France. 
"We have now Level 1 evidence that high-dose RT with long-term ADT must be the standard of care in high-risk prostate cancer patients," he said at the meeting. 
Dr. Hennequin noted that significantly more patients assigned to high-dose RT were treated with intensity modulated radiation therapy (IMRT) rather than conventional beam radiation, and emphasized that the superior results seen with the higher dose is likely due to the use of IMRT. 

Prior evidence 

Dr. Hennequin pointed to a meta-analysis published in The Lancet in 2022 which showed that among nearly 11,000 patients with a median follow-up of 11.4 years the addition of ADT to RT significantly improved metastasis-free survival, and that longer ADT reduced the risk of metastases by 16% compared with standard schedule ADT. 
He also cited the DART 01/05 trial results, which were published in 2022 in The Lancet: Oncology, which found a clinically relevant benefit for 24 months vs. 4 months of adjuvant ADT following a minimum of 76 Gy radiation in patients with high-risk disease, but not among patients with intermediate-risk disease.   
The GETUG-AFU 18 trial was designed to address the question of whether 80 Gy of radiation could improve outcomes compared with 70 Gy in patients treated with long-term ADT. 

Study details and results 

The investigators enrolled men with high-risk prostate cancer defined as either a prostate-specific antigen (PSA) level 20 ng/ml or greater, Gleason score 8 or higher, or clinical stage T3 or T4 disease, and after stratification by treatment center and lymph node resection randomly assigned them to receive either 70 Gy or 80 Gy RT followed by 3 years of ADT. 
Approximately two-thirds of the patients in each study arm had one risk factor and about one-fourth had two risk factors. The remaining patients had all three high-risk defining factors.  
Approximately 16.5% of patients in each arm had undergone lymph node dissection.  
The median ADT duration was 33.4 months. In all, 82.9% of patients underwent pelvic lymph node radiation; lymph node radiation was not performed in those patients who had negative node dissection results. 
Significantly more patients assigned to the 80 Gy dose were treated with IMRT (80.6% vs. 58.6%, P < .001).   
The cancer-specific survival rate was also higher for the group receiving the 80 Gy dose, with a 10 year rate of 95.6% vs. 90% for patients treated with 70 Gy. This difference translated into a HR of 0.48 (P = .0090).  
 

Comparable safety 

The safety analysis, which included 248 patients who received 80 Gy and 251 who received 70 Gy, showed that the incidence rates of both late genitourinary and gastrointestinal toxicities were low and comparable between the groups. Grade 3 or greater late genitourinary toxicities were seen in 2.0% of patients treated with 80 Gy and 3.2% of those treated with 70 Gy. In both arms, only 1.6% of patients had grade 3 or greater later GI toxicities.  
There were also no differences between the study arms in patient-reported quality of life measures related to either bowel or urinary symptoms. 
Invited discussant Neha Vapiwala, MD, FACR, from Penn Medicine in Philadelphia commented that the results of the GETUG-AFU 18 trial suggest that "if you had even lower-dose systemic therapy that the radiation control at the local level - local-regional level in this case - can in fact contribute to the prevention of distant metastases and can contribute to cancer-specific survival." 
She said that with the efficacy results and the comparable toxicity and quality of life measures, dose-escalated radiation therapy and long-term ADT appear to offer a synergistic benefit. 
The results are "practice-affirming for many, perhaps practice-changing for some if you're not already offering this," she said. 

For patients with high-risk prostate cancer, treatment with long-term androgen deprivation therapy (ADT) and high-dose radiation was associated with significantly better progression-free, cancer-specific, and overall survival compared with ADT and standard-dose radiation.
The investigators also found that the patients taking long-term ADT and high-dose radiation did not experience additional late urinary tract or gastrointestinal toxicities. Christophe Hennequin, MD, PhD, reported these and other findings of the Radiation Therapy in Treating Patients Receiving Hormone Therapy for Prostate Cancer (GETUG-AFU 18) trial, at the 2024 American Society for Clinical Oncology (ASCO) Genitourinary Cancers Symposium.  
Among 505 patients randomly assigned to be treated with radiation therapy (RT) at either the standard 70 Gy dose or a high, 80 Gy dose followed by 3 years of adjuvant  ADT, the 10-year progression-free survival (PFS) rate was 83.6% for patients who had received the 80 Gy dose, vs. 72.2% for patients who had received the 70 Gy dose. This translated into a hazard ratio (HR) for biochemical or clinical progression of 0.56 (P = .0005). 
This PFS advantage for high-dose radiation was also reflected by an overall survival (OS) advantage, with 10-year OS rates of 77% vs. 65.9%, respectively, translating into a 39% reduction in risk of death (HR 0.61, P = .0039) for patients who had received the higher radiation dose, reported Dr. Hennequin, of the Hospital Saint Louis in Paris, France. 
"We have now Level 1 evidence that high-dose RT with long-term ADT must be the standard of care in high-risk prostate cancer patients," he said at the meeting. 
Dr. Hennequin noted that significantly more patients assigned to high-dose RT were treated with intensity modulated radiation therapy (IMRT) rather than conventional beam radiation, and emphasized that the superior results seen with the higher dose is likely due to the use of IMRT. 

Prior evidence 

Dr. Hennequin pointed to a meta-analysis published in The Lancet in 2022 which showed that among nearly 11,000 patients with a median follow-up of 11.4 years the addition of ADT to RT significantly improved metastasis-free survival, and that longer ADT reduced the risk of metastases by 16% compared with standard schedule ADT. 
He also cited the DART 01/05 trial results, which were published in 2022 in The Lancet: Oncology, which found a clinically relevant benefit for 24 months vs. 4 months of adjuvant ADT following a minimum of 76 Gy radiation in patients with high-risk disease, but not among patients with intermediate-risk disease.   
The GETUG-AFU 18 trial was designed to address the question of whether 80 Gy of radiation could improve outcomes compared with 70 Gy in patients treated with long-term ADT. 

Study details and results 

The investigators enrolled men with high-risk prostate cancer defined as either a prostate-specific antigen (PSA) level 20 ng/ml or greater, Gleason score 8 or higher, or clinical stage T3 or T4 disease, and after stratification by treatment center and lymph node resection randomly assigned them to receive either 70 Gy or 80 Gy RT followed by 3 years of ADT. 
Approximately two-thirds of the patients in each study arm had one risk factor and about one-fourth had two risk factors. The remaining patients had all three high-risk defining factors.  
Approximately 16.5% of patients in each arm had undergone lymph node dissection.  
The median ADT duration was 33.4 months. In all, 82.9% of patients underwent pelvic lymph node radiation; lymph node radiation was not performed in those patients who had negative node dissection results. 
Significantly more patients assigned to the 80 Gy dose were treated with IMRT (80.6% vs. 58.6%, P < .001).   
The cancer-specific survival rate was also higher for the group receiving the 80 Gy dose, with a 10 year rate of 95.6% vs. 90% for patients treated with 70 Gy. This difference translated into a HR of 0.48 (P = .0090).  
 

Comparable safety 

The safety analysis, which included 248 patients who received 80 Gy and 251 who received 70 Gy, showed that the incidence rates of both late genitourinary and gastrointestinal toxicities were low and comparable between the groups. Grade 3 or greater late genitourinary toxicities were seen in 2.0% of patients treated with 80 Gy and 3.2% of those treated with 70 Gy. In both arms, only 1.6% of patients had grade 3 or greater later GI toxicities.  
There were also no differences between the study arms in patient-reported quality of life measures related to either bowel or urinary symptoms. 
Invited discussant Neha Vapiwala, MD, FACR, from Penn Medicine in Philadelphia commented that the results of the GETUG-AFU 18 trial suggest that "if you had even lower-dose systemic therapy that the radiation control at the local level - local-regional level in this case - can in fact contribute to the prevention of distant metastases and can contribute to cancer-specific survival." 
She said that with the efficacy results and the comparable toxicity and quality of life measures, dose-escalated radiation therapy and long-term ADT appear to offer a synergistic benefit. 
The results are "practice-affirming for many, perhaps practice-changing for some if you're not already offering this," she said. 

Circulating tumor DNA (ctDNA) has proven itself as a prognostic tool, but questions remain as to whether it can be used to guide the use of adjuvant chemotherapy in patients with colorectal cancer (CRC). Much of the uncertainty surrounds the sensitivity of ctDNA at the time when decisions regarding adjuvant therapy are being made.

Those were some of the key points made during a series of presentations and discussions on ctDNA at the ASCO Gastrointestinal Cancers Symposium.

In a morning session, Pashtoon Murtaza Kasi, MD, presented the first interim results from the multicenter, prospective observational BESPOKE CRC study, which included 689 patients with stage II or III colorectal cancer. The trial was designed to determine what effect ctDNA results would have on adjuvant chemotherapy treatment decisions. Over a median follow-up of 24.8 months, 623 patients had ctDNA results available. ctDNA positivity was associated with worse 2-year disease-free survival (DFS) at 29.86% versus 91.59% in the stage II/III combined group (hazard ratio [HR], 12.1; P < .0001) and in stage II (HR, 18.8; P < .0001) and stage III (HR, 9.9; P < .0001) analyzed separately.

In ctDNA-positive patients, adjuvant chemotherapy was associated with longer DFS than in those who did not undergo adjuvant chemotherapy (HR, 3.06; P = .0025), but there was no difference in DFS between ctDNA-negative patients who received adjuvant chemotherapy and those who didn’t. Patients who achieved ctDNA clearance had a longer median DFS (24.2 versus 13.8 months; HR, 0.4; P = .045).
 

Patient Anxiety Concerns

Dr. Kasi noted the importance of considering the patient’s view of ctDNA. There may be some concerns that such tests could cause patient anxiety, but he referenced a poster at ASCO GI which suggested the opposite. “It actually reduced anxiety, and 90% of the patients felt confident in the treatment they were receiving. They [said that] they will continue using the assay, and they value the additional information,” said Dr. Kasi, who is a medical oncologist at Weill Cornell Medicine in New York City.

During the Q&A after the talk, David Ellison, MD, a medical oncology and hematology specialist at Memorial Sloan Kettering Cancer Center, also in New York asked Dr. Kasi: “Did this [positive ctDNA] test just prompt earlier imaging? Was it any better than conventional surveillance like CEA (carcinoembryonic antigen) or imaging?” he asked.

Dr. Kasi responded that the data showed ctDNA positivity 6-9 months earlier than cancer detection through traditional imaging.

“It doesn’t necessarily replace the ongoing surveillance. This particular study did not guide or make it as a protocol as to what to do. Everything was done as part of standard of care, the usual surveillance that the cancer center follows, he said. “I think [ctDNA] would help complement the ongoing care and in conjunction with somebody who has, for example, an indeterminant lung nodule, but also has ctDNA positivity, I think it adds confidence to the decisions that one might be making.”

Eujung Kim, MD, PhD, an instructor of medicine at Harvard Medical School, Boston, Massachusetts, wondered if there might be chemoresistant tumor cells remaining that are not shedding DNA. “You have to keep the biology in mind as well make decisions in conjunction with the clinical situation, as opposed to in isolation with ctDNA results,” Dr. Kasi responded.

In the same session, Jeannie Tie, MD, described results from the AGITG DYNAMIC-Rectal trial, which was a randomized study to determine if ctDNA could inform adjuvant chemotherapy decisions in locally advanced rectal cancer. The analysis included 230 patients who were randomized to ctDNA-informed management (n = 155), with a positive test leading to adjuvant chemotherapy, or a standard arm where adjuvant therapy decisions were left to the physician (n = 75).

Adjuvant chemotherapy use was higher in the control arm (77% versus 46%; P < .001). Lymphovascular invasion was more common in the control arm (odds ratio [OR], 3.06; P = .023), and recurrence-free survival was higher in patients who remained ctDNA negative (HR, 0.29; P < .001) despite all ctDNA-positive patients and only 23% of ctDNA-negative patients undergoing chemotherapy.

The sites of relapses were also different, with 78% occurring in patients who were ctDNA negative after surgery occurring only in the lung, versus just 1% of metastases solely in the lung among those who were ctDNA positive.

In ctDNA-positive patients, 50% of relapses were only in the liver and 19% were in the liver and lung.

Over 36 months, 16% of ctDNA-negative patients developed distant relapses and 2.8% developed locoregional relapses, versus 36% and 7.1% in the ctDNA-positive group.

“Regrettably, we could not conclude about the noninferiority of [using ctDNA to guide adjuvant therapy decisions] due to the premature study closure and small sample size. We confirmed the significantly lower risk of recurrence in post-op ctDNA-negative patients compared to ctDNA-positive patients, as well as the differential pattern of relapse where lung metastases predominate in ctDNA-negative patients, while liver metastases were the dominant side of relapse in ctDNA-positive patients,” said Dr. Tie, who is a medical oncologist at the Peter MacCallum Cancer Centre, Victoria, Australia.
 

GALAXY Study Results Updated

In an afternoon session, Hiroki Yukami, MD, PhD, presented updated results of the GALAXY study, which examined 2998 patients with stage I-IV colorectal cancer who underwent ctDNA surveillance over a median 16.14 months following surgery. ctDNA-positive status was associated with worse DFS (HR, 10.53; P < .0001) in all stages as well as in stage II/III (HR, 12.05; P < .0001). The researchers also distinguished between patients with sustained ctDNA clearance and those with transient ctDNA clearance, in which a positive test occurred after an initial negative result. Recurrences occurred in 7.1% of patients with sustained ctDNA clearance, versus 85.2% of patients with transient clearance (P < .0001) and 89.4% of those with no clearance (P < .0001). “Sustained clearance indicates superior DFS compared to transient or no clearance,” said Dr. Yukami during his presentation.

Of 117 patients treated with adjuvant chemotherapy after testing ctDNA positive, subsequent ctDNA clearance was associated with better DFS (HR, 6.72; P < .0001). There were also better DFS outcomes among patients who saw a greater decline in ctDNA plasma levels after adjuvant chemotherapy (0%-50% versus 50%-100% reduction; HR, 2.41; P = .001).

Aparna Raj Parikh, MD, assistant professor of medicine at Harvard Medical School, served as a discussant for the GALAXY study. She acknowledged that ctDNA is the most powerful prognostic marker in oncology, but to be clinically useful it is necessary to consider its utility at the landmark time point, which is when decisions are made whether to treat with adjuvant chemotherapy. At that time point, the sensitivity of ctDNA is about 48% in the GALAXY study, which Dr. Parikh said is consistent with other data.
 

ctDNA ‘not sensitive enough’

“We know that postoperative ctDNA is only capturing 40%-50% of patients with recurrences in non–stage IV patients in multiple datasets to date. I think it’s really important to keep in mind the sensitivity of the different time points when you’re actually thinking about how to use this in clinic. The first generation of tests are certainly promising, but I would make the argument that these are just not sensitive enough,” said Dr. Parikh.

“Landmark testing is not yet sensitive enough to deescalate care in a patient where chemotherapy would otherwise be indicated, and surveillance testing has not yet demonstrated clinical utility. I think our goal to actually deescalate care would be to try to lower the ctDNA-negative population recurrence risk to akin to stage I patients, with that 5-year DFS of 93%-95%,” Dr. Parikh said.

Dr. Parikh offered some advice on how to use ctDNA outside of a clinical trial setting. She said that positive ctDNA results can help drive the decision to initiate adjuvant chemotherapy in concert with clinical and other factors.

“I’m pretty convinced by the data that ctDNA is prognostic, and though we still need outcomes data, in particular scenarios where I’m thinking of not giving chemotherapy, a positive test may sway me in that direction,” she said. She gave examples such as patients with a single high-risk feature, or a stage III patient with marginal performance status, or an elderly patient with low-risk stage III disease.

Dr. Kasi has financial relationships with Precision Biosensors, Elicio Therapeutics, Bayer, BostonGene, Daiichi Sankyo/AstraZeneca, Delcath Systems, Eisai, Elicio Therapeutics, Exact Sciences, Foundation Medicine, Guardant Health, Illumina, Ipsen, Lilly, MSD Oncology, Natera, NeoGenomics, QED Therapeutics, SAGA Diagnostics, Seagen, SERVIER, Taiho Oncology, Taiho Pharmaceutical, Advanced Accelerator Applications, Boston Scientific, and Tersera. Dr. Tie, Dr. Kim, Dr. Ellison, and Dr. Yukami did not disclose conflicts of interest. Dr. Parikh has financial relationships with Abbvie, Bayer, Biofidelity, CheckMate Pharmaceuticals, CVS, Delcath Systems, Foundation Medicine, Guardant Health, Illumina, Lily, SAGA Diagnostics, Scarce, Seagen, Taiho Oncology, Takeda, UpToDate, and Value Analytics Labs.

Circulating tumor DNA (ctDNA) has proven itself as a prognostic tool, but questions remain as to whether it can be used to guide the use of adjuvant chemotherapy in patients with colorectal cancer (CRC). Much of the uncertainty surrounds the sensitivity of ctDNA at the time when decisions regarding adjuvant therapy are being made.

Those were some of the key points made during a series of presentations and discussions on ctDNA at the ASCO Gastrointestinal Cancers Symposium.

In a morning session, Pashtoon Murtaza Kasi, MD, presented the first interim results from the multicenter, prospective observational BESPOKE CRC study, which included 689 patients with stage II or III colorectal cancer. The trial was designed to determine what effect ctDNA results would have on adjuvant chemotherapy treatment decisions. Over a median follow-up of 24.8 months, 623 patients had ctDNA results available. ctDNA positivity was associated with worse 2-year disease-free survival (DFS) at 29.86% versus 91.59% in the stage II/III combined group (hazard ratio [HR], 12.1; P < .0001) and in stage II (HR, 18.8; P < .0001) and stage III (HR, 9.9; P < .0001) analyzed separately.

In ctDNA-positive patients, adjuvant chemotherapy was associated with longer DFS than in those who did not undergo adjuvant chemotherapy (HR, 3.06; P = .0025), but there was no difference in DFS between ctDNA-negative patients who received adjuvant chemotherapy and those who didn’t. Patients who achieved ctDNA clearance had a longer median DFS (24.2 versus 13.8 months; HR, 0.4; P = .045).
 

Patient Anxiety Concerns

Dr. Kasi noted the importance of considering the patient’s view of ctDNA. There may be some concerns that such tests could cause patient anxiety, but he referenced a poster at ASCO GI which suggested the opposite. “It actually reduced anxiety, and 90% of the patients felt confident in the treatment they were receiving. They [said that] they will continue using the assay, and they value the additional information,” said Dr. Kasi, who is a medical oncologist at Weill Cornell Medicine in New York City.

During the Q&A after the talk, David Ellison, MD, a medical oncology and hematology specialist at Memorial Sloan Kettering Cancer Center, also in New York asked Dr. Kasi: “Did this [positive ctDNA] test just prompt earlier imaging? Was it any better than conventional surveillance like CEA (carcinoembryonic antigen) or imaging?” he asked.

Dr. Kasi responded that the data showed ctDNA positivity 6-9 months earlier than cancer detection through traditional imaging.

“It doesn’t necessarily replace the ongoing surveillance. This particular study did not guide or make it as a protocol as to what to do. Everything was done as part of standard of care, the usual surveillance that the cancer center follows, he said. “I think [ctDNA] would help complement the ongoing care and in conjunction with somebody who has, for example, an indeterminant lung nodule, but also has ctDNA positivity, I think it adds confidence to the decisions that one might be making.”

Eujung Kim, MD, PhD, an instructor of medicine at Harvard Medical School, Boston, Massachusetts, wondered if there might be chemoresistant tumor cells remaining that are not shedding DNA. “You have to keep the biology in mind as well make decisions in conjunction with the clinical situation, as opposed to in isolation with ctDNA results,” Dr. Kasi responded.

In the same session, Jeannie Tie, MD, described results from the AGITG DYNAMIC-Rectal trial, which was a randomized study to determine if ctDNA could inform adjuvant chemotherapy decisions in locally advanced rectal cancer. The analysis included 230 patients who were randomized to ctDNA-informed management (n = 155), with a positive test leading to adjuvant chemotherapy, or a standard arm where adjuvant therapy decisions were left to the physician (n = 75).

Adjuvant chemotherapy use was higher in the control arm (77% versus 46%; P < .001). Lymphovascular invasion was more common in the control arm (odds ratio [OR], 3.06; P = .023), and recurrence-free survival was higher in patients who remained ctDNA negative (HR, 0.29; P < .001) despite all ctDNA-positive patients and only 23% of ctDNA-negative patients undergoing chemotherapy.

The sites of relapses were also different, with 78% occurring in patients who were ctDNA negative after surgery occurring only in the lung, versus just 1% of metastases solely in the lung among those who were ctDNA positive.

In ctDNA-positive patients, 50% of relapses were only in the liver and 19% were in the liver and lung.

Over 36 months, 16% of ctDNA-negative patients developed distant relapses and 2.8% developed locoregional relapses, versus 36% and 7.1% in the ctDNA-positive group.

“Regrettably, we could not conclude about the noninferiority of [using ctDNA to guide adjuvant therapy decisions] due to the premature study closure and small sample size. We confirmed the significantly lower risk of recurrence in post-op ctDNA-negative patients compared to ctDNA-positive patients, as well as the differential pattern of relapse where lung metastases predominate in ctDNA-negative patients, while liver metastases were the dominant side of relapse in ctDNA-positive patients,” said Dr. Tie, who is a medical oncologist at the Peter MacCallum Cancer Centre, Victoria, Australia.
 

GALAXY Study Results Updated

In an afternoon session, Hiroki Yukami, MD, PhD, presented updated results of the GALAXY study, which examined 2998 patients with stage I-IV colorectal cancer who underwent ctDNA surveillance over a median 16.14 months following surgery. ctDNA-positive status was associated with worse DFS (HR, 10.53; P < .0001) in all stages as well as in stage II/III (HR, 12.05; P < .0001). The researchers also distinguished between patients with sustained ctDNA clearance and those with transient ctDNA clearance, in which a positive test occurred after an initial negative result. Recurrences occurred in 7.1% of patients with sustained ctDNA clearance, versus 85.2% of patients with transient clearance (P < .0001) and 89.4% of those with no clearance (P < .0001). “Sustained clearance indicates superior DFS compared to transient or no clearance,” said Dr. Yukami during his presentation.

Of 117 patients treated with adjuvant chemotherapy after testing ctDNA positive, subsequent ctDNA clearance was associated with better DFS (HR, 6.72; P < .0001). There were also better DFS outcomes among patients who saw a greater decline in ctDNA plasma levels after adjuvant chemotherapy (0%-50% versus 50%-100% reduction; HR, 2.41; P = .001).

Aparna Raj Parikh, MD, assistant professor of medicine at Harvard Medical School, served as a discussant for the GALAXY study. She acknowledged that ctDNA is the most powerful prognostic marker in oncology, but to be clinically useful it is necessary to consider its utility at the landmark time point, which is when decisions are made whether to treat with adjuvant chemotherapy. At that time point, the sensitivity of ctDNA is about 48% in the GALAXY study, which Dr. Parikh said is consistent with other data.
 

ctDNA ‘not sensitive enough’

“We know that postoperative ctDNA is only capturing 40%-50% of patients with recurrences in non–stage IV patients in multiple datasets to date. I think it’s really important to keep in mind the sensitivity of the different time points when you’re actually thinking about how to use this in clinic. The first generation of tests are certainly promising, but I would make the argument that these are just not sensitive enough,” said Dr. Parikh.

“Landmark testing is not yet sensitive enough to deescalate care in a patient where chemotherapy would otherwise be indicated, and surveillance testing has not yet demonstrated clinical utility. I think our goal to actually deescalate care would be to try to lower the ctDNA-negative population recurrence risk to akin to stage I patients, with that 5-year DFS of 93%-95%,” Dr. Parikh said.

Dr. Parikh offered some advice on how to use ctDNA outside of a clinical trial setting. She said that positive ctDNA results can help drive the decision to initiate adjuvant chemotherapy in concert with clinical and other factors.

“I’m pretty convinced by the data that ctDNA is prognostic, and though we still need outcomes data, in particular scenarios where I’m thinking of not giving chemotherapy, a positive test may sway me in that direction,” she said. She gave examples such as patients with a single high-risk feature, or a stage III patient with marginal performance status, or an elderly patient with low-risk stage III disease.

Dr. Kasi has financial relationships with Precision Biosensors, Elicio Therapeutics, Bayer, BostonGene, Daiichi Sankyo/AstraZeneca, Delcath Systems, Eisai, Elicio Therapeutics, Exact Sciences, Foundation Medicine, Guardant Health, Illumina, Ipsen, Lilly, MSD Oncology, Natera, NeoGenomics, QED Therapeutics, SAGA Diagnostics, Seagen, SERVIER, Taiho Oncology, Taiho Pharmaceutical, Advanced Accelerator Applications, Boston Scientific, and Tersera. Dr. Tie, Dr. Kim, Dr. Ellison, and Dr. Yukami did not disclose conflicts of interest. Dr. Parikh has financial relationships with Abbvie, Bayer, Biofidelity, CheckMate Pharmaceuticals, CVS, Delcath Systems, Foundation Medicine, Guardant Health, Illumina, Lily, SAGA Diagnostics, Scarce, Seagen, Taiho Oncology, Takeda, UpToDate, and Value Analytics Labs.

Circulating tumor DNA (ctDNA) has proven itself as a prognostic tool, but questions remain as to whether it can be used to guide the use of adjuvant chemotherapy in patients with colorectal cancer (CRC). Much of the uncertainty surrounds the sensitivity of ctDNA at the time when decisions regarding adjuvant therapy are being made.

Those were some of the key points made during a series of presentations and discussions on ctDNA at the ASCO Gastrointestinal Cancers Symposium.

In a morning session, Pashtoon Murtaza Kasi, MD, presented the first interim results from the multicenter, prospective observational BESPOKE CRC study, which included 689 patients with stage II or III colorectal cancer. The trial was designed to determine what effect ctDNA results would have on adjuvant chemotherapy treatment decisions. Over a median follow-up of 24.8 months, 623 patients had ctDNA results available. ctDNA positivity was associated with worse 2-year disease-free survival (DFS) at 29.86% versus 91.59% in the stage II/III combined group (hazard ratio [HR], 12.1; P < .0001) and in stage II (HR, 18.8; P < .0001) and stage III (HR, 9.9; P < .0001) analyzed separately.

In ctDNA-positive patients, adjuvant chemotherapy was associated with longer DFS than in those who did not undergo adjuvant chemotherapy (HR, 3.06; P = .0025), but there was no difference in DFS between ctDNA-negative patients who received adjuvant chemotherapy and those who didn’t. Patients who achieved ctDNA clearance had a longer median DFS (24.2 versus 13.8 months; HR, 0.4; P = .045).
 

Patient Anxiety Concerns

Dr. Kasi noted the importance of considering the patient’s view of ctDNA. There may be some concerns that such tests could cause patient anxiety, but he referenced a poster at ASCO GI which suggested the opposite. “It actually reduced anxiety, and 90% of the patients felt confident in the treatment they were receiving. They [said that] they will continue using the assay, and they value the additional information,” said Dr. Kasi, who is a medical oncologist at Weill Cornell Medicine in New York City.

During the Q&A after the talk, David Ellison, MD, a medical oncology and hematology specialist at Memorial Sloan Kettering Cancer Center, also in New York asked Dr. Kasi: “Did this [positive ctDNA] test just prompt earlier imaging? Was it any better than conventional surveillance like CEA (carcinoembryonic antigen) or imaging?” he asked.

Dr. Kasi responded that the data showed ctDNA positivity 6-9 months earlier than cancer detection through traditional imaging.

“It doesn’t necessarily replace the ongoing surveillance. This particular study did not guide or make it as a protocol as to what to do. Everything was done as part of standard of care, the usual surveillance that the cancer center follows, he said. “I think [ctDNA] would help complement the ongoing care and in conjunction with somebody who has, for example, an indeterminant lung nodule, but also has ctDNA positivity, I think it adds confidence to the decisions that one might be making.”

Eujung Kim, MD, PhD, an instructor of medicine at Harvard Medical School, Boston, Massachusetts, wondered if there might be chemoresistant tumor cells remaining that are not shedding DNA. “You have to keep the biology in mind as well make decisions in conjunction with the clinical situation, as opposed to in isolation with ctDNA results,” Dr. Kasi responded.

In the same session, Jeannie Tie, MD, described results from the AGITG DYNAMIC-Rectal trial, which was a randomized study to determine if ctDNA could inform adjuvant chemotherapy decisions in locally advanced rectal cancer. The analysis included 230 patients who were randomized to ctDNA-informed management (n = 155), with a positive test leading to adjuvant chemotherapy, or a standard arm where adjuvant therapy decisions were left to the physician (n = 75).

Adjuvant chemotherapy use was higher in the control arm (77% versus 46%; P < .001). Lymphovascular invasion was more common in the control arm (odds ratio [OR], 3.06; P = .023), and recurrence-free survival was higher in patients who remained ctDNA negative (HR, 0.29; P < .001) despite all ctDNA-positive patients and only 23% of ctDNA-negative patients undergoing chemotherapy.

The sites of relapses were also different, with 78% occurring in patients who were ctDNA negative after surgery occurring only in the lung, versus just 1% of metastases solely in the lung among those who were ctDNA positive.

In ctDNA-positive patients, 50% of relapses were only in the liver and 19% were in the liver and lung.

Over 36 months, 16% of ctDNA-negative patients developed distant relapses and 2.8% developed locoregional relapses, versus 36% and 7.1% in the ctDNA-positive group.

“Regrettably, we could not conclude about the noninferiority of [using ctDNA to guide adjuvant therapy decisions] due to the premature study closure and small sample size. We confirmed the significantly lower risk of recurrence in post-op ctDNA-negative patients compared to ctDNA-positive patients, as well as the differential pattern of relapse where lung metastases predominate in ctDNA-negative patients, while liver metastases were the dominant side of relapse in ctDNA-positive patients,” said Dr. Tie, who is a medical oncologist at the Peter MacCallum Cancer Centre, Victoria, Australia.
 

GALAXY Study Results Updated

In an afternoon session, Hiroki Yukami, MD, PhD, presented updated results of the GALAXY study, which examined 2998 patients with stage I-IV colorectal cancer who underwent ctDNA surveillance over a median 16.14 months following surgery. ctDNA-positive status was associated with worse DFS (HR, 10.53; P < .0001) in all stages as well as in stage II/III (HR, 12.05; P < .0001). The researchers also distinguished between patients with sustained ctDNA clearance and those with transient ctDNA clearance, in which a positive test occurred after an initial negative result. Recurrences occurred in 7.1% of patients with sustained ctDNA clearance, versus 85.2% of patients with transient clearance (P < .0001) and 89.4% of those with no clearance (P < .0001). “Sustained clearance indicates superior DFS compared to transient or no clearance,” said Dr. Yukami during his presentation.

Of 117 patients treated with adjuvant chemotherapy after testing ctDNA positive, subsequent ctDNA clearance was associated with better DFS (HR, 6.72; P < .0001). There were also better DFS outcomes among patients who saw a greater decline in ctDNA plasma levels after adjuvant chemotherapy (0%-50% versus 50%-100% reduction; HR, 2.41; P = .001).

Aparna Raj Parikh, MD, assistant professor of medicine at Harvard Medical School, served as a discussant for the GALAXY study. She acknowledged that ctDNA is the most powerful prognostic marker in oncology, but to be clinically useful it is necessary to consider its utility at the landmark time point, which is when decisions are made whether to treat with adjuvant chemotherapy. At that time point, the sensitivity of ctDNA is about 48% in the GALAXY study, which Dr. Parikh said is consistent with other data.
 

ctDNA ‘not sensitive enough’

“We know that postoperative ctDNA is only capturing 40%-50% of patients with recurrences in non–stage IV patients in multiple datasets to date. I think it’s really important to keep in mind the sensitivity of the different time points when you’re actually thinking about how to use this in clinic. The first generation of tests are certainly promising, but I would make the argument that these are just not sensitive enough,” said Dr. Parikh.

“Landmark testing is not yet sensitive enough to deescalate care in a patient where chemotherapy would otherwise be indicated, and surveillance testing has not yet demonstrated clinical utility. I think our goal to actually deescalate care would be to try to lower the ctDNA-negative population recurrence risk to akin to stage I patients, with that 5-year DFS of 93%-95%,” Dr. Parikh said.

Dr. Parikh offered some advice on how to use ctDNA outside of a clinical trial setting. She said that positive ctDNA results can help drive the decision to initiate adjuvant chemotherapy in concert with clinical and other factors.

“I’m pretty convinced by the data that ctDNA is prognostic, and though we still need outcomes data, in particular scenarios where I’m thinking of not giving chemotherapy, a positive test may sway me in that direction,” she said. She gave examples such as patients with a single high-risk feature, or a stage III patient with marginal performance status, or an elderly patient with low-risk stage III disease.

Dr. Kasi has financial relationships with Precision Biosensors, Elicio Therapeutics, Bayer, BostonGene, Daiichi Sankyo/AstraZeneca, Delcath Systems, Eisai, Elicio Therapeutics, Exact Sciences, Foundation Medicine, Guardant Health, Illumina, Ipsen, Lilly, MSD Oncology, Natera, NeoGenomics, QED Therapeutics, SAGA Diagnostics, Seagen, SERVIER, Taiho Oncology, Taiho Pharmaceutical, Advanced Accelerator Applications, Boston Scientific, and Tersera. Dr. Tie, Dr. Kim, Dr. Ellison, and Dr. Yukami did not disclose conflicts of interest. Dr. Parikh has financial relationships with Abbvie, Bayer, Biofidelity, CheckMate Pharmaceuticals, CVS, Delcath Systems, Foundation Medicine, Guardant Health, Illumina, Lily, SAGA Diagnostics, Scarce, Seagen, Taiho Oncology, Takeda, UpToDate, and Value Analytics Labs.

Officials at Dana-Farber Cancer Institute are moving to retract at least six published research papers and correct 31 others amid allegations of data manipulation.

News of the investigation follows a blog post by British molecular biologist Sholto David, MD, who flagged almost 60 papers published between 1997 and 2017 that contained image manipulation and other errors. Some of the papers were published by Dana-Farber’s chief executive officer, Laurie Glimcher, MD, and chief operating officer, William Hahn, MD, on topics including multiple myeloma and immune cells.

Mr. David, who blogs about research integrity, highlighted numerous errors and irregularities, including copying and pasting images across multiple experiments to represent different days within the same experiment, sometimes rotating or stretching images.

In one case, Mr. David equated the manipulation with tactics used by “hapless Chinese papermills” and concluded that “a swathe of research coming out of [Dana-Farber] authored by the most senior researchers and managers appears to be hopelessly corrupt with errors that are obvious from just a cursory reading the papers.” 

“Imagine what mistakes might be found in the raw data if anyone was allowed to look!” he wrote.

Barrett Rollins, MD, PhD, Dana-Farber Cancer Institute’s research integrity officer, declined to comment on whether the errors represent scientific misconduct, according to STAT. Rollins told ScienceInsider that the “presence of image discrepancies in a paper is not evidence of an author’s intent to deceive.” 

Access to new artificial intelligence tools is making it easier for data sleuths, like Mr. David, to unearth data manipulation and errors. 

The current investigation closely follows two other investigations into the published work of Harvard University’s former president, Claudine Gay, and Stanford University’s former president, Marc Tessier-Lavigne, which led both to resign their posts. 

A version of this article appeared on Medscape.com.

Officials at Dana-Farber Cancer Institute are moving to retract at least six published research papers and correct 31 others amid allegations of data manipulation.

News of the investigation follows a blog post by British molecular biologist Sholto David, MD, who flagged almost 60 papers published between 1997 and 2017 that contained image manipulation and other errors. Some of the papers were published by Dana-Farber’s chief executive officer, Laurie Glimcher, MD, and chief operating officer, William Hahn, MD, on topics including multiple myeloma and immune cells.

Mr. David, who blogs about research integrity, highlighted numerous errors and irregularities, including copying and pasting images across multiple experiments to represent different days within the same experiment, sometimes rotating or stretching images.

In one case, Mr. David equated the manipulation with tactics used by “hapless Chinese papermills” and concluded that “a swathe of research coming out of [Dana-Farber] authored by the most senior researchers and managers appears to be hopelessly corrupt with errors that are obvious from just a cursory reading the papers.” 

“Imagine what mistakes might be found in the raw data if anyone was allowed to look!” he wrote.

Barrett Rollins, MD, PhD, Dana-Farber Cancer Institute’s research integrity officer, declined to comment on whether the errors represent scientific misconduct, according to STAT. Rollins told ScienceInsider that the “presence of image discrepancies in a paper is not evidence of an author’s intent to deceive.” 

Access to new artificial intelligence tools is making it easier for data sleuths, like Mr. David, to unearth data manipulation and errors. 

The current investigation closely follows two other investigations into the published work of Harvard University’s former president, Claudine Gay, and Stanford University’s former president, Marc Tessier-Lavigne, which led both to resign their posts. 

A version of this article appeared on Medscape.com.

Officials at Dana-Farber Cancer Institute are moving to retract at least six published research papers and correct 31 others amid allegations of data manipulation.

News of the investigation follows a blog post by British molecular biologist Sholto David, MD, who flagged almost 60 papers published between 1997 and 2017 that contained image manipulation and other errors. Some of the papers were published by Dana-Farber’s chief executive officer, Laurie Glimcher, MD, and chief operating officer, William Hahn, MD, on topics including multiple myeloma and immune cells.

Mr. David, who blogs about research integrity, highlighted numerous errors and irregularities, including copying and pasting images across multiple experiments to represent different days within the same experiment, sometimes rotating or stretching images.

In one case, Mr. David equated the manipulation with tactics used by “hapless Chinese papermills” and concluded that “a swathe of research coming out of [Dana-Farber] authored by the most senior researchers and managers appears to be hopelessly corrupt with errors that are obvious from just a cursory reading the papers.” 

“Imagine what mistakes might be found in the raw data if anyone was allowed to look!” he wrote.

Barrett Rollins, MD, PhD, Dana-Farber Cancer Institute’s research integrity officer, declined to comment on whether the errors represent scientific misconduct, according to STAT. Rollins told ScienceInsider that the “presence of image discrepancies in a paper is not evidence of an author’s intent to deceive.” 

Access to new artificial intelligence tools is making it easier for data sleuths, like Mr. David, to unearth data manipulation and errors. 

The current investigation closely follows two other investigations into the published work of Harvard University’s former president, Claudine Gay, and Stanford University’s former president, Marc Tessier-Lavigne, which led both to resign their posts. 

A version of this article appeared on Medscape.com.

PARIS — Should clinicians promote active surveillance for non–muscle-invasive bladder tumors (NMIBT) and establish it as a comprehensive management approach, as with prostate and kidney cancers?

During the 117th congress of the French Association of Urology (AFU), Benjamin Pradère, MD, urologic surgeon at Croix du Sud Clinic in Quint-Fonsegrives, France, advocated for this approach, suggesting that the use of biomarkers could enhance its effectiveness.

In managing precancerous lesions like NMIBT, “implementing active surveillance is a safe, cost-effective option that improves the quality of life. However, it requires careful patient selection, proper information, and relevant follow-up,” said Dr. Pradère, who is a member of the AFU Cancer Committee (CCAFU).

Low-Grade Tumors

NMIBTs are precancerous lesions and constitute 70%-80% of diagnosed bladder tumors. The remaining tumors are more severe invasive tumors that infiltrate deep tissues. NMIBTs, however, entail a high risk for recurrence (reaching 80% after endoscopic resection), as well as a high risk for progression.

As a result, the diagnosis of NMIBT involves follow-up that significantly impacts patients’ quality of life due to repeated cystoscopies and endovesical treatments. “Tumors with the most impact are low-grade Ta tumors”, with longer-term monitoring required for these low-risk tumors.

Hematuria is the most frequent clinical sign. NMIBT diagnosis occurs after endoscopic tumor resection via transurethral resection, followed by an anatomopathological analysis to determine cell grade and tumor stage. Treatment depends on the risk of recurrence and progression, as well as the risk of therapeutic failure after the initial resection.

Risk stratification distinguishes the following four levels:

• Low-risk tumors: Low-grade pTa urothelial tumors, unifocal, < 3 cm, no history of bladder tumors. Low risk of recurrence and progression.
• Intermediate-risk tumors: Other low-grade pTa urothelial tumors with no high-risk criteria. Low risk of progression but high risk of recurrence.
• High-risk tumors: Tumors with at least one risk factor: Stage pT1, high grade, presence of carcinoma in situ. High risks of progression and recurrence.
• Very high-risk tumors: Tumors combining all risk factors (pT1 grade with carcinoma in situ). Very high and early risk of progression.

“We know that low-grade NMIBTs have no impact on survival,” said Dr. Pradère. For these tumors, which represent 60% of diagnosed NMIBTs, or approximately 250,000 new cases annually in France, specific survival is > 99%, meaning that most diagnosed patients will not die of bladder cancer.

The recurrence rate for low-grade tumors is 50%, but recurrences are “almost always low-grade and rarely invade the basement membrane,” said Pradère. Implementing active surveillance to limit surgical intervention to more advanced forms seems to be relevant for these tumors.

Cystoscopy Every 3 Months

According to CCAFU recommendations, “active surveillance is a therapeutic alternative that can be proposed for patients with recurrent low-risk NMIBT after the initial diagnosis.” Criteria include low-grade pTa, fewer than five tumors, size ≤ 15 mm, negative urinary cytology, asymptomatic nature, and the patient’s acceptance of closer monitoring.

While active surveillance has become the standard treatment for low-risk prostate cancer, this therapeutic option remains marginal in bladder cancer, as in kidney cancer. The goal is to defer or avoid surgical treatment by closely monitoring the natural progression of the disease.

For NMIBTs, follow-up modalities are not yet specifically recommended because of a lack of data, said Dr. Pradère. According to a consensus, cystoscopy should be repeated every 3 months for a year and then every 6 months. Unlike standard follow-up, it includes cytology “to not miss the transition to high grade.”

CCAFU recommends discontinuing active surveillance if any of the following criteria are present:

• More than 10 lesions
• Size > 30 mm
• Positive cytology
• Symptoms (hematuria, micturition disorders, and recurring infections).

Literature on the benefits of active surveillance in bladder tumors is still limited. Only seven studies are available. Overall, for nearly 600 included patients, tumors progressed in about 12% of cases. Progression to invasive tumors occurred in 0.8% of patients (n = 5).

13 Months’ Surveillance 

According to a long-term study (median follow-up of 38 months), patients mostly exit active surveillance in the first year. The median duration of active surveillance is 13 months. Active surveillance is discontinued to surgically treat tumors that turn out to be low-grade Ta tumors in 70% of cases.

The following factors predicting recurrence and progression of tumors have been identified: Multiple tumors, early recurrence (within a year of initial diagnosis), frequent recurrence (more than one recurrence per year), tumors > 3 cm, and failure of previous endovesical treatment.

Recent studies have shown that with at least three of these recurrence and progression factors, the median duration under active surveillance is 15 months compared with 28 months in the absence of such factors. “Considering these factors, it is possible to assess the benefit of active surveillance for the patient,” said Dr. Pradère.

If active surveillance for bladder tumors is still not widely practiced, then the contribution of imaging (MRI and ultrasound) and biomarkers could promote its adoption. “The use of biomarkers should change the game and encourage active surveillance in patients with small polyps,” said Dr. Pradère.

ADXBladder Test Utility

A study highlighted the importance of evaluating minichromosome maintenance protein 5 expression during active surveillance using the ADXBladder ELISA test on a urine sample. This test is usually used in bladder cancer diagnosis.

“This study showed that a negative result in two consecutive tests during active surveillance is associated with an almost zero recurrence risk. After two negative tests, most patients do not exit active surveillance,” said Dr. Pradère. But the positive predictive value of biomarkers remains low for low-grade tumors.

The future of active surveillance in bladder cancer should involve better patient selection that relies on risk factors, enhanced modalities through imaging and biomarkers, and the advent of artificial intelligence to analyze cystoscopy results, concluded Dr. Pradère. 
 

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

PARIS — Should clinicians promote active surveillance for non–muscle-invasive bladder tumors (NMIBT) and establish it as a comprehensive management approach, as with prostate and kidney cancers?

During the 117th congress of the French Association of Urology (AFU), Benjamin Pradère, MD, urologic surgeon at Croix du Sud Clinic in Quint-Fonsegrives, France, advocated for this approach, suggesting that the use of biomarkers could enhance its effectiveness.

In managing precancerous lesions like NMIBT, “implementing active surveillance is a safe, cost-effective option that improves the quality of life. However, it requires careful patient selection, proper information, and relevant follow-up,” said Dr. Pradère, who is a member of the AFU Cancer Committee (CCAFU).

Low-Grade Tumors

NMIBTs are precancerous lesions and constitute 70%-80% of diagnosed bladder tumors. The remaining tumors are more severe invasive tumors that infiltrate deep tissues. NMIBTs, however, entail a high risk for recurrence (reaching 80% after endoscopic resection), as well as a high risk for progression.

As a result, the diagnosis of NMIBT involves follow-up that significantly impacts patients’ quality of life due to repeated cystoscopies and endovesical treatments. “Tumors with the most impact are low-grade Ta tumors”, with longer-term monitoring required for these low-risk tumors.

Hematuria is the most frequent clinical sign. NMIBT diagnosis occurs after endoscopic tumor resection via transurethral resection, followed by an anatomopathological analysis to determine cell grade and tumor stage. Treatment depends on the risk of recurrence and progression, as well as the risk of therapeutic failure after the initial resection.

Risk stratification distinguishes the following four levels:

• Low-risk tumors: Low-grade pTa urothelial tumors, unifocal, < 3 cm, no history of bladder tumors. Low risk of recurrence and progression.
• Intermediate-risk tumors: Other low-grade pTa urothelial tumors with no high-risk criteria. Low risk of progression but high risk of recurrence.
• High-risk tumors: Tumors with at least one risk factor: Stage pT1, high grade, presence of carcinoma in situ. High risks of progression and recurrence.
• Very high-risk tumors: Tumors combining all risk factors (pT1 grade with carcinoma in situ). Very high and early risk of progression.

“We know that low-grade NMIBTs have no impact on survival,” said Dr. Pradère. For these tumors, which represent 60% of diagnosed NMIBTs, or approximately 250,000 new cases annually in France, specific survival is > 99%, meaning that most diagnosed patients will not die of bladder cancer.

The recurrence rate for low-grade tumors is 50%, but recurrences are “almost always low-grade and rarely invade the basement membrane,” said Pradère. Implementing active surveillance to limit surgical intervention to more advanced forms seems to be relevant for these tumors.

Cystoscopy Every 3 Months

According to CCAFU recommendations, “active surveillance is a therapeutic alternative that can be proposed for patients with recurrent low-risk NMIBT after the initial diagnosis.” Criteria include low-grade pTa, fewer than five tumors, size ≤ 15 mm, negative urinary cytology, asymptomatic nature, and the patient’s acceptance of closer monitoring.

While active surveillance has become the standard treatment for low-risk prostate cancer, this therapeutic option remains marginal in bladder cancer, as in kidney cancer. The goal is to defer or avoid surgical treatment by closely monitoring the natural progression of the disease.

For NMIBTs, follow-up modalities are not yet specifically recommended because of a lack of data, said Dr. Pradère. According to a consensus, cystoscopy should be repeated every 3 months for a year and then every 6 months. Unlike standard follow-up, it includes cytology “to not miss the transition to high grade.”

CCAFU recommends discontinuing active surveillance if any of the following criteria are present:

• More than 10 lesions
• Size > 30 mm
• Positive cytology
• Symptoms (hematuria, micturition disorders, and recurring infections).

Literature on the benefits of active surveillance in bladder tumors is still limited. Only seven studies are available. Overall, for nearly 600 included patients, tumors progressed in about 12% of cases. Progression to invasive tumors occurred in 0.8% of patients (n = 5).

13 Months’ Surveillance 

According to a long-term study (median follow-up of 38 months), patients mostly exit active surveillance in the first year. The median duration of active surveillance is 13 months. Active surveillance is discontinued to surgically treat tumors that turn out to be low-grade Ta tumors in 70% of cases.

The following factors predicting recurrence and progression of tumors have been identified: Multiple tumors, early recurrence (within a year of initial diagnosis), frequent recurrence (more than one recurrence per year), tumors > 3 cm, and failure of previous endovesical treatment.

Recent studies have shown that with at least three of these recurrence and progression factors, the median duration under active surveillance is 15 months compared with 28 months in the absence of such factors. “Considering these factors, it is possible to assess the benefit of active surveillance for the patient,” said Dr. Pradère.

If active surveillance for bladder tumors is still not widely practiced, then the contribution of imaging (MRI and ultrasound) and biomarkers could promote its adoption. “The use of biomarkers should change the game and encourage active surveillance in patients with small polyps,” said Dr. Pradère.

ADXBladder Test Utility

A study highlighted the importance of evaluating minichromosome maintenance protein 5 expression during active surveillance using the ADXBladder ELISA test on a urine sample. This test is usually used in bladder cancer diagnosis.

“This study showed that a negative result in two consecutive tests during active surveillance is associated with an almost zero recurrence risk. After two negative tests, most patients do not exit active surveillance,” said Dr. Pradère. But the positive predictive value of biomarkers remains low for low-grade tumors.

The future of active surveillance in bladder cancer should involve better patient selection that relies on risk factors, enhanced modalities through imaging and biomarkers, and the advent of artificial intelligence to analyze cystoscopy results, concluded Dr. Pradère. 
 

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

PARIS — Should clinicians promote active surveillance for non–muscle-invasive bladder tumors (NMIBT) and establish it as a comprehensive management approach, as with prostate and kidney cancers?

During the 117th congress of the French Association of Urology (AFU), Benjamin Pradère, MD, urologic surgeon at Croix du Sud Clinic in Quint-Fonsegrives, France, advocated for this approach, suggesting that the use of biomarkers could enhance its effectiveness.

In managing precancerous lesions like NMIBT, “implementing active surveillance is a safe, cost-effective option that improves the quality of life. However, it requires careful patient selection, proper information, and relevant follow-up,” said Dr. Pradère, who is a member of the AFU Cancer Committee (CCAFU).

Low-Grade Tumors

NMIBTs are precancerous lesions and constitute 70%-80% of diagnosed bladder tumors. The remaining tumors are more severe invasive tumors that infiltrate deep tissues. NMIBTs, however, entail a high risk for recurrence (reaching 80% after endoscopic resection), as well as a high risk for progression.

As a result, the diagnosis of NMIBT involves follow-up that significantly impacts patients’ quality of life due to repeated cystoscopies and endovesical treatments. “Tumors with the most impact are low-grade Ta tumors”, with longer-term monitoring required for these low-risk tumors.

Hematuria is the most frequent clinical sign. NMIBT diagnosis occurs after endoscopic tumor resection via transurethral resection, followed by an anatomopathological analysis to determine cell grade and tumor stage. Treatment depends on the risk of recurrence and progression, as well as the risk of therapeutic failure after the initial resection.

Risk stratification distinguishes the following four levels:

• Low-risk tumors: Low-grade pTa urothelial tumors, unifocal, < 3 cm, no history of bladder tumors. Low risk of recurrence and progression.
• Intermediate-risk tumors: Other low-grade pTa urothelial tumors with no high-risk criteria. Low risk of progression but high risk of recurrence.
• High-risk tumors: Tumors with at least one risk factor: Stage pT1, high grade, presence of carcinoma in situ. High risks of progression and recurrence.
• Very high-risk tumors: Tumors combining all risk factors (pT1 grade with carcinoma in situ). Very high and early risk of progression.

“We know that low-grade NMIBTs have no impact on survival,” said Dr. Pradère. For these tumors, which represent 60% of diagnosed NMIBTs, or approximately 250,000 new cases annually in France, specific survival is > 99%, meaning that most diagnosed patients will not die of bladder cancer.

The recurrence rate for low-grade tumors is 50%, but recurrences are “almost always low-grade and rarely invade the basement membrane,” said Pradère. Implementing active surveillance to limit surgical intervention to more advanced forms seems to be relevant for these tumors.

Cystoscopy Every 3 Months

According to CCAFU recommendations, “active surveillance is a therapeutic alternative that can be proposed for patients with recurrent low-risk NMIBT after the initial diagnosis.” Criteria include low-grade pTa, fewer than five tumors, size ≤ 15 mm, negative urinary cytology, asymptomatic nature, and the patient’s acceptance of closer monitoring.

While active surveillance has become the standard treatment for low-risk prostate cancer, this therapeutic option remains marginal in bladder cancer, as in kidney cancer. The goal is to defer or avoid surgical treatment by closely monitoring the natural progression of the disease.

For NMIBTs, follow-up modalities are not yet specifically recommended because of a lack of data, said Dr. Pradère. According to a consensus, cystoscopy should be repeated every 3 months for a year and then every 6 months. Unlike standard follow-up, it includes cytology “to not miss the transition to high grade.”

CCAFU recommends discontinuing active surveillance if any of the following criteria are present:

• More than 10 lesions
• Size > 30 mm
• Positive cytology
• Symptoms (hematuria, micturition disorders, and recurring infections).

Literature on the benefits of active surveillance in bladder tumors is still limited. Only seven studies are available. Overall, for nearly 600 included patients, tumors progressed in about 12% of cases. Progression to invasive tumors occurred in 0.8% of patients (n = 5).

13 Months’ Surveillance 

According to a long-term study (median follow-up of 38 months), patients mostly exit active surveillance in the first year. The median duration of active surveillance is 13 months. Active surveillance is discontinued to surgically treat tumors that turn out to be low-grade Ta tumors in 70% of cases.

The following factors predicting recurrence and progression of tumors have been identified: Multiple tumors, early recurrence (within a year of initial diagnosis), frequent recurrence (more than one recurrence per year), tumors > 3 cm, and failure of previous endovesical treatment.

Recent studies have shown that with at least three of these recurrence and progression factors, the median duration under active surveillance is 15 months compared with 28 months in the absence of such factors. “Considering these factors, it is possible to assess the benefit of active surveillance for the patient,” said Dr. Pradère.

If active surveillance for bladder tumors is still not widely practiced, then the contribution of imaging (MRI and ultrasound) and biomarkers could promote its adoption. “The use of biomarkers should change the game and encourage active surveillance in patients with small polyps,” said Dr. Pradère.

ADXBladder Test Utility

A study highlighted the importance of evaluating minichromosome maintenance protein 5 expression during active surveillance using the ADXBladder ELISA test on a urine sample. This test is usually used in bladder cancer diagnosis.

“This study showed that a negative result in two consecutive tests during active surveillance is associated with an almost zero recurrence risk. After two negative tests, most patients do not exit active surveillance,” said Dr. Pradère. But the positive predictive value of biomarkers remains low for low-grade tumors.

The future of active surveillance in bladder cancer should involve better patient selection that relies on risk factors, enhanced modalities through imaging and biomarkers, and the advent of artificial intelligence to analyze cystoscopy results, concluded Dr. Pradère. 
 

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

Men with localized prostate cancer face a number of treatment choices, including radical prostatectomy, radiotherapy with or without androgen deprivation therapy, and active surveillance. Understanding the likely functional outcomes of each treatment over time is important, as most patients are expected to live at least 15 years after diagnosis.

New research published Jan. 23 in JAMA parses functional outcome results from a population-based study of men diagnosed with localized prostate cancer. For their research, Bashir Al Hussein Al Awamlh, MD, of Vanderbilt University in Nashville, Tennessee, and his colleagues, looked at sexual function, urinary health, bowel function, hormonal function, and other outcomes in this cohort at 10 years’ follow-up.

Courtesy Vanderbilt University

Among 2455 patients for whom 10-year data were available, 1877 were deemed at baseline to have a favorable prognosis (defined as cT1-cT2bN0M0, prostate-specific antigen level less than 20 ng/mL, and grade group 1-2) and 568 had unfavorable-prognosis prostate cancer (defined as cT2cN0M0, prostate-specific antigen level of 20-50 ng/mL, or grade group 3-5). Follow-up data were collected by questionnaire through February 1, 2022. The men in the study were all younger than 80 years, and three-quarters of them were White.

At 10 years, outcomes differed based on the amount of time that had passed since diagnosis (they found different results at 3 and 5 year follow up, for example) and which treatment a patient received.

Among men with favorable prognoses at diagnosis, 20% underwent active surveillance for at least 1 year, while 56% received radical prostatectomy, 19% had external beam radiotherapy (EBRT) without ADT, and 5% had brachytherapy. Nearly a third of men originally opting for surveillance went on to undergo a therapeutic intervention by 10 years.

Dr. Al Hussein Al Awamlh and his colleagues found that while 3- and 5-year follow-up studies in this cohort had shown declines in sexual function among men who underwent surgery compared with those who had radiation or active surveillance, by 10 years those differences had faded, with no clinically meaningful differences in sexual function scores between the surgery and surveillance groups. In an interview, Dr. Al Hussein Al Awamlh said that this finding likely reflected mainly age-related declines in function across the study population — though it could also reflect declines after converting from surveillance to surgery or gradual decline with radiation treatment, he acknowledged.

Men with favorable prognoses at baseline who underwent surgery saw significantly worse urinary incontinence at 10 years compared with those started on radiotherapy or active surveillance. And EBRT was associated with fewer incontinence issues compared with active surveillance.

Among the group of men with an unfavorable prognosis at baseline, 64% of whom underwent radical prostatectomy and 36% EBRT with ADT, surgery was associated with worse urinary incontinence but not worse sexual function throughout 10 years of follow up, compared to radiotherapy with androgen deprivation therapy.

Radiation-treated patients with unfavorable prognoses, meanwhile, saw significantly worse bowel function and hormone function at 10 years compared with patients who had undergone surgery.

Dr. Al Hussein Al Awamlh said that a strength of this study was that “we had enough patients to stratify functional outcomes based on disease prognosis.” Another key finding was that some of the outcomes changed over time. “For example, among the patients with unfavorable prognoses, at 10-year follow-up there was slightly worse bowel and hormone function seen associated with radiation with ADT compared with surgery,” he said — something not seen at earlier follow-up points.

The findings may help offer a more nuanced way to counsel patients, Dr. Al Hussein Al Awamlh noted. For example, the side effects associated with sexual function “are not as relevant for those with unfavorable disease,” he said.

While current prostate cancer guidelines do address quality of life in shared decision-making, he said, “hopefully this data may provide more insight on that.” For patients with favorable prognosis, the findings reinforce that “active surveillance is a great option because it avoids the effects associated with those other treatments.”

Ultimately, Dr. Al Hussein Al Awamlh said, “this is a patient preference issue. It’s important for patients to understand how different functions are affected and to decide what is better for them — what they can live with and what they cannot, provided all the options are oncologically safe.”

The study authors disclosed as limitations of their study its observational design, the potential for response bias among study participants, and small numbers for some of the measured outcomes.

In an interview, urologist Mark S. Litwin, MD, of the University of California Los Angeles, characterized the study as “a well-conducted very-long-term longitudinal cohort that tracked men long past the initial diagnosis and treatment. That empowered the Vanderbilt team to find differences in quality of life many years later and compare them to other older men who had not received treatment.”

The new findings, Dr. Litwin said, “are critical in showing that most men with prostate cancer do not die from it; hence, the quality-of-life effects end up being the key issues for decision-making.”

Dr. Al Hussein Al Awamlh and colleagues’ study was funded by grants from the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Patient-Centered Outcomes Research Institute. Several coauthors disclosed funding from pharmaceutical and/or device manufacturers. Dr. Litwin disclosed no conflicts of interest related to his comment.

Men with localized prostate cancer face a number of treatment choices, including radical prostatectomy, radiotherapy with or without androgen deprivation therapy, and active surveillance. Understanding the likely functional outcomes of each treatment over time is important, as most patients are expected to live at least 15 years after diagnosis.

New research published Jan. 23 in JAMA parses functional outcome results from a population-based study of men diagnosed with localized prostate cancer. For their research, Bashir Al Hussein Al Awamlh, MD, of Vanderbilt University in Nashville, Tennessee, and his colleagues, looked at sexual function, urinary health, bowel function, hormonal function, and other outcomes in this cohort at 10 years’ follow-up.

Courtesy Vanderbilt University

Among 2455 patients for whom 10-year data were available, 1877 were deemed at baseline to have a favorable prognosis (defined as cT1-cT2bN0M0, prostate-specific antigen level less than 20 ng/mL, and grade group 1-2) and 568 had unfavorable-prognosis prostate cancer (defined as cT2cN0M0, prostate-specific antigen level of 20-50 ng/mL, or grade group 3-5). Follow-up data were collected by questionnaire through February 1, 2022. The men in the study were all younger than 80 years, and three-quarters of them were White.

At 10 years, outcomes differed based on the amount of time that had passed since diagnosis (they found different results at 3 and 5 year follow up, for example) and which treatment a patient received.

Among men with favorable prognoses at diagnosis, 20% underwent active surveillance for at least 1 year, while 56% received radical prostatectomy, 19% had external beam radiotherapy (EBRT) without ADT, and 5% had brachytherapy. Nearly a third of men originally opting for surveillance went on to undergo a therapeutic intervention by 10 years.

Dr. Al Hussein Al Awamlh and his colleagues found that while 3- and 5-year follow-up studies in this cohort had shown declines in sexual function among men who underwent surgery compared with those who had radiation or active surveillance, by 10 years those differences had faded, with no clinically meaningful differences in sexual function scores between the surgery and surveillance groups. In an interview, Dr. Al Hussein Al Awamlh said that this finding likely reflected mainly age-related declines in function across the study population — though it could also reflect declines after converting from surveillance to surgery or gradual decline with radiation treatment, he acknowledged.

Men with favorable prognoses at baseline who underwent surgery saw significantly worse urinary incontinence at 10 years compared with those started on radiotherapy or active surveillance. And EBRT was associated with fewer incontinence issues compared with active surveillance.

Among the group of men with an unfavorable prognosis at baseline, 64% of whom underwent radical prostatectomy and 36% EBRT with ADT, surgery was associated with worse urinary incontinence but not worse sexual function throughout 10 years of follow up, compared to radiotherapy with androgen deprivation therapy.

Radiation-treated patients with unfavorable prognoses, meanwhile, saw significantly worse bowel function and hormone function at 10 years compared with patients who had undergone surgery.

Dr. Al Hussein Al Awamlh said that a strength of this study was that “we had enough patients to stratify functional outcomes based on disease prognosis.” Another key finding was that some of the outcomes changed over time. “For example, among the patients with unfavorable prognoses, at 10-year follow-up there was slightly worse bowel and hormone function seen associated with radiation with ADT compared with surgery,” he said — something not seen at earlier follow-up points.

The findings may help offer a more nuanced way to counsel patients, Dr. Al Hussein Al Awamlh noted. For example, the side effects associated with sexual function “are not as relevant for those with unfavorable disease,” he said.

While current prostate cancer guidelines do address quality of life in shared decision-making, he said, “hopefully this data may provide more insight on that.” For patients with favorable prognosis, the findings reinforce that “active surveillance is a great option because it avoids the effects associated with those other treatments.”

Ultimately, Dr. Al Hussein Al Awamlh said, “this is a patient preference issue. It’s important for patients to understand how different functions are affected and to decide what is better for them — what they can live with and what they cannot, provided all the options are oncologically safe.”

The study authors disclosed as limitations of their study its observational design, the potential for response bias among study participants, and small numbers for some of the measured outcomes.

In an interview, urologist Mark S. Litwin, MD, of the University of California Los Angeles, characterized the study as “a well-conducted very-long-term longitudinal cohort that tracked men long past the initial diagnosis and treatment. That empowered the Vanderbilt team to find differences in quality of life many years later and compare them to other older men who had not received treatment.”

The new findings, Dr. Litwin said, “are critical in showing that most men with prostate cancer do not die from it; hence, the quality-of-life effects end up being the key issues for decision-making.”

Dr. Al Hussein Al Awamlh and colleagues’ study was funded by grants from the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Patient-Centered Outcomes Research Institute. Several coauthors disclosed funding from pharmaceutical and/or device manufacturers. Dr. Litwin disclosed no conflicts of interest related to his comment.

Men with localized prostate cancer face a number of treatment choices, including radical prostatectomy, radiotherapy with or without androgen deprivation therapy, and active surveillance. Understanding the likely functional outcomes of each treatment over time is important, as most patients are expected to live at least 15 years after diagnosis.

New research published Jan. 23 in JAMA parses functional outcome results from a population-based study of men diagnosed with localized prostate cancer. For their research, Bashir Al Hussein Al Awamlh, MD, of Vanderbilt University in Nashville, Tennessee, and his colleagues, looked at sexual function, urinary health, bowel function, hormonal function, and other outcomes in this cohort at 10 years’ follow-up.

Courtesy Vanderbilt University

Among 2455 patients for whom 10-year data were available, 1877 were deemed at baseline to have a favorable prognosis (defined as cT1-cT2bN0M0, prostate-specific antigen level less than 20 ng/mL, and grade group 1-2) and 568 had unfavorable-prognosis prostate cancer (defined as cT2cN0M0, prostate-specific antigen level of 20-50 ng/mL, or grade group 3-5). Follow-up data were collected by questionnaire through February 1, 2022. The men in the study were all younger than 80 years, and three-quarters of them were White.

At 10 years, outcomes differed based on the amount of time that had passed since diagnosis (they found different results at 3 and 5 year follow up, for example) and which treatment a patient received.

Among men with favorable prognoses at diagnosis, 20% underwent active surveillance for at least 1 year, while 56% received radical prostatectomy, 19% had external beam radiotherapy (EBRT) without ADT, and 5% had brachytherapy. Nearly a third of men originally opting for surveillance went on to undergo a therapeutic intervention by 10 years.

Dr. Al Hussein Al Awamlh and his colleagues found that while 3- and 5-year follow-up studies in this cohort had shown declines in sexual function among men who underwent surgery compared with those who had radiation or active surveillance, by 10 years those differences had faded, with no clinically meaningful differences in sexual function scores between the surgery and surveillance groups. In an interview, Dr. Al Hussein Al Awamlh said that this finding likely reflected mainly age-related declines in function across the study population — though it could also reflect declines after converting from surveillance to surgery or gradual decline with radiation treatment, he acknowledged.

Men with favorable prognoses at baseline who underwent surgery saw significantly worse urinary incontinence at 10 years compared with those started on radiotherapy or active surveillance. And EBRT was associated with fewer incontinence issues compared with active surveillance.

Among the group of men with an unfavorable prognosis at baseline, 64% of whom underwent radical prostatectomy and 36% EBRT with ADT, surgery was associated with worse urinary incontinence but not worse sexual function throughout 10 years of follow up, compared to radiotherapy with androgen deprivation therapy.

Radiation-treated patients with unfavorable prognoses, meanwhile, saw significantly worse bowel function and hormone function at 10 years compared with patients who had undergone surgery.

Dr. Al Hussein Al Awamlh said that a strength of this study was that “we had enough patients to stratify functional outcomes based on disease prognosis.” Another key finding was that some of the outcomes changed over time. “For example, among the patients with unfavorable prognoses, at 10-year follow-up there was slightly worse bowel and hormone function seen associated with radiation with ADT compared with surgery,” he said — something not seen at earlier follow-up points.

The findings may help offer a more nuanced way to counsel patients, Dr. Al Hussein Al Awamlh noted. For example, the side effects associated with sexual function “are not as relevant for those with unfavorable disease,” he said.

While current prostate cancer guidelines do address quality of life in shared decision-making, he said, “hopefully this data may provide more insight on that.” For patients with favorable prognosis, the findings reinforce that “active surveillance is a great option because it avoids the effects associated with those other treatments.”

Ultimately, Dr. Al Hussein Al Awamlh said, “this is a patient preference issue. It’s important for patients to understand how different functions are affected and to decide what is better for them — what they can live with and what they cannot, provided all the options are oncologically safe.”

The study authors disclosed as limitations of their study its observational design, the potential for response bias among study participants, and small numbers for some of the measured outcomes.

In an interview, urologist Mark S. Litwin, MD, of the University of California Los Angeles, characterized the study as “a well-conducted very-long-term longitudinal cohort that tracked men long past the initial diagnosis and treatment. That empowered the Vanderbilt team to find differences in quality of life many years later and compare them to other older men who had not received treatment.”

The new findings, Dr. Litwin said, “are critical in showing that most men with prostate cancer do not die from it; hence, the quality-of-life effects end up being the key issues for decision-making.”

Dr. Al Hussein Al Awamlh and colleagues’ study was funded by grants from the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Patient-Centered Outcomes Research Institute. Several coauthors disclosed funding from pharmaceutical and/or device manufacturers. Dr. Litwin disclosed no conflicts of interest related to his comment.

Although treatment of advanced gastroesophageal cancer is increasingly dependent on biomarkers, only about 40% of patients are tested.

For patients to fully benefit from the latest targeted therapies, biomarker testing needs to improve, explained Yelena Janjigian, MD, chief of gastrointestinal oncology at the Memorial Sloan Kettering Cancer Center in New York City.

“The biomarker revolution in this disease has been quite remarkable in the last 10 years, so it’s very important to routinely test for these biomarkers,” Dr. Janjigian said in a presentation at the 2024 ASCO Gastrointestinal Cancers Symposium.

Dr. Janjigian suspected that inertia and logistics are the main reasons biomarker testing rates have lagged. “Even at tertiary cancer centers like ours, we fall short,” she said. For practices that don’t see many patients with gastroesophageal cancer, the rates are probably worse.

Biomarker testing, however, is readily available, Dr. Janjigian said, and overall, it’s about “being obsessive about doing it and following up on it and training your staff.”

As for how to prioritize biomarker testing for treatment selection, Dr. Janjigian provided her top three picks.

Microsatellite instability (MSI) is the most important biomarker, followed by human epidermal growth factor receptor 2 (HER2) as well as tumors expressing programmed death–ligand 1 (PD-L1) with a combined positive score (CPS) of 5 or higher.

Claudin 18.2 testing is “a great newcomer” worth mentioning as well, she noted. Claudin 18.2 is “very druggable,” and several claudin-targeting drugs are currently being assessed, including zolbetuximab.

MSI testing earned the top spot for Dr. Janjigian given the overall survival results from the CHECKMATE 649 trial.

The trial, which Dr. Janjigian led, assessed treatment with first-line nivolumab plus chemotherapy, nivolumab plus ipilimumab, or chemotherapy alone in patients with advanced gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma.

Median overall survival among the small subset of patients with high MSI who received nivolumab plus chemotherapy (n = 23) was more than three times longer than that among those who received chemotherapy alone (n = 21) — 38.7 months vs 12.3 months. Median overall survival was not reached in patients with high MSI who received nivolumab plus ipilimumab at the trial’s 36-month follow-up.

Dr. Janjigian’s case for a PD-L1 CPS of 5 or higher also came, in part, from the CHECKMATE 649 trial. In a subgroup analysis, patients with a CPS of 5 or higher receiving nivolumab plus chemotherapy had a significantly higher median overall survival of 14.4 months vs 11.1 months with chemotherapy alone.

Dr. Janjigian made the case for HER2 testing based on outcomes from the KEYNOTE 811 trial.

This trial, also led by Dr. Janjigian, randomized HER2-positive patients with unresectable advanced gastroesophageal junction adenocarcinoma irrespective of PDL-1 status to pembrolizumab plus trastuzumab and chemotherapy or trastuzumab and chemotherapy alone.

Past studies have reported that targeting HER2 by itself is not a good idea, Dr. Janjigian said, but this trial demonstrated that dual PD-L1/HER2 blockade improves survival outcomes.

Median overall survival in HER2-positive patients with a PD-L1 CPS of 1 or more was 20.0 months vs 15.7 months (hazard ratio [HR], 0.81; 95% CI, 0.67-0.98) compared with 20.0 vs 16.8 months in the overall cohort (HR, 0.84; 95% CI, 0.70-1.01). However, patients with PD-L1 CPS below 1 showed limited benefit from pembrolizumab (HR, 1.41 for overall survival; 95% CI, 0.90-2.20).

To take advantage of the benefit, HER2 testing is “critical,” Dr. Janjigian said.

Overall, when it comes to targeted therapy for advanced disease, the evolution has been rapid. But “we are not done yet,” she said. “We need to be smarter about patient selection” by using biomarker testing.

Dr. Janjigian reported a range of industry ties, including travel expenses, honoraria, and research funding from nivolumab maker Bristol Myers Squibb and Merck, the maker of pembrolizumab. She also advises both companies.

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

Although treatment of advanced gastroesophageal cancer is increasingly dependent on biomarkers, only about 40% of patients are tested.

For patients to fully benefit from the latest targeted therapies, biomarker testing needs to improve, explained Yelena Janjigian, MD, chief of gastrointestinal oncology at the Memorial Sloan Kettering Cancer Center in New York City.

“The biomarker revolution in this disease has been quite remarkable in the last 10 years, so it’s very important to routinely test for these biomarkers,” Dr. Janjigian said in a presentation at the 2024 ASCO Gastrointestinal Cancers Symposium.

Dr. Janjigian suspected that inertia and logistics are the main reasons biomarker testing rates have lagged. “Even at tertiary cancer centers like ours, we fall short,” she said. For practices that don’t see many patients with gastroesophageal cancer, the rates are probably worse.

Biomarker testing, however, is readily available, Dr. Janjigian said, and overall, it’s about “being obsessive about doing it and following up on it and training your staff.”

As for how to prioritize biomarker testing for treatment selection, Dr. Janjigian provided her top three picks.

Microsatellite instability (MSI) is the most important biomarker, followed by human epidermal growth factor receptor 2 (HER2) as well as tumors expressing programmed death–ligand 1 (PD-L1) with a combined positive score (CPS) of 5 or higher.

Claudin 18.2 testing is “a great newcomer” worth mentioning as well, she noted. Claudin 18.2 is “very druggable,” and several claudin-targeting drugs are currently being assessed, including zolbetuximab.

MSI testing earned the top spot for Dr. Janjigian given the overall survival results from the CHECKMATE 649 trial.

The trial, which Dr. Janjigian led, assessed treatment with first-line nivolumab plus chemotherapy, nivolumab plus ipilimumab, or chemotherapy alone in patients with advanced gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma.

Median overall survival among the small subset of patients with high MSI who received nivolumab plus chemotherapy (n = 23) was more than three times longer than that among those who received chemotherapy alone (n = 21) — 38.7 months vs 12.3 months. Median overall survival was not reached in patients with high MSI who received nivolumab plus ipilimumab at the trial’s 36-month follow-up.

Dr. Janjigian’s case for a PD-L1 CPS of 5 or higher also came, in part, from the CHECKMATE 649 trial. In a subgroup analysis, patients with a CPS of 5 or higher receiving nivolumab plus chemotherapy had a significantly higher median overall survival of 14.4 months vs 11.1 months with chemotherapy alone.

Dr. Janjigian made the case for HER2 testing based on outcomes from the KEYNOTE 811 trial.

This trial, also led by Dr. Janjigian, randomized HER2-positive patients with unresectable advanced gastroesophageal junction adenocarcinoma irrespective of PDL-1 status to pembrolizumab plus trastuzumab and chemotherapy or trastuzumab and chemotherapy alone.

Past studies have reported that targeting HER2 by itself is not a good idea, Dr. Janjigian said, but this trial demonstrated that dual PD-L1/HER2 blockade improves survival outcomes.

Median overall survival in HER2-positive patients with a PD-L1 CPS of 1 or more was 20.0 months vs 15.7 months (hazard ratio [HR], 0.81; 95% CI, 0.67-0.98) compared with 20.0 vs 16.8 months in the overall cohort (HR, 0.84; 95% CI, 0.70-1.01). However, patients with PD-L1 CPS below 1 showed limited benefit from pembrolizumab (HR, 1.41 for overall survival; 95% CI, 0.90-2.20).

To take advantage of the benefit, HER2 testing is “critical,” Dr. Janjigian said.

Overall, when it comes to targeted therapy for advanced disease, the evolution has been rapid. But “we are not done yet,” she said. “We need to be smarter about patient selection” by using biomarker testing.

Dr. Janjigian reported a range of industry ties, including travel expenses, honoraria, and research funding from nivolumab maker Bristol Myers Squibb and Merck, the maker of pembrolizumab. She also advises both companies.

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

Although treatment of advanced gastroesophageal cancer is increasingly dependent on biomarkers, only about 40% of patients are tested.

For patients to fully benefit from the latest targeted therapies, biomarker testing needs to improve, explained Yelena Janjigian, MD, chief of gastrointestinal oncology at the Memorial Sloan Kettering Cancer Center in New York City.

“The biomarker revolution in this disease has been quite remarkable in the last 10 years, so it’s very important to routinely test for these biomarkers,” Dr. Janjigian said in a presentation at the 2024 ASCO Gastrointestinal Cancers Symposium.

Dr. Janjigian suspected that inertia and logistics are the main reasons biomarker testing rates have lagged. “Even at tertiary cancer centers like ours, we fall short,” she said. For practices that don’t see many patients with gastroesophageal cancer, the rates are probably worse.

Biomarker testing, however, is readily available, Dr. Janjigian said, and overall, it’s about “being obsessive about doing it and following up on it and training your staff.”

As for how to prioritize biomarker testing for treatment selection, Dr. Janjigian provided her top three picks.

Microsatellite instability (MSI) is the most important biomarker, followed by human epidermal growth factor receptor 2 (HER2) as well as tumors expressing programmed death–ligand 1 (PD-L1) with a combined positive score (CPS) of 5 or higher.

Claudin 18.2 testing is “a great newcomer” worth mentioning as well, she noted. Claudin 18.2 is “very druggable,” and several claudin-targeting drugs are currently being assessed, including zolbetuximab.

MSI testing earned the top spot for Dr. Janjigian given the overall survival results from the CHECKMATE 649 trial.

The trial, which Dr. Janjigian led, assessed treatment with first-line nivolumab plus chemotherapy, nivolumab plus ipilimumab, or chemotherapy alone in patients with advanced gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma.

Median overall survival among the small subset of patients with high MSI who received nivolumab plus chemotherapy (n = 23) was more than three times longer than that among those who received chemotherapy alone (n = 21) — 38.7 months vs 12.3 months. Median overall survival was not reached in patients with high MSI who received nivolumab plus ipilimumab at the trial’s 36-month follow-up.

Dr. Janjigian’s case for a PD-L1 CPS of 5 or higher also came, in part, from the CHECKMATE 649 trial. In a subgroup analysis, patients with a CPS of 5 or higher receiving nivolumab plus chemotherapy had a significantly higher median overall survival of 14.4 months vs 11.1 months with chemotherapy alone.

Dr. Janjigian made the case for HER2 testing based on outcomes from the KEYNOTE 811 trial.

This trial, also led by Dr. Janjigian, randomized HER2-positive patients with unresectable advanced gastroesophageal junction adenocarcinoma irrespective of PDL-1 status to pembrolizumab plus trastuzumab and chemotherapy or trastuzumab and chemotherapy alone.

Past studies have reported that targeting HER2 by itself is not a good idea, Dr. Janjigian said, but this trial demonstrated that dual PD-L1/HER2 blockade improves survival outcomes.

Median overall survival in HER2-positive patients with a PD-L1 CPS of 1 or more was 20.0 months vs 15.7 months (hazard ratio [HR], 0.81; 95% CI, 0.67-0.98) compared with 20.0 vs 16.8 months in the overall cohort (HR, 0.84; 95% CI, 0.70-1.01). However, patients with PD-L1 CPS below 1 showed limited benefit from pembrolizumab (HR, 1.41 for overall survival; 95% CI, 0.90-2.20).

To take advantage of the benefit, HER2 testing is “critical,” Dr. Janjigian said.

Overall, when it comes to targeted therapy for advanced disease, the evolution has been rapid. But “we are not done yet,” she said. “We need to be smarter about patient selection” by using biomarker testing.

Dr. Janjigian reported a range of industry ties, including travel expenses, honoraria, and research funding from nivolumab maker Bristol Myers Squibb and Merck, the maker of pembrolizumab. She also advises both companies.

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