Head & Neck/Thyroid Cancers

Purpose

The aim of this study is to quantify the frequency of Memorial Sloan Kettering (MSK) Precision Oncology Knowledge Base (OncoKB) Level 1 genetic alterations in Veterans with various solid organ malignancies and evaluate the clinical benefit and impact of testing on treatment of these patients.

Background

The VA National Precision Oncology Program (NPOP) facilitates comprehensive genomic profiling (CGP) testing of Veterans with advanced cancer. While CGP is increasingly utilized and routinely ordered in patients with advanced solid organ malignancies, the clinical utility and value has not been proven in certain cancers. We present data from 5,979 patients with head and neck (H&N), pancreatic, hepatocellular (HCC), esophageal and kidney cancers who underwent CGP.

Methods

Our cohort consists of Veterans that received CGP testing to identify somatic variants between 1/1/2019 and 4/2/2025. Identified variants and biomarkers were formatted for use with oncoKB-annotator, a publicly available tool to annotate genomic variants with FDA approved drug recommendations stored as Level 1 annotations in OncoKB, and prescribed drugs were extracted from the Veteran Health Administration’s (VHA) Corporate Data Warehouse (CDW). Cancers were grouped by MSK’s OncoTree codes, and summary counts of Veterans tested, Veterans recommended, Veterans prescribed recommended FDA approved drugs were determined. Percentages were calculated using the total number of Veterans tested as the denominator.

Results

Level 1 OncoKB alterations were infrequent in H&N (0.94%), kidney (0.45%), HCC(0.28%), and pancreatic adenocarcinomas (1%). The frequency of Level 1 alterations in esophageal adenocarcinomas (EAC) was 20%. Approximately 98% of the Level 1 alterations in EAC patients were HER2 positivity or MSI-High status, which can be determined by other diagnostic methodologies such as IHC. The remaining 2% of EAC patients with level 1 alterations had BRAF V600E or NTRK rearrangements.

Conclusions

The incidence of level 1 genetic variants in H&N, kidney, HCC and pancreatic adenocarcinoma is very low and would very uncommonly result in clinical benefit. Although there is an expanding number of precision oncology-based therapies available, the proportion of patients with the aforementioned solid organ malignancies who benefitted from CGP was low, suggesting CGP has minimal impact on the treatment of Veterans with these malignancies.

Purpose

The aim of this study is to quantify the frequency of Memorial Sloan Kettering (MSK) Precision Oncology Knowledge Base (OncoKB) Level 1 genetic alterations in Veterans with various solid organ malignancies and evaluate the clinical benefit and impact of testing on treatment of these patients.

Background

The VA National Precision Oncology Program (NPOP) facilitates comprehensive genomic profiling (CGP) testing of Veterans with advanced cancer. While CGP is increasingly utilized and routinely ordered in patients with advanced solid organ malignancies, the clinical utility and value has not been proven in certain cancers. We present data from 5,979 patients with head and neck (H&N), pancreatic, hepatocellular (HCC), esophageal and kidney cancers who underwent CGP.

Methods

Our cohort consists of Veterans that received CGP testing to identify somatic variants between 1/1/2019 and 4/2/2025. Identified variants and biomarkers were formatted for use with oncoKB-annotator, a publicly available tool to annotate genomic variants with FDA approved drug recommendations stored as Level 1 annotations in OncoKB, and prescribed drugs were extracted from the Veteran Health Administration’s (VHA) Corporate Data Warehouse (CDW). Cancers were grouped by MSK’s OncoTree codes, and summary counts of Veterans tested, Veterans recommended, Veterans prescribed recommended FDA approved drugs were determined. Percentages were calculated using the total number of Veterans tested as the denominator.

Results

Level 1 OncoKB alterations were infrequent in H&N (0.94%), kidney (0.45%), HCC(0.28%), and pancreatic adenocarcinomas (1%). The frequency of Level 1 alterations in esophageal adenocarcinomas (EAC) was 20%. Approximately 98% of the Level 1 alterations in EAC patients were HER2 positivity or MSI-High status, which can be determined by other diagnostic methodologies such as IHC. The remaining 2% of EAC patients with level 1 alterations had BRAF V600E or NTRK rearrangements.

Conclusions

The incidence of level 1 genetic variants in H&N, kidney, HCC and pancreatic adenocarcinoma is very low and would very uncommonly result in clinical benefit. Although there is an expanding number of precision oncology-based therapies available, the proportion of patients with the aforementioned solid organ malignancies who benefitted from CGP was low, suggesting CGP has minimal impact on the treatment of Veterans with these malignancies.

Purpose

The aim of this study is to quantify the frequency of Memorial Sloan Kettering (MSK) Precision Oncology Knowledge Base (OncoKB) Level 1 genetic alterations in Veterans with various solid organ malignancies and evaluate the clinical benefit and impact of testing on treatment of these patients.

Background

The VA National Precision Oncology Program (NPOP) facilitates comprehensive genomic profiling (CGP) testing of Veterans with advanced cancer. While CGP is increasingly utilized and routinely ordered in patients with advanced solid organ malignancies, the clinical utility and value has not been proven in certain cancers. We present data from 5,979 patients with head and neck (H&N), pancreatic, hepatocellular (HCC), esophageal and kidney cancers who underwent CGP.

Methods

Our cohort consists of Veterans that received CGP testing to identify somatic variants between 1/1/2019 and 4/2/2025. Identified variants and biomarkers were formatted for use with oncoKB-annotator, a publicly available tool to annotate genomic variants with FDA approved drug recommendations stored as Level 1 annotations in OncoKB, and prescribed drugs were extracted from the Veteran Health Administration’s (VHA) Corporate Data Warehouse (CDW). Cancers were grouped by MSK’s OncoTree codes, and summary counts of Veterans tested, Veterans recommended, Veterans prescribed recommended FDA approved drugs were determined. Percentages were calculated using the total number of Veterans tested as the denominator.

Results

Level 1 OncoKB alterations were infrequent in H&N (0.94%), kidney (0.45%), HCC(0.28%), and pancreatic adenocarcinomas (1%). The frequency of Level 1 alterations in esophageal adenocarcinomas (EAC) was 20%. Approximately 98% of the Level 1 alterations in EAC patients were HER2 positivity or MSI-High status, which can be determined by other diagnostic methodologies such as IHC. The remaining 2% of EAC patients with level 1 alterations had BRAF V600E or NTRK rearrangements.

Conclusions

The incidence of level 1 genetic variants in H&N, kidney, HCC and pancreatic adenocarcinoma is very low and would very uncommonly result in clinical benefit. Although there is an expanding number of precision oncology-based therapies available, the proportion of patients with the aforementioned solid organ malignancies who benefitted from CGP was low, suggesting CGP has minimal impact on the treatment of Veterans with these malignancies.

Background

GATA3 is a zinc finger transcription factor most commonly used as an immunohistochemical marker in breast and urothelial carcinomas, though it has also been detected—albeit infrequently—in other malignancies. While GATA3 expression is well established in esophageal squamous cell carcinoma, it is rarely documented in esophageal adenocarcinoma. We present a unique case of widely metastatic, strongly GATA3-positive esophageal adenocarcinoma.

Case Presentation

A 59-year-old male smoker with gastroesophageal reflux disease and a history of alcohol use disorder presented with progressive right hip pain following a fall. Imaging revealed multiple lytic bone lesions and a soft tissue mass near the right acetabulum. PET-CT demonstrated widespread osseous metastases and FDG-avid uptake in the distal esophagus and perigastric lymph nodes. Laboratory findings included a PSA of 14. Biopsy of the right pubic ramus revealed adenocarcinoma positive for GATA3, CK7, CK20 (patchy), CK40, and P63, and negative for PSA. Given the unexpected GATA3 positivity, the differential diagnosis included primary urothelial cancer. However, cystoscopy and urine cytology were unremarkable. EGD revealed Barrett’s esophagus without a discrete mass. Biopsy of the distal esophagus confirmed poorly differentiated adenocarcinoma with underlying dysplasia. Molecular profiling showed HER2-negative, microsatellite stable (MSS) disease with PD-L1 expression of 10%. Due to an ECOG performance status ≥3 and extensive metastatic burden, the patient was not a candidate for systemic therapy and was transitioned to hospice care.

Discussion

A large tissue microarray study of over 16,000 tumors found weak GATA3 expression in only 2.4% of esophageal adenocarcinomas, with strong or diffuse positivity virtually undocumented. In this case, the unusual immunoprofile initially raised concern for a primary urothelial tumor, but endoscopic biopsy confirmed an esophageal origin. Aberrant GATA3 expression in poorly differentiated gastrointestinal tumors may complicate diagnosis and has been associated with worse prognosis. Awareness of such atypical patterns is critical for accurate tumor classification and appropriate management in metastatic disease.

Conclusions

This case highlights a rare presentation of GATA3-positive esophageal adenocarcinoma. Further reporting may improve diagnostic accuracy and inform future therapeutic strategies for this unique subset of tumors.

Background

GATA3 is a zinc finger transcription factor most commonly used as an immunohistochemical marker in breast and urothelial carcinomas, though it has also been detected—albeit infrequently—in other malignancies. While GATA3 expression is well established in esophageal squamous cell carcinoma, it is rarely documented in esophageal adenocarcinoma. We present a unique case of widely metastatic, strongly GATA3-positive esophageal adenocarcinoma.

Case Presentation

A 59-year-old male smoker with gastroesophageal reflux disease and a history of alcohol use disorder presented with progressive right hip pain following a fall. Imaging revealed multiple lytic bone lesions and a soft tissue mass near the right acetabulum. PET-CT demonstrated widespread osseous metastases and FDG-avid uptake in the distal esophagus and perigastric lymph nodes. Laboratory findings included a PSA of 14. Biopsy of the right pubic ramus revealed adenocarcinoma positive for GATA3, CK7, CK20 (patchy), CK40, and P63, and negative for PSA. Given the unexpected GATA3 positivity, the differential diagnosis included primary urothelial cancer. However, cystoscopy and urine cytology were unremarkable. EGD revealed Barrett’s esophagus without a discrete mass. Biopsy of the distal esophagus confirmed poorly differentiated adenocarcinoma with underlying dysplasia. Molecular profiling showed HER2-negative, microsatellite stable (MSS) disease with PD-L1 expression of 10%. Due to an ECOG performance status ≥3 and extensive metastatic burden, the patient was not a candidate for systemic therapy and was transitioned to hospice care.

Discussion

A large tissue microarray study of over 16,000 tumors found weak GATA3 expression in only 2.4% of esophageal adenocarcinomas, with strong or diffuse positivity virtually undocumented. In this case, the unusual immunoprofile initially raised concern for a primary urothelial tumor, but endoscopic biopsy confirmed an esophageal origin. Aberrant GATA3 expression in poorly differentiated gastrointestinal tumors may complicate diagnosis and has been associated with worse prognosis. Awareness of such atypical patterns is critical for accurate tumor classification and appropriate management in metastatic disease.

Conclusions

This case highlights a rare presentation of GATA3-positive esophageal adenocarcinoma. Further reporting may improve diagnostic accuracy and inform future therapeutic strategies for this unique subset of tumors.

Background

GATA3 is a zinc finger transcription factor most commonly used as an immunohistochemical marker in breast and urothelial carcinomas, though it has also been detected—albeit infrequently—in other malignancies. While GATA3 expression is well established in esophageal squamous cell carcinoma, it is rarely documented in esophageal adenocarcinoma. We present a unique case of widely metastatic, strongly GATA3-positive esophageal adenocarcinoma.

Case Presentation

A 59-year-old male smoker with gastroesophageal reflux disease and a history of alcohol use disorder presented with progressive right hip pain following a fall. Imaging revealed multiple lytic bone lesions and a soft tissue mass near the right acetabulum. PET-CT demonstrated widespread osseous metastases and FDG-avid uptake in the distal esophagus and perigastric lymph nodes. Laboratory findings included a PSA of 14. Biopsy of the right pubic ramus revealed adenocarcinoma positive for GATA3, CK7, CK20 (patchy), CK40, and P63, and negative for PSA. Given the unexpected GATA3 positivity, the differential diagnosis included primary urothelial cancer. However, cystoscopy and urine cytology were unremarkable. EGD revealed Barrett’s esophagus without a discrete mass. Biopsy of the distal esophagus confirmed poorly differentiated adenocarcinoma with underlying dysplasia. Molecular profiling showed HER2-negative, microsatellite stable (MSS) disease with PD-L1 expression of 10%. Due to an ECOG performance status ≥3 and extensive metastatic burden, the patient was not a candidate for systemic therapy and was transitioned to hospice care.

Discussion

A large tissue microarray study of over 16,000 tumors found weak GATA3 expression in only 2.4% of esophageal adenocarcinomas, with strong or diffuse positivity virtually undocumented. In this case, the unusual immunoprofile initially raised concern for a primary urothelial tumor, but endoscopic biopsy confirmed an esophageal origin. Aberrant GATA3 expression in poorly differentiated gastrointestinal tumors may complicate diagnosis and has been associated with worse prognosis. Awareness of such atypical patterns is critical for accurate tumor classification and appropriate management in metastatic disease.

Conclusions

This case highlights a rare presentation of GATA3-positive esophageal adenocarcinoma. Further reporting may improve diagnostic accuracy and inform future therapeutic strategies for this unique subset of tumors.

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TOPLINE:

Adjuvant therapy with camrelizumab significantly improved 3-year event-free survival in patients with locoregionally advanced nasopharyngeal carcinoma compared with observation, according to findings from the phase 3 DIPPER trial.

METHODOLOGY:

• About 20%-30% of patients with locoregionally advanced nasopharyngeal carcinoma experience disease relapse after definitive chemoradiotherapy. Camrelizumab plus chemotherapy can improve progression-free survival in patients with recurrent or metastatic nasopharyngeal carcinoma, but its effectiveness as adjuvant therapy in locoregionally advanced disease remains unclear.
• Researchers conducted the randomized phase 3 DIPPER trial at 11 centers in China, enrolling 450 patients with T4N1M0 or T1-4N2-3M0 nasopharyngeal carcinoma who had completed induction-concurrent chemoradiotherapy.
• Participants were randomly assigned to receive either adjuvant camrelizumab (200 mg intravenously every 3 weeks for 12 cycles; n = 226) or observation (n = 224). The median follow-up duration was 39 months.
• The primary endpoint was event-free survival, defined as freedom from distant metastasis, locoregional relapse, or death due to any cause; secondary endpoints included distant metastasis–free survival, locoregional relapse–free survival, overall survival, and safety.

TAKEAWAY:

• Patients who received camrelizumab had a higher 3-year event-free survival rate than those who underwent observation (86.9% vs 77.3%; stratified hazard ratio [HR], 0.56; P = .01).
• The 3-year distant metastasis–free survival was also higher in the camrelizumab group (92.4% vs 84.5%; stratified HR, 0.54; P = .04).
• Patients in the camrelizumab group had higher locoregional relapse–free survival at 3 years than those in the observation group (92.8% vs 87.0%; stratified HR, 0.53; P = .046). However, the difference in overall survival between the groups was not significant.
• The safety analysis included 426 patients; 97.1% of those who received camrelizumab experienced at least one adverse event of any grade, the most common being reactive capillary endothelial proliferation compared with 85.5% of those in the observation group. Further, 11.2% of patients taking camrelizumab reported grade 3 or 4 events, including leukopenia and neutropenia compared with 3% in the observation group.

IN PRACTICE:

“The DIPPER trial demonstrated that adjuvant camrelizumab following induction-concurrent chemoradiotherapy significantly improved event-free survival by 9.6% with a favorable safety profile in patients with locoregionally advanced [nasopharyngeal carcinoma],” the authors wrote.

“If survival is eventually proven to be improved with induction chemoimmunotherapy, can we begin asking about de-escalation of chemoradiotherapy” for patients with nasopharyngeal carcinoma? “This question is exceptionally important, given the significant long-term consequences of radiotherapy on survivors,” the author of an accompanying editorial wrote.

SOURCE:

The study was led by Ye-Lin Liang, MD, Sun Yat-sen University Cancer Center in Guangzhou, China, and was published online in JAMA.

LIMITATIONS:

The study included patients from an endemic region where nasopharyngeal carcinoma is predominantly linked to Epstein-Barr virus infection, potentially affecting the generalizability of the findings to nonendemic populations. The open-label design may have introduced bias. Additionally, combined positive scores for programmed cell death ligand 1 (PD-L1) were unavailable for some patients, potentially affecting the analysis of the correlation between PD-L1 expression and clinical outcomes.

DISCLOSURES:

The study was supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project, National Natural Science Foundation of China, Guangzhou Municipal Health Commission, Key Area Research and Development Program of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. The authors reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Adjuvant therapy with camrelizumab significantly improved 3-year event-free survival in patients with locoregionally advanced nasopharyngeal carcinoma compared with observation, according to findings from the phase 3 DIPPER trial.

METHODOLOGY:

• About 20%-30% of patients with locoregionally advanced nasopharyngeal carcinoma experience disease relapse after definitive chemoradiotherapy. Camrelizumab plus chemotherapy can improve progression-free survival in patients with recurrent or metastatic nasopharyngeal carcinoma, but its effectiveness as adjuvant therapy in locoregionally advanced disease remains unclear.
• Researchers conducted the randomized phase 3 DIPPER trial at 11 centers in China, enrolling 450 patients with T4N1M0 or T1-4N2-3M0 nasopharyngeal carcinoma who had completed induction-concurrent chemoradiotherapy.
• Participants were randomly assigned to receive either adjuvant camrelizumab (200 mg intravenously every 3 weeks for 12 cycles; n = 226) or observation (n = 224). The median follow-up duration was 39 months.
• The primary endpoint was event-free survival, defined as freedom from distant metastasis, locoregional relapse, or death due to any cause; secondary endpoints included distant metastasis–free survival, locoregional relapse–free survival, overall survival, and safety.

TAKEAWAY:

• Patients who received camrelizumab had a higher 3-year event-free survival rate than those who underwent observation (86.9% vs 77.3%; stratified hazard ratio [HR], 0.56; P = .01).
• The 3-year distant metastasis–free survival was also higher in the camrelizumab group (92.4% vs 84.5%; stratified HR, 0.54; P = .04).
• Patients in the camrelizumab group had higher locoregional relapse–free survival at 3 years than those in the observation group (92.8% vs 87.0%; stratified HR, 0.53; P = .046). However, the difference in overall survival between the groups was not significant.
• The safety analysis included 426 patients; 97.1% of those who received camrelizumab experienced at least one adverse event of any grade, the most common being reactive capillary endothelial proliferation compared with 85.5% of those in the observation group. Further, 11.2% of patients taking camrelizumab reported grade 3 or 4 events, including leukopenia and neutropenia compared with 3% in the observation group.

IN PRACTICE:

“The DIPPER trial demonstrated that adjuvant camrelizumab following induction-concurrent chemoradiotherapy significantly improved event-free survival by 9.6% with a favorable safety profile in patients with locoregionally advanced [nasopharyngeal carcinoma],” the authors wrote.

“If survival is eventually proven to be improved with induction chemoimmunotherapy, can we begin asking about de-escalation of chemoradiotherapy” for patients with nasopharyngeal carcinoma? “This question is exceptionally important, given the significant long-term consequences of radiotherapy on survivors,” the author of an accompanying editorial wrote.

SOURCE:

The study was led by Ye-Lin Liang, MD, Sun Yat-sen University Cancer Center in Guangzhou, China, and was published online in JAMA.

LIMITATIONS:

The study included patients from an endemic region where nasopharyngeal carcinoma is predominantly linked to Epstein-Barr virus infection, potentially affecting the generalizability of the findings to nonendemic populations. The open-label design may have introduced bias. Additionally, combined positive scores for programmed cell death ligand 1 (PD-L1) were unavailable for some patients, potentially affecting the analysis of the correlation between PD-L1 expression and clinical outcomes.

DISCLOSURES:

The study was supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project, National Natural Science Foundation of China, Guangzhou Municipal Health Commission, Key Area Research and Development Program of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. The authors reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Adjuvant therapy with camrelizumab significantly improved 3-year event-free survival in patients with locoregionally advanced nasopharyngeal carcinoma compared with observation, according to findings from the phase 3 DIPPER trial.

METHODOLOGY:

• About 20%-30% of patients with locoregionally advanced nasopharyngeal carcinoma experience disease relapse after definitive chemoradiotherapy. Camrelizumab plus chemotherapy can improve progression-free survival in patients with recurrent or metastatic nasopharyngeal carcinoma, but its effectiveness as adjuvant therapy in locoregionally advanced disease remains unclear.
• Researchers conducted the randomized phase 3 DIPPER trial at 11 centers in China, enrolling 450 patients with T4N1M0 or T1-4N2-3M0 nasopharyngeal carcinoma who had completed induction-concurrent chemoradiotherapy.
• Participants were randomly assigned to receive either adjuvant camrelizumab (200 mg intravenously every 3 weeks for 12 cycles; n = 226) or observation (n = 224). The median follow-up duration was 39 months.
• The primary endpoint was event-free survival, defined as freedom from distant metastasis, locoregional relapse, or death due to any cause; secondary endpoints included distant metastasis–free survival, locoregional relapse–free survival, overall survival, and safety.

TAKEAWAY:

• Patients who received camrelizumab had a higher 3-year event-free survival rate than those who underwent observation (86.9% vs 77.3%; stratified hazard ratio [HR], 0.56; P = .01).
• The 3-year distant metastasis–free survival was also higher in the camrelizumab group (92.4% vs 84.5%; stratified HR, 0.54; P = .04).
• Patients in the camrelizumab group had higher locoregional relapse–free survival at 3 years than those in the observation group (92.8% vs 87.0%; stratified HR, 0.53; P = .046). However, the difference in overall survival between the groups was not significant.
• The safety analysis included 426 patients; 97.1% of those who received camrelizumab experienced at least one adverse event of any grade, the most common being reactive capillary endothelial proliferation compared with 85.5% of those in the observation group. Further, 11.2% of patients taking camrelizumab reported grade 3 or 4 events, including leukopenia and neutropenia compared with 3% in the observation group.

IN PRACTICE:

“The DIPPER trial demonstrated that adjuvant camrelizumab following induction-concurrent chemoradiotherapy significantly improved event-free survival by 9.6% with a favorable safety profile in patients with locoregionally advanced [nasopharyngeal carcinoma],” the authors wrote.

“If survival is eventually proven to be improved with induction chemoimmunotherapy, can we begin asking about de-escalation of chemoradiotherapy” for patients with nasopharyngeal carcinoma? “This question is exceptionally important, given the significant long-term consequences of radiotherapy on survivors,” the author of an accompanying editorial wrote.

SOURCE:

The study was led by Ye-Lin Liang, MD, Sun Yat-sen University Cancer Center in Guangzhou, China, and was published online in JAMA.

LIMITATIONS:

The study included patients from an endemic region where nasopharyngeal carcinoma is predominantly linked to Epstein-Barr virus infection, potentially affecting the generalizability of the findings to nonendemic populations. The open-label design may have introduced bias. Additionally, combined positive scores for programmed cell death ligand 1 (PD-L1) were unavailable for some patients, potentially affecting the analysis of the correlation between PD-L1 expression and clinical outcomes.

DISCLOSURES:

The study was supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project, National Natural Science Foundation of China, Guangzhou Municipal Health Commission, Key Area Research and Development Program of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. The authors reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Adding cetuximab (C) to postoperative radiotherapy (RT) improves disease-free survival (DFS) but not overall survival (OS) in intermediate-risk squamous cell carcinoma of the head and neck. Benefits were specifically observed in human papillomavirus–negative patients, who represented 80.2% of the study participants.

METHODOLOGY:

• Previous research showed that adding high-dose cisplatin to postoperative RT in patients with squamous cell carcinoma of the head and neck (SCCHN) improved outcomes in those with positive margins and nodal extracapsular extension of the tumor.
• The new phase 3 randomized trial, which enrolled patients from November 2009 to March 2018 included 577 individuals with resected SCCHN of the oral cavity, oropharynx, or larynx, specifically.
• Participants were randomly assigned 1:1 to receive either intensity-modulated RT (60-66 Gy) with weekly C (400 mg/m² loading dose, followed by 250 mg/m² weekly) or RT alone.
• The primary endpoint was OS in randomly assigned eligible patients, with DFS and toxicity as secondary endpoints.
• Analysis included stratified log-rank test for OS and DFS, while toxicity was compared using Fisher’s exact test.

TAKEAWAY:

• OS was not significantly improved with RT plus C vs RT alone (hazard ratio [HR], 0.81; 95% CI, 0.60-1.08; P = .0747), though 5-year OS rates were 76.5% vs 68.7%.
• DFS showed significant improvement with combined therapy (HR, 0.75; 95% CI, 0.57-0.98; P = .0168), with 5-year rates of 71.7% vs 63.6%.
• Grade 3-4 acute toxicity rates were significantly higher with combination therapy (70.3% vs 39.7%; P < .0001), primarily affecting skin and mucosa, though late toxicity rates were similar (33.2% vs 29.0%; P = .3101).
• The benefit of RT plus C was only observed in those patients who were human papillomavirus–negative, which comprised 80.2% of trial participants.

IN PRACTICE:

RT plus C “significantly improved DFS, but not OS, with no increase in long-term toxicity, compared with RT alone for resected, intermediate-risk SCCHN. RT plus C is an appropriate option for carefully selected patients with HPV-negative disease,” the authors of the study wrote.

SOURCE:

This study was led by Mitchell Machtay, MD, Penn State Health Milton S. Hershey Medical Center in Hershey, Pennsylvania. It was published online  in Journal of Clinical Oncology.

LIMITATIONS:

According to the researchers, the OS in the control group was higher than predicted, resulting in the trial being underpowered to detect the initial targeted HR. The authors noted that the better-than-expected survival rates could be attributed to improvements in surgical and radiotherapeutic techniques, including mandatory intensity-modulated RT for all patients. Additionally, the researchers pointed out that patient selection may have influenced outcomes, as only 30% of study participants had more than two risk factors.

DISCLOSURES:

This study was supported by grants from the US National Cancer Institute and Eli Lilly Inc. Machtay received grants from Lilly/ImClone, AstraZeneca, and Merck Sharp & Dohme. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Adding cetuximab (C) to postoperative radiotherapy (RT) improves disease-free survival (DFS) but not overall survival (OS) in intermediate-risk squamous cell carcinoma of the head and neck. Benefits were specifically observed in human papillomavirus–negative patients, who represented 80.2% of the study participants.

METHODOLOGY:

• Previous research showed that adding high-dose cisplatin to postoperative RT in patients with squamous cell carcinoma of the head and neck (SCCHN) improved outcomes in those with positive margins and nodal extracapsular extension of the tumor.
• The new phase 3 randomized trial, which enrolled patients from November 2009 to March 2018 included 577 individuals with resected SCCHN of the oral cavity, oropharynx, or larynx, specifically.
• Participants were randomly assigned 1:1 to receive either intensity-modulated RT (60-66 Gy) with weekly C (400 mg/m² loading dose, followed by 250 mg/m² weekly) or RT alone.
• The primary endpoint was OS in randomly assigned eligible patients, with DFS and toxicity as secondary endpoints.
• Analysis included stratified log-rank test for OS and DFS, while toxicity was compared using Fisher’s exact test.

TAKEAWAY:

• OS was not significantly improved with RT plus C vs RT alone (hazard ratio [HR], 0.81; 95% CI, 0.60-1.08; P = .0747), though 5-year OS rates were 76.5% vs 68.7%.
• DFS showed significant improvement with combined therapy (HR, 0.75; 95% CI, 0.57-0.98; P = .0168), with 5-year rates of 71.7% vs 63.6%.
• Grade 3-4 acute toxicity rates were significantly higher with combination therapy (70.3% vs 39.7%; P < .0001), primarily affecting skin and mucosa, though late toxicity rates were similar (33.2% vs 29.0%; P = .3101).
• The benefit of RT plus C was only observed in those patients who were human papillomavirus–negative, which comprised 80.2% of trial participants.

IN PRACTICE:

RT plus C “significantly improved DFS, but not OS, with no increase in long-term toxicity, compared with RT alone for resected, intermediate-risk SCCHN. RT plus C is an appropriate option for carefully selected patients with HPV-negative disease,” the authors of the study wrote.

SOURCE:

This study was led by Mitchell Machtay, MD, Penn State Health Milton S. Hershey Medical Center in Hershey, Pennsylvania. It was published online  in Journal of Clinical Oncology.

LIMITATIONS:

According to the researchers, the OS in the control group was higher than predicted, resulting in the trial being underpowered to detect the initial targeted HR. The authors noted that the better-than-expected survival rates could be attributed to improvements in surgical and radiotherapeutic techniques, including mandatory intensity-modulated RT for all patients. Additionally, the researchers pointed out that patient selection may have influenced outcomes, as only 30% of study participants had more than two risk factors.

DISCLOSURES:

This study was supported by grants from the US National Cancer Institute and Eli Lilly Inc. Machtay received grants from Lilly/ImClone, AstraZeneca, and Merck Sharp & Dohme. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Adding cetuximab (C) to postoperative radiotherapy (RT) improves disease-free survival (DFS) but not overall survival (OS) in intermediate-risk squamous cell carcinoma of the head and neck. Benefits were specifically observed in human papillomavirus–negative patients, who represented 80.2% of the study participants.

METHODOLOGY:

• Previous research showed that adding high-dose cisplatin to postoperative RT in patients with squamous cell carcinoma of the head and neck (SCCHN) improved outcomes in those with positive margins and nodal extracapsular extension of the tumor.
• The new phase 3 randomized trial, which enrolled patients from November 2009 to March 2018 included 577 individuals with resected SCCHN of the oral cavity, oropharynx, or larynx, specifically.
• Participants were randomly assigned 1:1 to receive either intensity-modulated RT (60-66 Gy) with weekly C (400 mg/m² loading dose, followed by 250 mg/m² weekly) or RT alone.
• The primary endpoint was OS in randomly assigned eligible patients, with DFS and toxicity as secondary endpoints.
• Analysis included stratified log-rank test for OS and DFS, while toxicity was compared using Fisher’s exact test.

TAKEAWAY:

• OS was not significantly improved with RT plus C vs RT alone (hazard ratio [HR], 0.81; 95% CI, 0.60-1.08; P = .0747), though 5-year OS rates were 76.5% vs 68.7%.
• DFS showed significant improvement with combined therapy (HR, 0.75; 95% CI, 0.57-0.98; P = .0168), with 5-year rates of 71.7% vs 63.6%.
• Grade 3-4 acute toxicity rates were significantly higher with combination therapy (70.3% vs 39.7%; P < .0001), primarily affecting skin and mucosa, though late toxicity rates were similar (33.2% vs 29.0%; P = .3101).
• The benefit of RT plus C was only observed in those patients who were human papillomavirus–negative, which comprised 80.2% of trial participants.

IN PRACTICE:

RT plus C “significantly improved DFS, but not OS, with no increase in long-term toxicity, compared with RT alone for resected, intermediate-risk SCCHN. RT plus C is an appropriate option for carefully selected patients with HPV-negative disease,” the authors of the study wrote.

SOURCE:

This study was led by Mitchell Machtay, MD, Penn State Health Milton S. Hershey Medical Center in Hershey, Pennsylvania. It was published online  in Journal of Clinical Oncology.

LIMITATIONS:

According to the researchers, the OS in the control group was higher than predicted, resulting in the trial being underpowered to detect the initial targeted HR. The authors noted that the better-than-expected survival rates could be attributed to improvements in surgical and radiotherapeutic techniques, including mandatory intensity-modulated RT for all patients. Additionally, the researchers pointed out that patient selection may have influenced outcomes, as only 30% of study participants had more than two risk factors.

DISCLOSURES:

This study was supported by grants from the US National Cancer Institute and Eli Lilly Inc. Machtay received grants from Lilly/ImClone, AstraZeneca, and Merck Sharp & Dohme. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

New research, with the caveat of a relatively short follow-up, adds to encouraging data showing an overall low risk of the development of thyroid cancer associated with glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment.

However, a notably increased rate of thyroid cancer detections limited only to the first year after drug initiation — but not later, coupled with an increased rate of thyroid cancer screening during that period, raises the suggestion that a thyroid cancer concern among the millions of patients taking the immensely popular drugs could exacerbate the already problematic over-detection of incidental thyroid cancers.

“Our study confirms the increased likelihood of being diagnosed with what appears to be low-risk thyroid cancer after treatment with GLP-1 RAs — but not because patients treated with GLP-1 RAs are more likely to develop thyroid cancer but rather because they are more likely to be diagnosed with it because we, as clinicians, are more likely to look for it,” senior author Rozalina G. McCoy, MD, associate professor and associate division chief for clinical research in the Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine at the University of Maryland School of Medicine, in Baltimore, told this news organization.

The findings were published in JAMA Otolaryngology-Head & Neck Surgery.

Thyroid cancer concerns surrounding GLP-1 RAs stem from preclinical studies showing a risk for medullary thyroid cancer in rodents, resulting in a boxed warning from the US Food and Drug Administration recommending that those with a family history of the condition avoid the drugs.

More recent studies showing GLP-1 receptors in human papillary thyroid cancer cells has further raised concerns of a risk beyond medullary thyroid cancer, however, recent studies evaluating the risk have been inconclusive.

To further investigate, McCoy and colleagues evaluated claims data on 351,913 adult enrollees in Medicare Advantage and fee-for-service plans in the United States who had type 2 diabetes, a moderate risk for cardiovascular disease, and no history of thyroid cancer.

Of the patients, who were about half women, 41,112 started treatments with GLP-1 RAs; 76,093, started with dipeptidyl peptidase-4 (DPP-4) inhibitors; 43,499, with sodium-glucose cotransporter 2 (SGLT2i) inhibitors; and 191,209 with sulfonylurea therapy between January 2014 and December 2021.

After inverse probability weighting, baseline characteristics in the drug groups were well-balanced.

Overall, with median follow-up times of 660 days (range, 254-1157 days) in the GLP-1 RA group; approximately 4 years in the sulfonylurea and DPP-4 inhibitor groups; and about 2.5 years in the SGLT2 inhibitor group, the absolute risk for thyroid cancer diagnoses in the treatment groups were low, with a rate of 0.17% in the GLP-1 RA group, 0.23% in the DPP-4 inhibitor group, 0.17% in the SGLT2 inhibitor group, and 0.20% in the sulfonylurea group.

The modified intention to treat analysis concluded no increase with GLP-1 RA use in thyroid cancer risk compared with the other three diabetes drugs (hazard ratio [HR], 1.24).

 

Higher Cancers Detected in First Year Likely From Higher Screening

Importantly, the risk for thyroid cancer was significantly higher within the first year after GLP-1 RA initiation (HR, 1.85) and was also higher among patients who stayed on the medication and didn’t add other medication (HR, 2.07).

With the latency period for the development of thyroid cancer from external exposures taking several years (such as radiation, taking approximately 2.5 years), some studies in fact exclude patients diagnosed with cancers within a year of starting GLP-1s, as it is implausible for a cancer to develop so soon.

Cancers detected that early therefore are considered to likely have been found due to stepped up screening resulting from an increased concern of thyroid cancer with GLP-1 use.

In support of that theory, the study showed that those in the GLP-1 group had a significantly higher rate of receiving thyroid ultrasounds than those in the non−GLP-1 group, at 1.2% at 6 months for GLP-1RA initiators vs 0.8% for non−GLP-1 RA initiators, and an estimated 2.1% at 12 months for GLP-1RA initiators vs 1.5% for non−GLP-1RA initiators (P < .01).

Though the percentages were small, in relative terms, the 6-month rate of screening in the GLP-1 RA group is a 50% increase, and the 12-month rate represents a 40% increase, McCoy pointed out. 

“If we think about 1.2% of people getting an ultrasound in the context of over 41,000 patients, that is a lot of ultrasounds,” she said. 

“To my knowledge, this is the first study to actually look at rates of thyroid ultrasounds with GLP-1 RA initiation, so it will definitely be important to look at the trends more broadly,” McCoy added.

McCoy noted that a key caveat of the study is the relatively short follow-up of only about 2 years.

“We have not been able to follow patients for decades to know if there is risk of new thyroid cancers developing after prolonged exposure,” she said. “But we generally don’t know this for any medication until it is used by many millions of people for many decades.”

 

Consistent Findings in Recent Research

In another recent study evaluating the risk for thyroid cancer among patients receiving GLP-1s, with a longer follow-up of 3.9 years, Bjorn Pasternak, MD, PhD, of the Division of Clinical Epidemiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden, and colleagues reported similar findings — the overall risk for thyroid cancer with GLP-1s was not increased (HR, 0.93), and the risk beginning 1 year after treatment initiation was lower, at 0.83. 

However, the risk in that study only looking at the first year alone was again higher, at HR 1.47.

“Our analyses indicating a nominally increased risk restricted to the first year after starting treatment might be consistent with an increased detection of thyroid cancer among patients using GLP-1 RAs,” he told this news organization.

In addition to the short follow-up of the current study, Pasternak noted the caveat of the study’s inclusion mainly of patients who initiated the four diabetes drug groups, which is a limitation “because a high proportion of the patients with type 2 diabetes in routine care who start GLP-1 RAs have started it as their third, fourth, or even fifth diabetes drug, especially if they have had diabetes for some time.”

“To capture a larger proportion of the full population of GLP-1 RA users, it would have been preferable to create three different cohorts for the purpose of this study and investigate them separately, including GLP-1 vs DPP4i; GLP-1 vs SGLT2i; GLP-1 vs sulfonylurea,” he said.

 

Rise in Incidental Thyroid Cancer Detection, An Ongoing Concern

The advent of more advanced imaging and thyroid cancer testing in recent years has already led to a significant problem of over-detection and sometimes over-treatment of incidental, small thyroid cancers that will likely remain harmless in the majority of patients. 

With approximately 64 million prescriptions of GLP-1 RAs dispensed between 2000 and 2015 and the percentage increasing at a rate of about 10%-30% per year, increased thyroid testing among those patients could indeed add to the problem.

Meanwhile, thyroid testing is currently not recommended for patients on GLP-1s who do not have a thyroid cancer risk, and the results from the current and Pasternak’s studies, as well as several other recent studies, appear to support those recommendations.

“Collectively, these reassuring data could potentially help reduce [thyroid cancer] over-detection and screening,” Pasternak said. 

McCoy echoed that the evidence indicates that “for the vast majority of people there is no indication that GLP-1 RA causes thyroid cancer.”

She underscored that overdiagnosis can have important implications, sharing her own personal experience on the receiving end of a cancer diagnosis.

“Overdiagnosis of these low-risk thyroid cancers may ultimately lead to more harm for the patient than not making the diagnosis, since surgery for thyroid cancer carries real risks (including of death) and there are downstream consequences to having your thyroid removed and relying on lifelong hormone replacement,” McCoy said.

“As a cancer survivor myself, though of lymphoma, not thyroid cancer, I also know the profound impact that a cancer diagnosis has on the individual and their loved ones,” McCoy said.

“It is not something I would wish for anyone, which is why I always speak to my patients about searching for something we may not want to — or need to — find.”

The authors and Pasternak had no disclosures to report.

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

New research, with the caveat of a relatively short follow-up, adds to encouraging data showing an overall low risk of the development of thyroid cancer associated with glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment.

However, a notably increased rate of thyroid cancer detections limited only to the first year after drug initiation — but not later, coupled with an increased rate of thyroid cancer screening during that period, raises the suggestion that a thyroid cancer concern among the millions of patients taking the immensely popular drugs could exacerbate the already problematic over-detection of incidental thyroid cancers.

“Our study confirms the increased likelihood of being diagnosed with what appears to be low-risk thyroid cancer after treatment with GLP-1 RAs — but not because patients treated with GLP-1 RAs are more likely to develop thyroid cancer but rather because they are more likely to be diagnosed with it because we, as clinicians, are more likely to look for it,” senior author Rozalina G. McCoy, MD, associate professor and associate division chief for clinical research in the Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine at the University of Maryland School of Medicine, in Baltimore, told this news organization.

The findings were published in JAMA Otolaryngology-Head & Neck Surgery.

Thyroid cancer concerns surrounding GLP-1 RAs stem from preclinical studies showing a risk for medullary thyroid cancer in rodents, resulting in a boxed warning from the US Food and Drug Administration recommending that those with a family history of the condition avoid the drugs.

More recent studies showing GLP-1 receptors in human papillary thyroid cancer cells has further raised concerns of a risk beyond medullary thyroid cancer, however, recent studies evaluating the risk have been inconclusive.

To further investigate, McCoy and colleagues evaluated claims data on 351,913 adult enrollees in Medicare Advantage and fee-for-service plans in the United States who had type 2 diabetes, a moderate risk for cardiovascular disease, and no history of thyroid cancer.

Of the patients, who were about half women, 41,112 started treatments with GLP-1 RAs; 76,093, started with dipeptidyl peptidase-4 (DPP-4) inhibitors; 43,499, with sodium-glucose cotransporter 2 (SGLT2i) inhibitors; and 191,209 with sulfonylurea therapy between January 2014 and December 2021.

After inverse probability weighting, baseline characteristics in the drug groups were well-balanced.

Overall, with median follow-up times of 660 days (range, 254-1157 days) in the GLP-1 RA group; approximately 4 years in the sulfonylurea and DPP-4 inhibitor groups; and about 2.5 years in the SGLT2 inhibitor group, the absolute risk for thyroid cancer diagnoses in the treatment groups were low, with a rate of 0.17% in the GLP-1 RA group, 0.23% in the DPP-4 inhibitor group, 0.17% in the SGLT2 inhibitor group, and 0.20% in the sulfonylurea group.

The modified intention to treat analysis concluded no increase with GLP-1 RA use in thyroid cancer risk compared with the other three diabetes drugs (hazard ratio [HR], 1.24).

 

Higher Cancers Detected in First Year Likely From Higher Screening

Importantly, the risk for thyroid cancer was significantly higher within the first year after GLP-1 RA initiation (HR, 1.85) and was also higher among patients who stayed on the medication and didn’t add other medication (HR, 2.07).

With the latency period for the development of thyroid cancer from external exposures taking several years (such as radiation, taking approximately 2.5 years), some studies in fact exclude patients diagnosed with cancers within a year of starting GLP-1s, as it is implausible for a cancer to develop so soon.

Cancers detected that early therefore are considered to likely have been found due to stepped up screening resulting from an increased concern of thyroid cancer with GLP-1 use.

In support of that theory, the study showed that those in the GLP-1 group had a significantly higher rate of receiving thyroid ultrasounds than those in the non−GLP-1 group, at 1.2% at 6 months for GLP-1RA initiators vs 0.8% for non−GLP-1 RA initiators, and an estimated 2.1% at 12 months for GLP-1RA initiators vs 1.5% for non−GLP-1RA initiators (P < .01).

Though the percentages were small, in relative terms, the 6-month rate of screening in the GLP-1 RA group is a 50% increase, and the 12-month rate represents a 40% increase, McCoy pointed out. 

“If we think about 1.2% of people getting an ultrasound in the context of over 41,000 patients, that is a lot of ultrasounds,” she said. 

“To my knowledge, this is the first study to actually look at rates of thyroid ultrasounds with GLP-1 RA initiation, so it will definitely be important to look at the trends more broadly,” McCoy added.

McCoy noted that a key caveat of the study is the relatively short follow-up of only about 2 years.

“We have not been able to follow patients for decades to know if there is risk of new thyroid cancers developing after prolonged exposure,” she said. “But we generally don’t know this for any medication until it is used by many millions of people for many decades.”

 

Consistent Findings in Recent Research

In another recent study evaluating the risk for thyroid cancer among patients receiving GLP-1s, with a longer follow-up of 3.9 years, Bjorn Pasternak, MD, PhD, of the Division of Clinical Epidemiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden, and colleagues reported similar findings — the overall risk for thyroid cancer with GLP-1s was not increased (HR, 0.93), and the risk beginning 1 year after treatment initiation was lower, at 0.83. 

However, the risk in that study only looking at the first year alone was again higher, at HR 1.47.

“Our analyses indicating a nominally increased risk restricted to the first year after starting treatment might be consistent with an increased detection of thyroid cancer among patients using GLP-1 RAs,” he told this news organization.

In addition to the short follow-up of the current study, Pasternak noted the caveat of the study’s inclusion mainly of patients who initiated the four diabetes drug groups, which is a limitation “because a high proportion of the patients with type 2 diabetes in routine care who start GLP-1 RAs have started it as their third, fourth, or even fifth diabetes drug, especially if they have had diabetes for some time.”

“To capture a larger proportion of the full population of GLP-1 RA users, it would have been preferable to create three different cohorts for the purpose of this study and investigate them separately, including GLP-1 vs DPP4i; GLP-1 vs SGLT2i; GLP-1 vs sulfonylurea,” he said.

 

Rise in Incidental Thyroid Cancer Detection, An Ongoing Concern

The advent of more advanced imaging and thyroid cancer testing in recent years has already led to a significant problem of over-detection and sometimes over-treatment of incidental, small thyroid cancers that will likely remain harmless in the majority of patients. 

With approximately 64 million prescriptions of GLP-1 RAs dispensed between 2000 and 2015 and the percentage increasing at a rate of about 10%-30% per year, increased thyroid testing among those patients could indeed add to the problem.

Meanwhile, thyroid testing is currently not recommended for patients on GLP-1s who do not have a thyroid cancer risk, and the results from the current and Pasternak’s studies, as well as several other recent studies, appear to support those recommendations.

“Collectively, these reassuring data could potentially help reduce [thyroid cancer] over-detection and screening,” Pasternak said. 

McCoy echoed that the evidence indicates that “for the vast majority of people there is no indication that GLP-1 RA causes thyroid cancer.”

She underscored that overdiagnosis can have important implications, sharing her own personal experience on the receiving end of a cancer diagnosis.

“Overdiagnosis of these low-risk thyroid cancers may ultimately lead to more harm for the patient than not making the diagnosis, since surgery for thyroid cancer carries real risks (including of death) and there are downstream consequences to having your thyroid removed and relying on lifelong hormone replacement,” McCoy said.

“As a cancer survivor myself, though of lymphoma, not thyroid cancer, I also know the profound impact that a cancer diagnosis has on the individual and their loved ones,” McCoy said.

“It is not something I would wish for anyone, which is why I always speak to my patients about searching for something we may not want to — or need to — find.”

The authors and Pasternak had no disclosures to report.

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

New research, with the caveat of a relatively short follow-up, adds to encouraging data showing an overall low risk of the development of thyroid cancer associated with glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment.

However, a notably increased rate of thyroid cancer detections limited only to the first year after drug initiation — but not later, coupled with an increased rate of thyroid cancer screening during that period, raises the suggestion that a thyroid cancer concern among the millions of patients taking the immensely popular drugs could exacerbate the already problematic over-detection of incidental thyroid cancers.

“Our study confirms the increased likelihood of being diagnosed with what appears to be low-risk thyroid cancer after treatment with GLP-1 RAs — but not because patients treated with GLP-1 RAs are more likely to develop thyroid cancer but rather because they are more likely to be diagnosed with it because we, as clinicians, are more likely to look for it,” senior author Rozalina G. McCoy, MD, associate professor and associate division chief for clinical research in the Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine at the University of Maryland School of Medicine, in Baltimore, told this news organization.

The findings were published in JAMA Otolaryngology-Head & Neck Surgery.

Thyroid cancer concerns surrounding GLP-1 RAs stem from preclinical studies showing a risk for medullary thyroid cancer in rodents, resulting in a boxed warning from the US Food and Drug Administration recommending that those with a family history of the condition avoid the drugs.

More recent studies showing GLP-1 receptors in human papillary thyroid cancer cells has further raised concerns of a risk beyond medullary thyroid cancer, however, recent studies evaluating the risk have been inconclusive.

To further investigate, McCoy and colleagues evaluated claims data on 351,913 adult enrollees in Medicare Advantage and fee-for-service plans in the United States who had type 2 diabetes, a moderate risk for cardiovascular disease, and no history of thyroid cancer.

Of the patients, who were about half women, 41,112 started treatments with GLP-1 RAs; 76,093, started with dipeptidyl peptidase-4 (DPP-4) inhibitors; 43,499, with sodium-glucose cotransporter 2 (SGLT2i) inhibitors; and 191,209 with sulfonylurea therapy between January 2014 and December 2021.

After inverse probability weighting, baseline characteristics in the drug groups were well-balanced.

Overall, with median follow-up times of 660 days (range, 254-1157 days) in the GLP-1 RA group; approximately 4 years in the sulfonylurea and DPP-4 inhibitor groups; and about 2.5 years in the SGLT2 inhibitor group, the absolute risk for thyroid cancer diagnoses in the treatment groups were low, with a rate of 0.17% in the GLP-1 RA group, 0.23% in the DPP-4 inhibitor group, 0.17% in the SGLT2 inhibitor group, and 0.20% in the sulfonylurea group.

The modified intention to treat analysis concluded no increase with GLP-1 RA use in thyroid cancer risk compared with the other three diabetes drugs (hazard ratio [HR], 1.24).

 

Higher Cancers Detected in First Year Likely From Higher Screening

Importantly, the risk for thyroid cancer was significantly higher within the first year after GLP-1 RA initiation (HR, 1.85) and was also higher among patients who stayed on the medication and didn’t add other medication (HR, 2.07).

With the latency period for the development of thyroid cancer from external exposures taking several years (such as radiation, taking approximately 2.5 years), some studies in fact exclude patients diagnosed with cancers within a year of starting GLP-1s, as it is implausible for a cancer to develop so soon.

Cancers detected that early therefore are considered to likely have been found due to stepped up screening resulting from an increased concern of thyroid cancer with GLP-1 use.

In support of that theory, the study showed that those in the GLP-1 group had a significantly higher rate of receiving thyroid ultrasounds than those in the non−GLP-1 group, at 1.2% at 6 months for GLP-1RA initiators vs 0.8% for non−GLP-1 RA initiators, and an estimated 2.1% at 12 months for GLP-1RA initiators vs 1.5% for non−GLP-1RA initiators (P < .01).

Though the percentages were small, in relative terms, the 6-month rate of screening in the GLP-1 RA group is a 50% increase, and the 12-month rate represents a 40% increase, McCoy pointed out. 

“If we think about 1.2% of people getting an ultrasound in the context of over 41,000 patients, that is a lot of ultrasounds,” she said. 

“To my knowledge, this is the first study to actually look at rates of thyroid ultrasounds with GLP-1 RA initiation, so it will definitely be important to look at the trends more broadly,” McCoy added.

McCoy noted that a key caveat of the study is the relatively short follow-up of only about 2 years.

“We have not been able to follow patients for decades to know if there is risk of new thyroid cancers developing after prolonged exposure,” she said. “But we generally don’t know this for any medication until it is used by many millions of people for many decades.”

 

Consistent Findings in Recent Research

In another recent study evaluating the risk for thyroid cancer among patients receiving GLP-1s, with a longer follow-up of 3.9 years, Bjorn Pasternak, MD, PhD, of the Division of Clinical Epidemiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden, and colleagues reported similar findings — the overall risk for thyroid cancer with GLP-1s was not increased (HR, 0.93), and the risk beginning 1 year after treatment initiation was lower, at 0.83. 

However, the risk in that study only looking at the first year alone was again higher, at HR 1.47.

“Our analyses indicating a nominally increased risk restricted to the first year after starting treatment might be consistent with an increased detection of thyroid cancer among patients using GLP-1 RAs,” he told this news organization.

In addition to the short follow-up of the current study, Pasternak noted the caveat of the study’s inclusion mainly of patients who initiated the four diabetes drug groups, which is a limitation “because a high proportion of the patients with type 2 diabetes in routine care who start GLP-1 RAs have started it as their third, fourth, or even fifth diabetes drug, especially if they have had diabetes for some time.”

“To capture a larger proportion of the full population of GLP-1 RA users, it would have been preferable to create three different cohorts for the purpose of this study and investigate them separately, including GLP-1 vs DPP4i; GLP-1 vs SGLT2i; GLP-1 vs sulfonylurea,” he said.

 

Rise in Incidental Thyroid Cancer Detection, An Ongoing Concern

The advent of more advanced imaging and thyroid cancer testing in recent years has already led to a significant problem of over-detection and sometimes over-treatment of incidental, small thyroid cancers that will likely remain harmless in the majority of patients. 

With approximately 64 million prescriptions of GLP-1 RAs dispensed between 2000 and 2015 and the percentage increasing at a rate of about 10%-30% per year, increased thyroid testing among those patients could indeed add to the problem.

Meanwhile, thyroid testing is currently not recommended for patients on GLP-1s who do not have a thyroid cancer risk, and the results from the current and Pasternak’s studies, as well as several other recent studies, appear to support those recommendations.

“Collectively, these reassuring data could potentially help reduce [thyroid cancer] over-detection and screening,” Pasternak said. 

McCoy echoed that the evidence indicates that “for the vast majority of people there is no indication that GLP-1 RA causes thyroid cancer.”

She underscored that overdiagnosis can have important implications, sharing her own personal experience on the receiving end of a cancer diagnosis.

“Overdiagnosis of these low-risk thyroid cancers may ultimately lead to more harm for the patient than not making the diagnosis, since surgery for thyroid cancer carries real risks (including of death) and there are downstream consequences to having your thyroid removed and relying on lifelong hormone replacement,” McCoy said.

“As a cancer survivor myself, though of lymphoma, not thyroid cancer, I also know the profound impact that a cancer diagnosis has on the individual and their loved ones,” McCoy said.

“It is not something I would wish for anyone, which is why I always speak to my patients about searching for something we may not want to — or need to — find.”

The authors and Pasternak had no disclosures to report.

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

The evidence is clear: Alcohol can cause cancer.

Earlier this month, US surgeon general Vivek Murthy, MD, issued an advisory, calling for alcoholic beverages to carry a warning label about cancer risk. The advisory flagged alcohol as the third leading preventable cause of cancer in the United States, after tobacco and obesity, and highlighted people’s limited awareness about the relationship between alcohol and cancer risk.

But, when it comes to cancer risk, are all types of alcohol created equal?

For many years, red wine seemed to be an outlier, with studies indicating that, in moderation, it might even be good for you. Red wine has anti-inflammatory and antioxidant properties — most notably, it contains the antioxidant resveratrol. Starting in the 1990s, research began to hint that the compound might protect against heart disease, aging, and cancer, though much of this work was done in animals or test tubes.

The idea that red wine carries health benefits, however, has been called into question more recently. A recent meta-analysis, for instance, suggests that many previous studies touting the health benefits of more moderate drinking were likely biased, potentially leading to “misleading positive health associations.” And one recent study found that alcohol consumption, largely red wine and beer, at all levels was linked to an increased risk for cardiovascular disease.

Although wine’s health halo is dwindling, there might be an exception: Cancer risk.

Overall, research shows that even light to moderate drinking increases the risk for at least seven types of cancer, but when focusing on red wine, in particular, that risk calculus can look different.

“It’s very complicated and nuanced,” said Timothy Rebbeck, PhD, professor of cancer prevention, Harvard T.H. Chan School of Public Health, Boston. “And ‘complicated and nuanced’ doesn’t work very well in public health messages.”

The Knowns About Alcohol and Cancer Risk

Some things about the relationship between alcohol and cancer risk are crystal clear. “There’s no question that alcohol is a group 1 carcinogen,” Rebbeck said. “Alcohol can cause cancer.”

Groups including the International Agency for Research on Cancer (IARC) and American Cancer Society agree that alcohol use is an established cause of seven types of cancer: Those of the oral cavity, larynx, pharynx, esophagus (squamous cell carcinoma), liver (hepatocellular carcinoma), breast, and colon/rectum. Heavy drinking — at least 8 standard drinks a week for women and 15 for men — and binge drinking — 4 or more drinks in 2 hours for women and 5 or more for men — only amplify that risk. (A “standard” drink has 14 g of alcohol, which translates to a 5-oz glass of wine.)

“We’re most concerned about high-risk drinking — more than 2 drinks a day — and/or binge drinking,” said Noelle LoConte, MD, of the Division of Hematology, Medical Oncology and Palliative Care, University of Wisconsin School of Medicine and Public Health, Madison, who authored a 2018 statement on alcohol and cancer risk from the American Society of Clinical Oncology (ASCO).

Compared with not drinking, heavy drinking is linked with a roughly fivefold increase in the risk for oral cavity, pharyngeal, and esophageal cancers, and a 61% increase in the risk for breast cancer, according to LoConte and colleagues.

Things get murkier when it comes to moderate drinking — defined as up to 1 standard drink per day for women and 2 per day for men. There is evidence, LoConte said, that moderate drinking is associated with increased cancer risks, though the magnitude is generally much less than heavier drinking.

Cancer type also matters. One analysis found that the risk for breast cancer increased with even light to moderate alcohol consumption. Compared with no drinking, light to moderate drinking has also been linked to increased risks for oral cavity, pharynx, larynx, and esophageal cancers.

As for whether the type of alcoholic beverage matters, LoConte said, there’s no clear physiological reason that wine would be less risky than beer or liquor. Research indicates that ethanol is the problematic ingredient: Once ingested, it’s metabolized into acetaldehyde, a DNA-damaging substance that’s considered a probable human carcinogen. Ethanol can also alter circulating levels of estrogens and androgens, LoConte said, which is thought to drive its association with breast cancer risk.

“It likely doesn’t matter how you choose to get your ethanol,” she said. “It’s a question of volume.”

Hints That Wine Is an Outlier

Still, some studies suggest that how people ingest ethanol could make a difference.

A study published in August in JAMA Network Open is a case in point. The study found that, among older adults, light to heavy drinkers had an increased risk of dying from cancer, compared with occasional drinkers (though the increased risk among light to moderate drinkers occurred only among people who also had chronic health conditions, such as diabetes or high blood pressure, or were of lower socioeconomic status).

Wine drinkers fared differently. Most notably, drinkers who “preferred” wine — consuming over 80% of total ethanol from wine — or those who drank only with meals showed a small reduction in their risk for cancer mortality and all-cause mortality (hazard ratio [HR], 0.94 for both). The small protective association was somewhat stronger among people who reported both patterns (HR, 0.88), especially if they were of lower socioeconomic status (HR, 0.79).

The findings are in line with other research suggesting that wine drinkers may be outliers when it comes to cancer risk. A 2023 meta-analysis of 26 observational studies, for instance, found no association between wine consumption and any cancer type, with the caveat that there was «substantial» heterogeneity among the studies.

This heterogeneity caveat speaks to the inherent limitations of observational research, said Tim Stockwell, PhD, of the Canadian Institute for Substance Use Research, University of Victoria in British Columbia, Canada.

“Individual studies of alcohol and cancer risk do find differences by type of drink, or patterns of drinking,” Stockwell said. “But it’s so hard to unpack the confounding that goes along with the type of person who’s a wine drinker or a beer drinker or a spirit drinker. The beverage of choice seems to come with a lot of baggage.”

Compared with people who favor beer or liquor, he noted, wine aficionados are typically higher-income, exercise more often, smoke less, and have different diets, for example. The “best” studies, Rebbeck said, try to adjust for those differences, but it’s challenging.

The authors of the 2023 meta-analysis noted that “many components in wine could have anticarcinogenic effects” that theoretically could counter the ill effects of ethanol. Besides resveratrol, which is mainly found in red wine, the list includes anthocyanins, quercetin, and tannins. However, the authors also acknowledged that they couldn’t account for whether other lifestyle habits might explain why wine drinkers, overall, showed no increased cancer risks and sometimes lower risks.

Still, groups such as the IARC and ASCO hold that there is no known “safe” level, or type, of alcohol when it comes to cancer.

In the latest Canadian guidelines on alcohol use, the scientific panel calculated that people who have 6 drinks a week throughout adulthood (whatever the source of the alcohol) could shave 11 weeks from their life expectancy, on average, said Stockwell, who was on the guideline panel. Compare that with heavy drinking, where 4 drinks a day could rob the average person of 2 or 3 years. “If you’re drinking a lot, you could get huge benefits from cutting down,” Stockwell explained. “If you’re a moderate drinker, the benefits would obviously be less.”

Stockwell said that choices around drinking and breast cancer risk, specifically, can be “tough.” Unlike many of the other alcohol-associated cancers, he noted, breast cancer is common — so even small relative risk increases may be concerning. Based on a 2020 meta-analysis of 22 cohort studies, the risk for breast cancer rises by about 10%, on average, for every 10 g of alcohol a woman drinks per day. This study also found no evidence that wine is any different from other types of alcohol.

In real life, the calculus around wine consumption and cancer risk will probably vary widely from person to person, Rebbeck said. One woman with a family history of breast cancer might decide that having wine with dinner isn’t worth it. Another with the same family history might see that glass of wine as a stress reliever and opt to focus on other ways to reduce her breast cancer risk — by exercising and maintaining a healthy weight, for example.

“The bottom line is, in human studies, the data on light to moderate drinking and cancer are limited and messy, and you can’t draw firm conclusions from them,” Rebbeck said. “It probably raises risk in some people, but we don’t know who those people are. And the risk increases are relatively small.”

A Conversation Few Are Having

Even with many studies highlighting the connection between alcohol consumption and cancer risk, most people remain unaware about this risk.

A 2023 study by the National Cancer Institute found that only a minority of US adults knew that drinking alcohol is linked to increased cancer risk, and they were much less likely to say that was true of wine: Only 20% did, vs 31% who said that liquor can boost cancer risk. Meanwhile, 10% believed that wine helps prevent cancer. Other studies show that even among cancer survivors and patients undergoing active cancer treatment, many drink — often heavily.

“What we know right now is, physicians almost never talk about this,” LoConte said.

That could be due to time constraints, according to Rebbeck, or clinicians’ perceptions that the subject is too complicated and/or their own confusion about the data. There could also be some “cognitive dissonance” at play, LoConte noted, because many doctors drink alcohol.

It’s critical, she said, that conversations about drinking habits become “normalized,” and that should include informing patients that alcohol use is associated with certain cancers. Again, LoConte said, it’s high-risk drinking that’s most concerning and where reducing intake could have the biggest impact on cancer risk and other health outcomes.

“From a cancer prevention standpoint, it’s probably best not to drink,” she said. “But people don’t make choices based solely on cancer risk. We don’t want to come out with recommendations saying no one should drink. I don’t think the data support that, and people would buck against that advice.”

Rebbeck made a similar point. Even if there’s uncertainty about the risks for a daily glass of wine, he said, people can use that information to make decisions. “Everybody’s preferences and choices are going to be different,” Rebbeck said. “And that’s all we can really do.”

A version of this article appeared on Medscape.com.

The evidence is clear: Alcohol can cause cancer.

Earlier this month, US surgeon general Vivek Murthy, MD, issued an advisory, calling for alcoholic beverages to carry a warning label about cancer risk. The advisory flagged alcohol as the third leading preventable cause of cancer in the United States, after tobacco and obesity, and highlighted people’s limited awareness about the relationship between alcohol and cancer risk.

But, when it comes to cancer risk, are all types of alcohol created equal?

For many years, red wine seemed to be an outlier, with studies indicating that, in moderation, it might even be good for you. Red wine has anti-inflammatory and antioxidant properties — most notably, it contains the antioxidant resveratrol. Starting in the 1990s, research began to hint that the compound might protect against heart disease, aging, and cancer, though much of this work was done in animals or test tubes.

The idea that red wine carries health benefits, however, has been called into question more recently. A recent meta-analysis, for instance, suggests that many previous studies touting the health benefits of more moderate drinking were likely biased, potentially leading to “misleading positive health associations.” And one recent study found that alcohol consumption, largely red wine and beer, at all levels was linked to an increased risk for cardiovascular disease.

Although wine’s health halo is dwindling, there might be an exception: Cancer risk.

Overall, research shows that even light to moderate drinking increases the risk for at least seven types of cancer, but when focusing on red wine, in particular, that risk calculus can look different.

“It’s very complicated and nuanced,” said Timothy Rebbeck, PhD, professor of cancer prevention, Harvard T.H. Chan School of Public Health, Boston. “And ‘complicated and nuanced’ doesn’t work very well in public health messages.”

The Knowns About Alcohol and Cancer Risk

Some things about the relationship between alcohol and cancer risk are crystal clear. “There’s no question that alcohol is a group 1 carcinogen,” Rebbeck said. “Alcohol can cause cancer.”

Groups including the International Agency for Research on Cancer (IARC) and American Cancer Society agree that alcohol use is an established cause of seven types of cancer: Those of the oral cavity, larynx, pharynx, esophagus (squamous cell carcinoma), liver (hepatocellular carcinoma), breast, and colon/rectum. Heavy drinking — at least 8 standard drinks a week for women and 15 for men — and binge drinking — 4 or more drinks in 2 hours for women and 5 or more for men — only amplify that risk. (A “standard” drink has 14 g of alcohol, which translates to a 5-oz glass of wine.)

“We’re most concerned about high-risk drinking — more than 2 drinks a day — and/or binge drinking,” said Noelle LoConte, MD, of the Division of Hematology, Medical Oncology and Palliative Care, University of Wisconsin School of Medicine and Public Health, Madison, who authored a 2018 statement on alcohol and cancer risk from the American Society of Clinical Oncology (ASCO).

Compared with not drinking, heavy drinking is linked with a roughly fivefold increase in the risk for oral cavity, pharyngeal, and esophageal cancers, and a 61% increase in the risk for breast cancer, according to LoConte and colleagues.

Things get murkier when it comes to moderate drinking — defined as up to 1 standard drink per day for women and 2 per day for men. There is evidence, LoConte said, that moderate drinking is associated with increased cancer risks, though the magnitude is generally much less than heavier drinking.

Cancer type also matters. One analysis found that the risk for breast cancer increased with even light to moderate alcohol consumption. Compared with no drinking, light to moderate drinking has also been linked to increased risks for oral cavity, pharynx, larynx, and esophageal cancers.

As for whether the type of alcoholic beverage matters, LoConte said, there’s no clear physiological reason that wine would be less risky than beer or liquor. Research indicates that ethanol is the problematic ingredient: Once ingested, it’s metabolized into acetaldehyde, a DNA-damaging substance that’s considered a probable human carcinogen. Ethanol can also alter circulating levels of estrogens and androgens, LoConte said, which is thought to drive its association with breast cancer risk.

“It likely doesn’t matter how you choose to get your ethanol,” she said. “It’s a question of volume.”

Hints That Wine Is an Outlier

Still, some studies suggest that how people ingest ethanol could make a difference.

A study published in August in JAMA Network Open is a case in point. The study found that, among older adults, light to heavy drinkers had an increased risk of dying from cancer, compared with occasional drinkers (though the increased risk among light to moderate drinkers occurred only among people who also had chronic health conditions, such as diabetes or high blood pressure, or were of lower socioeconomic status).

Wine drinkers fared differently. Most notably, drinkers who “preferred” wine — consuming over 80% of total ethanol from wine — or those who drank only with meals showed a small reduction in their risk for cancer mortality and all-cause mortality (hazard ratio [HR], 0.94 for both). The small protective association was somewhat stronger among people who reported both patterns (HR, 0.88), especially if they were of lower socioeconomic status (HR, 0.79).

The findings are in line with other research suggesting that wine drinkers may be outliers when it comes to cancer risk. A 2023 meta-analysis of 26 observational studies, for instance, found no association between wine consumption and any cancer type, with the caveat that there was «substantial» heterogeneity among the studies.

This heterogeneity caveat speaks to the inherent limitations of observational research, said Tim Stockwell, PhD, of the Canadian Institute for Substance Use Research, University of Victoria in British Columbia, Canada.

“Individual studies of alcohol and cancer risk do find differences by type of drink, or patterns of drinking,” Stockwell said. “But it’s so hard to unpack the confounding that goes along with the type of person who’s a wine drinker or a beer drinker or a spirit drinker. The beverage of choice seems to come with a lot of baggage.”

Compared with people who favor beer or liquor, he noted, wine aficionados are typically higher-income, exercise more often, smoke less, and have different diets, for example. The “best” studies, Rebbeck said, try to adjust for those differences, but it’s challenging.

The authors of the 2023 meta-analysis noted that “many components in wine could have anticarcinogenic effects” that theoretically could counter the ill effects of ethanol. Besides resveratrol, which is mainly found in red wine, the list includes anthocyanins, quercetin, and tannins. However, the authors also acknowledged that they couldn’t account for whether other lifestyle habits might explain why wine drinkers, overall, showed no increased cancer risks and sometimes lower risks.

Still, groups such as the IARC and ASCO hold that there is no known “safe” level, or type, of alcohol when it comes to cancer.

In the latest Canadian guidelines on alcohol use, the scientific panel calculated that people who have 6 drinks a week throughout adulthood (whatever the source of the alcohol) could shave 11 weeks from their life expectancy, on average, said Stockwell, who was on the guideline panel. Compare that with heavy drinking, where 4 drinks a day could rob the average person of 2 or 3 years. “If you’re drinking a lot, you could get huge benefits from cutting down,” Stockwell explained. “If you’re a moderate drinker, the benefits would obviously be less.”

Stockwell said that choices around drinking and breast cancer risk, specifically, can be “tough.” Unlike many of the other alcohol-associated cancers, he noted, breast cancer is common — so even small relative risk increases may be concerning. Based on a 2020 meta-analysis of 22 cohort studies, the risk for breast cancer rises by about 10%, on average, for every 10 g of alcohol a woman drinks per day. This study also found no evidence that wine is any different from other types of alcohol.

In real life, the calculus around wine consumption and cancer risk will probably vary widely from person to person, Rebbeck said. One woman with a family history of breast cancer might decide that having wine with dinner isn’t worth it. Another with the same family history might see that glass of wine as a stress reliever and opt to focus on other ways to reduce her breast cancer risk — by exercising and maintaining a healthy weight, for example.

“The bottom line is, in human studies, the data on light to moderate drinking and cancer are limited and messy, and you can’t draw firm conclusions from them,” Rebbeck said. “It probably raises risk in some people, but we don’t know who those people are. And the risk increases are relatively small.”

A Conversation Few Are Having

Even with many studies highlighting the connection between alcohol consumption and cancer risk, most people remain unaware about this risk.

A 2023 study by the National Cancer Institute found that only a minority of US adults knew that drinking alcohol is linked to increased cancer risk, and they were much less likely to say that was true of wine: Only 20% did, vs 31% who said that liquor can boost cancer risk. Meanwhile, 10% believed that wine helps prevent cancer. Other studies show that even among cancer survivors and patients undergoing active cancer treatment, many drink — often heavily.

“What we know right now is, physicians almost never talk about this,” LoConte said.

That could be due to time constraints, according to Rebbeck, or clinicians’ perceptions that the subject is too complicated and/or their own confusion about the data. There could also be some “cognitive dissonance” at play, LoConte noted, because many doctors drink alcohol.

It’s critical, she said, that conversations about drinking habits become “normalized,” and that should include informing patients that alcohol use is associated with certain cancers. Again, LoConte said, it’s high-risk drinking that’s most concerning and where reducing intake could have the biggest impact on cancer risk and other health outcomes.

“From a cancer prevention standpoint, it’s probably best not to drink,” she said. “But people don’t make choices based solely on cancer risk. We don’t want to come out with recommendations saying no one should drink. I don’t think the data support that, and people would buck against that advice.”

Rebbeck made a similar point. Even if there’s uncertainty about the risks for a daily glass of wine, he said, people can use that information to make decisions. “Everybody’s preferences and choices are going to be different,” Rebbeck said. “And that’s all we can really do.”

A version of this article appeared on Medscape.com.

The evidence is clear: Alcohol can cause cancer.

Earlier this month, US surgeon general Vivek Murthy, MD, issued an advisory, calling for alcoholic beverages to carry a warning label about cancer risk. The advisory flagged alcohol as the third leading preventable cause of cancer in the United States, after tobacco and obesity, and highlighted people’s limited awareness about the relationship between alcohol and cancer risk.

But, when it comes to cancer risk, are all types of alcohol created equal?

For many years, red wine seemed to be an outlier, with studies indicating that, in moderation, it might even be good for you. Red wine has anti-inflammatory and antioxidant properties — most notably, it contains the antioxidant resveratrol. Starting in the 1990s, research began to hint that the compound might protect against heart disease, aging, and cancer, though much of this work was done in animals or test tubes.

The idea that red wine carries health benefits, however, has been called into question more recently. A recent meta-analysis, for instance, suggests that many previous studies touting the health benefits of more moderate drinking were likely biased, potentially leading to “misleading positive health associations.” And one recent study found that alcohol consumption, largely red wine and beer, at all levels was linked to an increased risk for cardiovascular disease.

Although wine’s health halo is dwindling, there might be an exception: Cancer risk.

Overall, research shows that even light to moderate drinking increases the risk for at least seven types of cancer, but when focusing on red wine, in particular, that risk calculus can look different.

“It’s very complicated and nuanced,” said Timothy Rebbeck, PhD, professor of cancer prevention, Harvard T.H. Chan School of Public Health, Boston. “And ‘complicated and nuanced’ doesn’t work very well in public health messages.”

The Knowns About Alcohol and Cancer Risk

Some things about the relationship between alcohol and cancer risk are crystal clear. “There’s no question that alcohol is a group 1 carcinogen,” Rebbeck said. “Alcohol can cause cancer.”

Groups including the International Agency for Research on Cancer (IARC) and American Cancer Society agree that alcohol use is an established cause of seven types of cancer: Those of the oral cavity, larynx, pharynx, esophagus (squamous cell carcinoma), liver (hepatocellular carcinoma), breast, and colon/rectum. Heavy drinking — at least 8 standard drinks a week for women and 15 for men — and binge drinking — 4 or more drinks in 2 hours for women and 5 or more for men — only amplify that risk. (A “standard” drink has 14 g of alcohol, which translates to a 5-oz glass of wine.)

“We’re most concerned about high-risk drinking — more than 2 drinks a day — and/or binge drinking,” said Noelle LoConte, MD, of the Division of Hematology, Medical Oncology and Palliative Care, University of Wisconsin School of Medicine and Public Health, Madison, who authored a 2018 statement on alcohol and cancer risk from the American Society of Clinical Oncology (ASCO).

Compared with not drinking, heavy drinking is linked with a roughly fivefold increase in the risk for oral cavity, pharyngeal, and esophageal cancers, and a 61% increase in the risk for breast cancer, according to LoConte and colleagues.

Things get murkier when it comes to moderate drinking — defined as up to 1 standard drink per day for women and 2 per day for men. There is evidence, LoConte said, that moderate drinking is associated with increased cancer risks, though the magnitude is generally much less than heavier drinking.

Cancer type also matters. One analysis found that the risk for breast cancer increased with even light to moderate alcohol consumption. Compared with no drinking, light to moderate drinking has also been linked to increased risks for oral cavity, pharynx, larynx, and esophageal cancers.

As for whether the type of alcoholic beverage matters, LoConte said, there’s no clear physiological reason that wine would be less risky than beer or liquor. Research indicates that ethanol is the problematic ingredient: Once ingested, it’s metabolized into acetaldehyde, a DNA-damaging substance that’s considered a probable human carcinogen. Ethanol can also alter circulating levels of estrogens and androgens, LoConte said, which is thought to drive its association with breast cancer risk.

“It likely doesn’t matter how you choose to get your ethanol,” she said. “It’s a question of volume.”

Hints That Wine Is an Outlier

Still, some studies suggest that how people ingest ethanol could make a difference.

A study published in August in JAMA Network Open is a case in point. The study found that, among older adults, light to heavy drinkers had an increased risk of dying from cancer, compared with occasional drinkers (though the increased risk among light to moderate drinkers occurred only among people who also had chronic health conditions, such as diabetes or high blood pressure, or were of lower socioeconomic status).

Wine drinkers fared differently. Most notably, drinkers who “preferred” wine — consuming over 80% of total ethanol from wine — or those who drank only with meals showed a small reduction in their risk for cancer mortality and all-cause mortality (hazard ratio [HR], 0.94 for both). The small protective association was somewhat stronger among people who reported both patterns (HR, 0.88), especially if they were of lower socioeconomic status (HR, 0.79).

The findings are in line with other research suggesting that wine drinkers may be outliers when it comes to cancer risk. A 2023 meta-analysis of 26 observational studies, for instance, found no association between wine consumption and any cancer type, with the caveat that there was «substantial» heterogeneity among the studies.

This heterogeneity caveat speaks to the inherent limitations of observational research, said Tim Stockwell, PhD, of the Canadian Institute for Substance Use Research, University of Victoria in British Columbia, Canada.

“Individual studies of alcohol and cancer risk do find differences by type of drink, or patterns of drinking,” Stockwell said. “But it’s so hard to unpack the confounding that goes along with the type of person who’s a wine drinker or a beer drinker or a spirit drinker. The beverage of choice seems to come with a lot of baggage.”

Compared with people who favor beer or liquor, he noted, wine aficionados are typically higher-income, exercise more often, smoke less, and have different diets, for example. The “best” studies, Rebbeck said, try to adjust for those differences, but it’s challenging.

The authors of the 2023 meta-analysis noted that “many components in wine could have anticarcinogenic effects” that theoretically could counter the ill effects of ethanol. Besides resveratrol, which is mainly found in red wine, the list includes anthocyanins, quercetin, and tannins. However, the authors also acknowledged that they couldn’t account for whether other lifestyle habits might explain why wine drinkers, overall, showed no increased cancer risks and sometimes lower risks.

Still, groups such as the IARC and ASCO hold that there is no known “safe” level, or type, of alcohol when it comes to cancer.

In the latest Canadian guidelines on alcohol use, the scientific panel calculated that people who have 6 drinks a week throughout adulthood (whatever the source of the alcohol) could shave 11 weeks from their life expectancy, on average, said Stockwell, who was on the guideline panel. Compare that with heavy drinking, where 4 drinks a day could rob the average person of 2 or 3 years. “If you’re drinking a lot, you could get huge benefits from cutting down,” Stockwell explained. “If you’re a moderate drinker, the benefits would obviously be less.”

Stockwell said that choices around drinking and breast cancer risk, specifically, can be “tough.” Unlike many of the other alcohol-associated cancers, he noted, breast cancer is common — so even small relative risk increases may be concerning. Based on a 2020 meta-analysis of 22 cohort studies, the risk for breast cancer rises by about 10%, on average, for every 10 g of alcohol a woman drinks per day. This study also found no evidence that wine is any different from other types of alcohol.

In real life, the calculus around wine consumption and cancer risk will probably vary widely from person to person, Rebbeck said. One woman with a family history of breast cancer might decide that having wine with dinner isn’t worth it. Another with the same family history might see that glass of wine as a stress reliever and opt to focus on other ways to reduce her breast cancer risk — by exercising and maintaining a healthy weight, for example.

“The bottom line is, in human studies, the data on light to moderate drinking and cancer are limited and messy, and you can’t draw firm conclusions from them,” Rebbeck said. “It probably raises risk in some people, but we don’t know who those people are. And the risk increases are relatively small.”

A Conversation Few Are Having

Even with many studies highlighting the connection between alcohol consumption and cancer risk, most people remain unaware about this risk.

A 2023 study by the National Cancer Institute found that only a minority of US adults knew that drinking alcohol is linked to increased cancer risk, and they were much less likely to say that was true of wine: Only 20% did, vs 31% who said that liquor can boost cancer risk. Meanwhile, 10% believed that wine helps prevent cancer. Other studies show that even among cancer survivors and patients undergoing active cancer treatment, many drink — often heavily.

“What we know right now is, physicians almost never talk about this,” LoConte said.

That could be due to time constraints, according to Rebbeck, or clinicians’ perceptions that the subject is too complicated and/or their own confusion about the data. There could also be some “cognitive dissonance” at play, LoConte noted, because many doctors drink alcohol.

It’s critical, she said, that conversations about drinking habits become “normalized,” and that should include informing patients that alcohol use is associated with certain cancers. Again, LoConte said, it’s high-risk drinking that’s most concerning and where reducing intake could have the biggest impact on cancer risk and other health outcomes.

“From a cancer prevention standpoint, it’s probably best not to drink,” she said. “But people don’t make choices based solely on cancer risk. We don’t want to come out with recommendations saying no one should drink. I don’t think the data support that, and people would buck against that advice.”

Rebbeck made a similar point. Even if there’s uncertainty about the risks for a daily glass of wine, he said, people can use that information to make decisions. “Everybody’s preferences and choices are going to be different,” Rebbeck said. “And that’s all we can really do.”

A version of this article appeared on Medscape.com.

MRI-invisible prostate lesions. It sounds like the stuff of science fiction and fantasy, a creation from the minds of H.G. Wells, who wrote The Invisible Man, or J.K. Rowling, who authored the Harry Potter series.

But MRI-invisible prostate lesions are real. And what these lesions may, or may not, indicate is the subject of intense debate.

MRI plays an increasingly important role in detecting and diagnosing prostate cancer, staging prostate cancer as well as monitoring disease progression. However, on occasion, a puzzling phenomenon arises. Certain prostate lesions that appear when pathologists examine biopsied tissue samples under a microscope are not visible on MRI. The prostate tissue will, instead, appear normal to a radiologist’s eye.

Why are certain lesions invisible with MRI? And is it dangerous for patients if these lesions are not detected? 

Some experts believe these MRI-invisible lesions are nothing to worry about.

If the clinician can’t see the cancer on MRI, then it simply isn’t a threat, according to Mark Emberton, MD, a pioneer in prostate MRIs and director of interventional oncology at University College London, England.

Laurence Klotz, MD, of the University of Toronto, Ontario, Canada, agreed, noting that “invisible cancers are clinically insignificant and don’t require systematic biopsies.”

Emberton and Klotz compared MRI-invisible lesions to grade group 1 prostate cancer (Gleason score ≤ 6) — the least aggressive category that indicates the cancer that is not likely to spread or kill. For patients on active surveillance, those with MRI-invisible cancers do drastically better than those with visible cancers, Klotz explained.

But other experts in the field are skeptical that MRI-invisible lesions are truly innocuous.

Although statistically an MRI-visible prostate lesion indicates a more aggressive tumor, that is not always the case for every individual, said Brian Helfand, MD, PhD, chief of urology at NorthShore University Health System, Evanston, Illinois.

MRIs can lead to false negatives in about 10%-20% of patients who have clinically significant prostate cancer, though estimates vary.

In one analysis, 16% of men with no suspicious lesions on MRI had clinically significant prostate cancer identified after undergoing a systematic biopsy. Another analysis found that about 35% of MRI-invisible prostate cancers identified via biopsy were clinically significant.

Other studies, however, have indicated that negative MRI results accurately indicate patients at low risk of developing clinically significant cancers. A recent JAMA Oncology analysis, for instance, found that only seven of 233 men (3%) with negative MRI results at baseline who completed 3 years of monitoring were diagnosed with clinically significant prostate cancer.

When a patient has an MRI-invisible prostate tumor, there are a couple of reasons the MRI may not be picking it up, said urologic oncologist Alexander Putnam Cole, MD, assistant professor of surgery, Harvard Medical School, Boston, Massachusetts. “One is that the cancer is aggressive but just very small,” said Cole.

“Another possibility is that the cancer looks very similar to background prostate tissue, which is something that you might expect if you think about more of a low-grade cancer,” he explained.

The experience level of the radiologist interpreting the MRI can also play into the accuracy of the reading.

But Cole agreed that “in general, MRI visibility is associated with molecular and histologic features of progression and aggressiveness and non-visible cancers are less likely to have aggressive features.”

The genomic profiles of MRI-visible and -invisible cancers bear this out.

According to Todd Morgan, MD, chief of urologic oncology at Michigan Medicine, University of Michigan, Ann Arbor, the gene expression in visible disease tends to be linked to more aggressive prostate tumors whereas gene expression in invisible disease does not.

In one analysis, for instance, researchers found that four genes — PHYHD1, CENPF, ALDH2, and GDF15 — associated with worse progression-free survival and metastasis-free survival in prostate cancer also predicted MRI visibility.

“Genes that are associated with visibility are essentially the same genes that are associated with aggressive cancers,” Klotz said.

 

Next Steps After Negative MRI Result

What do MRI-invisible lesions mean for patient care? If, for instance, a patient has elevated PSA levels but a normal MRI, is a targeted or systematic biopsy warranted?

The overarching message, according to Klotz, is that “you don’t need to find them.” Klotz noted, however, that patients with a negative MRI result should still be followed with periodic repeat imaging.

Several trials support this approach of using MRI to decide who needs a biopsy and delaying a biopsy in men with normal MRIs.

The recent JAMA Oncology analysis found that, among men with negative MRI results, 86% avoided a biopsy over 3 years, with clinically significant prostate cancer detected in only 4% of men across the study period — four in the initial diagnostic phase and seven in the 3-year monitoring phase. However, during the initial diagnostic phase, more than half the men with positive MRI findings had clinically significant prostate cancer detected.

Another recent study found that patients with negative MRI results were much less likely to upgrade to higher Gleason scores over time. Among 522 patients who underwent a systematic and targeted biopsy within 18 months of their grade group 1 designation, 9.2% with negative MRI findings had tumors reclassified as grade group 2 or higher vs 27% with positive MRI findings, and 2.3% with negative MRI findings had tumors reclassified as grade group 3 or higher vs 7.8% with positive MRI findings.

These data suggest that men with grade group 1 cancer and negative MRI result “may be able to avoid confirmatory biopsies until a routine surveillance biopsy in 2-3 years,” according to study author Christian Pavlovich, MD, professor of urologic oncology at the Johns Hopkins University School of Medicine, Baltimore.

Cole used MRI findings to triage who gets a biopsy. When a biopsy is warranted, “I usually recommend adding in some systematic sampling of the other side to assess for nonvisible cancers,” he noted.

Sampling prostate tissue outside the target area “adds maybe 1-2 minutes to the procedure and doesn’t drastically increase the morbidity or risks,” Cole said. It also can help “confirm there is cancer in the MRI target and also confirm there is no cancer in the nonvisible areas.” 

According to Klotz, if imaging demonstrates progression, patients should receive a biopsy — in most cases, a targeted biopsy only. And, Klotz noted, skipping routine prostate biopsies in men with negative MRI results can save thousands of men from these procedures, which carry risks for infections and sepsis.

Looking beyond Gleason scores for risk prediction, MRI “visibility is a very powerful risk stratifier,” he said.

A version of this article appeared on Medscape.com.

MRI-invisible prostate lesions. It sounds like the stuff of science fiction and fantasy, a creation from the minds of H.G. Wells, who wrote The Invisible Man, or J.K. Rowling, who authored the Harry Potter series.

But MRI-invisible prostate lesions are real. And what these lesions may, or may not, indicate is the subject of intense debate.

MRI plays an increasingly important role in detecting and diagnosing prostate cancer, staging prostate cancer as well as monitoring disease progression. However, on occasion, a puzzling phenomenon arises. Certain prostate lesions that appear when pathologists examine biopsied tissue samples under a microscope are not visible on MRI. The prostate tissue will, instead, appear normal to a radiologist’s eye.

Why are certain lesions invisible with MRI? And is it dangerous for patients if these lesions are not detected? 

Some experts believe these MRI-invisible lesions are nothing to worry about.

If the clinician can’t see the cancer on MRI, then it simply isn’t a threat, according to Mark Emberton, MD, a pioneer in prostate MRIs and director of interventional oncology at University College London, England.

Laurence Klotz, MD, of the University of Toronto, Ontario, Canada, agreed, noting that “invisible cancers are clinically insignificant and don’t require systematic biopsies.”

Emberton and Klotz compared MRI-invisible lesions to grade group 1 prostate cancer (Gleason score ≤ 6) — the least aggressive category that indicates the cancer that is not likely to spread or kill. For patients on active surveillance, those with MRI-invisible cancers do drastically better than those with visible cancers, Klotz explained.

But other experts in the field are skeptical that MRI-invisible lesions are truly innocuous.

Although statistically an MRI-visible prostate lesion indicates a more aggressive tumor, that is not always the case for every individual, said Brian Helfand, MD, PhD, chief of urology at NorthShore University Health System, Evanston, Illinois.

MRIs can lead to false negatives in about 10%-20% of patients who have clinically significant prostate cancer, though estimates vary.

In one analysis, 16% of men with no suspicious lesions on MRI had clinically significant prostate cancer identified after undergoing a systematic biopsy. Another analysis found that about 35% of MRI-invisible prostate cancers identified via biopsy were clinically significant.

Other studies, however, have indicated that negative MRI results accurately indicate patients at low risk of developing clinically significant cancers. A recent JAMA Oncology analysis, for instance, found that only seven of 233 men (3%) with negative MRI results at baseline who completed 3 years of monitoring were diagnosed with clinically significant prostate cancer.

When a patient has an MRI-invisible prostate tumor, there are a couple of reasons the MRI may not be picking it up, said urologic oncologist Alexander Putnam Cole, MD, assistant professor of surgery, Harvard Medical School, Boston, Massachusetts. “One is that the cancer is aggressive but just very small,” said Cole.

“Another possibility is that the cancer looks very similar to background prostate tissue, which is something that you might expect if you think about more of a low-grade cancer,” he explained.

The experience level of the radiologist interpreting the MRI can also play into the accuracy of the reading.

But Cole agreed that “in general, MRI visibility is associated with molecular and histologic features of progression and aggressiveness and non-visible cancers are less likely to have aggressive features.”

The genomic profiles of MRI-visible and -invisible cancers bear this out.

According to Todd Morgan, MD, chief of urologic oncology at Michigan Medicine, University of Michigan, Ann Arbor, the gene expression in visible disease tends to be linked to more aggressive prostate tumors whereas gene expression in invisible disease does not.

In one analysis, for instance, researchers found that four genes — PHYHD1, CENPF, ALDH2, and GDF15 — associated with worse progression-free survival and metastasis-free survival in prostate cancer also predicted MRI visibility.

“Genes that are associated with visibility are essentially the same genes that are associated with aggressive cancers,” Klotz said.

 

Next Steps After Negative MRI Result

What do MRI-invisible lesions mean for patient care? If, for instance, a patient has elevated PSA levels but a normal MRI, is a targeted or systematic biopsy warranted?

The overarching message, according to Klotz, is that “you don’t need to find them.” Klotz noted, however, that patients with a negative MRI result should still be followed with periodic repeat imaging.

Several trials support this approach of using MRI to decide who needs a biopsy and delaying a biopsy in men with normal MRIs.

The recent JAMA Oncology analysis found that, among men with negative MRI results, 86% avoided a biopsy over 3 years, with clinically significant prostate cancer detected in only 4% of men across the study period — four in the initial diagnostic phase and seven in the 3-year monitoring phase. However, during the initial diagnostic phase, more than half the men with positive MRI findings had clinically significant prostate cancer detected.

Another recent study found that patients with negative MRI results were much less likely to upgrade to higher Gleason scores over time. Among 522 patients who underwent a systematic and targeted biopsy within 18 months of their grade group 1 designation, 9.2% with negative MRI findings had tumors reclassified as grade group 2 or higher vs 27% with positive MRI findings, and 2.3% with negative MRI findings had tumors reclassified as grade group 3 or higher vs 7.8% with positive MRI findings.

These data suggest that men with grade group 1 cancer and negative MRI result “may be able to avoid confirmatory biopsies until a routine surveillance biopsy in 2-3 years,” according to study author Christian Pavlovich, MD, professor of urologic oncology at the Johns Hopkins University School of Medicine, Baltimore.

Cole used MRI findings to triage who gets a biopsy. When a biopsy is warranted, “I usually recommend adding in some systematic sampling of the other side to assess for nonvisible cancers,” he noted.

Sampling prostate tissue outside the target area “adds maybe 1-2 minutes to the procedure and doesn’t drastically increase the morbidity or risks,” Cole said. It also can help “confirm there is cancer in the MRI target and also confirm there is no cancer in the nonvisible areas.” 

According to Klotz, if imaging demonstrates progression, patients should receive a biopsy — in most cases, a targeted biopsy only. And, Klotz noted, skipping routine prostate biopsies in men with negative MRI results can save thousands of men from these procedures, which carry risks for infections and sepsis.

Looking beyond Gleason scores for risk prediction, MRI “visibility is a very powerful risk stratifier,” he said.

A version of this article appeared on Medscape.com.

MRI-invisible prostate lesions. It sounds like the stuff of science fiction and fantasy, a creation from the minds of H.G. Wells, who wrote The Invisible Man, or J.K. Rowling, who authored the Harry Potter series.

But MRI-invisible prostate lesions are real. And what these lesions may, or may not, indicate is the subject of intense debate.

MRI plays an increasingly important role in detecting and diagnosing prostate cancer, staging prostate cancer as well as monitoring disease progression. However, on occasion, a puzzling phenomenon arises. Certain prostate lesions that appear when pathologists examine biopsied tissue samples under a microscope are not visible on MRI. The prostate tissue will, instead, appear normal to a radiologist’s eye.

Why are certain lesions invisible with MRI? And is it dangerous for patients if these lesions are not detected? 

Some experts believe these MRI-invisible lesions are nothing to worry about.

If the clinician can’t see the cancer on MRI, then it simply isn’t a threat, according to Mark Emberton, MD, a pioneer in prostate MRIs and director of interventional oncology at University College London, England.

Laurence Klotz, MD, of the University of Toronto, Ontario, Canada, agreed, noting that “invisible cancers are clinically insignificant and don’t require systematic biopsies.”

Emberton and Klotz compared MRI-invisible lesions to grade group 1 prostate cancer (Gleason score ≤ 6) — the least aggressive category that indicates the cancer that is not likely to spread or kill. For patients on active surveillance, those with MRI-invisible cancers do drastically better than those with visible cancers, Klotz explained.

But other experts in the field are skeptical that MRI-invisible lesions are truly innocuous.

Although statistically an MRI-visible prostate lesion indicates a more aggressive tumor, that is not always the case for every individual, said Brian Helfand, MD, PhD, chief of urology at NorthShore University Health System, Evanston, Illinois.

MRIs can lead to false negatives in about 10%-20% of patients who have clinically significant prostate cancer, though estimates vary.

In one analysis, 16% of men with no suspicious lesions on MRI had clinically significant prostate cancer identified after undergoing a systematic biopsy. Another analysis found that about 35% of MRI-invisible prostate cancers identified via biopsy were clinically significant.

Other studies, however, have indicated that negative MRI results accurately indicate patients at low risk of developing clinically significant cancers. A recent JAMA Oncology analysis, for instance, found that only seven of 233 men (3%) with negative MRI results at baseline who completed 3 years of monitoring were diagnosed with clinically significant prostate cancer.

When a patient has an MRI-invisible prostate tumor, there are a couple of reasons the MRI may not be picking it up, said urologic oncologist Alexander Putnam Cole, MD, assistant professor of surgery, Harvard Medical School, Boston, Massachusetts. “One is that the cancer is aggressive but just very small,” said Cole.

“Another possibility is that the cancer looks very similar to background prostate tissue, which is something that you might expect if you think about more of a low-grade cancer,” he explained.

The experience level of the radiologist interpreting the MRI can also play into the accuracy of the reading.

But Cole agreed that “in general, MRI visibility is associated with molecular and histologic features of progression and aggressiveness and non-visible cancers are less likely to have aggressive features.”

The genomic profiles of MRI-visible and -invisible cancers bear this out.

According to Todd Morgan, MD, chief of urologic oncology at Michigan Medicine, University of Michigan, Ann Arbor, the gene expression in visible disease tends to be linked to more aggressive prostate tumors whereas gene expression in invisible disease does not.

In one analysis, for instance, researchers found that four genes — PHYHD1, CENPF, ALDH2, and GDF15 — associated with worse progression-free survival and metastasis-free survival in prostate cancer also predicted MRI visibility.

“Genes that are associated with visibility are essentially the same genes that are associated with aggressive cancers,” Klotz said.

 

Next Steps After Negative MRI Result

What do MRI-invisible lesions mean for patient care? If, for instance, a patient has elevated PSA levels but a normal MRI, is a targeted or systematic biopsy warranted?

The overarching message, according to Klotz, is that “you don’t need to find them.” Klotz noted, however, that patients with a negative MRI result should still be followed with periodic repeat imaging.

Several trials support this approach of using MRI to decide who needs a biopsy and delaying a biopsy in men with normal MRIs.

The recent JAMA Oncology analysis found that, among men with negative MRI results, 86% avoided a biopsy over 3 years, with clinically significant prostate cancer detected in only 4% of men across the study period — four in the initial diagnostic phase and seven in the 3-year monitoring phase. However, during the initial diagnostic phase, more than half the men with positive MRI findings had clinically significant prostate cancer detected.

Another recent study found that patients with negative MRI results were much less likely to upgrade to higher Gleason scores over time. Among 522 patients who underwent a systematic and targeted biopsy within 18 months of their grade group 1 designation, 9.2% with negative MRI findings had tumors reclassified as grade group 2 or higher vs 27% with positive MRI findings, and 2.3% with negative MRI findings had tumors reclassified as grade group 3 or higher vs 7.8% with positive MRI findings.

These data suggest that men with grade group 1 cancer and negative MRI result “may be able to avoid confirmatory biopsies until a routine surveillance biopsy in 2-3 years,” according to study author Christian Pavlovich, MD, professor of urologic oncology at the Johns Hopkins University School of Medicine, Baltimore.

Cole used MRI findings to triage who gets a biopsy. When a biopsy is warranted, “I usually recommend adding in some systematic sampling of the other side to assess for nonvisible cancers,” he noted.

Sampling prostate tissue outside the target area “adds maybe 1-2 minutes to the procedure and doesn’t drastically increase the morbidity or risks,” Cole said. It also can help “confirm there is cancer in the MRI target and also confirm there is no cancer in the nonvisible areas.” 

According to Klotz, if imaging demonstrates progression, patients should receive a biopsy — in most cases, a targeted biopsy only. And, Klotz noted, skipping routine prostate biopsies in men with negative MRI results can save thousands of men from these procedures, which carry risks for infections and sepsis.

Looking beyond Gleason scores for risk prediction, MRI “visibility is a very powerful risk stratifier,” he said.

A version of this article appeared on Medscape.com.

When the Food and Drug Administration (FDA) grants cancer drugs accelerated approval, a key aim is to provide patients faster access to therapies that can benefit them. 

The downside of a speedier approval timeline, however, is that it’s often not yet clear whether the new drugs will actually allow a patient to live longer or better. Information on overall survival and quality of life typically comes years later, after drugs undergo confirmatory trials, or sometimes not at all, if companies fail to conduct these trials. 

During this waiting period, patients may be receiving a cancer drug that provides no real clinical benefit but comes with a host of toxicities. 

In fact, the odds are about as good as a coin flip. For cancer drugs that have confirmatory trial data, more than half don’t ultimately provide an overall survival or quality of life benefit.

Inherent to the accelerated approval process is the assumption that patients are willing to accept this uncertainty in exchange for faster access.

But is that really the case? 

A recent survey published in The Lancet Oncology aimed to tease out people’s preferences for confirmed clinical benefit vs speedier access. The researchers asked about 870 adults with experience of cancer challenges — either their own cancer diagnosis or that of family or a close friend — whether they valued faster access or certainty that a drug really works. 

In the study, participants imagined they had been diagnosed with cancer and could choose between two cancer drugs under investigation in clinical trials but with uncertain effectiveness, and a current standard treatment. Participants had to make a series of choices based on five scenarios. 

The first two scenarios were based on the impact of the current standard treatment: A patient’s life expectancy on the standard treatment (6 months up to 3 years), and a patient’s physical health on the standard treatment (functional status restricted only during strenuous activities up to completely disabled).

The remaining three scenarios dealt with the two new drugs: The effect of the new drugs on a surrogate endpoint, progression-free survival (whether the drugs slowed tumor growth for an extra month or 5 additional months compared with the standard treatment), certainty that slowing tumor growth will improve survival (very low to high), and the wait time to access the drugs (immediately to as long as 2 years).

The researchers assessed the relative importance of survival benefit certainty vs wait time and how that balance shifted depending on the different scenarios. 

Overall, the researchers found that, if there was no evidence linking the surrogate endpoint (progression-free survival) to overall survival, patients were willing to wait about 8 months for weak evidence of an overall survival benefit (ie, low certainty the drug will extend survival by 1-5 months), about 16 months for moderate certainty, and almost 22 months for high certainty. 

Despite a willingness to wait for greater certainty, participants did value speed as well. Overall, respondents showed a strong preference against a 1-year delay in FDA approval time. People who were aged 55 years or more and were non-White individuals made less than $40,000 year as well as those with the lowest life expectancy on a current standard treatment were most sensitive to wait times while those with better functional status and longer life expectancies on a current treatment were less sensitive to longer wait times.

“Our results indicate that some patients (except those with the poorest prognoses) would find the additional time required to generate evidence on the survival benefit of new cancer drugs an acceptable tradeoff,” the study authors concluded.

Although people do place high value on timely access to new cancer drugs, especially if there are limited treatment options, many are willing to wait for greater certainty that a new drug provides an overall survival benefit, lead author Robin Forrest, MSc, with the Department of Health Policy, London School of Economics in England, said in an interview. 

In the study, respondents also did not place significant value on whether the drug substantially slowed cancer growth. “In other words, substantial progression-free survival benefit of a drug did not compensate for lack of certainty about a drug’s benefit on survival in respondents’ drug choices,” the authors explained.

“In an effort to move quickly, we have accepted progression-free survival [as a surrogate endpoint],” Jyoti D. Patel, MD, oncologist with Northwestern Memorial Hospital, Chicago, Illinois, who wasn’t involved in the study. But a growing body of evidence indicates that progression-free survival is often a poor surrogate for overall survival. And what this study suggests is that “patients uniformly care about improvements in overall survival and the quality of that survival,” Patel said.

Bishal Gyawali, MD, PhD, was not surprised by the findings. 

“I always thought this was the real-world scenario, but the problem is the voices of ordinary patients are not heard,” Gyawali, with Queen’s University, Kingston, Ontario, Canada, who also wasn’t involved in the study, said in an interview. 

“What is heard is the loud noise of ‘we need access now, today, yesterday’ — ‘we don’t care if the drug doesn’t improve overall survival, we just need a drug, any drug’ — ‘we don’t care how much it costs, we need access today,’ ” Gyawali said. “Not saying this is wrong, but this is not the representation of all patients.”

However, the voices of patients who are more cautious and want evidence of benefit before accepting toxicities don’t make headlines, he added. 

What this survey means from a policy perspective, said Gyawali, is that accelerated approvals that do not mandate survival endpoint in confirmatory trials are ignoring the need of many patients who prioritize certainty of benefit over speed of access.

The study was funded by the London School of Economics and Political Science Phelan United States Centre. Forrest had no relevant disclosures. Gyawali has received consulting fees from Vivio Health. Patel has various relationships with AbbVie, Anheart, AstraZeneca, Bristol-Myers Squibb, Guardant, Tempus, Sanofi, BluePrint, Takeda, and Gilead.

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

When the Food and Drug Administration (FDA) grants cancer drugs accelerated approval, a key aim is to provide patients faster access to therapies that can benefit them. 

The downside of a speedier approval timeline, however, is that it’s often not yet clear whether the new drugs will actually allow a patient to live longer or better. Information on overall survival and quality of life typically comes years later, after drugs undergo confirmatory trials, or sometimes not at all, if companies fail to conduct these trials. 

During this waiting period, patients may be receiving a cancer drug that provides no real clinical benefit but comes with a host of toxicities. 

In fact, the odds are about as good as a coin flip. For cancer drugs that have confirmatory trial data, more than half don’t ultimately provide an overall survival or quality of life benefit.

Inherent to the accelerated approval process is the assumption that patients are willing to accept this uncertainty in exchange for faster access.

But is that really the case? 

A recent survey published in The Lancet Oncology aimed to tease out people’s preferences for confirmed clinical benefit vs speedier access. The researchers asked about 870 adults with experience of cancer challenges — either their own cancer diagnosis or that of family or a close friend — whether they valued faster access or certainty that a drug really works. 

In the study, participants imagined they had been diagnosed with cancer and could choose between two cancer drugs under investigation in clinical trials but with uncertain effectiveness, and a current standard treatment. Participants had to make a series of choices based on five scenarios. 

The first two scenarios were based on the impact of the current standard treatment: A patient’s life expectancy on the standard treatment (6 months up to 3 years), and a patient’s physical health on the standard treatment (functional status restricted only during strenuous activities up to completely disabled).

The remaining three scenarios dealt with the two new drugs: The effect of the new drugs on a surrogate endpoint, progression-free survival (whether the drugs slowed tumor growth for an extra month or 5 additional months compared with the standard treatment), certainty that slowing tumor growth will improve survival (very low to high), and the wait time to access the drugs (immediately to as long as 2 years).

The researchers assessed the relative importance of survival benefit certainty vs wait time and how that balance shifted depending on the different scenarios. 

Overall, the researchers found that, if there was no evidence linking the surrogate endpoint (progression-free survival) to overall survival, patients were willing to wait about 8 months for weak evidence of an overall survival benefit (ie, low certainty the drug will extend survival by 1-5 months), about 16 months for moderate certainty, and almost 22 months for high certainty. 

Despite a willingness to wait for greater certainty, participants did value speed as well. Overall, respondents showed a strong preference against a 1-year delay in FDA approval time. People who were aged 55 years or more and were non-White individuals made less than $40,000 year as well as those with the lowest life expectancy on a current standard treatment were most sensitive to wait times while those with better functional status and longer life expectancies on a current treatment were less sensitive to longer wait times.

“Our results indicate that some patients (except those with the poorest prognoses) would find the additional time required to generate evidence on the survival benefit of new cancer drugs an acceptable tradeoff,” the study authors concluded.

Although people do place high value on timely access to new cancer drugs, especially if there are limited treatment options, many are willing to wait for greater certainty that a new drug provides an overall survival benefit, lead author Robin Forrest, MSc, with the Department of Health Policy, London School of Economics in England, said in an interview. 

In the study, respondents also did not place significant value on whether the drug substantially slowed cancer growth. “In other words, substantial progression-free survival benefit of a drug did not compensate for lack of certainty about a drug’s benefit on survival in respondents’ drug choices,” the authors explained.

“In an effort to move quickly, we have accepted progression-free survival [as a surrogate endpoint],” Jyoti D. Patel, MD, oncologist with Northwestern Memorial Hospital, Chicago, Illinois, who wasn’t involved in the study. But a growing body of evidence indicates that progression-free survival is often a poor surrogate for overall survival. And what this study suggests is that “patients uniformly care about improvements in overall survival and the quality of that survival,” Patel said.

Bishal Gyawali, MD, PhD, was not surprised by the findings. 

“I always thought this was the real-world scenario, but the problem is the voices of ordinary patients are not heard,” Gyawali, with Queen’s University, Kingston, Ontario, Canada, who also wasn’t involved in the study, said in an interview. 

“What is heard is the loud noise of ‘we need access now, today, yesterday’ — ‘we don’t care if the drug doesn’t improve overall survival, we just need a drug, any drug’ — ‘we don’t care how much it costs, we need access today,’ ” Gyawali said. “Not saying this is wrong, but this is not the representation of all patients.”

However, the voices of patients who are more cautious and want evidence of benefit before accepting toxicities don’t make headlines, he added. 

What this survey means from a policy perspective, said Gyawali, is that accelerated approvals that do not mandate survival endpoint in confirmatory trials are ignoring the need of many patients who prioritize certainty of benefit over speed of access.

The study was funded by the London School of Economics and Political Science Phelan United States Centre. Forrest had no relevant disclosures. Gyawali has received consulting fees from Vivio Health. Patel has various relationships with AbbVie, Anheart, AstraZeneca, Bristol-Myers Squibb, Guardant, Tempus, Sanofi, BluePrint, Takeda, and Gilead.

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

When the Food and Drug Administration (FDA) grants cancer drugs accelerated approval, a key aim is to provide patients faster access to therapies that can benefit them. 

The downside of a speedier approval timeline, however, is that it’s often not yet clear whether the new drugs will actually allow a patient to live longer or better. Information on overall survival and quality of life typically comes years later, after drugs undergo confirmatory trials, or sometimes not at all, if companies fail to conduct these trials. 

During this waiting period, patients may be receiving a cancer drug that provides no real clinical benefit but comes with a host of toxicities. 

In fact, the odds are about as good as a coin flip. For cancer drugs that have confirmatory trial data, more than half don’t ultimately provide an overall survival or quality of life benefit.

Inherent to the accelerated approval process is the assumption that patients are willing to accept this uncertainty in exchange for faster access.

But is that really the case? 

A recent survey published in The Lancet Oncology aimed to tease out people’s preferences for confirmed clinical benefit vs speedier access. The researchers asked about 870 adults with experience of cancer challenges — either their own cancer diagnosis or that of family or a close friend — whether they valued faster access or certainty that a drug really works. 

In the study, participants imagined they had been diagnosed with cancer and could choose between two cancer drugs under investigation in clinical trials but with uncertain effectiveness, and a current standard treatment. Participants had to make a series of choices based on five scenarios. 

The first two scenarios were based on the impact of the current standard treatment: A patient’s life expectancy on the standard treatment (6 months up to 3 years), and a patient’s physical health on the standard treatment (functional status restricted only during strenuous activities up to completely disabled).

The remaining three scenarios dealt with the two new drugs: The effect of the new drugs on a surrogate endpoint, progression-free survival (whether the drugs slowed tumor growth for an extra month or 5 additional months compared with the standard treatment), certainty that slowing tumor growth will improve survival (very low to high), and the wait time to access the drugs (immediately to as long as 2 years).

The researchers assessed the relative importance of survival benefit certainty vs wait time and how that balance shifted depending on the different scenarios. 

Overall, the researchers found that, if there was no evidence linking the surrogate endpoint (progression-free survival) to overall survival, patients were willing to wait about 8 months for weak evidence of an overall survival benefit (ie, low certainty the drug will extend survival by 1-5 months), about 16 months for moderate certainty, and almost 22 months for high certainty. 

Despite a willingness to wait for greater certainty, participants did value speed as well. Overall, respondents showed a strong preference against a 1-year delay in FDA approval time. People who were aged 55 years or more and were non-White individuals made less than $40,000 year as well as those with the lowest life expectancy on a current standard treatment were most sensitive to wait times while those with better functional status and longer life expectancies on a current treatment were less sensitive to longer wait times.

“Our results indicate that some patients (except those with the poorest prognoses) would find the additional time required to generate evidence on the survival benefit of new cancer drugs an acceptable tradeoff,” the study authors concluded.

Although people do place high value on timely access to new cancer drugs, especially if there are limited treatment options, many are willing to wait for greater certainty that a new drug provides an overall survival benefit, lead author Robin Forrest, MSc, with the Department of Health Policy, London School of Economics in England, said in an interview. 

In the study, respondents also did not place significant value on whether the drug substantially slowed cancer growth. “In other words, substantial progression-free survival benefit of a drug did not compensate for lack of certainty about a drug’s benefit on survival in respondents’ drug choices,” the authors explained.

“In an effort to move quickly, we have accepted progression-free survival [as a surrogate endpoint],” Jyoti D. Patel, MD, oncologist with Northwestern Memorial Hospital, Chicago, Illinois, who wasn’t involved in the study. But a growing body of evidence indicates that progression-free survival is often a poor surrogate for overall survival. And what this study suggests is that “patients uniformly care about improvements in overall survival and the quality of that survival,” Patel said.

Bishal Gyawali, MD, PhD, was not surprised by the findings. 

“I always thought this was the real-world scenario, but the problem is the voices of ordinary patients are not heard,” Gyawali, with Queen’s University, Kingston, Ontario, Canada, who also wasn’t involved in the study, said in an interview. 

“What is heard is the loud noise of ‘we need access now, today, yesterday’ — ‘we don’t care if the drug doesn’t improve overall survival, we just need a drug, any drug’ — ‘we don’t care how much it costs, we need access today,’ ” Gyawali said. “Not saying this is wrong, but this is not the representation of all patients.”

However, the voices of patients who are more cautious and want evidence of benefit before accepting toxicities don’t make headlines, he added. 

What this survey means from a policy perspective, said Gyawali, is that accelerated approvals that do not mandate survival endpoint in confirmatory trials are ignoring the need of many patients who prioritize certainty of benefit over speed of access.

The study was funded by the London School of Economics and Political Science Phelan United States Centre. Forrest had no relevant disclosures. Gyawali has received consulting fees from Vivio Health. Patel has various relationships with AbbVie, Anheart, AstraZeneca, Bristol-Myers Squibb, Guardant, Tempus, Sanofi, BluePrint, Takeda, and Gilead.

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

Rose Gerber was 39, mother to a third grader and a kindergartener, when the diagnosis came: Advanced HER2-positive breast cancer.

“On one of my first or second appointments, I took in a little picture of Alexander and Isabella,” Gerber said. Gerber showed her oncologist the picture and told her: “I’ll do anything. I just want to be there for them.”

That was 21 years ago. Today, her current cancer status is “no evidence of disease.”

Over the past 2 decades, Gerber has gotten to be there for her children. Her youngest is now a television producer and her oldest, a CPA.

In that time, Gerber has had one constant: Her oncologist, Kandhasamy Jagathambal, MD, or Dr. Jaga, as she’s often called. 

“I’ve seen multiple physicians over my 21 years, but my oncologist has always been the focal point, guiding me in the right direction,” Gerber said in an interview.

Over the years, Jaga guided Gerber through a range of treatment decisions, including a Herceptin clinical trial that the mom of two views as lifesaving. Jaga often took on the role of both doctor and therapist, even providing comfort in the smaller moments when Gerber would fret about her weight gain.

The oncologist-patient “bond is very, very, very special,” said Gerber, who now works as director of patient advocacy and education at the Community Oncology Alliance.

Gerber isn’t alone in calling out the depth of the oncologist-patient bond.

Over years, sometimes decades, patients and oncologists can experience a whole world together: The treatment successes, relapses, uncertainties, and tough calls. As a result, a deep therapeutic alliance often develops. And with each new hurdle or decision, that collaborative, human connection between doctor and patient continues to form new layers.

“It’s like a shared bonding experience over trauma, like strangers trapped on a subway and then we get out, and we’re now on the other side, celebrating together,” said Saad Khan, MD, an associate professor of medicine (oncology) at Stanford University in California.

 

Connecting Through Stress

Although studies exploring the oncologist-patient bond are limited, some research suggests that a strong therapeutic alliance between patients and oncologists not only provides a foundation for quality care but can also help improve patients’ quality of life, protect against suicidal ideation, and increase treatment adherence.

Because of how stressful and frightening a cancer diagnosis can be, creating “a trusting, uninterrupted, almost sacred environment for them” is paramount for Khan. “I have no doubt that the most important part of their treatment is that they find an oncologist in whom they have total confidence,” Khan wrote in a blog.

The stress that patients with cancer experience is well documented, but oncologists take on a lot themselves and can also experience intense stress (.

“I consider my patient’s battles to be my battles,” Khan wrote.

The stress can start with the daily schedule. Oncologists often have a high volume of patients and tend to spend more time with each individual than most.

According to a 2023 survey, oncologists see about 68 patients a week, on average, but some oncologists, like Khan, have many more. Khan typically sees 20-30 patients a day and continues to care for many over years.

The survey also found that oncologists tend to spend a lot of time with their patients. Compared with other physicians, oncologists are two times more likely to spend at least 25 minutes with each patient.

With this kind of patient volume and time, Khan said, “you’re going to be exhausted.”

What can compound the exhaustion are the occasions oncologists need to deliver bad news — this treatment isn’t working, your cancer has come roaring back and, perhaps the hardest, we have no therapeutic options left. The end-of-life conversations, in particular, can be heartbreaking, especially when a patient is young and not ready to stop trying.

“It can be hard for doctors to discuss the end of life,” Don Dizon, MD, director of the Pelvic Malignancies Program at Lifespan Cancer Institute and director of Medical Oncology at Rhode Island Hospital, Providence, wrote in a column in 2023. Instead, it can be tempting and is often easier to focus on the next treatment, “instilling hope that there’s more that can be done,” even if doing more will only do harm.

In the face of these challenging decisions, growing a personal connection with patients over time can help keep oncologists going.

“We’re not just chemotherapy salesmen,” Khan said in an interview. “We get to know their social support network, who’s going to be driving them [to and from appointments], where they go on vacation, their cat’s name, who their neighbors are.”

 

A ‘Special Relationship’

Ralph V. Boccia, MD, is often asked what he does.

The next question that often comes — “Why do I do what I do?” — is Boccia’s favorite.

“Someone needs to take these patients through their journey,” Boccia, the founder of The Center for Cancer and Blood Disorders, Bethesda, Maryland, typically responds. He also often notes that “it is a special relationship you develop with the patient and their families.”

Boccia thinks about one long-term patient who captures this bond.

Joan Pinson, 70, was diagnosed with multiple myeloma about 25 years ago, when patients’ average survival was about 4 years.

Over a quarter century, Pinson has pivoted to different treatments, amid multiple relapses and remissions. Throughout most of this cancer journey, Boccia has been her primary oncologist, performing a stem cell transplant in 2000 and steering her to six clinical trials.

Her last relapse was 2 years ago, and since then she has been doing well on oral chemotherapy.

“Every time I relapsed, by the next appointment, he’d say, ‘here is what we are going to do,’ ” Pinson recalled. “I never worried, I never panicked. I knew he would take care of me.”

Over the years, Pinson and Boccia have shared many personal moments, sometimes by accident. One special moment happened early on in Pinson’s cancer journey. During an appointment, Boccia had “one ear to the phone” as his wife was about to deliver their first baby, Pinson recalled.

Later, Pinson met that child as a young man working in Boccia’s lab. She has also met Boccia’s wife, a nurse, when she filled in one day in the chemotherapy room.

Boccia now also treats Pinson’s husband who has prostate cancer, and he ruled out cancer when Pinson’s son, now in his 40s, had some worrisome symptoms.

More than 2 decades ago, Pinson told Boccia her goal was to see her youngest child graduate from high school. Now, six grandsons later, she has lived far beyond that goal.

“He has kept me alive,” said Pinson.

 

The Dying Patient

Harsha Vyas, MD, FACP, remembers the first encounter his office had with a 29-year-old woman referred with a diagnosis of stage IV breast cancer.

After just 15 minutes in the waiting room, the woman announced she was leaving. Although office staff assured the woman that she was next, the patient walked out.

Several months later, Vyas was called for an inpatient consult. It was the same woman.

Her lungs were full of fluid, and she was struggling to breathe, said Vyas, president and CEO of the Cancer Center of Middle Georgia, Dublin, and assistant professor at Augusta University in Georgia.

The woman, a single mother, told Vyas about her three young kids at home and asked him, “Doc, do something, please help me,” he recalled.

“Absolutely,” Vyas told her. But he had to be brutally honest about her prognosis and firm that she needed to follow his instructions. “You have a breast cancer I cannot cure,” he said. “All I can do is control the disease.”

From that first day, until the day she died, she came to every appointment and followed the treatment plan Vyas laid out.

For about 2 years, she responded well to treatment. And as the time passed and the trust grew, she began to open up to him. She showed him pictures. She talked about her children and being a mother.

“I’ve got to get my kids in a better place. I’m going to be there for them,” he recalled her saying.

Vyas admired her resourcefulness. She held down a part-time job, working retail and at a local restaurant. She figured out childcare so she could get to her chemotherapy appointments every 3 weeks and manage the copays.

Several years later, when she knew she was approaching the end of her life, she asked Vyas a question that hit hard.

“Doc, I don’t want to die and my kids find me dead. What can we do about it?”

Vyas, who has three daughters, imagined how traumatic this would be for a child. She and Vyas made the shared decision to cease treatment and begin home hospice. When the end was approaching, a hospice worker took over, waiting for bodily functions to cease.

When news of a death comes, “I say a little prayer, it’s almost like a send-off for that soul. That helps me absorb the news ... and let it go.”

But when the bond grows strong over time, as with his patient with breast cancer, Vyas said, “a piece of her is still with me.”

Khan had no relevant disclosures. Boccia and Vyas had no disclosures.

A version of this article appeared on Medscape.com.

Rose Gerber was 39, mother to a third grader and a kindergartener, when the diagnosis came: Advanced HER2-positive breast cancer.

“On one of my first or second appointments, I took in a little picture of Alexander and Isabella,” Gerber said. Gerber showed her oncologist the picture and told her: “I’ll do anything. I just want to be there for them.”

That was 21 years ago. Today, her current cancer status is “no evidence of disease.”

Over the past 2 decades, Gerber has gotten to be there for her children. Her youngest is now a television producer and her oldest, a CPA.

In that time, Gerber has had one constant: Her oncologist, Kandhasamy Jagathambal, MD, or Dr. Jaga, as she’s often called. 

“I’ve seen multiple physicians over my 21 years, but my oncologist has always been the focal point, guiding me in the right direction,” Gerber said in an interview.

Over the years, Jaga guided Gerber through a range of treatment decisions, including a Herceptin clinical trial that the mom of two views as lifesaving. Jaga often took on the role of both doctor and therapist, even providing comfort in the smaller moments when Gerber would fret about her weight gain.

The oncologist-patient “bond is very, very, very special,” said Gerber, who now works as director of patient advocacy and education at the Community Oncology Alliance.

Gerber isn’t alone in calling out the depth of the oncologist-patient bond.

Over years, sometimes decades, patients and oncologists can experience a whole world together: The treatment successes, relapses, uncertainties, and tough calls. As a result, a deep therapeutic alliance often develops. And with each new hurdle or decision, that collaborative, human connection between doctor and patient continues to form new layers.

“It’s like a shared bonding experience over trauma, like strangers trapped on a subway and then we get out, and we’re now on the other side, celebrating together,” said Saad Khan, MD, an associate professor of medicine (oncology) at Stanford University in California.

 

Connecting Through Stress

Although studies exploring the oncologist-patient bond are limited, some research suggests that a strong therapeutic alliance between patients and oncologists not only provides a foundation for quality care but can also help improve patients’ quality of life, protect against suicidal ideation, and increase treatment adherence.

Because of how stressful and frightening a cancer diagnosis can be, creating “a trusting, uninterrupted, almost sacred environment for them” is paramount for Khan. “I have no doubt that the most important part of their treatment is that they find an oncologist in whom they have total confidence,” Khan wrote in a blog.

The stress that patients with cancer experience is well documented, but oncologists take on a lot themselves and can also experience intense stress (.

“I consider my patient’s battles to be my battles,” Khan wrote.

The stress can start with the daily schedule. Oncologists often have a high volume of patients and tend to spend more time with each individual than most.

According to a 2023 survey, oncologists see about 68 patients a week, on average, but some oncologists, like Khan, have many more. Khan typically sees 20-30 patients a day and continues to care for many over years.

The survey also found that oncologists tend to spend a lot of time with their patients. Compared with other physicians, oncologists are two times more likely to spend at least 25 minutes with each patient.

With this kind of patient volume and time, Khan said, “you’re going to be exhausted.”

What can compound the exhaustion are the occasions oncologists need to deliver bad news — this treatment isn’t working, your cancer has come roaring back and, perhaps the hardest, we have no therapeutic options left. The end-of-life conversations, in particular, can be heartbreaking, especially when a patient is young and not ready to stop trying.

“It can be hard for doctors to discuss the end of life,” Don Dizon, MD, director of the Pelvic Malignancies Program at Lifespan Cancer Institute and director of Medical Oncology at Rhode Island Hospital, Providence, wrote in a column in 2023. Instead, it can be tempting and is often easier to focus on the next treatment, “instilling hope that there’s more that can be done,” even if doing more will only do harm.

In the face of these challenging decisions, growing a personal connection with patients over time can help keep oncologists going.

“We’re not just chemotherapy salesmen,” Khan said in an interview. “We get to know their social support network, who’s going to be driving them [to and from appointments], where they go on vacation, their cat’s name, who their neighbors are.”

 

A ‘Special Relationship’

Ralph V. Boccia, MD, is often asked what he does.

The next question that often comes — “Why do I do what I do?” — is Boccia’s favorite.

“Someone needs to take these patients through their journey,” Boccia, the founder of The Center for Cancer and Blood Disorders, Bethesda, Maryland, typically responds. He also often notes that “it is a special relationship you develop with the patient and their families.”

Boccia thinks about one long-term patient who captures this bond.

Joan Pinson, 70, was diagnosed with multiple myeloma about 25 years ago, when patients’ average survival was about 4 years.

Over a quarter century, Pinson has pivoted to different treatments, amid multiple relapses and remissions. Throughout most of this cancer journey, Boccia has been her primary oncologist, performing a stem cell transplant in 2000 and steering her to six clinical trials.

Her last relapse was 2 years ago, and since then she has been doing well on oral chemotherapy.

“Every time I relapsed, by the next appointment, he’d say, ‘here is what we are going to do,’ ” Pinson recalled. “I never worried, I never panicked. I knew he would take care of me.”

Over the years, Pinson and Boccia have shared many personal moments, sometimes by accident. One special moment happened early on in Pinson’s cancer journey. During an appointment, Boccia had “one ear to the phone” as his wife was about to deliver their first baby, Pinson recalled.

Later, Pinson met that child as a young man working in Boccia’s lab. She has also met Boccia’s wife, a nurse, when she filled in one day in the chemotherapy room.

Boccia now also treats Pinson’s husband who has prostate cancer, and he ruled out cancer when Pinson’s son, now in his 40s, had some worrisome symptoms.

More than 2 decades ago, Pinson told Boccia her goal was to see her youngest child graduate from high school. Now, six grandsons later, she has lived far beyond that goal.

“He has kept me alive,” said Pinson.

 

The Dying Patient

Harsha Vyas, MD, FACP, remembers the first encounter his office had with a 29-year-old woman referred with a diagnosis of stage IV breast cancer.

After just 15 minutes in the waiting room, the woman announced she was leaving. Although office staff assured the woman that she was next, the patient walked out.

Several months later, Vyas was called for an inpatient consult. It was the same woman.

Her lungs were full of fluid, and she was struggling to breathe, said Vyas, president and CEO of the Cancer Center of Middle Georgia, Dublin, and assistant professor at Augusta University in Georgia.

The woman, a single mother, told Vyas about her three young kids at home and asked him, “Doc, do something, please help me,” he recalled.

“Absolutely,” Vyas told her. But he had to be brutally honest about her prognosis and firm that she needed to follow his instructions. “You have a breast cancer I cannot cure,” he said. “All I can do is control the disease.”

From that first day, until the day she died, she came to every appointment and followed the treatment plan Vyas laid out.

For about 2 years, she responded well to treatment. And as the time passed and the trust grew, she began to open up to him. She showed him pictures. She talked about her children and being a mother.

“I’ve got to get my kids in a better place. I’m going to be there for them,” he recalled her saying.

Vyas admired her resourcefulness. She held down a part-time job, working retail and at a local restaurant. She figured out childcare so she could get to her chemotherapy appointments every 3 weeks and manage the copays.

Several years later, when she knew she was approaching the end of her life, she asked Vyas a question that hit hard.

“Doc, I don’t want to die and my kids find me dead. What can we do about it?”

Vyas, who has three daughters, imagined how traumatic this would be for a child. She and Vyas made the shared decision to cease treatment and begin home hospice. When the end was approaching, a hospice worker took over, waiting for bodily functions to cease.

When news of a death comes, “I say a little prayer, it’s almost like a send-off for that soul. That helps me absorb the news ... and let it go.”

But when the bond grows strong over time, as with his patient with breast cancer, Vyas said, “a piece of her is still with me.”

Khan had no relevant disclosures. Boccia and Vyas had no disclosures.

A version of this article appeared on Medscape.com.

Rose Gerber was 39, mother to a third grader and a kindergartener, when the diagnosis came: Advanced HER2-positive breast cancer.

“On one of my first or second appointments, I took in a little picture of Alexander and Isabella,” Gerber said. Gerber showed her oncologist the picture and told her: “I’ll do anything. I just want to be there for them.”

That was 21 years ago. Today, her current cancer status is “no evidence of disease.”

Over the past 2 decades, Gerber has gotten to be there for her children. Her youngest is now a television producer and her oldest, a CPA.

In that time, Gerber has had one constant: Her oncologist, Kandhasamy Jagathambal, MD, or Dr. Jaga, as she’s often called. 

“I’ve seen multiple physicians over my 21 years, but my oncologist has always been the focal point, guiding me in the right direction,” Gerber said in an interview.

Over the years, Jaga guided Gerber through a range of treatment decisions, including a Herceptin clinical trial that the mom of two views as lifesaving. Jaga often took on the role of both doctor and therapist, even providing comfort in the smaller moments when Gerber would fret about her weight gain.

The oncologist-patient “bond is very, very, very special,” said Gerber, who now works as director of patient advocacy and education at the Community Oncology Alliance.

Gerber isn’t alone in calling out the depth of the oncologist-patient bond.

Over years, sometimes decades, patients and oncologists can experience a whole world together: The treatment successes, relapses, uncertainties, and tough calls. As a result, a deep therapeutic alliance often develops. And with each new hurdle or decision, that collaborative, human connection between doctor and patient continues to form new layers.

“It’s like a shared bonding experience over trauma, like strangers trapped on a subway and then we get out, and we’re now on the other side, celebrating together,” said Saad Khan, MD, an associate professor of medicine (oncology) at Stanford University in California.

 

Connecting Through Stress

Although studies exploring the oncologist-patient bond are limited, some research suggests that a strong therapeutic alliance between patients and oncologists not only provides a foundation for quality care but can also help improve patients’ quality of life, protect against suicidal ideation, and increase treatment adherence.

Because of how stressful and frightening a cancer diagnosis can be, creating “a trusting, uninterrupted, almost sacred environment for them” is paramount for Khan. “I have no doubt that the most important part of their treatment is that they find an oncologist in whom they have total confidence,” Khan wrote in a blog.

The stress that patients with cancer experience is well documented, but oncologists take on a lot themselves and can also experience intense stress (.

“I consider my patient’s battles to be my battles,” Khan wrote.

The stress can start with the daily schedule. Oncologists often have a high volume of patients and tend to spend more time with each individual than most.

According to a 2023 survey, oncologists see about 68 patients a week, on average, but some oncologists, like Khan, have many more. Khan typically sees 20-30 patients a day and continues to care for many over years.

The survey also found that oncologists tend to spend a lot of time with their patients. Compared with other physicians, oncologists are two times more likely to spend at least 25 minutes with each patient.

With this kind of patient volume and time, Khan said, “you’re going to be exhausted.”

What can compound the exhaustion are the occasions oncologists need to deliver bad news — this treatment isn’t working, your cancer has come roaring back and, perhaps the hardest, we have no therapeutic options left. The end-of-life conversations, in particular, can be heartbreaking, especially when a patient is young and not ready to stop trying.

“It can be hard for doctors to discuss the end of life,” Don Dizon, MD, director of the Pelvic Malignancies Program at Lifespan Cancer Institute and director of Medical Oncology at Rhode Island Hospital, Providence, wrote in a column in 2023. Instead, it can be tempting and is often easier to focus on the next treatment, “instilling hope that there’s more that can be done,” even if doing more will only do harm.

In the face of these challenging decisions, growing a personal connection with patients over time can help keep oncologists going.

“We’re not just chemotherapy salesmen,” Khan said in an interview. “We get to know their social support network, who’s going to be driving them [to and from appointments], where they go on vacation, their cat’s name, who their neighbors are.”

 

A ‘Special Relationship’

Ralph V. Boccia, MD, is often asked what he does.

The next question that often comes — “Why do I do what I do?” — is Boccia’s favorite.

“Someone needs to take these patients through their journey,” Boccia, the founder of The Center for Cancer and Blood Disorders, Bethesda, Maryland, typically responds. He also often notes that “it is a special relationship you develop with the patient and their families.”

Boccia thinks about one long-term patient who captures this bond.

Joan Pinson, 70, was diagnosed with multiple myeloma about 25 years ago, when patients’ average survival was about 4 years.

Over a quarter century, Pinson has pivoted to different treatments, amid multiple relapses and remissions. Throughout most of this cancer journey, Boccia has been her primary oncologist, performing a stem cell transplant in 2000 and steering her to six clinical trials.

Her last relapse was 2 years ago, and since then she has been doing well on oral chemotherapy.

“Every time I relapsed, by the next appointment, he’d say, ‘here is what we are going to do,’ ” Pinson recalled. “I never worried, I never panicked. I knew he would take care of me.”

Over the years, Pinson and Boccia have shared many personal moments, sometimes by accident. One special moment happened early on in Pinson’s cancer journey. During an appointment, Boccia had “one ear to the phone” as his wife was about to deliver their first baby, Pinson recalled.

Later, Pinson met that child as a young man working in Boccia’s lab. She has also met Boccia’s wife, a nurse, when she filled in one day in the chemotherapy room.

Boccia now also treats Pinson’s husband who has prostate cancer, and he ruled out cancer when Pinson’s son, now in his 40s, had some worrisome symptoms.

More than 2 decades ago, Pinson told Boccia her goal was to see her youngest child graduate from high school. Now, six grandsons later, she has lived far beyond that goal.

“He has kept me alive,” said Pinson.

 

The Dying Patient

Harsha Vyas, MD, FACP, remembers the first encounter his office had with a 29-year-old woman referred with a diagnosis of stage IV breast cancer.

After just 15 minutes in the waiting room, the woman announced she was leaving. Although office staff assured the woman that she was next, the patient walked out.

Several months later, Vyas was called for an inpatient consult. It was the same woman.

Her lungs were full of fluid, and she was struggling to breathe, said Vyas, president and CEO of the Cancer Center of Middle Georgia, Dublin, and assistant professor at Augusta University in Georgia.

The woman, a single mother, told Vyas about her three young kids at home and asked him, “Doc, do something, please help me,” he recalled.

“Absolutely,” Vyas told her. But he had to be brutally honest about her prognosis and firm that she needed to follow his instructions. “You have a breast cancer I cannot cure,” he said. “All I can do is control the disease.”

From that first day, until the day she died, she came to every appointment and followed the treatment plan Vyas laid out.

For about 2 years, she responded well to treatment. And as the time passed and the trust grew, she began to open up to him. She showed him pictures. She talked about her children and being a mother.

“I’ve got to get my kids in a better place. I’m going to be there for them,” he recalled her saying.

Vyas admired her resourcefulness. She held down a part-time job, working retail and at a local restaurant. She figured out childcare so she could get to her chemotherapy appointments every 3 weeks and manage the copays.

Several years later, when she knew she was approaching the end of her life, she asked Vyas a question that hit hard.

“Doc, I don’t want to die and my kids find me dead. What can we do about it?”

Vyas, who has three daughters, imagined how traumatic this would be for a child. She and Vyas made the shared decision to cease treatment and begin home hospice. When the end was approaching, a hospice worker took over, waiting for bodily functions to cease.

When news of a death comes, “I say a little prayer, it’s almost like a send-off for that soul. That helps me absorb the news ... and let it go.”

But when the bond grows strong over time, as with his patient with breast cancer, Vyas said, “a piece of her is still with me.”

Khan had no relevant disclosures. Boccia and Vyas had no disclosures.

A version of this article appeared on Medscape.com.