Prostate Cancer Therapeutic Decision-Making Is Better Informed With an Expanded Genetic Panel

The following article features coverage from the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. Click here to read more of Oncology Nurse Advisor‘s conference coverage.

Use of an expanded 84-gene panel genetic test identified more medically actionable germline pathogenic variants (GPVs) than testing for BRCA1/2 genes alone or using prostate cancer panels with 12 genes. These findings were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

Germline pathogenic variants (GPVs) occur in approximately 12% to 17% of all patients with prostate cancer (PCa). Identifying GPVs allows for precision-based, therapeutic decision-making; however, genetic testing in this patient population is underutilized due in part to restrictive and complex guidelines. This study was conducted to determine the incidence of GPVs among patients with prostate cancer who did and did not meet the National Comprehensive Cancer Network (NCCN) 2019 prostate cancer germline genetic testing criteria.

Researchers initiated an institutional review board-approved, prospective registry across 15 community and academic sites in the United States. Participating clinicians completed Health Insurance Portability and Accountability Act (HIPAA)-compliant electronic case report forms that collected information about patient diagnoses, NCCN testing criteria, and results-based recommendations.

Eligibility criteria included a prostate cancer diagnosis unselected for personal or family history, stage, or histology, and the patient had not previously undergone genetic testing. Consecutive patients aged 18 to 90 years were recruited. A clinical case report form and an 84-gene germline panel test were completed for all enrolled patients. The goal was to collect data from 1000 patients.

To date, 615 patients (median age 70 years) have been evaluated. Overall, GPVs were detected in 51 (8%) patients, 19% of which were in the BRCA1/2 genes. Most of the other GPVs occurred in homologous recombinant repair genes.

Of the evaluated patients, 58% (358 patients) met NCCN criteria (in-criteria cohort), and 42% (257 patients) did not (out-of-criteria cohort). Using a large cancer panel (84 genes), GPV rate was 9.5% vs 6.5% in the in-criteria and out-of-criteria cohorts, respectively. GPV rate was 6.7% vs 4.7%, respectively, using the prostate cancer panel (12 genes). “Now these data indicate that current NCCN criteria are a poor predictor of the presence of GPV in any particular patient,” explained Neal Shore, MD, of the Carolina Urologic Research Center in Myrtle Beach, South Carolina.

Self-reported ethnicity of participants included 475 who identified as White/Caucasian, 104 as Black/African American, and 36 as Asian, Hispanic, or other. Stratified by self-reported ethnicity, GPV rate was significantly higher among White patients compared with Black patients in the in-criteria group (approximately 12% vs <2%); yet a higher percentage of GPVs were identified among the Black patients in the out-of-criteria group (approximately 5%).

No statistically significant difference was noted in the yield of GPVs between patients who were in criteria compared with those who were out of criteria for prostate cancer genetic germline testing. These data demonstrated that a significant number of GPVs would be missed if only NCCN guidelines were required for genetic testing.

Use of an expanded panel genetic test identifies more medically actionable GPVs than testing for BRCA1/2 genes alone or using prostate cancer panels with 12 genes. Although 18% of the study population self-identified as Black/African American, the GPV rate was lower (2%) relative to other groups. This indicated that more research is needed to understand genetic variation among underrepresented and underserved patient populations with prostate cancer.

Disclosure: This research was supported by Invitae. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Read more of Oncology Nurse Advisor’s coverage of the 2021 ASCO Annual Meeting by visiting the conference page.

Reference

Esplin ED, Cahn DJ, Mazzarella B, et al. Underdiagnosis of germline genetic prostate cancer: are genetic testing guidelines an aid or an impediment? J Clin Oncol. 2021;39(suppl15; abstr 10504). doi:10.1200/JCO.2021.39.15_suppl.10504