Prostate cancer (PCa) patients with pathogenic/likely pathogenic germline variants (PGVs) in cancer predisposition genes may be eligible for U.S. Food and Drug Administration-approved targeted therapies, clinical trials, or enhanced screening.
Studies suggest that eligible patients are missing genetics-informed care due to restrictive testing criteria.
To establish the prevalence of actionable PGVs among prospectively accrued, unselected PCa patients, stratified by their guideline eligibility.
Consecutive, unselected PCa patients were enrolled at 15 sites in the USA from October 2019 to August 2021, and had multigene cancer panel testing.
Correlates between the prevalence of PGVs and clinician-reported demographic and clinical characteristics were examined.
Among 958 patients (median [quartiles] age at diagnosis 65 [60, 71] yr), 627 (65%) had low- or intermediate-risk disease (grade group 1, 2, or 3). A total of 77 PGVs in 17 genes were identified in 74 patients (7.7%, 95% confidence interval [CI] 6.2-9.6%). No significant difference was found in the prevalence of PGVs among patients who met the 2019 National Comprehensive Cancer Network Prostate criteria (8.8%, 43/486, 95% CI 6.6-12%) versus those who did not (6.6%, 31/472, 95% CI 4.6-9.2%; odds ratio 1.38, 95% CI 0.85-2.23), indicating that these criteria would miss 42% of patients (31/74, 95% CI 31-53%) with PGVs. The criteria were less effective at predicting PGVs in patients from under-represented populations. Most PGVs (81%, 60/74) were potentially clinically actionable. Limitations include the inability to stratify analyses based on individual ethnicity due to low numbers of non-White patients with PGVs.
Our results indicate that almost half of PCa patients with PGVs are missed by current testing guidelines. Comprehensive germline genetic testing should be offered to all patients with PCa.
One in 13 patients with prostate cancer carries an inherited variant that may be actionable for the patient's current care or prevention of future cancer, and could benefit from expanded testing criteria.
European urology oncology. 2023 Aug 12 [Epub ahead of print]
Neal Shore, Mukaram Gazi, Christopher Pieczonka, Sean Heron, Rishi Modh, David Cahn, Laurence H Belkoff, Aaron Berger, Brian Mazzarella, Joseph Veys, Charles Idom, David Morris, Gautam Jayram, Alexander Engelman, Raviender Bukkapatnam, Paul Dato, Richard Bevan-Thomas, Robert Cornell, David R Wise, Mary Kay Hardwick, Ryan D Hernandez, Susan Rojahn, Paige Layman, Kathryn E Hatchell, Brandie Heald, Robert L Nussbaum, Sarah M Nielsen, Edward D Esplin
Carolina Urologic Research Center, Myrtle Beach, SC, USA. Electronic address: ., University Urology Associates of New Jersey, Hamilton, NJ, USA., Associated Medical Professionals, Syracuse, NY, USA., Advanced Urology Institute, St. Petersburg, FL, USA., Colorado Urology, Lakewood, CO, USA., MidLantic Urology, Bala Cynwyd, PA, USA., Associated Urological Specialists, Chicago Ridge, IL, USA., Urology Austin, Austin, TX, USA., North Georgia Urology, Dalton, GA, USA., Urology Associates, P.C., Nashville, TN, USA., TGH Cancer Institute, Tampa, FL, USA., Florida Urology Partners, Tampa, FL, USA., Genesis Healthcare Partners, San Diego, CA, USA., Urology Partners, Arlington, TX, USA., Urosurgery Houston, Houston, TX, USA., Perlmutter Cancer Center, NYU Langone Health, New York, NY, USA., Invitae Corporation, San Francisco, CA, USA., Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA., Invitae Corporation, San Francisco, CA, USA; Volunteer Faculty, University of California San Francisco, San Francisco, CA, USA.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/37574391