There is increasing awareness that patients with prostate cancer frequently harbor germline variants that may carry important implications for them and their family members. Given variable clinical guidelines, there remains a need to better understand which patients with prostate cancer are likely to harbor pathogenic or likely pathogenic (P/LP) germline variants. We sought to understand factors associated with P/LP germline variants in patients with metastatic or localized prostate cancer qualifying for NCCN genetic testing criteria.
Patients diagnosed with prostate cancer were offered genetic testing in accordance with National Comprehensive Cancer Network (NCCN) guidelines. Patient-level factors, including demographic, clinical, and pathologic data, were tracked in a prospectively collected registry. The association of the presence of a P/LP variant in germline testing results with patient-level factors was assessed using univariate and multivariate logistic regression. Variables were tested for overall significance with chi-squared tests.
505 patients underwent germline testing and had clinical data available. Rates of P/LP germline variants were 7.6% (20/264) in patients with metastatic disease, and 11.2% (27/241) in patients with localized disease. The most prevalent P/LP variants were CHEK2 (34%), BRCA2 (22%), ATM (10%), and HOXB13 (10%).
In this cohort of patients undergoing guideline-informed germline testing, P/LP germline variants were found in similar proportions across all age ranges and clinical characteristics. Only age at genetic testing for patients with metastatic disease was demonstrated to be predictive of the presence of a P/LP germline variant, highlighting the challenges associated with refining current clinical testing guidelines.
Urology practice. 2024 Oct 09 [Epub ahead of print]
Sophia M Abusamra, Marissa A Solorzano, Jake Quarles, Mallory Luke, Milan Patel, Randy Vince, Ralph Jiang, Joshua Volin, Michelle F Jacobs, Samuel Kaffenberger, Simpa S Salami, Phillip Palmbos, Megan E V Caram, Brent K Hollenbeck, Ganesh S Palapattu, Sofia D Merajver, Elena M Stoffel, Jason Hafron, Todd M Morgan, Zachery R Reichert
Department of Urology, University of Michigan, Ann Arbor, MI, USA., Michigan Institute of Urology, 130 Town Center Drive, Suite 101, Troy, MI, USA., Department of Urology, Loyola University Medical Center, Maywood, IL., Department of Biostatics, University of Michigan, Ann Arbor, MI, USA., Oakland University William Beaumont School of Medicine, Beaumont Hospital, Royal Oak, MI, USA., Department of Internal Medicine, Division of Genetic Medicine, University of Michigan, Ann Arbor, MI, USA., Department of Internal Medicine, Hematology/Oncology Division, University of Michigan Medical School, Ann Arbor, MI, USA.