This study aimed to investigate the prevalence of pathogenic germline variants (PGV) in hereditary cancer genes utilizing a universal testing approach and to determine the rate of PGV that would have been missed based on National Comprehensive Cancer Network (NCCN) guidelines in genitourinary (GU) malignancies.
A multi-site, single-institution prospective germline genetic test (GGT) was universally offered to patients with new or active diagnoses of GU malignancies (prostate, bladder, and renal) from April 2018 to March 2020 at Mayo Clinic sites. Participants were offered GGT using a next-generation sequencing panel of > 80 genes. Demographic, tumor characteristics, and genetic results were evaluated. NCCN GU cancer guidelines were used to identify whether patients had incremental findings, defined as PGV-positive patients who would not have received testing based on NCCN guidelines.
Of 3095 individuals enrolled in the study, 601 patients had GU cancer (prostate = 358, bladder = 106, and renal = 137). The mean enrollment age was 67 years (SD 9.1), 89% were male, and 86% of patients were non-Hispanic white. PGV were identified in 82 (14%) of all GU patients. PGV prevalence breakdown by cancer type was: 14% prostate, 14% bladder, and 13% renal cancer. Nearly one-third of identified PGV were high-penetrance and the majority of these (67%) were clinically actionable. Incremental PGV were identified in 28 (57%) prostate, 15 (100%) bladder, and renal 14 (78%) cancer patients. Of the 82 patients with PGV findings, 29 (35%) had at least one relative undergo cascade testing for the familial variant(s) identified.
More than 1 in 8 patients with GU malignancies were found to carry a PGV, with 67% of patients with high penetrance PGV undergoing clinically actionable changes. The majority of these PGV would not have been identified based on current testing criteria. These findings support universal GGT for GU malignancies and underscore its potential to enhance risk-assessment and guide precision interventions in urologic oncology.
The Journal of urology. 2024 Jun 11 [Epub ahead of print]
Mouneeb M Choudry, Adri M Durant, Victoria S Edmonds, Christopher J Warren, Katie L Kunze, Michael A Golafshar, Sarah M Nielsen, Edward D Esplin, Jack R Andrews, N Jewel Samadder, Mark D Tyson
Department of Urology, Mayo Clinic, Phoenix, Arizona., Department of Quantitative Health Sciences, Mayo Clinic, Scottsdale, Arizona., Invitae Corporation, San Francisco, California., Department of Clinical Genomics, Mayo Clinic, Phoenix, Arizona.