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BACKGROUND: 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. OBJECTIVE: To establish the prevalence of actionable PGVs among prospectively accrued, unselected PCa patients, stratified by their guideline eligibility. DESIGN, SETTING, AND PARTICIPANTS: Consecutive, unselected PCa patients were enrolled at 15 sites in the USA from October 2019 to August 2021, and had multigene cancer panel testing. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Correlates between the prevalence of PGVs and clinician-reported demographic and clinical characteristics were examined. RESULTS AND LIMITATIONS: 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. CONCLUSIONS: 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. PATIENT SUMMARY: 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.
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OBJECTIVE: The prognostic value of deoxyribonucleic acid (DNA) ploidy in renal cell carcinoma (RCC) is not well-defined among modern surgical nephrectomy series. We sought to determine which variables correlated with overall survival and recurrence-free survival in the modern era. METHODS: We reviewed all patients from 1992 to 2000, who prospectively had DNA ploidy analysis of their primary tumor determined at the time of nephrectomy for nonmetastatic RCC. Variables examined included age, gender, ethnicity, presentation (incidental vs. symptomatic), preoperative laboratory studies, American Society for Anesthesiology class, tumor size, tumor-nodes-metastasis stage, histology, Fuhrman grade, and diploid versus nondiploid tumor. Statistical analyses of overall survival and recurrence-free survival were performed using the Kaplan-Meier method, log-rank test, and Cox regression model using commercially available software. RESULTS: Sixty men and 41 women, median age 61 years (range, 23-85), were included. Pathologic stage included T1 (54 patients), T2 (14), and T3 (33). Eighty-four patients had conventional RCC. A total of 58 patients had well-differentiated (Fuhrman Grade 1 [12] or Grade 2 [46]), 28 had moderately differentiated (Grade 3), 12 had poorly differentiated tumors (Grade 4), and 3 were not specified. There were 52 patients who had diploid tumors, and 49 had aneuploid tumors. Median follow-up was 39 months (range, 0-109). Actuarial 5-year overall survival was 70%, and 5-year recurrence-free survival was 76%. Diploid tumors were significantly associated with better recurrence-free survival (P = 0.02) but not overall survival (P = 0.17). On multivariate analysis, the American Society for Anesthesiology class (P = 0.01), abnormal preoperative platelet count (P = 0.03), and tumor differentiation (P = 0.01) were independent predictors of overall survival, whereas only tumor differentiation (P = 0.05) was an independent predictor of recurrence-free survival. CONCLUSIONS: In the modern era, DNA ploidy is not an independent predictor of either overall survival or recurrence-free survival in patients with nonmetastatic RCC. The most important predictor of recurrence-free survival is tumor differentiation.
