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Title: Efficacy of National Comprehensive Cancer Network Guidelines in Identifying Pathogenic Germline Variants Among Unselected Patients with Prostate Cancer: The PROCLAIM Trial.
Author: Shore N, Gazi M, Pieczonka C, Heron S, Modh R, Cahn D, Belkoff LH, Berger A, Mazzarella B, Veys J, Idom C, Morris D, Jayram G, Engelman A, Bukkapatnam R, Dato P, Bevan-Thomas R, Cornell R, Wise DR, Hardwick MK, Hernandez RD, Rojahn S, Layman P, Hatchell KE, Heald B, Nussbaum RL, Nielsen SM, Esplin ED.
Journal: Eur Urol Oncol; 2023 Oct; 6(5):477-483. PubMed ID: 37574391.
Abstract:
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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