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  • Title: Prognostic value of germline mutations in metastatic hormone-sensitive prostate cancer (mHSPC).
    Author: Custodio-Cabello S, Pacheco-Barcia V, Palka-Kotlowska M, Fernández-Hernández L, Del Álamo JF, Oliveros-Acebes E, Cabezón-Gutiérrez L.
    Journal: Urol Oncol; 2024 Oct; 42(10):331.e13-331.e24. PubMed ID: 38926076.
    Abstract:
    BACKGROUND: About 8% to 12% of patients presenting with mHSPC exhibit germline pathogenic variants (PV) in cancer predisposition genes. The aim of this study is to assess the presence of germline PV as a prognostic factor in the setting of mHSPC and to determine whether mutational status can predict rapid progression to castration resistance. METHODS: Genetic analysis using a multigene next-generation sequencing (NGS) panel was performed on 34 patients diagnosed with mHSPC undergoing treatment. We assessed the prevalence of germline PV and examined differences based on clinical-pathological characteristics, family history (FH), prostate-specific antigen (PSA) response, impact on time to castration-resistant prostate cancer (TTCRPC), and overall survival (OS). RESULTS: Germline PV were identified in 6 patients (17,6%). When comparing the clinical-pathological characteristics of PV carriers (n = 6) to noncarriers (n = 28), no significant associations were observed except for the presence of FH of hereditary breast and ovarian cancer (HBOC) syndrome and/or Lynch syndrome (P = 0.024). At a median follow-up of 33 months, significant differences in OS were observed based on the presence of PV (26 months in carriers vs. 74 months in noncarriers; P < 0.01). Patients who harbored a BRCA2 mutation (n = 3) showed a worse clinical outcome, presenting a shorter TTCRPC (7 months vs. 23 months; P = 0.005) and lower OS (7 months vs. 74 months; P < 0.001) compared to noncarriers (n = 31). CONCLUSION: mHSPC germline PV carriers had a worse survival outcome. Furthermore, BRCA2 germline mutation was an independent poor prognostic factor for mHSPC disease, associated with earlier progression to castration-resistant prostate cancer, and shorter OS. These results highlight the importance of evaluating germline mutational status in patients with hormone-sensitive prostate cancer.
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