The prevalence of gene mutations in homologous recombination repair pathways in Japanese patients with metastatic castration-resistant prostate cancer in real-world clinical practice: The multi-institutional observational ZENSHIN study

Hiroji Uemura, Mototsugu Oya, Toshiyuki Kamoto, Mikio Sugimoto, Kenta Shinozaki, Kiyomi Morita, Ryo Koto, Mai Takahashi, Masahiro Nii, Eisei Shin, Norio Nonomura

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Background: Metastatic castration-resistant prostate cancer (mCRPC) is a genetically heterogeneous disease with a poor prognosis. The prevalence of mutations in homologous recombination repair (HRR) pathway genes, including BRCA1/2, as well as treatment patterns and clinical outcomes, are not well characterized among Japanese men with mCRPC. Methods: This multicenter, noninterventional cohort study enrolled Japanese men with mCRPC from 24 institutions between 2014 and 2018. Mutations in the 15 HRR-related genes were assessed using archival primary or metastatic tumor samples. Patterns of sequential therapies for mCRPC were investigated. Patients were followed up for survival evaluation including prostate-specific antigen progression-free survival (PSA-PFS) and overall survival (OS). Results: Of the 143 patients analyzed, HRR-related mutations were detected in 51 patients (35.7%). The most frequently mutated genes were CDK12 (N = 19, 13.3%), followed by BRCA2 (N = 18, 12.6%), ATM (N = 8, 5.6%), and CHEK2 (N = 3, 2.1%). The most common type of first-line therapy for mCRPC was next-generation hormonal agents (NHA, 44.4%), followed by first-generation antiandrogens (FGA, 30.3%), and taxanes (22.5%). Commonly prescribed first−/second-line sequential regimens included FGA/NHA (17.6%), NHA/NHA (15.5%), and NHA/taxanes (14.1%). The median PSA-PFS and OS for the entire cohort were 5.6 and 26.1 months, respectively. Patients carrying BRCA1/2 mutations had numerically shorter PSA-PFS (median 3.3 vs. 5.9 months) and OS (median 20.7 vs. 27.3 months) than those without mutations. Conclusions: In conclusion, approximately one-third of Japanese patients with mCRPC carried mutations in HRR-related genes in this study. The real-world outcomes of mCRPC are poor with conventional therapy, warranting an expansion of treatment options based on genetic abnormalities of the disease.

Original languageEnglish
Pages (from-to)5265-5274
Number of pages10
JournalCancer medicine
Volume12
Issue number5
DOIs
Publication statusPublished - 2023 Mar

Keywords

  • BRCA
  • homologous recombination repair
  • metastatic castration-resistance prostate cancer
  • survival

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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