Data from Germline DNA Damage Repair Variants and Prognosis of Patients with High-Risk or Metastatic Prostate Cancer

<div>AbstractPurpose:<p>Deleterious germline variants in certain DNA repair genes are risk factors for developing aggressive prostate cancer. The objective was to quantify their prognostic impact after prostate cancer diagnosis.</p>Experimental Design:<p>Men with prostate cancer, predominantly of European ancestry, were included from four cohorts with long-term follow-up. Pathogenic or likely pathogenic germline variants in 26 DNA repair genes were assessed in relation to metastasis-free survival in high-risk localized prostate cancer and to overall survival in metastatic castration-sensitive prostate cancer (mCSPC) and metastatic castration-resistant prostate cancer (mCRPC).</p>Results:<p>Among 3,525 patients initially diagnosed with nonmetastatic prostate cancer, 2,594 had high-risk localized prostate cancer, 429 had mCSPC, and 502 had mCRPC at inclusion. <i>BRCA2</i> variant carriers did not have worse metastasis-free survival in high-risk localized prostate cancer [hazard ratio (HR), 1.01; 95% confidence interval (CI), 0.69–1.46] or overall survival in mCSPC (HR, 0.46; 95% CI, 0.14–1.45) or mCRPC (HR, 0.60; 95% CI, 0.31–1.17) compared with noncarriers of DNA repair variants. Among 868 additional patients with <i>de novo</i> metastatic (M1) prostate cancer, <i>BRCA2</i> variant carriers tended to have worse overall survival (HR, 1.59; 95% CI, 1.01–2.51). <i>BRCA2</i> prognostic associations were not explained by radiation, PARP inhibitor, or platinum therapy. Results for other genes were limited in precision because variants were less common.</p>Conclusions:<p>Among patients with high-risk or metastatic prostate cancer who were initially diagnosed with and treated for nonmetastatic tumors, germline DNA repair variants in <i>BRCA2</i> do not confer a substantially worse prognosis.</p></div>