Association of BRCA2 protein expression by immunohistochemistry with biochemical recurrence in localized prostate cancer treated with radiotherapy: A long-term outcome analysis.

Radiotherapy (RT) is a standard treatment for localized prostate cancer (CaP); however, reliable biomarkers for predicting biochemical outcomes after RT remain limited. Although genomic BRCA2 alterations have been associated with aggressive disease, the clinical significance of BRCA2 protein expression following RT has not been well defined. We retrospectively analyzed 174 patients with localized CaP treated with definitive RT between 2007 and 2017. BRCA2 protein expression was assessed by immunohistochemistry (IHC) on biopsy specimens, with ≥10% nuclear positivity defined as BRCA2 positive. Survival outcomes were compared using Kaplan-Meier and Cox regression analyses. The median follow-up period was 114.7 months. Among 174 patients, 53 (30.5%) were BRCA2 positive. During follow-up, 31 patients (17.8%) developed biochemical recurrence (BCR), 19 (10.9%) progressed to castration-resistant prostate cancer (CRPC), 11 (6.3%) had distant metastases and 4 (2.3%) died of the disease. BRCA2 positive patients had significantly worse BCR-free survival (mean 140.3 vs. 169.3 months, P = 0.028), while metastasis-free, CRPC-free, or cancer-specific survival did not differ significantly. On multivariate analysis, BRCA2 positive was independently associated with BCR (hazard ratio 2.05; 95% confidence interval 1.17-4.34; P = 0.041). BRCA2 positive was associated with an increased risk of BCR following RT in localized CaP, suggesting that BRCA2 protein expression by IHC may help identify patients at increased risk of BCR after RT. IHC-based assessment of BRCA2 protein expression may offer clinically useful prognostic information. Prospective studies are warranted to validate these findings.