Effect of germ-line BRCA mutations in biochemical relapse and survival after treatment for localized prostate cancer.

Abstract

29 Background: Biochemical relapse after local treatment for prostate cancer (PCa) indicates recurrent disease and is associated with shorter cause-specific survival (CSS). Germline BRCA mutations are associated with worse PrCa outcomes. In this study, we analyzed biochemical-progression free survival (bPFS) after conventional treatments for localized PCa in a cohort of BRCA patients from the UK. Currently, BRCA1/2 carriers are treated with the same protocols used for non-carriers. Methods: In this retrospective case-control study, each BRCA carrier (10 BRCA1 and 34 BRCA2) treated with radical prostatectomy (RP) or external beam radiotherapy (RT) was matched with 3 non-carriers (NC) by: age at diagnosis (±5 yrs), TNM stage, Gleason score, presenting PSA, local treatment (RT or RP), androgen-deprivation therapy (ADT) and year of treatment (±5yrs). All NC were screened for BRCA1 and BRCA2 mutations. Biochemical failure was reviewed according to ASTRO and NCCN criteria. The Kaplan-Meier method and a multivariate Cox regression model adjusted by matching factors were employed. Results: 176 patients (pts) were included. Median follow-up was 97 months (ms). Median age at diagnosis was 58.5 yrs (43-75). 80 pts received RT (16 BRCA2, 4 BRCA1, 60 NC) and 85% also received ADT≥6 ms. 96pts underwent RP (18 BRCA2, 6 BRCA1 and 72 NC). Following RT treatment, 5yrs-CSS was 96% in NC and 47% in BRCA carriers (p=2x10-5), whilst no difference was seen after RP (5yrs-CSS was 98.5% in NC vs 93.3% in BRCA). Five-years bFPFS after RT was 74% in NC and 24% in BRCA (p=0.002). No difference was observed in 5yrs-bPFS between BRCA carriers and NC treated with RP (52% vs 66% , p=0.346). The adjusted MVA (including tumour stage, local treatment, ADT and BRCA status) confirmed the independent prognostic value of BRCA status for bPFS and CSS. Among BRCA carriers, the independent risk was greater when the analysis was limited to BRCA2 pts . Conclusions: Our results suggest that BRCA carriers have worse local disease control than NC when conventionally treated with RT. No differences in bPFS were observed in pts treated with RP after >8 yrs median follow-up. These results may have implications for tailoring clinical management in these patients.