Salvage Low Dose Rate Prostate Brachytherapy: Clinical Outcomes of a Phase II Trial for Local Recurrence after External Beam Radiotherapy (NRG/RTOG -0526)

Abstract

Prior studies of low dose rate (LDR) prostate brachytherapy (BT) for salvage of local recurrence (LR) of prostate cancer (PCa) after external beam radiotherapy (EBRT) are limited by retrospective reporting. We previously reported adverse events (AEs) of a prospective Phase II trial (NCT00450411) and now report efficacy outcomes with a minimum potential follow up of 5 yrs. Eligible patients had low or intermediate risk PCa prior to EBRT and biopsy-proven LR > 30 mos after EBRT, with PSA < 10 ng/mL and no regional or distant disease. Prescribed minimum target dose was 140 Gy with I-125, or 120 Gy with Pd-103. The primary endpoint, late GI/GU AEs occurring 9-24 mos after BT (CTCAE V3.0 > Grade 3; attributed to BT) was 14%. All eligible patients were followed for a minimum of 5 yrs after salvage BT and analyzed for secondary clinical outcomes. Disease-free (DFS), disease-specific (DSS), and overall (OS)survivals were estimated using the Kaplan-Meier method and 95% confidence intervals computed using Cox proportional hazards models. Local tumor progression (LR), distant failure (DF), and biochemical failure (BF) were estimated using nonparametric estimation of cumulative incidence accounting for competing risk events. Time to LR, DF and BF were modeled by cause-specific Cox proportional hazards regression and adjusted for clinical and treatment factors. From May 2007 – January 2014, 20 centers registered 100 patients with 92 analyzable. Median follow up is 6.9 yrs (range: 0.3-11.2); median age 70 (IQR: 66-74). Initial Gleason score was 7 in 48% and PSA >10 ng/mL in 16%. Median prior EBRT dose was 74 Gy (IQR: 70-76). Androgen deprivation was combined with salvage BT in 16%. Median interval from prior EBRT was 85 mos (IQR: 60-119). 10-yr OS is 70% (95% CI: 58 -83). Nineteen patients died (5 PCa, 10 other, 4 unknown). 4 had LR (one biopsy-confirmed). 10-yr LF rate is 5% (95% CI:1-11). 14 patients had DF (10-yr rate 19% (95% CI:10-29)). The 10-yr freedom from BF rate is 54% (95% CI:43-66). DFS is 61% at 5 yrs (includes death from any cause) but falls to 33% at 10 yrs. None of the baseline characteristics, including % of prostate covered by 100% of the prescription dose and interval from EBRT to BT were significantly associated with OS, DFS, local, distant, or biochemical failure. This is the first prospective multicenter trial to report outcomes of salvage LDR BT for LR after EBRT. We previously reported late grade 3 GU/GI adverse events occurring in14%. We now report 5-yr freedom from biochemical failure at 68%, comparable to other salvage modalities. Although further local LF is rare (5%), there is a continued toll of PCa recurrence such that freedom from biochemical failure at 10 yrs is 54%.