Background: While there is no standard therapy for BCR PC following local therapy, intermittent ADT is widely used. We evaluated utility of APA alone, ADT (luteinizing hormone–releasing hormone agonist [LHRHa]) alone, or APA + LHRHa in ADT-naïve BCR PC pts. Methods: Pts with BCR PC after primary definitive local therapy and prostate-specific antigen (PSA) doubling time (PSADT) ≤ 12 mo were randomized 1:1:1 to open-label 240 mg APA daily, LHRHa alone, or APA + LHRHa for 12 mo, followed by a 12-mo observation period off therapy. Pts were stratified by PSADT (< 6 vs 6-12 mo) and age (≤ 70 vs > 70 y). Primary end point: mean change from baseline (BL) in health-related quality of life (HRQoL) per Functional Assessment of Cancer Therapy-Prostate total score at 12 mo. Secondary end points included PSA nadir < 0.2 ng/mL by 7 mo, time to PSA progression (TTPpsa), and time to testosterone (T) recovery. Results: 90 pts (APA, n = 29; LHRHa, n = 30; APA + LHRHa, n = 31) were treated for median of 12 mo with similar distribution of BL characteristics across groups: 67% age ≤ 70 y; 67% PSADT < 6 mo. There was no significant difference in HRQoL in APA vs LHRHa at 12 mo, or between LHRHa vs APA + LHRHa groups. At median follow-up of 30-33 mo, TTPpsa in APA, LHRHa, and APA + LHRHa groups was 26 mo, 31 mo, and 36 mo, respectively. Compared to LHRHa alone, APA + LHRHa resulted in a trend toward improved TTPpsa (HR [95% CI] 0.56 [0.23-1.36], p = 0.196), and APA alone resulted in a trend for shorter TTPpsa (HR 1.09 [0.49-2.43], p = 0.824). PSA nadir < 0.2 ng/mL was reached in 89%, 89%, and 97% in APA, LHRHa, and APA + LHRHa pts. Median time to T recovery was similar in LHRHa and APA + LHRHa groups (23 mo vs 24 mo). Grade 3-4 adverse events (AEs) occurred in 17% of APA, 14% of LHRHa, and 29% of APA + LHRHa pts. The only grade 3-4 AE reported in > 1 pt per group was hypertension (APA, 3%; LHRHa, 0; APA + LHRHa, 13%). Conclusions: Addition of APA to LHRHa resulted in a trend for longer TTPpsa and a higher proportion of pts achieving optimal PSA nadir without significant difference in HRQoL or time to T recovery. Observed AEs were consistent with known safety profiles. Results support further evaluation of APA + LHRHa for a specified duration in BCR PC. Clinical trial information: NCT01790126