Background: Active surveillance (AS) is a standard of care for low-risk prostate cancer (PC). However, 20 to 50% of patients (pts) will ultimately require a local treatment following AS. The aim of this study is to assess whether apalutamide could decrease the proportion of pts requiring local treatment within 3 years. We report the 1-year safety and quality of life analyses. Methods: multicentric phase II study conducted in patients with low to intermediate risk PC randomized between apalutamide 6 months (240 mg/d) with AS vs AS alone. Toxicity was evaluated each month during treatment and every 3 months thereafter for both arms. Quality of life (SF12) was assessed at baseline, 6 and 12 months post enrollment. Results: Patients were randomized: 51 in apalutamide and 40 in AS arm. Only 50 pts received apalutamide (one refusal). Median age was 64 yrs (47-76), median PSA 5.9 (1.5-21.5), only 2 pts had Gleason ISUP 2, 14% had >T2, the median cancer positive cores was 14.3%. The median testosterone level was 4.7 mg/l. Only 88 were available for safety analyses (48 in apalutamide arm). Maximal grades of reported adverse events during the first year were for the experimental arm: 25%, 56%, 19% and control arm: 20%, 15% 12.5% for G1, G2, G3 respectively. In the experimental arm, grade 1/2 related adverse events (AE) were cutaneous (25%) and HTA (15%), nausea 15%, diarrhea 10%, arthralgia or musculoskeletal event 17% and anemia 6%. Attention disorders were observed in 6% and hypothyroidism in 8%. The most frequent sexual dysfunctions were erectile dysfunction observed in 29% (7.5% in AS arm), gynecomastia in 60%, loss of libido in 21%, and nipple pain in 33%. One-year post enrollment, the testosterone level was 4.86 mg/l (1.5-9.8) vs 4.6 (2-7.7) in apalutamide and AS arm, respectively. Digestive symptoms were Grade 3. Related AEs were an HTA for 2 pts, rash for 1 pt, asthenia for 1 pt, erectile dysfunction for 1 pt, and decreased libido for 1 pt. One serious related AE was reported: grade 2 cerebral ischemic attack. A reduced dose was required for 16.67% of pts and 33.3% had transient discontinuation. The treatment was stopped for toxicity in 3 pts; 94% completed the 6 months of treatment. No differences were observed in physical component summary (PCS) and mental component summary (MCS) of SF12 for treatment vs AS at 6 mo (PCS: 55.1 vs 56.4; MCS 43.4 vs 41.4) and 12 mo (PCS: 53.6 vs 54.1; MCS 44.1 vs 42.9). Conclusions: This is a large randomized study evaluating apalutamide with active surveillance vs active surveillance. No new safety issues were observed and the safety profile was consistent relative to those previously described with apalutamide and castration, no falls or fracture were observed. No detrimental effect of apalutamide on QOL was observed during and after treatment. AEs are important for pts candidates for active surveillance. Clinical trial information: NCT03088124.