Background: PEACE-1 demonstrated that combining ADT and docetaxel with abiraterone acetate plus prednisone (AAP) improves both overall survival (OS) and radiographic progression-free-survival (rPFS) in men with de novo mCSPC. The present analysis examines the second pre-planned primary endpoint of PEACE-1 in the low-volume population: the impact of prostate irradiation (RT) in men receiving intensified systemic treatment. Methods: PEACE-1 is an academic, multicentre, international, 2x2 design, phase 3 trial. The co-primary endpoints for each question were rPFS and OS. The standard of care (SOC) was ADT alone or ADT plus docetaxel (Doce) at investigator’s discretion until 2017, then accrual was restricted to men receiving ADT+Doce. RT (74 Gy/37 fractions) was delivered after Doce completion when applicable. SOC included continuous ADT, with or without Doce at 75 mg/m² every 3 weeks for 6 cycles. AAP, 1000 mg/day with prednisone 10 mg/day was given to men randomized to the AAP arms until disease progression or intolerance. The overall type I error testing the RT effect was 5% (4.9% for OS, 0.1% for rPFS). In the low-volume population, 299 and 213 events were required to detect an HR of 0.62 for rPFS and 0.68 for OS with 80% power, respectively. Results: Between 11/2013 and 12/2018, 1172 men were randomized to receive either SOC (+/- AAP) plus RT (n=584) or SOC (+/- AAP) without RT (n=588). 505 patients had low-volume disease (0-3 bone metastases +/- lymph nodes), 252 in the RT arms, 253 in the non-RT arms. Baseline characteristics were similar across arms. With a median follow-up of 6.1 years, 303 rPFS and 214 OS events were recorded for the low-volume population. A qualitative interaction between RT and AAP was observed for rPFS (p=0.026) and therefore, each experimental arm was assessed individually. RT did not improve rPFS with a median of 3 years (99.9%CI 2.3-4.8) for SOC vs 2.6 (1.7-4.6) for SOC+RT; HR=1.12 (0.68-1.85). When compared individually to SOC, rPFS was improved by SOC+AAP+RT (median 7.5 years (99.9%CI: 4.0-NR); HR=0.49, [0.28-0.87], p<0.0001) and borderline improved by SOC+AAP (median 4.4 years (95% CI: 2.5-7.6); HR=0.74, [0.44-1.26], p=0.066). The HR between AAP arms was 0.66 [0.36-1.19]. For OS the predefined threshold for a statistical interaction was not reached (p=0.11). OS was not improved by RT: median OS was 6.9 years (95.1%CI: 5.9-7.5) without RT vs 7.5 (6.0-NR) with RT (HR=0.97 [0.74-1.27], p=0.81). Median OS was 7.1 years in the SOC arm and not yet reached in the SOC+AAP+RT arm. Data on the RT prevention effect on severe urinary symptoms are pending. Conclusions: Combining prostate RT to systemic treatment did not improve OS in men with de novo mCSPC and low metastatic burden. However, best outcomes (rPFS and OS) were observed in men receiving SOC+AAP+RT. The impact of RT on severe urinary symptom prevention will be presented. Clinical trial information: NCT01957436.