In the open-label, randomized, phase III PEACE-1 trial, The addition of prostate radiotherapy (RT) to standard of care (SOC) did not lead to significant improvement in overall survival (OS) among men with de novo metastatic castration-sensitive prostate cancer (#mCSPC) and a low tumor volume. However, the most favourable outcomes, in terms of radiographic progression-free survival (rPFS) and overall survival (OS), were observed in men who received SOC along with androgen deprivation therapy (ADT), #abiraterone acetate (Abi), and #radiation therapy (RT).

In this randomized trial, The trial used a 2 x 2 factorial design aimed at answering two questions, the role of abiraterone and the role of prostate RT on top of the standard of care (SOC). 1172 patients with mCSPC were randomized to receive SOC, SOC + Abi, SOC + prostate RT, or SOC + Abi + prostate RT. RT was delivered as 74 Gy in 37 fractions. SOC included continuous ADT, with or without Docetaxel at 75 mg/m² every 3 weeks for 6 cycles (The trial began accruing in 2013 when The SOC was ADT alone then became restricted to ADT plus docetaxel after 2017 with the publication of CHAARTED and STAMPEDE data). Abi, 1000 mg/day with prednisone 10 mg/day was given to men randomized to the Abi arms until disease progression or intolerance. The arms evaluating prostate RT were pooled with corresponding systemic therapy arms to analyze the benefit of Abi + SOC vs. SOC.

The co-primary end points were rPFS and OS. Multiple secondary end points including CRPC-free survival, time to pain progression, time to chemotherapy for CRPC, prostate-cancer-specific survival, and quality of life. Baseline characteristics was similar between all arms. The median baseline PSA was 12.6 – 13.1 and 60% had received prior docetaxel. The trial enrolled a relatively high-risk population, which included 63% high volume and 11% with visceral metastases. Overall, 60% of patients received concurrent docetaxel with ADT (the first cycle 6 weeks to 3 months after initiation of ADT) and Abi (started within 6 weeks of ADT).

This trial has previously demonstrated that addition of Abi to SOC (ADT +/- docetaxel +/- radiotherapy) was associated with rPFS (HR: 0.54, p<0.0001) and OS improvements (HR: 0.82, p=0.03). In the docetaxel subgroup, the addition of Abi (triplet therapy) had a significant rPFS benefit (4.5 years vs. 2 years, HR=0.50, p < 0.0001), which were similar irrespective of disease volume. The addition of Abi also led to a significant OS improvement (median OS not reached vs. 4.5 years, HR 0.75, p = 0.017), especially in patients with high-volume disease (median OS 5.1 vs. 3.5 years, HR 0.72 (0.55–0.95), p = 0.019).

In the updated report, the results of the analysis of the efficacy and safety of prostate radiotherapy for patients with low volume, de novo mCSPC. 43% of patients in each arm had low-volume disease (0-3 bone metastases +/- lymph nodes). 50% of patients in this low-volume cohort had received docetaxel. Addition of prostate RT to SOC + abi was associated with significant rPFS benefits (median 7.5 versus 4.4 years, p=0.02). Conversely, addition of RT to SOC alone was not associated with rPFS benefits (median 2.6 versus 3.0 years; HR: 1.11, p=0.61). The addition of prostate RT to either SOC alone or SOC + Abi was not associated with OS improvements. In the SOC + abiraterone arms, addition of prostate radiotherapy was associated modest, non-significant OS benefits (HR: 0.77, p=0.21). Similarly, addition of prostate radiotherapy to SOC alone did not improve OS (HR: 1.18, 95% CI: 0.81- 1.71, p=0.39).

On the other hand, patients in the low-volume population who received RT had significantly longer castration resistance-free survival. The median was 3.4 years in patients who received RT and 2.5 years in those who did not (HR, 0.74, P =.007).

In the overall study population, there were 58 serious genitourinary events in patients who received RT and 106 in patients who did not (P =.0001). In the low-volume population, there were 24 serious genitourinary events in patients who received RT and 52 events in patients who did not (P =0.0006).