Abstract
Background
Prostate-specific membrane antigen positron emission tomography (PSMA-PET) improves lesion detection, leading to treatment intensification via PSMA-guided radiotherapy (PSMAgRT), but its impact on patient outcomes remains undefined.Objective
We evaluated whether PSMAgRT improves failure-free survival (FFS).Design, setting, and participants
This phase 2, two-center, open-label randomized trial enrolled patients planned for standard-of-care (SOC) radiotherapy (RT).Intervention
Patients were randomized 1:1 to SOC or PSMAgRT to all detected sites across four strata: salvage post-radical prostatectomy (RP), high-risk, oligometastatic, and salvage post-RT. Between 2018 and 2021, 262 patients were randomized (253 treated/analyzed).Outcome measurements and statistical analysis
The primary FFS end point (measured from RT completion) comprised prostate-specific antigen (PSA)/radiological progression, next-line therapy, or death. Secondary end points included freedom from biochemical progression (FFBP; PSA rise ≥0.2 ng/ml post-RP or ≥2 ng/ml above nadir in other strata). Prespecified analyses used a one-sided threshold of p1 Results and limitations
Among 253 patients, median follow-up was 66 mo (range 9-91). The 5-yr primary FFS was 66% with PSMAgRT versus 62% in controls (hazard ratio [HR] = 0.80; one-sided 90% CI, upper bound 1.04; p1 = 0.14). FFBP favored PSMAgRT: 72% versus 65% overall (subdistribution HR [sHR] 0.70, one-sided 90% CI upper bound 0.92; p1 = 0.048), 81% versus 66% in patients with high-risk disease (sHR 0.54; p1 = 0.07), and 80% versus 68% in patients in post-RP stratum (sHR 0.54; p1 = 0.037). In an exploratory, post hoc analysis combining patients with high-risk disease and those in the post-RP stratum, FFBP favored PSMAgRT (sHR 0.54, 95% CI = 0.32-0.91; two-sided p = 0.02). Only one grade ≥3 event was possibly related to dose escalation. Limitations include a phase 2 design with a heterogeneous population.Conclusions
Although the primary FFS end point was not met in the overall population, treatment-effect estimates favored PSMAgRT in the high-risk and post-RP strata. These findings provide a meaningful rationale for the target populations currently being evaluated in the definitive phase 3 PATRON trial.Trial registration
ClinicalTrials.gov NCT03525288.