PSMA-PET/CT-guided Intensification of Radiation Therapy for Prostate Cancer (PSMAgRT): 5-yr Analysis of a Phase 2 Randomized Controlled Trial.

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 < 0.10, whereas post hoc analyses used two-sided p < 0.05 thresholds and 95% confidence intervals (CIs).

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.