LBA 12 - PSMA-PET/CT-Guided Intensification of Radiation Therapy for Prostate Cancer (PSMAgRT) : Five-Year Primary Endpoint of a Phase 2 Randomized Controlled Trial
Presenter(s)
C. Belliveau1, F. Saad2, D. Duplan3, C. Petit4, G. Delouya1, C. Lambert1, D. Taussky1, M. Barkati1, M. C. Beauchemin1, S. Clavel3, G. Mok3, A. S. Gauthier-Pare3, L. Igidbashian3, T. V. Nguyen-Huynh5, P. Y. McLaughlin6, K. V. Keu7, J. DaSilva8, D. Juneau9, and C. Menard10; 1Département de radio-oncologie, Centre Hospitalier de l'Université de Montréal (CHUM), Montréal, QC, Canada, 2Département d'urologie, Centre Hospitalier de l'Université de Montréal (CHUM), Montréal, QC, Canada, 3Département de radio-oncologie, Centre Intégré de Santé et de Services Sociaux de Laval, Laval, QC, Canada, 4Département de radiothérapie, Institut Paoli Calmettes, Marseille, France, 5Département de radio-oncologie, Hôpital de Charles-Le Moyne, Longueuil, Québec, Canada, Longueuil, QC, Canada, 6Division of Radiation Oncology, The Ottawa Hospital, Ottawa, ON, Canada, 7Département d'imagerie médicale, service de médecine nucléaire, Hôpital de la Cité-de-la-Santé, Laval, QC, Canada, 8Département de Radiochimie et cyclotron, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM)., Montréal, QC, Canada, 9Département de médecine nucléaire, Centre Hospitalier de l'Université de Montréal (CHUM), Montréal, QC, Canada, 10Département de radio-oncologie, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada
Purpose/Objective(s):
Prostate-specific membrane antigen PET (PSMA-PET) enables improved lesion detection and treatment intensification via PSMA-guided radiotherapy (PSMAgRT). In a predefined interim analysis, improved failure-free survival (FFS) was observed in the salvage post–radical prostatectomy (RP) stratum at 3 years (Belliveau et al., JAMA Oncology). We now report 5-year outcomes for the primary endpoint and key secondary analyses for all clinical strata.Materials/Methods:
PSMAgRT is a phase 2, two-center, registry-based randomized controlled trial. Patients with prostate cancer planned for standard of care (SOC) RT were randomized 1:1 to SOC RT or PSMAgRT to all detected sites across four strata: salvage post-RP (PoRP), High-risk (HiR; CAPRA =6 or cN1), Oligometastatic and salvage post-RT. Between May 2018 and February 2021, 262 patients were enrolled (253 treated). The primary FFS endpoint was measured from the end of RT and defined as PSA progression (nadir +0.2 ng/mL for PoRP; nadir +2 ng/mL for other strata), radiologic progression, initiation of next-line therapy, or death. Due to sample size limitations, subgroup analyses were limited to the HiR and PoRP cohorts. A post hoc pooled HiR/PoRP analysis was performed to reflect the subsequent phase III population (NCT04557501). Prespecified analyses used a one-sided threshold of p1 < 0.10, whereas post hoc used two-sided p < 0.05 thresholds with 95% CIs.Results:
Among 253 patients (128 PoRP, 86 HiR, 23 Oligometastatic, 16 Salvage ost-RT), median follow-up was 66 months (range 9-91 months) with 5 year primary FFS endpoint estimates of 66% in PSMAgRT vs 62% in controls (HR = 0.80; 90% CI, 0.62–1.04; p1= 0.14). Subgroup analyses showed 5 years estimates of 72% versus 62% in HiR patients (HR = 0.70; 90% CI, 0.44–1.12; p1=0.16) and 72% vs. 65% in the PoRP cohort (HR = 0.66; 90% CI, 0.44–0.99; p1=0.09). Biochemical progression-free survival (BPFS) favored PSMAgRT : 72% vs 65% overall (sHR 0.70, 90% CI 0.53–0.92; p1=0.05), 81% vs 66% in High-Risk (sHR 0.54; p1=0.07), and 80% vs 68% in Post-RP patients (sHR 0.54; p1=0.04). No statistically significant differences in metastasis-free survival were observed across the overall or subgroup analyses (all p1>0.10). In a post hoc combined analysis of HiR and PoRP patients, BPFS significantly favored PSMAgRT; 80% vs. 67% (sHR 0.54, 95% CI 0.32–0.91; two-sided p=0.02). Grade 3 toxicities occurred in 10% vs 7% of patients (p=0.38), with only one possibly related to dose escalation; no grade 4–5 events occurred.Conclusion:
While the primary FFS endpoint was not met in this heterogeneous population, PSMA-PET-guided treatment intensification was associated with improved biochemical disease control, with outcomes in the localized high-risk and post-RP strata consistent with the hypothesized treatment effect. These findings demonstrate the potential clinical value of PSMA-PET-guided intensification and validate the target populations currently being evaluated in the definitive phase III PATRON trial.