186 - Randomized Controlled Trial of PSMA-PET Image Guided Intensification of Salvage Radiotherapy after Radical Prostatectomy: Which Patients Are Most Likely to Benefit and Other Secondary Analyses

C. Belliveau¹, F. Saad², D. Duplan Jr³, C. Petit⁴, G. Delouya¹, D. Taussky¹, M. Barkati¹, C. Lambert¹, M. C. Beauchemin¹, S. Clavel³, G. Mok³, 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 lUniversité de Montréal (CHUM), Montréal, QC, Canada, ²Département durologie, Centre Hospitalier de lUniversité de Montréal (CHUM), Montreal, 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 dimagerie 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 lUniversité de Montréal (CRCHUM)., Montréal, QC, Canada, ⁹Département de médecine nucléaire, Centre Hospitalier de lUniversité de Montréal (CHUM), Montréal, QC, Canada, ¹⁰Département de radio-oncologie, Centre de Recherche du Centre Hospitalier de lUniversité de Montréal (CRCHUM), Montréal, QC, Canada

Purpose/Objective(s): The primary endpoint of our randomized trial was recently reported (Belliveau & al, EAU2024) and demonstrated that intensified salvage radiotherapy guided by PSMA-PET (PSMAiSRT) after radical prostatectomy (RP) resulted in improved failure free survival (FFS). The aim of the present study was to evaluate which subgroups most benefited from PSMAiSRT, evaluate treatment free survival (TFS) outcomes, and determine whether intensification led to heightened toxicity or impact on quality of life (QoL). Materials/

Methods: Between May 2018 and February 2021, 128 subjects with biochemical recurrence (BCR) after RP planned for salvage radiotherapy (SRT) were enrolled in the post-RP stratum of a phase II multicenter registry-based randomized controlled trial (RCT-NCT03525288). Patients were randomized 1:1 to standard of care SRT or 18F-DCFPyL PSMA-PET/CT with intensified SRT guided by newly identified disease sites. Secondary endpoints and subgroup analysis were analyzed using cox regression (Hazard Ratio (HR)) and Kaplan-Meier (survival curves and log-rank). Updated toxicity events (CTCAEv5.0) grade = 2 and minimal important decline (MID) quality of life (QoL) events based on EPIC-CP in 87 patients (n=49 PSMAiSRT, n=38 control) were analyzed.
Results: As recently published (Petit & al. IJROBP 2023), study arms were balanced with median PSA 0.3 ng/ml (range 0.1-3) and intensified SRT was delivered in 33/64 imaged subjects (n=16 addition of pelvic SRT, n=2 addition of metastases-directed RT (MDRT), n=19 lymph node boost, n=15 prostate bed boost). The use of adjuvant hormone therapy (HT) was equally high in both arms (86% control vs. 84% PSMAiSRT). At median follow up of 37 months, PSMAiSRT most improved FFS outcomes in patients with PSA = median 0.3 ng/mL (log rank p=0.01, HR 0.17 95% CI 0.04-0.79) and without adjuvant HT (log rank p=0.01, HR 0.009 95% CI 0.00-16.20). In secondary endpoint analysis, there was improved TFS with a higher rate of next-line HT events (+/- MDRT) in the control arm (PSMAiSRT 4 events vs. control 12 events, log rank p =0.04, HR 0.32 95% CI 0.11-1.02). There were no statistically significant differences in toxicity events at median follow up (grade =2 PSMAiSRT 35 events vs control 39 events, log rank p = 0.716, grade =3 PSMAiSRT 6 events vs. control 3 events, log rank p=0.25). Two grade = 3 events were found attributable to intensified RT. No significant differences were found in the rate of MIDs for all QoL domains at 12 and 24 months. (p=NS).
Conclusion: The results of this randomized trial demonstrates no significant differences in toxicities or impact in QoL with intensified SRT after RP informed by PSMA-PET/CT, with improved FFS leading to improved TFS. In subgroup analysis, there was a pronounced advantage favoring PSMAisRT in patients with PSA = median 0.3 ng/mL and without adjuvant HT. A Phase III RCT (NCT04557501) has completed accrual and will shed further light on those patients who benefit most from PSMAiSRT.