Randomized Controlled Trial of PSMA PET/CT Guided Intensification of Radiotherapy for Prostate Cancer: Detection Rates and Impact on Radiotherapeutic Management

Abstract

PSMA PET/CT is more sensitive in detecting prostate cancer than current imaging standard of care, and commonly influences patient management despite lack of evidence of impact on patient outcomes. Through the conduct of a Phase II randomized controlled trial (RCT - NCT03525288), we primarily sought to determine if intensification of radiotherapy based on PSMA PET/CT could lead to improved failure-free survival outcomes. Here, we report on our secondary endpoints in terms of rates of new lesion detection and radiotherapy (RT) intensification. One hundred thirty-six patients with high-risk prostate cancer (n = 60, minimum CAPRA 6), or with biochemical failure after radical prostatectomy (n = 76, minimum PSA 0.1ng/mL) were enrolled across 2 institutions between May 2018 and February 2020. Those randomized (1:1) to the investigational arm underwent PSMA PET/CT with [18F]DCFPyL prior to radiotherapy. Based on imaging results, treating physicians intensified radiotherapy (volume/dose) unless widely metastatic disease was found, in which case systemic therapy was intensified. The minimum EQD2 (α/β = 1.4) dose to newly detected sites were 66Gy for involved lymph nodes or oligometastases, and 72Gy for prostate bed recurrences, while respecting standard-of-care exposures to organs at risk. New lesions were detected in 46% (high-risk) and 45% (post-op salvage) of patients who underwent PSMA PET/CT, leading to an intensification of radiotherapy. Sites of newly detected lesions were: pelvic lymph nodes (53%), oligometastases (27%), and prostate bed (13%). In 75% of cases, sites were located outside of initial planned radiotherapy fields. Widely metastatic disease was found in only 2 patients (3% of patients imaged), whereby radiotherapy was de-intensified in favor of an escalation in systemic therapy. PSMA PET/CT resulted in intensification of RT in nearly half of patient imaged on the investigational study arm. The impact of such change in RT management on failure-free survival, toxicity, and quality of life remains to be determined with continued follow-up. Based on these results, expansion to a Phase III RCT is now planned.