PSMA-Guided Metastasis-Directed Therapy for Oligometastatic Renal Cell Carcinoma: The Proof-of-Concept PEDESTAL Study

Metastasis-directed therapy (MDT) in oligometastatic renal cell carcinoma (RCC) is typically based on conventional imaging. Prostate-specific membrane antigen (PSMA) PET/CT has shown superiority over conventional imaging. Our objective was to perform a proof-of-concept study to evaluate the efficacy of PSMA-guided MDT in oligometastatic RCC. <b>Methods:</b> A PSMA PET/CT database was queried for oligometastatic RCC patients undergoing MDT from 2014 to 2020. The primary endpoint was progression-free survival. Secondary endpoints included freedom from local progression, freedom from change in systemic therapy strategy, and overall survival. <b>Results:</b> A search of 3,095 PSMA PET/CT scans identified 83 RCC patients and 34 receiving MDT to 60 sites. The median follow-up was 4.1 y. Six patients (18%) had synchronous metastatic disease. The median number of metastases was 1 (interquartile range, 1-2). Common sites included bone (19, 32%) and lung (19, 32%). Radiation therapy was delivered to 56 metastases (93%), including stereotactic ablative body and conventional radiotherapy (38 and 18 metastases, respectively), and 4 (7%) underwent surgery. One-, 3-, and 5-y freedom from local progression was 94% (95% CI, 85%-98%), 85% (95% CI, 69%-94%), and 85% (95% CI, 69%-94%), respectively. One-, 3-, and 5-y overall survival was 88% (95% CI, 71%-95%), 71% (95% CI, 52%-84%), and 64% (95% CI, 45%-79%), respectively. One-, 3-, and 5-y progression-free survival was 47% (95% CI, 30%-63%), 26% (95% CI, 13%-42%), and 8% (95% CI, 2%-22%), respectively. One-, 3-, and 5-y freedom from change in systemic therapy strategy was 76% (95% CI, 57%-87%), 65% (95% CI, 45%-79%), and 43% (95% CI, 19%-65%), respectively. <b>Conclusion:</b> In this proof-of-concept study, PSMA-guided MDT provided durable oncologic outcomes for oligometastatic RCC, even at 5 y. To our knowledge, this study had the first cohort uniformly undergoing PSMA-guided MDT and one of the longest follow-ups of MDT for oligometastatic RCC. With increasing availability, PSMA PET/CT can be rapidly instituted to select patients for MDT and improve outcomes for patients with oligometastatic RCC.