Multimodal strategies combining primary and metastasis-directed therapy (MDT) with short-term intensified systemic therapy may improve outcomes in oligometastatic castrate-sensitive prostate cancer (omCSPC) while minimizing long-term toxicity. This post hoc analysis of two prospective phase 2 trials, SOLAR (NCT03298087) and SATURN (NCT03902951), evaluated oncologic outcomes in prostate-specific membrane antigen positron emission tomography-defined synchronous and metachronous omCSPC (≤5 M1a-b lesions), respectively. All patients received 6 mo of intensified systemic therapy (leuprolide, abiraterone acetate with prednisone, and apalutamide) and stereotactic body radiotherapy to oligometastases. SOLAR patients were treatment-naïve and also underwent radical prostatectomy (RP) or definitive prostate-directed radiotherapy (dRT). SATURN enrolled patients with post-RP recurrences: among the 26 patients who completed protocol therapy, 12 (46%) had prior androgen deprivation therapy (ADT), six (23%) had prior MDT, and 17 (65%) had one to three prior recurrences. The primary endpoint for both studies was prostate-specific antigen (PSA) response, defined as <0.05 ng/ml after RP or <2 ng/ml after dRT at 6 mo after testosterone recovery (≥150 ng/dl). Secondary endpoints included progression-free survival (PFS) and eugonadal PFS starting from the time of testosterone recovery. Progression was determined biochemically using PSA thresholds of ≥0.05 ng/ml for post-RP and ≥2 ng/ml for post-dRT patients. Among 50 patients (24 synchronous and 26 metachronous), the synchronous omCSPC group had a significantly higher PSA response rate (83% vs 50%; p = 0.018) and significantly longer PFS and eugonadal PFS (p < 0.05). The metachronous subgroup with prior ADT had worse outcomes, suggesting increasing resistance with repeated systemic therapy.
European urology oncology. 2025 Jun 19 [Epub ahead of print]
Jesus E Juarez Casillas, John Nikitas, Matthew B Rettig, Robert E Reiter, Alan Lee, Michael L Steinberg, Luca Valle, Tahmineh R Kalbasi, Jeremie Calais, Johannes Czernin, Michelle A Eala, Sonny Tsai, Nathanael Kane, Abhishek A Solanki, Rachael Sexton, Sai Duriseti, Gholam R Berenji, William J Aronson, Isla P Garraway, Michael G Chang, Robert Kwon, Steve P Lee, Nicholas G Nickols, Amar U Kishan
Department of Radiation Oncology, University of California-Los Angeles, Los Angeles, CA, USA., Department of Urology, University of California-Los Angeles, Los Angeles, CA, USA; Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA., Department of Urology, University of California-Los Angeles, Los Angeles, CA, USA., Department of Radiation Oncology, University of California-Los Angeles, Los Angeles, CA, USA; Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA., Department of Medicine Statistics Core, University of California-Los Angeles, Los Angeles, CA, USA., Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California-Los Angeles, Los Angeles, CA, USA., Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA., Department of Radiation Oncology, Loyola University and Hines VA Medical Center, Chicago, IL, USA., Cancer Research and Biostatistics, Seattle, WA, USA., Hunter Holmes McGuire VA Medical Center, Richmond, VA, USA., Veterans Affairs Long Beach Healthcare System, Long Beach, CA, USA., Department of Radiation Oncology, University of California-Los Angeles, Los Angeles, CA, USA; Department of Urology, University of California-Los Angeles, Los Angeles, CA, USA; Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA., Department of Radiation Oncology, University of California-Los Angeles, Los Angeles, CA, USA; Department of Urology, University of California-Los Angeles, Los Angeles, CA, USA. Electronic address: .