Pooled Analysis of the SOLAR and SATURN Clinical Trials Comparing Progression of Synchronous Versus Metachronous Prostate-specific Membrane Antigen-defined Oligometastatic Prostate Cancer Following Systemic and Tumor-directed Therapy.

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.