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

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

doi:10.1016/j.euo.2025.05.027

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

Eur Urol Oncol. 2025 Jun 19:S2588-9311(25)00169-5. doi: 10.1016/j.euo.2025.05.027. Online ahead of print.

Authors

Jesus E Juarez Casillas¹, John Nikitas¹, Matthew B Rettig², Robert E Reiter³, Alan Lee¹, Michael L Steinberg¹, Luca Valle⁴, Tahmineh R Kalbasi⁵, Jeremie Calais⁶, Johannes Czernin⁶, Michelle A Eala¹, Sonny Tsai⁷, Nathanael Kane⁴, Abhishek A Solanki⁸, Rachael Sexton⁹, Sai Duriseti⁷, Gholam R Berenji⁷, William J Aronson², Isla P Garraway², Michael G Chang¹⁰, Robert Kwon¹¹, Steve P Lee¹¹, Nicholas G Nickols¹², Amar U Kishan¹³

Affiliations

¹ Department of Radiation Oncology, University of California-Los Angeles, Los Angeles, CA, USA.
² Department of Urology, University of California-Los Angeles, Los Angeles, CA, USA; Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
³ Department of Urology, University of California-Los Angeles, Los Angeles, CA, USA.
⁴ Department of Radiation Oncology, University of California-Los Angeles, Los Angeles, CA, USA; Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
⁵ Department of Medicine Statistics Core, University of California-Los Angeles, Los Angeles, CA, USA.
⁶ Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California-Los Angeles, Los Angeles, CA, USA.
⁷ Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
⁸ Department of Radiation Oncology, Loyola University and Hines VA Medical Center, Chicago, IL, USA.
⁹ Cancer Research and Biostatistics, Seattle, WA, USA.
¹⁰ Hunter Holmes McGuire VA Medical Center, Richmond, VA, USA.
¹¹ Veterans Affairs Long Beach Healthcare System, Long Beach, CA, USA.
¹² 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.
¹³ 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: aukishan@mednet.ucla.edu.

PMID: 40541485
DOI: 10.1016/j.euo.2025.05.027

Abstract

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.

Keywords: Abiraterone acetate; Androgen annihilation therapy; Apalutamide; Castrate-sensitive prostate cancer; Leuprolide; Metastasis-directed therapy; Oligorecurrence; Prostate cancer; Stereotactic body radiotherapy.