3289 - Veterans Affairs seamless phase II/III randomized trial of STAndard systemic theRapy with or without PET-directed local therapy for Oligometastatic pRosTate cancer (VA STARPORT)

A. A. Solanki^1,2, D. Campbell², K. Carlson², I. Garraway^3,4, E. Henry^2,5, J. Jones⁶, T. Koppes², C. Newman², M. Quek^2,7, M. Rettig^4,8, T. A. Ritter⁹, L. Robin², J. K. Salama¹⁰, A. Skipworth², E. Zacny², K. Zheng², and N. G. Nickols^4,11; ¹Department of Radiation Oncology, Stritch School of Medicine, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL, ²Edward Hines Jr VA Hospital, Hines, IL, ³Department of Urology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, ⁴VA Greater Los Angeles Health System, Los Angeles, CA, ⁵The Mednet, New York, NY, ⁶Houston VA Medical Center, Houston, TX, ⁷Department of Urology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, ⁸Department of Medical Oncology, University of California, Los Angeles, Los Angeles, CA, ⁹Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA, ¹⁰Department of Radiation Oncology, Duke University Medical Center, Durham, NC, ¹¹Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA

Purpose/Objective(s): The concept of metastasis-directed therapy (MDT) using radiotherapy (RT) or surgery for oligometastatic (OM) prostate cancer (pCa) has evolved from an anecdotal hypothesis to a promising approach that may optimally balance toxicity and oncologic efficacy. Recently, there have been multiple phase II randomized trials that have shown a signal of efficacy for MDT in OM pCa. Most of these studies compared MDT to observation alone as the control arm, included only recurrent OM patients, and included up to 3-5 sites of metastasis. Simultaneously, multiple RCTs have demonstrated improved survival with earlier aggressive systemic therapy. It is in this context, that VA STARPORT was initiated in 2021 to definitively determine the role of MDT in Veterans with oligorecurrent pCa in 1-5 sites. Yet, the diagnosis and management of metastatic pCa continues to evolve. The SABR-COMET-10 trial recently completed enrollment and compares systemic therapy alone or with MDT in patients with 1-10 metastases from various histologies. While pCa PET/CT imaging was only available for Veterans with biochemical recurrence in 2021, PSMA PET/CT now allows for the improved diagnosis of OM in Veterans with de novo pCa—a growing cohort of patients without a clear standard of care. Therefore, to maximize the impact and generalizability of the trial, VA STARPORT has been amended to allow for de novo OM and 1-10 metastases. The primary goal of VA STARPORT is to determine if adding PET-directed local therapy (PDLT) to standard systemic therapy (SST) improves disease control compared to SST alone in Veterans with recurrent and de novo OM pCa. Materials/

Methods: VA STARPORT is a phase II/III randomized trial open at 18 VA medical centers comparing SST alone (Arm 1) or with PDLT (Arm 2) in Veterans with OM pCa. Eligibility criteria include recurrent or de novo hormone-sensitive metastatic pCa and 1-10 metastatic lesions on any pCa PET/CT. The primary endpoint is castration-resistant pCa (CRPC)-free survival. Secondary endpoints include radiographic progression-free survival (PFS), clinical PFS, freedom from index lesion progression, CTCAE v5 toxicity, quality of life, and pCa-specific and overall survival. SST is delivered using any NCCN guideline-concordant regimen in both arms. For de novo patients, Arm 1 patients receive prostate-directed RT and Arm 2 patients receive PDLT to all metastases and the prostate. For recurrent patients, Arm 1 patients receive SST alone, while Arm 2 patients receive PDLT. PDLT can be either RT or surgery. Both SBRT and elective nodal RT with simultaneous integrated boost are allowed. All participants undergo somatic tumor sequencing using the VA National Precision Oncology Program. Assuming a hazard ratio of 0.60 for SST + PDLT vs SST, two-sided alpha = 0.05 and 90% power, a total of 464 participants will be randomized to generate 166 CRPC-free survival events by the end of the 48-month active study phase. Recruitment is ongoing and 150 patients have been randomized to date.

Results: TBD

Conclusion: TBD