ASCO 2025: PSMA-DC: An Open-Label, Multicenter, Randomized Phase 3 Study of 177Lu-PSMA-617 Versus Observation in Patients with Metachronous PSMA-Positive Oligometastatic Prostate Cancer

(UroToday.com) The 2025 ASCO annual meeting featured a prostate cancer trials in progress session and a presentation by Dr. Oliver Sartor discussing PSMA-DC, an open-label, multicenter, randomized phase 3 study of ¹⁷⁷Lu-PSMA-617 versus observation in patients with metachronous PSMA-positive oligometastatic prostate cancer. ADT ± androgen receptor pathway inhibitor therapy is a primary treatment for metastatic hormone-sensitive prostate cancer, but is noncurative and has significant toxicities when used long-term. In patients with oligometastatic prostate cancer for whom delaying ADT is appropriate, metastasis-directed therapy such as stereotactic body radiation therapy has been shown to provide local disease control. However, many patients do not experience a complete PSA response and develop poly-metastatic disease. ¹⁷⁷Lu-PSMA-617 is a PSMA-targeted radioligand therapy with demonstrated efficacy and a manageable safety profile in patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) in the VISION¹ and PSMAfore² trials. PSMA-DC is an ongoing, international, randomized phase 3 trial to evaluate the efficacy of ¹⁷⁷Lu-PSMA-617 versus observation after stereotactic body radiation therapy in delaying castration and disease progression in patients with PSMA-positive oligometastatic prostate cancer.

Eligible patients have:

Histologically confirmed prostate cancer
Biochemical recurrence post-definitive treatment
Oligometastatic prostate cancer with ≤ 5 PSMA-positive metastatic lesions including ≥ 1 distant metastasis on PSMA PET/CT scans (all must be amenable to stereotactic body radiation therapy)
PSA doubling time < 10 months
Non-castration testosterone levels (> 100 ng/dL)

Exclusion criteria include distant metastasis by conventional imaging (CT/MRI and bone scans) at screening, prior ADT (except adjuvant ADT completed > 12 months before randomization), or other systemic therapy for metastatic prostate cancer:

Patients (n = ~450) will be randomized 2:1 to ¹⁷⁷Lu-PSMA-617 or observation and will receive stereotactic body radiation therapy to all metastatic lesions within 14 days, completed within 3 weeks. Patients will then receive either IV ¹⁷⁷Lu-PSMA-617 (7.4 GBq/6 weeks; 4 cycles), starting 7–21 days after stereotactic body radiation therapy, or undergo observation only. Additional stereotactic body radiation therapy for new lesions is allowed. ADT is allowed after a metastasis free survival event by conventional imaging confirmed by blinded independent review committee. The trial design for PSMA-DC is as follows:

Safety follow-up will occur 42 days after the last ¹⁷⁷Lu-PSMA-617 dose and at the week 24 visit for the observational arm. Long-term follow-up for the ¹⁷⁷Lu-PSMA-617 arm will include safety assessments every ~32 weeks. The primary endpoint is metastasis free survival by conventional imaging as assessed by blinded independent review committee using RECIST v1.1, or death. To provide 90% power to detect a hazard ratio of 0.6, 187 metastasis free survival events are required. The key secondary endpoint is time to next hormonal therapy, and additional secondary endpoints include time to PSA progression, radiographic progression-free survival, symptomatic progression, patient-reported health-related quality of life, overall survival and safety. As of May 2025, patient enrollment has commenced in 23/26 countries and the site initiation visit has been completed in 114/134 sites:

Presented by: A. Oliver Sartor, MD, Mayo Clinic, Rochester, MN

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting, Chicago, IL, Fri, May 30 – Tues, Jun 3, 2025.

Related content: PSMA DC Trial: Lutetium + SBRT to Delay ADT in Oligometastatic Prostate Cancer - Oliver Sartor

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