Safety and Efficacy of Metastasis-directed Local Ablative Image-guided Radiotherapy for Gallium-68 Prostate-specific Membrane Antigen PET-staged Castration-sensitive Oligometastatic Prostate Cancer: The OLI-P Prospective Phase 2 Clinical Trial

Abstract

Background: Metastasis-directed local ablative radiotherapy (aRT) for oligometastatic prostate cancer (PCa) is promising and is a focus of clinical research. Objective: We hypothesized that aRT is safe and effective in patients with oligometastatic PCa staged by gallium-68 prostate-specific membrane antigen targeted positron emission tomography (PSMA-PET). Design, setting, and participants: This nonrandomized, prospective, investigator-initiated phase 2 clinical trial enrolled patients with oligometastatic castration-sensitive PCa, defined as five or fewer lymph node or osseous metastases, after local curative therapy. Patients had no significant comorbidity and were not receiving androgen deprivation therapy (ADT). Recruitment occurred at two German centers from 2014 to 2018. Intervention: All PSMA-PET-positive metastatic lesions were treated with local ablative image-guided radiotherapy. No systemic therapy was initiated. Outcome measurements and statistical analysis: The primary endpoint was treatment-related grade ≥2 toxicity at 24 mo after aRT. A one-sided single-sample test of proportions was planned to test whether this endpoint occurred in <15% of patients. Key secondary endpoints were time to prostate-specific antigen (PSA) progression and time to ADT; associations with potential prognostic factors were evaluated using Cox regression. Results and limitations: Among 72 patients, 63 received aRT, corresponding to a 13% dropout rate. Median follow-up was 37.2 mo. No treatment-related grade ≥2 toxicity was observed 2 yr after treatment. Median time to PSA progression was 13.2 mo, and median time to ADT was 20.6 mo. At 3 yr, 21.4% of patients were free from PSA progression. Conclusions: In this prospective phase 2 trial, aRT was observed to be safe, and midterm PSA progression-free and ADT-free intervals were achieved in one of five patients. Randomized clinical trials are warranted to further evaluate delaying ADT in selected patients. Patient summary: In this trial, 63 patients with prostate cancer and up to five metastases who were not receiving ADT underwent local ablative radiotherapy. Treatment was safe, and one in five patients had no recurrent PSA value after 3 yr. Local ablative radiotherapy may be an option to avoid systemic therapy in selected patients.