Toxicity and Efficacy of Local Ablative, Image-guided Radiotherapy in Gallium-68 Prostate-specific Membrane Antigen Targeted Positron Emission Tomography–staged, Castration-sensitive Oligometastatic Prostate Cancer: The OLI-P Phase 2 Clinical Trial

Abstract

BackgroundLocal ablative radiotherapy (aRT) of oligometastatic prostate cancer (PCa) is very promising and has become a focus of current clinical research. ObjectiveWe hypothesize that aRT is safe and effective in gallium-68 prostate-specific membrane antigen targeted positron emission tomography (PSMA-PET)-staged oligometastatic PCa patients. Design, setting, and participantsA nonrandomized, prospective, investigator-initiated phase 2 trial recruited patients with oligometastatic PCa (five or fewer lymph node or osseous metastases) after local curative therapy, without significant comorbidity and androgen deprivation therapy (ADT), at two German centers from 2014 to 2018. InterventionAll PSMA-PET–positive metastases were treated with aRT. No systemic therapy was initiated. Outcome measurements and statistical analysisThe primary endpoint was treatment-related toxicity (grade ≥2) 24 mo after aRT. A one-sided single-sample test of proportions was planned to test whether the endpoint occurs in <15% of the patients. Key secondary endpoints were time to progression of prostate-specific antigen (PSA) and time to ADT, which were associated with potential prognostic factors by Cox regression. Results and limitationsOf 72 patients, 63 received aRT (13% dropout rate). The median follow-up was 37.2 mo. No treatment-related grade ≥2 toxicity was observed 2 yr after treatment. The median time to PSA progression and time to ADT were 13.2 and 20.6 mo, respectively. Of the patients, 21.4% were free of PSA progression after 3 yr. ConclusionsIt was observed that aRT is safe, and midterm PSA progression and ADT-free time were achieved in one of five patients. Randomized clinical trials are indicated to further evaluate the option of delaying ADT in selected patients. Patient summaryIn this clinical trial, 63 patients with up to five metastases of prostate cancer without androgen deprivation therapy were included. We showed that local ablative radiotherapy is safe and that one in five patients had no recurrent prostate-specific antigen value after 3 yr. Local ablative radiotherapy might be an option to avoid systemic therapy in selected patients.