Stereotactic body radiotherapy as metastasis-directed therapy in oligometastatic prostate cancer: a systematic review and meta-analysis of randomized controlled trials.

Abstract

Background: The use of stereotactic body radiotherapy (SBRT) to definitively treat oligometastases in prostate cancer has drawn large clinical and research interests within radiation oncology. However, the evidence is considered in its early stages and there is currently no systematic review of randomized controlled trials (RCTs) in this field. We aimed to evaluate the efficacy and safety of SBRT as metastasis-directed therapy (MDT) in oligometastatic prostate cancer (OMPC) compared to no MDT reported in RCTs.

Methods: MEDLINE, Embase, CINAHL Complete, and Cochrane Library were searched on October 28, 2023. Eligible studies were RCTs comparing SBRT as MDT with no MDT in extracranial OMPC, without restrictions on follow-up time, publication status, language, or year. Participant subsets fulfilling the eligibility criteria were included. Critical outcomes were overall survival and grade ≥ 3 toxicity, and additional important outcomes were progression-free survival (PFS), local control, grade 5 toxicity, health-related quality of life, and systemic therapy-free survival. Meta-analyses were planned. Risk of bias was assessed using the Cochrane risk-of-bias tool version 2, and the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation.

Results: In total, 1825 unique study reports were identified and seven phase II RCTs with 559 eligible participants were included. Four trials included multiple types of primary cancer. Outcome definitions were heterogeneous except for overall survival and toxicity. For overall survival, only one study reported events in both arms. Meta-analysis of the grade ≥ 3 toxicity results from two trials showed no difference (pooled risk ratio 0.78, 95% confidence interval 0.37-1.65, p = 0.52). Four trials reported significantly longer PFS, with a pooled hazard ratio of 0.31 (95% confidence interval 0.21-0.45, p < 0.00001). Risk of bias was of some concerns or high. Quality of evidence was low or moderate.

Conclusions: Phase II trials have shown promising improvements in PFS for several OMPC states without excess toxicity. Overall survival comparisons are immature. In future confirmatory phase III trials, adequately large sample sizes, blinding of outcome assessors, and/or increased adherence to assigned intervention could improve the quality of evidence. PROSPERO registration number: CRD42021230131.