Metastasis-Directed Therapy in Oligometastatic Prostate Cancer: Biological Rationale and Systematic Review of Published Data

Introduction: Metastasis-directed therapy (MDT) alone may be effective in preventing disease progression and positively affecting overall survival (OS) in oligometastatic prostate cancer (OMPC). Objective: We systematically reviewed the current literature to analyse the biological rationale for integrating MDT into treatment strategies for OMPC and investigate the current evidence on its role in OMPC. Evidence acquisition: MEDLINE/PUBMED and the EMBASE Database were systematically searched to identify eligible reports published up to January 2024. The proceedings of the European Society for Radiotherapy and Oncology, European Society of Medical Oncology, American Society for Radiation Oncology, American Society of Clinical Oncology, European Uro-Oncology Group, and American Urological Association annual meetings were analysed. Results: Eighteen studies published between 2014 and 2024 were selected for the analysis. The studies included 1058 patients treated with metastasis-directed radiotherapy. No statistically significant differences were found in terms of treatment-escalation-free survival between hormone-naïve patients treated with MDT alone and those treated with MDT and hormonal manipulation. By contrast, the combination treatment significantly increased both 2 year and 4 year disease-progression-free survival (DPFS) rates (p-values < 0.00001 and 0.006, respectively). In patients with castration-sensitive disease treated with MDT alone, the estimated 2 year and 4 year OS rates were 96.4% (95% confidence interval [CI], 92.9–100%) and 89.1% (95% CI, 82.3–96.5%), respectively. The estimated 2 year and 4 year overall survival rates in the combination treatment group were 86.1% (95% CI 79.2–93.7%) and 74.8% (95% CI 64.6.3–86.5%), respectively. Conclusions: MDT alone is associated with promising outcomes in OMPC and represents a valuable, valid, and often preferable strategy. Combined with ADT improves significantly disease-progression-free survival, but its impact on overall survival remains uncertain. Given these findings, the decision to incorporate ADT should be tailored to individual patient characteristics and clinical context. Future research should integrate biomarker-based approaches to optimise MDT use and select the best candidates for a multimodal approach.