Integrating systemic therapy and metastasis-directed therapy in oligometastatic hormone-sensitive prostate cancer

Oligometastatic hormone-sensitive prostate cancer (omHSPC) represents a favorable and potentially curable disease state in which metastasis-directed therapy (MDT) improves outcomes. The combination of MDT and systemic treatment is the next frontier of omHSPC.

To review and synthesize current evidence from prospective trials evaluating MDT alone or combined with systemic therapy in synchronous and metachronous omHSPC, and to highlight the evolving role of advanced imaging, genomics, and ongoing efforts in refining treatment strategies.

This review synthesizes data from prospective trials, meta-analyses, and ongoing studies assessing MDT in omHSPC. Key trials include STOMP, ORIOLE, EXTEND, RADIOSA, and the X-MET meta-analysis, with emphasis on clinical outcomes and biomarkers RESULTS: In metachronous omHSPC, STOMP and ORIOLE phase II trials demonstrated that MDT significantly improves progression-free survival (PFS) and delays androgen deprivation therapy (ADT) compared to observation. The EXTEND and RADIOSA trials suggest combining MDT with short-term ADT further improves outcomes. The X-MET meta-analysis confirmed benefits in PFS, radiographic PFS, and castration-resistance-free survival with MDT. No randomized trial has yet evaluated MDT with current standard of care ADT + androgen receptor pathway inhibitor (ARPI) therapy, though EXTEND did include a limited subset of patients receiving ARPI. Advanced imaging, especially PSMA-PET, is transforming MDT planning by enabling more accurate lesion detection than conventional imaging. In synchronous omHSPC, the role of MDT remains under investigation in ongoing trials such as TERPS, STAMPEDE2 and START-MET.

MDT offers clinical benefit in metachronous omHSPC, particularly when combined with systemic therapy. Advanced imaging and genomic profiling are critical tools for refining patient selection. Most data stem from phase II studies without ADT + ARPI control groups; larger randomized trials are needed to define the role of MDT in standard practice and optimize personalized care strategies.