Presenter(s)
D. Chen1, E. Khoshkish1, J. Yi1, K. Arnold1, J. Jomy2, M. Liu3, D. A. Palma4, X. Y. Ye5, Z. Liu6, G. Boldt7, P. Wong8, and S. Raman8; 1University of Toronto, Toronto, ON, Canada, 2Princess Margaret Cancer Centre, Toronto, ON, Canada, 3BC Cancer Vancouver, Vancouver, BC, Canada, 4Division of Radiation Oncology, London Health Sciences Centre, London, ON, Canada, 5Department of Biostatistics, University Health Network, Toronto, ON, Canada, 6Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada, 7Western University, London, ON, Canada, 8Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada
Purpose/Objective(s): Metastasis-directed therapy (MDT) represents a promising therapeutic strategy in oligometastatic cancer, a distinct clinical state between localized and widespread metastatic disease. The safety and efficacy of the addition of MDT to standard treatments remains uncertain. This systematic review and meta-analysis evaluates the efficacy and safety of MDT interventions and describes the primary endpoints and reporting quality among randomized controlled trials (RCTs) of MDT interventions for oligometastatic cancer.
Materials/Methods: A comprehensive literature search of MEDLINE, Embase, and Cochrane CENTRAL was conducted from inception to June 9, 2025. Eligible RCTs included MDT interventions in patients with oligometastatic cancer (=5 lesions).
Results: A total of 37 records representing 29 studies and 3,500 participants were included. The addition of MDT improved progression-free survival (PFS) (HR=0.52, 95% CI [0.42–0.65]) and overall survival (OS) (HR=0.70, 95% CI [0.56–0.89]) compared to standard of care alone. Subgroup analyses demonstrated that upfront MDT was associated with improved PFS (HR=0.45, 95% CI [0.32–0.64]) and OS (HR=0.49, 95% CI [0.38–0.64]), while consolidation MDT improved PFS only (HR=0.56, 95% CI [0.40–0.78]) but not OS (HR=0.89, 95% CI [0.60–1.31]). MDT improved PFS (HR=0.50, 95% CI [0.32–0.78]) but not OS (HR=0.74, 95% CI [0.45–1.20]) in patients with de novo oligometastatic disease, whereas both PFS (HR=0.57, 95% CI [0.42–0.78]) and OS (HR=0.70, 95% CI [0.52–0.93]) were improved in the recurrent setting. By primary tumor site, MDT showed significant PFS benefit in prostate (HR=0.47, 95% CI [0.31–0.72]) and lung cancer (HR=0.57, 95% CI [0.41–0.79]), but not in breast cancer (HR=0.92, 95% CI [0.72–1.17]). MDT was associated with an increased odds of severe adverse events (OR=1.77, 95% CI [1.30–2.41]).
Conclusion: Taken together, our review confirms that the addition of MDT is associated with improved OS, PFS, and increased toxicity in oligometastatic cancer patients. Future trials that aim to refine the role of MDT across demographic strata, such as molecular biomarkers, tumor histology, and synchronicity of metastases development, and evaluate long-term clinical outcomes are warranted.