Impact of Local Treatment of the Primary Tumor on Overall Survival in De Novo Metastatic Breast Cancer: A Systematic Review and Meta-analysis

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Background/Aim: The prognostic impact of local treatment (LT) of the primary tumor in patients with de novo metastatic breast cancer (dnMBC) remains unclear. We conducted a systematic review and meta-analysis to evaluate whether surgery and/or radiotherapy of the primary tumor improves overall survival (OS). Materials and Methods: Electronic databases (PubMed, Embase, Cochrane) were searched up to March 2025 for studies comparing LT (surgery and/or radiotherapy) plus systemic therapy versus systemic therapy alone. Hazard ratios (HRs) for OS were pooled using a random-effects model. Subgroup analyses were performed by study design, treatment modality, biological subtype, and metastatic site. Heterogeneity was quantified using I², and meta-regression was used to explore potential moderators. Results: Twenty studies, including randomized controlled trials (RCTs) and retrospective studies, were included. In pooled analyses, LT was associated with improved OS compared to systemic therapy alone. [HR=0.62; 95% confidence interval (CI)=0.52–0.75; p<0.0001; I²=97.3%]. In RCTs, the difference was not significant (HR=0.91; 95% CI=0.67–1.25; p=0.57). Surgery of the primary tumor was associated with improved OS (pooled HR=0.62; 95% CI=0.52–0.75). In the radiotherapy-only subgroup, based on a very limited number of heterogeneous retrospective studies, no survival benefit was observed (pooled HR=1.51; 95% CI=0.87–2.63). Given the very limited number of studies and the substantial heterogeneity (I²=91.5%), these findings need to be interpreted with caution. Subgroup analyses showed a non-significant trend in hormone receptor–positive disease (HR=0.78; 95% CI=0.58–1.04) and no benefit in HER2-positive (HR=0.90; 95% CI=0.61–1.33) or liver-limited disease (HR=1.17; 95% CI=0.77–1.78). No covariates were significantly associated with OS in meta-regression. Conclusion: Although pooled analyses suggest an association between local treatment and improved OS, this effect appears largely driven by retrospective data and is not confirmed in randomized trials.

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