Primary Tumor Resection in Patients With Unresectable Metastatic Colorectal Cancer: A Systematic Review and Meta‐Analysis

ABSTRACT Aim The benefit of primary tumor resection (PTR) in patients with asymptomatic, unresectable metastatic colorectal cancer (mCRC) remains uncertain. Previous systematic reviews often included symptomatic cases or cohorts with imbalanced chemotherapy use, weakening comparisons between upfront PTR followed by chemotherapy and chemotherapy alone. This analysis focused exclusively on studies involving asymptomatic patients with adequate chemotherapy administration in both groups. Methods A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. Eligible studies explicitly excluded symptomatic cases and reported modern chemotherapy regimens. Overall survival (OS) was the primary outcome. Secondary outcomes included progression‐free survival (PFS), perioperative complications, 30‐day mortality, and tumor‐related emergency interventions in the non‐resection (NR) group. Results Seventeen studies involving 9317 patients met inclusion criteria: 5581 underwent PTR (PR group), and 3736 did not (NR group). A pooled analysis of 16 studies showed no significant OS benefit with PTR (hazard ratio [HR] = 1.10, 95% confidence interval [CI]: 0.84–1.44). No improvement in PFS was observed (HR = 0.89, 95% CI: 0.68–1.16). Postoperative morbidity and 30‐day mortality in the PR group were 19.8% and 2.0%, respectively. Emergency surgery was required in 6.4% of NR group patients, with a 30‐day mortality rate of 5.3%. Conclusion Upfront PTR did not improve survival outcomes in asymptomatic patients with unresectable mCRC and introduced substantial perioperative risks. Routine PTR is not advisable in this population. Clinical decision‐making should be individualized based on patient risk factors and tumor behavior. Trial Registration PROSPERO: CRD420251065487