Primary tumor resection versus systemic therapy alone in patients with colorectal cancer and unresectable distant metastases: a systematic review and meta-analysis

Abstract Background The role of primary tumor resection (PTR) in patients with colorectal cancer (CRC) and unresectable distant metastases remains controversial. While PTR may prevent tumor-related complications, it delays systemic therapy and carries surgical risks. This systematic review and meta-analysis synthesizes evidence from randomized controlled trials (RCTs) comparing PTR followed by systemic therapy versus systemic therapy alone. Methods This systematic review was registered with PROSPERO (registration number CRD42024533819) and conducted according to PRISMA 2020 guidelines. We searched PubMed, Cochrane Library, CINAHL, Scopus, and Google Scholar on August 6, 2024 for RCTs comparing PTR plus systemic therapy versus systemic therapy alone in patients with CRC and unresectable metastases. Study selection and data extraction were performed independently by two reviewers. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool. Meta-analyses were performed using random-effects models for overall survival (OS), mortality, and delayed PTR rates. Heterogeneity was assessed using I² statistics. Results Five RCTs comprising 1,122 patients were included. Meta-analysis of four studies ( n = 1,074) showed no significant difference in OS between PTR plus systemic therapy and systemic therapy alone (pooled HR 0.87, 95% CI 0.69–1.10, p = 0.15, I²=44%). Mortality analysis of three studies ( n = 409) demonstrated a non-significant trend toward higher mortality with PTR (pooled RR 1.78, 95% CI 0.67–4.73, I²=36%). Delayed PTR in the chemotherapy-alone arm occurred in 8% of patients (95% CI 3–18%, I²=79%). Conclusions Current evidence from RCTs does not support routine PTR in asymptomatic or minimally symptomatic patients with CRC and unresectable metastases. Systemic therapy alone appears to have acceptable rates of tumor-related complications.