Upfront primary tumor resection versus upfront systemic therapy for metastatic colorectal cancer: a systematic review and meta-analysis from randomized controlled trials and propensity score matched studies.

Purpose: The standard initial treatment for metastatic colorectal cancer (mCRC) remains debated. This study investigated whether upfront primary tumor resection (PTR) or upfront systemic therapy (ST) provides better survival outcomes for patients with mCRC. Methods: The PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched for studies published at any time from January 1, 2004, to December 31, 2022. Randomized controlled trials (RCTs) and prospective or retrospective cohort studies (RCSs) utilizing propensity score matching (PSM) or inverse probability treatment weighting (IPTW) were included. We evaluated overall survival (OS) and short-term (60-day) mortality in these studies. Results: After reviewing 3,626 articles, we identified 10 studies including a total of 38,947 patients. OS differed significantly between the upfront PTR and upfront ST arms (hazard ratio [HR] 0.62; 95% CI: 0.57–0.68; p < 0.001). However, a subgroup analysis identified no significant difference in OS in RCTs (HR 0.97; 95% CI: 0.7–1.34; p = 0.83), whereas significant difference in OS occurred between the treatment arms in RCSs with PSM or IPTW (HR 0.59; 95% CI: 0.54–0.64; p < 0.001). Short-term mortality was analyzed in three RCTs, and 60-day mortality differed significantly between the treatment arms (risk ratio [RR] 3.47; 95% CI: 1.21–9.96; p = 0.02). Conclusions: In RCTs, upfront PTR for mCRC did not improve OS and enhanced the risk of 60-day mortality. By contrast, in RCSs, PSM or IPTW provided improved OS. Therefore, whether upfront PTR should be used for mCRC remains unclear. Further large RCTs are required.