Upfront primary tumor resection versus upfront systemic therapy for metastatic colorectal cancer: a systematic review and meta-analysis

Abstract

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. MethodsThe 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. ResultsAfter reviewing 3,626 articles, we identi ed 10 studies including a total of 38,947 patients. OS differed signi cantly 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 identi ed no signi cant difference in OS in RCTs (HR 0.97; 95% CI: 0.7-1.34; p = 0.83), whereas signi cant 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 signi cantly between the treatment arms (risk ratio [RR] 3.47; 95% CI: 1.21-9.96; p = 0.02). ConclusionsIn 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.