Meta-analysis of outcomes of patients with stage IV colorectal cancer managed with chemotherapy/radiochemotherapy with and without primary tumor resection

Abstract

Ko-Chao Lee,1 Yu-Che Ou,2 Wan-Hsiang Hu,1 Chia-Cheng Liu,3 Hong-Hwa Chen1 1Division of Colorectal Surgery, Department of Surgery, 2Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, 3Department of Surgery, Pingtung Christian Hospital, Pingtung, Taiwan Background: Colorectal cancer is the third leading cause of death worldwide. Currently, novel chemotherapeutic agents are first-line therapy for unresectable stage IV colorectal cancer, while benefits of noncurative primary tumor resection in advanced disease remain debatable. Objective: This meta-analysis evaluated outcomes of patients with unresectable stage IV colorectal cancer receiving systemic chemotherapy with or without primary tumor resection. Materials and methods: A database search of PubMed and Cochrane Library databases identified 167 studies that were screened for relevance. After 119 were excluded, 48 were assessed for eligibility and 26 were included for meta-analysis, including 24 retrospective studies, one prospective study, and one randomized, controlled trial. Extracted data included patient demographics (age, sex), clinical data (tumor stage, metastasis), targeted therapy agents, and surgical data (with/without tumor resection). Patients’ overall and progression-free survival was compared between groups with/without primary tumor resection. Results: The 26 studies included 43,903 patients with colorectal cancer, with 29,639 receiving chemotherapy/radiotherapy plus primary tumor resection, and 14,264 managed medically with chemotherapy/chemoradiotherapy alone without primary tumor resection. Patients receiving primary tumor resection plus chemotherapy/radiotherapy had longer overall survival (hazard ratio [HR 0.59], 95% confidence interval [CI] 0.51–0.68; P<0.001), with significant differences in overall survival between patients with and without primary tumor resection (HR 0.58, 95% CI 0.49–0.68; P<0.001). Longer overall survival was also found among patients receiving primary tumor resection who were treated with bevacizumab/cetuximab targeted therapy agents (HR 0.63, 95% CI 0.46–0.86; P=0.003). Patients from three studies who received primary tumor resection had longer progression-free survival (HR 0.73, 95% CI 0.58–0.91; P=0.005). Results are limited by retrospective data, inconsistent complications data, and publication bias. Conclusion: Study results support primary tumor resection in stage IV colorectal cancer, but significant biases in studies suggest that randomized trials are warranted to confirm findings. Keywords: chemotherapy, colorectal cancer, outcomes, tumor resection