Impact of resection versus no resection of the primary tumor on survival in patients with colorectal cancer and synchronous unresectable metastases: protocol for a randomized multicenter study (CR4)

Abstract

Purpose: The purpose of this study was to determine whether patients diagnosed with colorectal cancer and synchronous unresectable metastases (stage IV) can benefit from resection of the primary tumor in terms of an improvement in cancer-specific survival.

Methods: Stage IV colorectal cancer patients are eligible for inclusion in a randomized multicenter study carried out in 22 hospitals throughout Spain. Exclusion criteria are rectal tumors below 12 cm from the anal verge or locally advanced tumors, multiple bone or central nervous system metastases, and history of another primary cancer. The parallel design of the trial includes an arm of systemic chemotherapy alone versus an arm of resection of the primary tumor plus systemic chemotherapy after surgery. The primary endpoint of the study is cancer-specific survival that is assessed with a minimum follow-up of 24 months. Secondary endpoints are postoperative morbidity and mortality associated with resection of the primary tumor, complications and need of surgery in patients treated with systemic chemotherapy only, safety of systemic chemotherapy in both treatment strategies, and quality of life.

Conclusions: Confirmation of a survival benefit of surgical resection of the primary tumor in stage IV colorectal cancer patients not amenable to curative therapy is very relevant from a clinical and societal perspective, particularly considering the increase in the incidence and prevalence of colorectal cancer in developed countries. ClinicalTrials.gov Identifier: NCT02015923.

Keywords: Colorectal cancer; Primary tumor; Randomized trial; Survival; Unresectable metastasis.