Combined results of the European randomised, controlled SYNCHRONOUS and CCRe-IV studies investigating the impact of primary tumour resection on overall survival (OS) in patients with stage IV colon cancer with synchronous unresectable metastases and an asymptomatic primary tumour provide compelling evidence that up-front primary tumour resection in treatment-naïve stage IV colon cancer not amenable for curative treatment does not prolong OS.
A relatively low incidence of serious adverse events in patients with an intact primary tumour together with a considerable number of patients who did not receive any chemotherapy in the primary tumour resection group provides further arguments against resection of the primary tumour in this group of patients. The findings are reported by Dr. Jürgen Weitz of the Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, National Centre for Tumour Diseases in Dresden, Germany, and colleagues on 27 February 2024 in the JCO.
The authors wrote in the background that there is a broad consensus that tumour-related complications such as obstruction/ileus, bleeding, or perforation should prompt primary tumour resection before chemotherapy. It has, however, remained controversial if in patients with colon cancer with asymptomatic or mildly symptomatic primary and synchronous unresectable metastases, the primary tumour should be resected before systemic treatment.
Prevention of local complications during the course of chemotherapy has been held as an argument in favour of primary tumour resection, whereas the risk of postoperative morbidity and mortality with a potential delay of systemic therapy has been an argument against this treatment strategy. In the absence of randomised controlled studies, this controversial debate has, however, been primarily caused by inconsistent data from various studies on the impact of primary tumour resection on patients' long-term survival.
The investigators analysed the prognostic value of primary tumour resection in patients with newly diagnosed stage IV colon cancer who were not amenable to curative treatment. Patients enroled in the multicentre, randomised SYNCHRONOUS and CCRe-IV studies were included in this analysis. Patients with colon cancer with synchronous unresectable metastases were randomly assigned at 100 sites in Austria, Germany, and Spain to undergo primary tumour resection or up-front chemotherapy. The chemotherapy regimen was left at discretion of the local team. Patients with tumour-related symptoms, inability to tolerate surgery and/or systemic chemotherapy, and history of another cancer were excluded. The primary endpoint was OS, and the analyses were performed with intention-to-treat.
Between November 2011 and March 2017, a total of 187 patients were randomly assigned to undergo primary tumour resection and 206 to up-front chemotherapy. Chemotherapy was not administered to 6.4% in the up-front chemotherapy group and in 24.1% of patients in the primary tumour resection group. The median follow-up time was 36.7 months (95% confidence interval [CI] 36.6 to 37.3).
The median OS was 16.7 months (95% CI 13.2 to 19.2) in the primary tumour resection group and 18.6 months (95% CI 16.2 to 22.3) in the up-front chemotherapy group (p = 0.191). Comparable OS between the study groups was further confirmed on multivariate analysis with hazard ratio of 0.944 (95% CI 0.738 to 1.209, p = 0.65) and across all subgroups.
Patients with serious adverse events were more common in the up-front chemotherapy group (10.2% versus 18.0%; p = 0.027)
The findings were previously presented at the ASCO 2022 Annual Meeting.
This work was supported by a grant from Deutsche Forschungsgemeinschaft. The study Cre-IV was funded by Instituto Carlos III, Fondo de Investigación en Salud, Ministry of Economy and Competitiveness, Government of Spain.
Reference
Biondo S, Frago R, Feißt M, et al., on behalf of the SYNCHRONOUS and CCRe-IV Trial Groups. Primary Tumor Resection Before Systemic Therapy in Patients With Colon Cancer and Unresectable Metastases: Combined Results of the SYNCHRONOUS and CCRe-IV Trials. JCO; Published online 27 February 2024. DOI: https://doi.org/10.1200/JCO.23.01540