Long-Term Survival on Extent of Lymphadenectomy for Right-Sided Colon Cancer: Five-Year Follow-up Results of a Randomized Controlled Trial (RELARC Trial)

Abstract

Objective: To compare the overall survival (OS) and cancer-specific survival (CSS) of right-sided colon cancer patients undergoing CME versus D2 surgery after 5 years of follow-up, and to assess the heterogeneity of treatment effectiveness of CME between different subgroups.

Summary background data: The 3-year result of the Radical Extent of lymphadenectomy of Laparoscopic Right Colectomy for colon cancer (RELARC) trial showed that standard D2 dissection should be performed in right-sided colon cancer patients. In patients with lymph node metastasis, complete mesocolic excision (CME) showed potentially favorable results.

Methods: The parallel, open label, randomized controlled trial was conducted between January, 2016 to December, 2019 in 17 hospitals in China. Of a total of 1072 eligible patients enrolled, 995 patients were included in the modified intention-to-treat analysis. In the present study, the primary outcome was 5-year OS and the secondary outcome was 5-year CSS. The trial is registered with ClinicalTrials.gov (Identifier: NCT02619942).

Results: 995 patients were included in the final analysis. There was no significant difference between the 5-year OS (HR: 0.74, 95%CI: 0.51-1.07, P=0.105) or CSS (HR: 0.72, 95%CI: 0.49-1.06, P=0.091) in the CME and D2 groups. CME appears to improve 5-year outcomes in patients with stage III disease (OS: HR: 0.58, 95% CI: 0.37-0.93, P=0.023; CSS: HR: 0.59, 95% CI: 0.37-0.94, P=0.028), particularly in those with pN2 (OS: HR: 0.25, 95% CI: 0.11-0.57, P=0.001; CSS: HR: 0.25, 95% CI: 0.11-0.57, P=0.001), where a statistically significant interaction was identified. Patients with lymphovascular invasion also demonstrated favorable outcomes with CME with significant interaction effect (OS: HR: 0.34, 95% CI: 0.17-0.70; interaction P=0.009; CSS: HR: 0.32, 95% CI: 0.15-0.67, interaction P=0.008).

Conclusion: The standard D2 dissection provides oncologic outcomes comparable to CME on the 5-year follow-up. However, CME seems to improve 5-year outcomes in patients with stage III, particularly those with pN2 status, and may confer benefit in patients with LVI.

Keywords: complete mesocolic excision; overall survival; randomized controlled trial; right-sided colon cancer.