The phase III ACTS-RC (Adjuvant Chemotherapy for Stage II/III Rectal Cancer) trial showed benefits in relapse-free survival (RFS) in rectal cancer with tegafur, 5-chloro-2,4-dihydropyrimidine, and potassium oxonate (S-1) adjuvant chemotherapy in comparison with uracil and tegafur (UFT) therapy. Lateral lymph node dissection (LLND) has been one of the standard treatments for lower rectal cancer patients in Japan. However, it has been debated whether LLND has survival benefits. The aim of this study was to evaluate the impact of lateral LLND on the outcomes in the ACTS-RC randomized clinical trial.
In a total of 445 lower rectal cancer cases (Stage I/II/IIIA/IIIB/IIIC: 1/130/10/59/165/80) from 959 rectal cancer cases in the ACTS-RC trial, 215 underwent LLND and 230 did not. UFT and S-1 therapy was prescribed for 110 and 105 patients with LLND, respectively, and for 111 and 119 patients without LLND, respectively.
There were no significant differences in patient background characteristics, except for age and pathological T stage, between the LLND and without-LLND groups. Younger patients were often selected as candidates for LLND, and LLND had no impact on RFS or overall survival (OS) in all patients with lower rectal cancer (hazard ratio [HR]=0.941, 95% confidence interval [CI]: 0.696–1.271). In Stage IIIB/C patients, LLND improved the RFS (HR = 0.762, 95% CI: 0.533–1.091). This trend was the same in both the S-1 (HR = 0.766, 95% CI: 0.449–1.306) and UFT arms (HR = 0.790, 95% CI: 0.487–1.283), despite the better RFS in the S-1 arm than in the UFT arm. LLND did not show a major impact on OS in Stage IIIB/C patients.
This exploratory analysis showed that LLND improves RFS in patients receiving either UFT or S-1 therapy, although the results were not significant. LLND has an additional impact on improving RFS of patients with lower rectal cancer undergoing adjuvant chemotherapy.
Clinical trial identification
Legal entity responsible for the study
Japanese foudation for multidiscipilinary treatment of cancer
E. Oki: Honoraria for lecturing from Taiho Pharmaceutical Co., Ltd.; Yakult Honsha Co., Ltd.; and Chugai Pharmaceutical Co., Ltd. Y. Maehara: Honoraria for lecturing from Taiho Pharmaceutical Co., Ltd.; Yakult Honsha Co., Ltd.; and Chugai Pharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.