Chemoradiotherapy and Local Excision vs Total Mesorectal Excision in T2-T3ab, N0, M0 Rectal Cancer

Importance According to international guidelines, the standard treatment for stage T2-T3ab, N0, M0 rectal cancer is total mesorectal excision (TME), but it is associated with high morbidity and quality of life disorders. Objective To analyze locoregional recurrence (LR) after a follow-up of 2 years, applying a 1-sided noninferiority margin of 10%, and to assess distant recurrence (DR), overall survival (OS), and disease-free survival (DFS). Design, Setting, and Participants This was a multicenter, prospective, open-label, noninferiority, phase 3 randomized clinical trial comparing TME (TME group) with chemoradiotherapy followed by local excision with transanal endoscopic microsurgery (CRT-TEM group). This study involved 17 hospitals in Spain. Eligibility criteria included patients with rectal adenocarcinoma located lower than 10 cm from the anal verge; stage T2-T3ab N0, M0; tumor size less than or equal to 4 cm in diameter; and American Society of Anesthesiologists stage III or less with no metastasis. Sample size was calculated with a 1-sided significance level of 2.5% and a power of 80%, assuming a nonrecurrence rate of 95% in each arm and a possible loss of 15%. Randomization was performed with a 1:1 allocation ratio. Data were analyzed from July 2010 to October 2021. Interventions The 2 treatment groups were CRT-TEM and TME. Main Outcomes and Measures The main study outcome was LR. Results From July 2010 to October 2021, 173 patients (median [IQR] age, 67 [59-75] years; 116 male [67.1%]) were included (CRT-TEM, n = 86; TME, n = 87). In the 5-year modified intention-to-treat analysis, LR was 6.2% (5 of 81 patients) in the TME group and 7.4% (6 of 81 patients) in the CRT-TEM group (difference, −1.23%; 95% CI, 6.51% to −8.98%). DR was 17.3% (14 of 81 patients) in the TME group and 12.3% (10 of 81 patients) in the CRT-TEM group (difference, 4.94%; 95% CI, 15.85% to −5.98%). OS was 85.2% (69 of 81 patients) in the TME group and 82.7% (67 of 81 patients) in the CRT-TEM group (difference, 2.47%; 95% CI, 0.38%-1.78%). DFS in both groups was 88.9% (72 of 81), with a 95% CI of 9.68 to −9.68. Conclusions and Relevance Results of this randomized clinical trial reveal that CRT-TEM achieved noninferior results compared with standard TME treatment in terms of LR and similar results in terms of DR, OS, and DFS. CRT-TEM appears to be a suitable treatment option for patients with T2-T3ab, N0, M0 rectal cancer. Trial Registration ClinicalTrials.gov Identifier: NCT01308190