5 year oncological outcomes of the HIGHLOW randomized clinical trial

Introduction: The oncological outcomes of low ligation (LL) compared to high ligation (HL) of the inferior mesenteric artery (IMA) during low-anterior rectal resection (LAR) with total mesorectal excision are still debated. The aim of this study is to report the 5 year oncologic outcomes of patients undergoing laparoscopic LAR with either HL vs. LL of the IMA MATERIALS AND METHODS: Between June 2014 and December 2016, patients who underwent elective laparoscopic LAR + TME in 6 Italian non-academic hospitals were randomized to HL or LL of IMA after meeting the inclusion criteria (HighLow trial; ClinicalTrials.gov Identifier NCT02153801). We analyzed the rate of local recurrence, distant metastasis, overall survival, disease-specific survival, and disease-free survival at 5 years of patients previously enrolled. Results: Five-year follow up data were available for 196 patients. Recurrence happened in 42 (21.4%) of patients. There was no statistically significant difference in the distant recurrence rate (15.8% HL vs. 18.9% LL; P = 0.970) and pelvic recurrence rate (4,9% HL vs 3,2% LL; P = 0.843). No statistically significant difference was found in 5-year OS (p = 0.545), DSS (p = 0.732) or DFS (p = 0.985) between HL and LL. Low vs medium and upper rectum site of tumor, conversion rate, Clavien-Dindo post-operative grade ≥3 complications and tumor stage were found statistically significantly associated to poor oncological outcomes in univariate analysis; in multivariate analysis, however, only conversion rate and stage 3 cancer were found to be independent risk factors for poor DFS at 5 years. Conclusion: We confirmed the results found in the previous 3-year survival analysis, the level of inferior mesenteric artery ligation does not affect OS, DSS and DFS at 5-year follow-up.