• Claus A Bertelsen, Anders U Neuenschwander, Jens E Jansen, Jutaka R Tenma, Michael Wilhelmsen, Anders Kirkegaard-Klitbo, Else R Iversen, Birgitte Bols, Peter Ingeholm, Leif A Rasmussen, Lars V Jepsen, Pernille W Born, Bent Kristensen, and Jakob Kleif.
• Department of Surgery, Nordsjællands Hospital Hillerød, University of Copenhagen, Hillerød, Denmark. Electronic address: claus.anders.bertelsen@regionh.dk.
• Lancet Oncol. 2019 Nov 1; 20 (11): 155615651556-1565.

BackgroundThe benefits of extensive lymph node dissection as performed in complete mesocolic excision are still debated, although recent studies have shown an association with improved long-term outcomes. However, none of these studies had an intention-to-treat design or aimed to show a causal effect; therefore in this study, we aimed to estimate the causal oncological treatment effects of complete mesocolic excision on right-sided colon cancer.MethodsWe did a population-based cohort study involving prospective data collected from four hospitals in Denmark. We compared the oncological outcome data of patients at one centre performing central lymph node dissection and vascular division after almost complete exposure of the proximal part of the superior mesenteric vein (ie, the complete mesocolic excision group) with three other centres performing conventional resections with unstandardised and limited lymph node dissection (ie, non-complete mesocolic excision; control group). We included data for all patients in the Capital Region of Denmark undergoing elective curative-intent right-sided colon resections for stages I-III colon cancer, as categorised by the Union for International Cancer Control (UICC; 5th edition), from June 1, 2008, to Dec 31, 2013. Patients were followed-up for 5·2 years after surgery. The primary outcome was the cumulative incidence of recurrence after 5·2 years of surgery. Inverse probability of treatment weighting and competing risk analyses were used to estimate the possible causal effects of complete mesocolic excision. This study is registered with ClinicalTrials.gov, number NCT03754075.Findings1069 patients (813 in the control group and 256 in the complete mesocolic excision group) underwent curative-intent elective surgery for right-sided colon cancer during the study period. None of the patients were lost to follow-up regarding survival or recurrence status, and consequently no patient was censored in the analyses. The 5·2-year cumulative incidence of recurrence was 9·7% (95% CI 6·3-13·1) in the complete mesocolic excision group compared with 17·9% (15·3-20·5) in the control group, and the absolute risk reduction of complete mesocolic excision after 5·2 years was 8·2% (95% CI 4·0-12·4; p=0·00015). In the control group, 145 (18%) of 813 patients were diagnosed with a recurrence and 281 (35%) died during follow-up, whereas in the complete mesocolic excision group 25 (10%) of 256 patients were diagnosed with a recurrence and 75 (29%) died during follow-up.InterpretationThis study shows a causal treatment effect of central mesocolic lymph node excision on risk of recurrence after resection for right-sided colon adenocarcinoma. Complete mesocolic excision has the potential to reduce the risk of recurrence and improve long-term outcome after resection for all UICC stages I-III of right-sided colon adenocarcinomas.FundingThe Tvergaard Fund, Helen Rude Fund, Krista and Viggo Petersen Fund, Olga Bryde Nielsen Fund, and Else and Mogens Wedell-Wedellsborg Fund.Copyright © 2019 Elsevier Ltd. All rights reserved.

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