Eric Rullier1, Philippe Rouanet2, Jean-Jacques Tuech3, Alain Valverde4, Bernard Lelong5, Michel Rivoire6, Jean-Luc Faucheron7, Mehrdad Jafari8, Guillaume Portier9, Bernard Meunier10, Igor Sileznieff11, Michel Prudhomme12, Frédéric Marchal13, Marc Pocard14, Denis Pezet15, Anne Rullier16, Véronique Vendrely17, Quentin Denost18, Julien Asselineau19, Adélaïde Doussau19. 1. Department of Colorectal Surgery, Haut-Lévèque Hospital, Pessac, CHU Bordeaux, France. Electronic address: eric.rullier@chu-bordeaux.fr. 2. Département de Chirurgie Oncologique, ICM Val d'Aurelle, Montpellier, France. 3. Service de Chirurgie Digestive, CHU Charles Nicolle, Rouen, France. 4. Service de Chirurgie Digestive, Groupe Hospitalier Diaconesses Croix Saint-Simon, Paris, France. 5. Département de Chirurgie Oncologique, Institut Paoli Calmette, Marseille, France. 6. Département de Chirurgie Oncologique, Centre Léon Bérard, Lyon, France. 7. Service de Chirurgie Digestive, Hôpital A Michallon, La Tronche, France. 8. Département de Chirurgie Oncologique, Centre Oscar Lambret, Lille, France. 9. Service de Chirurgie Digestive, Hôpital Purpan, Toulouse, France. 10. Service de Chirurgie Viscérale, CHU Pontchaillou, Rennes, France. 11. Service de Chirurgie Digestive, CHU Timone, Marseille, France. 12. Département de Chirurgie Digestive et de Cancérologie Digestive, Hôpital Universitaire Carémeau, Nimes, France. 13. Département de Chirurgie Oncologique, Institut de Cancérologie de Lorraine, CRAN, UMR 7039, Université de Lorraine, CNRS, Vandoeuvre les Nancy, France. 14. Département Médico-Chirurgical de Pathologie Digestive, Hôpital Lariboisière, Paris, France. 15. Service de Chirurgie Générale et Digestive, Hôtel Dieu, Clermont-Ferrand, France. 16. Service d'Anatomopathologie, Hôpital Pellegrin, Bordeaux, CHU Bordeaux, France. 17. Service de Radiothérapie, Haut-Lévèque Hospital, Pessac, CHU Bordeaux, France. 18. Department of Colorectal Surgery, Haut-Lévèque Hospital, Pessac, CHU Bordeaux, France. 19. Unité de Soutien Méthodologique à la Recherche Clinique et Epidémiologique du CHU de Bordeaux, Université Bordeaux, Bordeaux, France.
Abstract
BACKGROUND: Organ preservation is a concept proposed for patients with rectal cancer after a good clinical response to neoadjuvant chemotherapy, to potentially avoid morbidity and side-effects of rectal excision. The objective of this study was to compare local excision and total mesorectal excision in patients with a good response after chemoradiotherapy for lower rectal cancer. METHODS: We did a prospective, randomised, open-label, multicentre, phase 3 trial at 15 tertiary centres in France that were experts in the treatment of rectal cancer. Patients aged 18 years and older with stageT2T3 lower rectal carcinoma, of maximum size 4 cm, who had a good clinical response to neoadjuvant chemoradiotherapy (residual tumour ≤2 cm) were centrally randomly assigned by the surgeon before surgery to either local excision or total mesorectal excision surgery. Randomisation, which was done via the internet, was not stratified and used permuted blocks of size eight. In the local excision group, a completion total mesorectal excision was required if tumour stage was ypT2-3. The primary endpoint was a composite outcome of death, recurrence, morbidity, and side-effects at 2 years after surgery, to show superiority of local excision over total mesorectal excision in the modified intention-to-treat (ITT) population (expected proportions of patients having at least one event were 25% vs 60% for superiority). This trial was registered with ClinicalTrials.gov, number NCT00427375. FINDINGS:From March 1, 2007, to Sept 24, 2012, 186 patients receivedchemoradiotherapy and were enrolled in the study. 148 good clinical responders were randomly assigned to treatment, three were excluded (because they had metastatic disease, tumour >8 cm from anal verge, and withdrew consent), and 145 were analysed: 74 in the local excision group and 71 in the total mesorectal excision group. In the local excision group, 26 patients had a completion total mesorectal excision. At 2 years in the modified ITT population, one or more events from the composite primary outcome occurred in 41 (56%) of 73 patients in the local excision group and 33 (48%) of 69 in the total mesorectal excision group (odds ratio 1·33, 95% CI 0·62-2·86; p=0·43). In the modified ITT analysis, there was no difference between the groups in all components of the composite outcome, and superiority was not shown for local excision over total mesorectal excision. INTERPRETATION: We failed to show superiority of local excision over total mesorectal excision, because many patients in the local excision group received a completion total mesorectal excision that probably increased morbidity and side-effects, and compromised the potential advantages of local excision. Better patient selection to avoid unnecessary completion total mesorectal excision could improve the strategy. FUNDING: National Cancer Institute of France, Sanofi, Roche Pharma.
RCT Entities:
BACKGROUND: Organ preservation is a concept proposed for patients with rectal cancer after a good clinical response to neoadjuvant chemotherapy, to potentially avoid morbidity and side-effects of rectal excision. The objective of this study was to compare local excision and total mesorectal excision in patients with a good response after chemoradiotherapy for lower rectal cancer. METHODS: We did a prospective, randomised, open-label, multicentre, phase 3 trial at 15 tertiary centres in France that were experts in the treatment of rectal cancer. Patients aged 18 years and older with stage T2T3 lower rectal carcinoma, of maximum size 4 cm, who had a good clinical response to neoadjuvant chemoradiotherapy (residual tumour ≤2 cm) were centrally randomly assigned by the surgeon before surgery to either local excision or total mesorectal excision surgery. Randomisation, which was done via the internet, was not stratified and used permuted blocks of size eight. In the local excision group, a completion total mesorectal excision was required if tumour stage was ypT2-3. The primary endpoint was a composite outcome of death, recurrence, morbidity, and side-effects at 2 years after surgery, to show superiority of local excision over total mesorectal excision in the modified intention-to-treat (ITT) population (expected proportions of patients having at least one event were 25% vs 60% for superiority). This trial was registered with ClinicalTrials.gov, number NCT00427375. FINDINGS: From March 1, 2007, to Sept 24, 2012, 186 patients received chemoradiotherapy and were enrolled in the study. 148 good clinical responders were randomly assigned to treatment, three were excluded (because they had metastatic disease, tumour >8 cm from anal verge, and withdrew consent), and 145 were analysed: 74 in the local excision group and 71 in the total mesorectal excision group. In the local excision group, 26 patients had a completion total mesorectal excision. At 2 years in the modified ITT population, one or more events from the composite primary outcome occurred in 41 (56%) of 73 patients in the local excision group and 33 (48%) of 69 in the total mesorectal excision group (odds ratio 1·33, 95% CI 0·62-2·86; p=0·43). In the modified ITT analysis, there was no difference between the groups in all components of the composite outcome, and superiority was not shown for local excision over total mesorectal excision. INTERPRETATION: We failed to show superiority of local excision over total mesorectal excision, because many patients in the local excision group received a completion total mesorectal excision that probably increased morbidity and side-effects, and compromised the potential advantages of local excision. Better patient selection to avoid unnecessary completion total mesorectal excision could improve the strategy. FUNDING: National Cancer Institute of France, Sanofi, Roche Pharma.
Authors: A Barina; A De Paoli; P Delrio; M Guerrieri; A Muratore; F Bianco; D Vespa; C Asteria; E Morpurgo; A Restivo; C Coco; U Pace; C Belluco; C Aschele; S Lonardi; V Valentini; G Mantello; I Maretto; P Del Bianco; A Perin; S Pucciarelli Journal: Tech Coloproctol Date: 2017-07-28 Impact factor: 3.781