. Pr, Yann Parc, Hôpital Saint-Antoine

K. Pr and . Médhi, Hôpital Pitié Salpetrière, Paris, medhi.karoui@psl.aphp.fr 4. Pr

. Pr, . Tuech-jean-jacques, . Chu-rouen, . Rouen, . M. Jean-jacques-dr et al., tuech@chu-rouen.fr 14

. Pr, G. Berger-anne, . Pompidou, and . Paris, aphp.fr 18. Pr. Pruvot François-René, CHRU de Lille, frpruvot@chru-lille.fr 19, Dr. Eddy COTTE

. Dr, M. Laurent, and . Institut-sainte-catherine, Avignon, l.mineur@isc84.org 22. Dr, Jérôme DESRAME

. Dr, B. Laura, and H. Nord, Marseille, laura.beyer@ap-hm.fr 26. Dr. Frédérique-Sophie PESCHAUD, Hôpital Ambroise Paré, pp.1471-2407417

A. Publique-hôpitaux-de and P. , Department of Digestive Surgery, Hôpital Saint-Antoine, 184, rue du Fbg Saint-Antoine, 75012 Paris, France. 2 University Pierre & Marie Curie (UPMC-Paris 06), Department of Clinical Pharmacology, Hôpital Saint-Antoine

A. Bouvier, L. Remontet, and E. Jougla, Incidence of gastrointestinal cancers in France, Gastroent?rologie Clinique et Biologique, vol.28, issue.10, pp.877-881, 2004.
DOI : 10.1016/S0399-8320(04)95152-4

URL : https://hal.archives-ouvertes.fr/hal-00427551

R. Heald and R. Ryall, RECURRENCE AND SURVIVAL AFTER TOTAL MESORECTAL EXCISION FOR RECTAL CANCER, The Lancet, vol.327, issue.8496, pp.1479-1482, 1986.
DOI : 10.1016/S0140-6736(86)91510-2

J. Macfarlane, R. Ryall, and R. Heald, Mesorectal excision for rectal cancer, The Lancet, vol.341, issue.8843, pp.457-460, 1993.
DOI : 10.1016/0140-6736(93)90207-W

A. Martling, B. Cedermark, H. Johansson, L. Rutqvist, and T. Holm, The surgeon as a prognostic factor after the introduction of total mesorectal excision in the treatment of rectal cancer, British Journal of Surgery, vol.24, issue.8, pp.891008-1013, 2002.
DOI : 10.1046/j.1365-2168.2002.02151.x

A. Martling, T. Holm, L. Rutqvist, H. Johansson, B. Moran et al., Impact of a surgical training programme on rectal cancer outcomes in Stockholm, British Journal of Surgery, vol.345, issue.2, pp.225-229, 2005.
DOI : 10.1002/bjs.4834

A. Gerard, J. Berrod, F. Pene, J. Loygue, A. Laugier et al., Preoperative Radiotherapy and Radical Surgery as Combined Treatment in Rectal Cancer, Recent Results Cancer Res, vol.110, pp.130-133, 1988.
DOI : 10.1007/978-3-642-83293-2_19

E. Kapiteijn, C. Marijnen, I. Nagtegaal, H. Putter, W. Steup et al., Preoperative Radiotherapy Combined with Total Mesorectal Excision for Resectable Rectal Cancer, New England Journal of Medicine, vol.345, issue.9, pp.345638-646, 2001.
DOI : 10.1056/NEJMoa010580

C. Marijnen, E. Kapiteijn, C. Van-de-velde, H. Martijn, W. Steup et al., Acute Side Effects and Complications After Short-Term Preoperative Radiotherapy Combined With Total Mesorectal Excision in Primary Rectal Cancer: Report of a Multicenter Randomized Trial, Journal of Clinical Oncology, vol.20, issue.3, pp.817-825, 2002.
DOI : 10.1200/JCO.2002.20.3.817

K. Peeters, C. Van-de-velde, J. Leer, H. Martijn, J. Junggeburt et al., Late Side Effects of Short-Course Preoperative Radiotherapy Combined With Total Mesorectal Excision for Rectal Cancer: Increased Bowel Dysfunction in Irradiated Patients?A Dutch Colorectal Cancer Group Study, Journal of Clinical Oncology, vol.23, issue.25, pp.236199-6206, 2005.
DOI : 10.1200/JCO.2005.14.779

G. Portier, Comment choisir les th?rapeutiques n?oadjuvantes ?, Gastroent?rologie Clinique et Biologique, vol.31, issue.1, pp.23-33, 2007.
DOI : 10.1016/S0399-8320(07)91503-1

J. Bosset, L. Collette, G. Calais, L. Mineur, P. Maingon et al., Chemotherapy with Preoperative Radiotherapy in Rectal Cancer, New England Journal of Medicine, vol.355, issue.11, pp.3551114-1123, 2006.
DOI : 10.1056/NEJMoa060829

URL : https://hal.archives-ouvertes.fr/hal-00484917

J. Bosset, G. Calais, L. Mineur, P. Maingon, L. Radosevic-jelic et al., Enhanced Tumorocidal Effect of Chemotherapy With Preoperative Radiotherapy for Rectal Cancer: Preliminary Results?EORTC 22921, Journal of Clinical Oncology, vol.23, issue.24, pp.235620-5627, 2005.
DOI : 10.1200/JCO.2005.02.113

A. Habr-gama, R. Perez, W. Nadalin, J. Sabbaga, U. Ribeiro et al., Operative Versus Nonoperative Treatment for Stage 0 Distal Rectal Cancer Following Chemoradiation Therapy, Transactions of the ... Meeting of the American Surgical Association, vol.CXXII, issue.&NA;, pp.711-717, 2004.
DOI : 10.1097/01.sla.0000141194.27992.32

URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1356472

L. De-campos-lobato, L. Stocchi, M. Da-luz, D. Geisler, D. Dietz et al., Pathologic Complete Response After Neoadjuvant Treatment for Rectal Cancer Decreases Distant Recurrence and Could Eradicate Local Recurrence, Annals of Surgical Oncology, vol.51, issue.6, pp.1590-1598, 2011.
DOI : 10.1007/s10350-007-9148-5

D. Medich, J. Mcginty, D. Parda, S. Karlovits, C. Davis et al., Preoperative chemoradiotherapy and radical surgery for locally advanced distal rectal adenocarcinoma, Diseases of the Colon & Rectum, vol.44, issue.8, pp.441123-1128, 2001.
DOI : 10.1007/BF02234632

N. Kim, S. Baik, J. Seong, H. Kim, J. Roh et al., Oncologic Outcomes After Neoadjuvant Chemoradiation Followed by Curative Resection With Tumor-Specific Mesorectal Excision for Fixed Locally Advanced Rectal Cancer, Annals of Surgery, vol.244, issue.6, pp.2441024-1030, 2006.
DOI : 10.1097/01.sla.0000225360.99257.73

URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1856621

S. Hiotis, S. Weber, A. Cohen, B. Minsky, P. Paty et al., Assessing the predictive value of clinical complete response to neoadjuvant therapy for rectal cancer: an analysis of 488 patients1 1No competing interests declared., Journal of the American College of Surgeons, vol.194, issue.2, pp.131-135, 2002.
DOI : 10.1016/S1072-7515(01)01159-0

Y. Francois, C. Nemoz, J. Baulieux, J. Vignal, J. Grandjean et al., Influence of the Interval Between Preoperative Radiation Therapy and Surgery on Downstaging and on the Rate of Sphincter-Sparing Surgery for Rectal Cancer: The Lyon R90-01 Randomized Trial, Journal of Clinical Oncology, vol.17, issue.8, p.172396, 1999.
DOI : 10.1200/JCO.1999.17.8.2396

C. Rodel, P. Martus, T. Papadoupolos, L. Fuzesi, M. Klimpfinger et al., Prognostic Significance of Tumor Regression After Preoperative Chemoradiotherapy for Rectal Cancer, Journal of Clinical Oncology, vol.23, issue.34, pp.238688-8696, 2005.
DOI : 10.1200/JCO.2005.02.1329

J. Gerard, T. Conroy, F. Bonnetain, O. Bouche, O. Chapet et al., Preoperative Radiotherapy With or Without Concurrent Fluorouracil and Leucovorin in T3-4 Rectal Cancers: Results of FFCD 9203, Journal of Clinical Oncology, vol.24, issue.28, pp.244620-4625, 2006.
DOI : 10.1200/JCO.2006.06.7629

F. Stipa, D. Chessin, J. Shia, P. Paty, M. Weiser et al., A Pathologic Complete Response of Rectal Cancer to Preoperative Combined-Modality Therapy Results in Improved Oncological Outcome Compared With Those Who Achieve No Downstaging on the Basis of Preoperative Endorectal Ultrasonography, Annals of Surgical Oncology, vol.20, issue.16 Pt 1, pp.131047-1053, 2006.
DOI : 10.1245/ASO.2006.03.053

J. Garcia-aguilar, E. Hernandez-de-anda, P. Sirivongs, S. Lee, R. Madoff et al., A Pathologic Complete Response to Preoperative Chemoradiation Is Associated With Lower Local Recurrence and Improved Survival in Rectal Cancer Patients Treated by Mesorectal Excision, Diseases of the Colon & Rectum, vol.46, issue.3, pp.298-304, 2003.
DOI : 10.1007/s10350-004-6545-x

L. Ruo, S. Tickoo, D. Klimstra, B. Minsky, L. Saltz et al., Long-Term Prognostic Significance of Extent of Rectal Cancer Response to Preoperative Radiation and Chemotherapy, Annals of Surgery, vol.236, issue.1, pp.75-81, 2002.
DOI : 10.1097/00000658-200207000-00012

H. Moore, A. Gittleman, B. Minsky, D. Wong, P. Paty et al., Rate of Pathologic Complete Response With Increased Interval Between Preoperative Combined Modality Therapy and Rectal Cancer Resection, Diseases of the Colon & Rectum, vol.47, issue.3, pp.47279-286, 2004.
DOI : 10.1007/s10350-003-0062-1

D. Stein, N. Mahmoud, P. Anne, D. Rose, G. Isenberg et al., Longer Time Interval Between Completion of Neoadjuvant Chemoradiation and Surgical Resection Does Not Improve Downstaging of Rectal Carcinoma, Diseases of the Colon & Rectum, vol.46, issue.4, pp.448-453, 2003.
DOI : 10.1007/s10350-004-6579-0

H. Tulchinsky, E. Shmueli, A. Figer, J. Klausner, and M. Rabau, An Interval >7?Weeks between Neoadjuvant Therapy and Surgery Improves Pathologic Complete Response and Disease?Free Survival in Patients with Locally Advanced Rectal Cancer, Annals of Surgical Oncology, vol.42, issue.10, pp.152661-2667, 2008.
DOI : 10.1016/S0360-3016(98)00345-9

M. Kalady, L. De-campos-lobato, L. Stocchi, D. Geisler, D. Dietz et al., Predictive Factors of Pathologic Complete Response After Neoadjuvant Chemoradiation for Rectal Cancer, Transactions of the ... Meeting of the American Surgical Association, vol.127, issue.4, pp.582-589, 2009.
DOI : 10.1097/SLA.0b013e3181b91e63

S. Lim, H. Choi, S. Jeong, D. Kim, K. Jung et al., Optimal Surgery Time After Preoperative Chemoradiotherapy for Locally Advanced Rectal Cancers, Annals of Surgery, vol.248, issue.2, pp.243-251, 2008.
DOI : 10.1097/SLA.0b013e31817fc2a0

S. Yeo, D. Kim, T. Kim, H. Chang, J. Oh et al., Pathologic Complete Response of Primary Tumor Following Preoperative Chemoradiotherapy for Locally Advanced Rectal Cancer, Annals of Surgery, vol.252, issue.6, pp.252998-1004, 2010.
DOI : 10.1097/SLA.0b013e3181f3f1b1

L. De-campos-lobato, D. Geisler, M. Da-luz, L. Stocchi, D. Dietz et al., Neoadjuvant Therapy for Rectal Cancer: The Impact of Longer Interval Between Chemoradiation and Surgery, Journal of Gastrointestinal Surgery, vol.11, issue.3, pp.444-450, 2011.
DOI : 10.1007/s10147-008-0849-0

K. Bujko, Timing of Surgery Following Preoperative Therapy in Rectal Cancer, Diseases of the Colon & Rectum, vol.55, issue.3, pp.31-32
DOI : 10.1097/DCR.0b013e31823f86cb

A. Rullier and C. Laurent, [Recommendations for clinical practice Therapeutic choices for rectal cancer What quality criteria are important for surgical http, Gastroenterol Clin Biol, vol.13417, issue.31 1, pp.34-51, 2007.

P. Quirke, P. Durdey, M. Dixon, and N. Williams, Local recurrence of rectal adenocarcinoma due to inadequate surgical resection. Histopathological study of lateral tumour spread and surgical excision, Lancet, vol.2, issue.8514, pp.996-999, 1986.

H. Tranchart, J. Lefevre, M. Svrcek, J. Flejou, E. Tiret et al., What is the Incidence of Metastatic Lymph Node Involvement After Significant Pathologic Response of Primary Tumor Following Neoadjuvant Treatment for Locally Advanced Rectal Cancer?, Annals of Surgical Oncology, vol.2, issue.5, pp.1551-1559
DOI : 10.1001/archsurg.137.2.206

O. Dworak, L. Keilholz, and A. Hoffmann, Pathological features of rectal cancer after preoperative radiochemotherapy, International Journal of Colorectal Disease, vol.12, issue.1, pp.19-23, 1997.
DOI : 10.1007/s003840050072

P. Clavien, J. Barkun, M. De-oliveira, J. Vauthey, D. Dindo et al., The Clavien-Dindo Classification of Surgical Complications, Annals of Surgery, vol.250, issue.2, pp.187-196, 2009.
DOI : 10.1097/SLA.0b013e3181b13ca2

D. Dindo, N. Demartines, and P. Clavien, Classification of Surgical Complications, Annals of Surgery, vol.240, issue.2, pp.205-213, 2004.
DOI : 10.1097/01.sla.0000133083.54934.ae

URL : http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1360123

P. Armitage, Interim analysis in clinical trials, Statistics in Medicine, vol.5, issue.6, pp.925-935, 1991.
DOI : 10.1038/bjc.1976.220

A. Kramar and S. Mathoulin-pelissier, Methodes biostatistiques appliquées à la recherche clinique en cancérologie, 2011.

J. Evans, D. Tait, I. Swift, K. Pennert, P. Tekkis et al., Timing of surgery following preoperative therapy in rectal cancer: the need for a prospective randomized trial? Dis Colon Rectum, pp.541251-1259, 2011.

N. Methy, L. Bedenne, T. Conroy, O. Bouche, O. Chapet et al., Surrogate end points for overall survival and local control in neoadjuvant rectal cancer trials: statistical evaluation based on the FFCD 9203 trial, Annals of Oncology, vol.21, issue.3, pp.518-524, 2010.
DOI : 10.1093/annonc/mdp340

. Lefevre, A multicentric randomized controlled trial on the impact of lengthening the interval between neoadjuvant radiochemotherapy and surgery on complete pathological response in rectal cancer (GRECCAR-6 trial): rationale and design, BMC Cancer, vol.21, issue.3, p.417, 2013.
DOI : 10.1093/annonc/mdp340

URL : https://hal.archives-ouvertes.fr/hal-01548289