Predictive Factors of Recurrence in Patients with Pathological Complete Response After Esophagectomy Following Neoadjuvant Chemoradiotherapy for Esophageal Cancer: A Multicenter Study

Abstract

Background

Minimal data have previously emerged from studies regarding the factors associated with recurrence in patients with ypT0N0M0 status. The purpose of the study was to predict survival and recurrence in patients with pathological complete response (pCR) following chemoradiotherapy (CRT) and surgery for esophageal cancer (EC).

Methods

Among 2944 consecutive patients with EC operations in 30 centers between 2000 and 2010, patients treated with neoadjuvant CRT followed by surgery who achieved pCR (n = 191) were analyzed. The factors associated with survival and recurrence were analyzed using a Cox proportional hazard regression analysis.

Results

Among 593 patients who underwent neoadjuvant CRT followed by esophagectomy, pCR was observed in 191 patients (32.2 %). Recurrence occurred in 56 (29.3 %) patients. The median time to recurrence was 12 months. The factors associated with recurrence were postoperative complications grade 3–4 [odds ratio (OR): 2.100; 95 % confidence interval (CI) 1.008–4.366; p = 0.048) and adenocarcinoma histologic subtype (OR 2.008; 95 % CI 0.1.06–0.3.80; p = 0.032). The median overall survival was 63 months (95 % CI 39.3–87.1), and the median disease-free survival was 48 months (95 % CI 18.3–77.4). Age (>65 years) [hazard ratio (HR): 2.166; 95 % CI 1.170–4.010; p = 0.014), postoperative complications grades 3–4 [HR 2.099; 95 % CI 1.137–3.878; p = 0.018], and radiation dose (<40 Gy) (HR 0.361; 95 % CI 0.159–0.820; p = 0.015) were identified as factors associated with survival.

Conclusions

An intensive follow-up may be beneficial for patients with EC who achieve pCR and who develop major postoperative complications or the adenocarcinoma histologic subtype.

Appendix

The members of the FREGAT (French Eso-Gastric Tumors) working group, FRENCH (Fédération de Recherche EN CHirurgie) and AFC (Association Française de Chirurgie) are given below.

Abdennahceur Dhahri, MD, PhD, Delphine Lignier, MD, Cyril Cossé, MD, Jean-Marc Regimbeau, MD, PhD, Department of Digestive Surgery Amiens, France; Magalie Cabau, MD, Department of Digestive Surgery Bordeaux, France; Jacques Jougon MD, PhD, Department of Thoracic Surgery Bordeaux, France; Bogdan Badic, MD, Patrick Lozach, MD, Jean Pierre Bail, MD, Department of Digestive Surgery, Brest, France; Serge Cappeliez, MD, PhD, Issam El Nakadi, MD, PhD, Department of Digestive Surgery, Brussel ULB Erasme Bordet University, Brussel, Belgium; Gil Lebreton, MD, Arnaud Alves, MD, PhD, Department of Digestive Surgery, Caen, France; Renaud Flamein, MD, Denis Pezet, MD, PhD, Department of Digestive Surgery, Clermont-Ferrand, France; Federica Pipitone, MD, Bogdan Stan-Iuga, MD, Nicolas Contival, MD, Eric Pappalardo, MD, Simon Msika, MD, PhD, Department of Digestive Surgery, Louis Mourier University Hospital, Colombes, France; Styliani Mantziari, MD, Nicolas Demartines, Department of Digestive Surgery, Lausanne University Hospital, Lausanne, Switzerland; Flora Hec, MD, Marguerite Vanderbeken, MD, Williams Tessier, MD, Nicolas Briez, MD, Department of Digestive Surgery, Lille, France; Fabien Fredon, MD, Alain Gainant, MD, Muriel Mathonnet, MD, PhD, Department of Digestive Surgery, Limoges, France; Salim Mezoughi, MD, Christian Ducerf, MD, Jacques Baulieux, MD, Jean-Yves Mabrut, MD, PhD, Department of Digestive Surgery, Croix Rousse University Hospital, Lyon, France; Arnaud Pasquer, MD, Oussama Baraket, MD, Gilles Poncet, MD, Mustapha Adam, MD, PhD, Department of Digestive Surgery, Edouard Herriot University Hospital, Lyon, France; Delphine Vaudoyer, MD, Peggy Jourdan Enfer, MD, Laurent Villeneuve, MD, Olivier Glehen, MD, PhD, Department of Digestive Surgery, Lyon Sud University Hospital, Lyon, France; Thibault Coste, MD, Jean-Michel Fabre, MD, Department of Digestive Surgery, Montpellier, France; Frédéric Marchal, MD, Department of Digestive Surgery, Institut de cancérologie de Lorraine, Nancy, France; Romain Frisoni, MD, Ahmet Ayav, MD, PhD, Laurent Brunaud, MD, PhD, Laurent Bresler, MD, Department of Digestive Surgery, Nancy, France; Charlotte Cohen, MD, Olivier Aze, MD, Nicolas Venissac, MD, Daniel Pop, MD, Jérôme Mouroux, MD, Department of Thoracic Surgery, Nice, France; Ion Donici, MD, Michel Prudhomme, MD, PhD, Department of Digestive Surgery, Nîmes, France; Emanuele Felli, MD, Stéphanie Lisunfui, MD, Marie Seman, MD, Gaelle Godiris Petit, MD, Mehdi Karoui, MD, PhD, Christophe Tresallet, MD, PhD, Fabrice Ménégaux, MD, PhD, Jean-Christophe Vaillant, MD, Laurent Hannoun, MD, Department of Digestive Surgery, Pitié-Salpétrière University Hospital, Paris, France; Brice Malgras, MD, Denis Lantuas, MD, Karine Pautrat, MD, Marc Pocard, MD, PhD, Patrice Valleur, MD, Department of Digestive Surgery, Lariboisière University Hospital, Paris, France; Najim Chafai, MD, Pierre Balladur, MD, Magalie Lefrançois, MD, Yann Parc, MD, PhD, François Paye, MD, PhD Emmanuel Tiret, MD Department of Digestive Surgery, Saint-Antoine University Hospital, Paris, France; Marius Nedelcu, MD, Letizia Laface, MD, Thierry Perniceni, MD, Brice Gayet, MD, Department of Digestive Surgery, Institut Mutualiste Montsouris, Paris, France; Bernard Meunier, MD, Department of Digestive Surgery, Rennes, France; Alexandre Filipello, MD, Jack Porcheron, MD, Olivier Tiffet, MD, PhD, Department of Digestive Surgery, Saint-Etienne, France; Noémie Kamlet, MD, Rodrigue Chemaly, MD, Amandine Klipfel, MD, Patrick Pessaux, MD, PhD, Cecile Brigand, MD, PhD, Serge Rohr MD, Department of Digestive Surgery, Strasbourg, France; Nicolas Carrère, MD, PhD, Department of Digestive Surgery, Toulouse, France; Chiara Da Re, MD, Frédéric Dumont, MD, Diane Goéré, MD, PhD, Dominique Elias, MD, Department of Digestive Surgery Institut Gustave-Roussy,Villejuif, France; Claude Bertrand, MD, Mont-Godinne University Hospital, Yvoir, Belgium.