Sex-related differences in oncologic outcomes, operative complications and health-related quality of life after curative-intent oesophageal cancer treatment: multicentre retrospective analysis
Authors: Mantziari Styliani , Elliott Jessie A , Markar Sheraz R , Klevebro Fredrik , Goense Lucas , Johar Asif , Lagergren Pernilla , Zaninotto Giovanni , van Hillegersberg Richard , van Berge Henegouwen Mark I , Schäfer Markus , Nilsson Magnus , Hanna George B , Reynolds John V ,   ENSURE Study Group, Van Veer Hans , Depypere Lieven , Coosemans Willy , Nafteux Philippe , Carroll Paul , Allison Frances , Darling Gail , Findlay John M , Everden Serenydd , Maynard Nicholas D , Ariyarathenam Arun , Sanders Grant , Jaunoo Shameen , Singh Pritam , Parsons Simon , Saunders John , Vohra Ravinder , Sinha Aaditya , Tan Benjamin H L , Whiting John G , Boshier Piers R , Markar Sheraz R , Zaninotto Giovanni , Hanna George B , Phillips Alexander W , Griffin S Michael , Walker Robert C , Underwood Tim J , Piessen Guillaume , Theisen Jorg , Friess Hans , Bruns Christiane J , Schröder Wolfgang , Collins Chris G , McAnena Oliver J , Rooney Siobhan , Quinn Aoife , Toale Conor , Murphy Thomas J , Elliott Jessie A , Ravi Narayanasamy , Donohoe Claire L , Reynolds John V , Scarpa Marco , Bardini Romeo , Degasperi Silvia , Saadeh Luca , Castoro Carlo , Alfieri Rita , Pinto Eleonora , Mattara Genny , Kalff Marianne C , Gisbertz Suzanne S , van Berge Henegouwen Mark I , van Hootegem Sander J M , Lagarde Sjoerd M , Kingma B Feike , Goense Lucas , Ruurda Jelle P , van Hillegersberg Richard , Kennedy Raymond , Carey P Declan , Prodehl Leanne , Lamb Peter J , Skipworth Richard J E , Cero Mariagiulia Dal , Pera Manuel , Huang Biying , Klevebro Fredrik , Nilsson Magnus , Johar Asif , Lagergren Pernilla , Linder Gustav , Sundbom Magnus , Mantziari Styliani , Schäfer Markus , Demartines Nicolas 
Published: April 2024

Abstract

Background
Oesophageal cancer, in particular adenocarcinoma, has a strong male predominance. However, the impact of patient sex on operative and oncologic outcomes and recovery of health-related quality of life is poorly documented, and was the focus of this large multicentre cohort study.

Methods
All consecutive patients who underwent oncological oesophagectomy from 2009 to 2015 in the 20 European iNvestigation of SUrveillance after Resection for Esophageal cancer study group centres were assessed. Clinicopathologic variables, therapeutic approach, postoperative complications, survival and health-related quality of life data were compared between male and female patients. Multivariable analyses adjusted for age, sex, tumour histology, treatment protocol and major complications. Specific subgroup analyses comparing adenocarcinoma versus squamous cell cancer for all key outcomes were performed.

Results
Overall, 3974 patients were analysed, 3083 (77.6%) male and 891 (22.4%) female; adenocarcinoma was predominant in both groups, while squamous cell cancer was observed more commonly in female patients (39.8% versus 15.1%, P &lt; 0.001). Multivariable analysis demonstrated improved outcomes in female patients for overall survival (HRmales 1.24, 95% c.i. 1.07 to 1.44) and disease-free survival (HRmales 1.22, 95% c.i. 1.05 to 1.43), which was caused by the adenocarcinoma subgroup, whereas this difference was not confirmed in squamous cell cancer. Male patients presented higher health-related quality of life functional scores but also a higher risk of financial problems, while female patients had lower overall summary scores and more persistent gastrointestinal symptoms.

Conclusion
This study reveals uniquely that female sex is associated with more favourable long-term survival after curative treatment for oesophageal cancer, especially adenocarcinoma, although long-term overall and gastrointestinal health-related quality of life are poorer in women.