Surgical outcomes of gallbladder cancer: the OMEGA retrospective, multicentre, international cohort study
Anita Balakrishnan, Petros Barmpounakis, Nikolaos Demiris, Asif Jah, Harry Spiers, Shibojit Talukder, Jack L. Martin, Paul Gibbs, Simon Harper, Emmanuel Huguet, Vasilis Kosmoliaptsis, Siong S Liau, Raaj Praseedom, Bristi Basu, X. De Aretxabala, Javier Lendoire, Shishir K. Maithel, Alejandro Brañes, Bodil Andersson, Alejandro Serrablo, Volkan Adsay, Tomoyuki Abe, Moh'd Abu Hilal, Maria del Mar Achalandabaso Boira, Mustapha Adham, Mohamed Adam, Maryam Ahmad, Bilal Al‐Sarireh, Maite Albiol, Nassir Alhaboob, Adnan Alseidi, Houssem Ammar, Akshay Anand, Bodil Andersson, Pantelis Antonakis, Verónica Araya, Stanley W. Ashley, Georgi Atanasov, Fabio Ausania, Ricardo Balestri, Abhirup Banerjee, Sudeep Banerjee, Simon Banting, Giedrius Barauskas, F. Bartsch, Andrea Belli, Simona Beretta, Frederik Berrevoet, Ramesh Singh Bhandari, Gerardo Blanco‐Fernández, Louisa Bolm, Mathieu Bonal, Emre Bozkurt, Andries E. Braat, Luke Bradshaw, Konstantinos Bramis, Alejandro Brañes, Lyle Burdine, Matthew Byrne, Maria Caceres, Maria Jesús Castro Santiago, Benjamin Chan, Lynn Chong, Ahmet Çöker, María Conde Rodríguez, Daniel Croagh, Alyn Crutchley, Carmen Cutolo, Mathieu D’Hondt, D.M. D'Souza, Freek Daams, Raffaele Dalla Valle, José Davide, Mario De Bellis, M. de Boer, Céline De Meyere, Philip de Reuver, Matthew Dixon, Panagiotis Dorovinis, Gabriela Echeverría Bauer, Maria Eduarda, Hasan H. Eker, Joris I. Erdmann, Mert Erkan, Evangelos Felekouras, Emanuele Felli, Eduardo Fernandes, Eduardo Figueroa Rivera, Andras Fulop, Daniel Galun, Michael F. Gerhards, Poya Ghorbani, Fabio Giannone, Luis Gil, Emmanouil Giorgakis, Mario Giuffrida, Felice Giuliante, Ioannis Gkekas, Miguel Ángel Gómez‐Bravo, Bas Groot Koerkamp
Abstract
Background: Gallbladder cancer (GBC) is rare but aggressive. The extent of surgical intervention for different GBC stages is non-uniform, ranging from cholecystectomy alone to extended resections including major hepatectomy, resection of adjacent organs and routine extrahepatic bile duct resection (EBDR). Robust evidence here is lacking, however, and survival benefit poorly defined. This study assesses factors associated with recurrence-free survival (RFS), overall survival (OS) and morbidity and mortality following GBC surgery in high income countries (HIC) and low and middle income countries (LMIC). Methods: The multicentre, retrospective Operative Management of Gallbladder Cancer (OMEGA) cohort study included all patients who underwent GBC resection across 133 centres between 1st January 2010 and 31st December 2020. Regression analyses assessed factors associated with OS, RFS and morbidity. Findings: On multivariable analysis of all 3676 patients, wedge resection and segment IVb/V resection failed to improve RFS (HR 1.04 [0.84-1.29], p = 0.711 and HR 1.18 [0.95-1.46], p = 0.13 respectively) or OS (HR 0.96 [0.79-1.17], p = 0.67 and HR 1.48 [1.16-1.88], p = 0.49 respectively), while major hepatectomy was associated with worse RFS (HR 1.33 [1.02-1.74], p = 0.037) and OS (HR 1.26 [1.03-1.53], p = 0.022). Furthermore, EBDR (OR 2.86 [2.3-3.52], p < 0.0010), resection of additional organs (OR 2.22 [1.62-3.02], p < 0.0010) and major hepatectomy (OR 3.81 [2.55-5.73], p < 0.0010) were all associated with increased morbidity and mortality. Compared to LMIC, patients in HIC were associated with poorer RFS (HR 1.18 [1.02-1.37], p = 0.031) but not OS (HR 1.05 [0.91-1.22], p = 0.48). Adjuvant and neoadjuvant treatments were infrequently used. Interpretation: In this large, multicentre analysis of GBC surgical outcomes, liver resection was not conclusively associated with improved survival, and extended resections were associated with greater morbidity and mortality without oncological benefit. Aggressive upfront resections do not benefit higher stage GBC, and international collaborations are needed to develop evidence-based neoadjuvant and adjuvant treatment strategies to minimise surgical morbidity and prioritise prognostic benefit. Funding: Cambridge Hepatopancreatobiliary Department Research Fund.