Surgical outcomes of gallbladder cancer: the OMEGA retrospective, multicentre, international cohort study

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.

Keywords: Cholangiocarcinoma; Gallbladder cancer; Liver resection; Surgical outcomes.

Fig. 1

Distribution of countries participating in the OMEGA study (marked by red squares) superimposed on estimated global age-standardized incidence rates (ASR) of gallbladder cancer per 100,000 individuals. Adapted with permission from the International Agency for Research on Cancer's GLOBOCAN database, ref. , IARC.

Fig. 2

Forest plots and multivariable Cox proportional hazard regression analysis of factors influencing RFS (A) and OS (B). EBDR – extrahepatic bile duct resection, CI – confidence intervals.

Fig. 3

Recurrence-free survival (RFS) curves for T1a (A), T1b (B), T2 (C), T3 (D) and T4 (E) stages of GBC according to extent of surgery performed. CO – cholecystectomy only, WR – wedge resection, SR – segment IVb/V resection, MH – major hepatectomy. Censored numbers in brackets. p-value of Kaplan–Meier curve calculated by log-rank test and hazard estimates by univariable Cox proportional hazards model compared to “cholecystectomy only”.

Fig. 4

Forest plot and multivariable logistic regression analysis of factors influencing 30-day severe morbidity and mortality (Clavien-Dindo Grade IIIA and above). EBDR – extrahepatic bile duct resection, CI – confidence intervals, OR – odds ratio.