Aims of the collaborative
Building a global evidence base for a rare and aggressive cancer.
Gallbladder cancer is the most common cancer of the biliary tract, but it is rare in most parts of the world and highly aggressive. Because of this, there have been no randomised controlled trials and few large prospective studies to guide surgical treatment. Practice varies widely between centres and countries, ranging from cholecystectomy alone to extended resections involving major hepatectomy, bile duct resection and removal of adjacent organs.
OMEGA (Operative Management of Gallbladder Cancer) was established to address this gap. It brings together hepatopancreatobiliary surgeons and pathologists from across the world to pool data at a scale no single centre could achieve, and to produce findings that are relevant in both high income and low and middle income settings.
What the collaborative set out to do
- Map how gallbladder cancer is managed internationally and identify where practice diverges from consensus guidelines.
- Determine which surgical strategies improve recurrence-free and overall survival, and which add morbidity without oncological benefit.
- Compare outcomes between high income and low and middle income countries to understand global disparities.
- Develop practical prognostic tools, such as nodal risk scores, that can be applied at the bedside.
- Build the case for international collaborative trials of neoadjuvant and adjuvant treatment strategies.
Approach
Collaborating centres were recruited through the three international HPB associations: the European-African HPB Association, the Americas HPB Association, and the Asia-Pacific HPB Association. The retrospective cohort covers all gallbladder cancer resections carried out between 1 January 2010 and 31 December 2020, staged using the 8th edition AJCC classification and reported in line with STROBE guidelines. Ethical approval was led by Cambridge University Hospitals NHS Foundation Trust, with further approvals obtained locally by participating centres.
Why it matters
The collaborative's central message is that aggressive upfront surgery does not benefit higher stage gallbladder cancer, and that extended resections carry substantial risk without clear survival gain. The work points towards a shift away from surgical morbidity and towards multimodality treatment, supported by globally relevant, evidence-based guidelines.
Research outputs to date
Peer-reviewed publications from the OMEGA collaborative.
Surgical outcomes of gallbladder cancer: the OMEGA retrospective, multicentre, international cohort study
Balakrishnan A, Barmpounakis P, Demiris N, et al. eClinicalMedicine. 2023;59:101951.
https://doi.org/10.1016/j.eclinm.2023.101951
- The largest cohort study of surgical outcomes in gallbladder cancer to date, spanning high income and low and middle income countries.
- Wedge resection and segment IVb/V resection did not improve recurrence-free or overall survival.
- Major hepatectomy was associated with worse recurrence-free and overall survival.
- Bile duct resection, resection of additional organs and major hepatectomy each increased 30-day severe morbidity and mortality, with roughly a 1 in 4 risk of serious complication or death compared with cholecystectomy alone.
- Neoadjuvant and adjuvant treatments were used infrequently across the whole cohort.
Assessment of nodal staging and risk factors for nodal involvement in gallbladder cancer
Balakrishnan A, Barmpounakis P, Demiris N, et al. BJS Open. 2025;9(3):zraf056.
https://doi.org/10.1093/bjsopen/zraf056
- Tumour stage, lymphovascular and perineural infiltration, and tumour differentiation carried the greatest risk of positive nodes.
- These three parameters form the OMEGA Node Positivity Prediction Score (OMEGA-NOPPS), with a C-statistic of 0.81 in training and 0.79 in test data.
- The number of positive nodes was the most discriminative prognostic model for nodal staging.
- Incidental gallbladder cancer with these high-risk features, including early T stages, should be considered for further treatment.
Heterogeneity of management practices surrounding operable gallbladder cancer: results of the OMEGA-S international HPB surgical survey
Balakrishnan A, Jah A, Lesurtel M, et al. HPB (Oxford). 2022;24(11):2006–2012.
https://doi.org/10.1016/j.hpb.2022.06.014
- A survey of international HPB surgeons on diagnostic workup, operative approach, and use of neoadjuvant and adjuvant therapies.
- High-volume liver resection units discussed gallbladder cancers in an HPB multidisciplinary team more often than low-volume units.
- Contrary to guidelines, anatomical liver resections were favoured for T3 and above, lymphadenectomy extent was lower than recommended, and a minority still routinely excised the common bile duct or port sites.
- The findings established the case for transcontinental collaborative studies, which became the OMEGA cohort.
Online calculators
Interactive tools based on prognostic models developed from OMEGA data.
Node Positivity Prediction Score
Estimates the probability of node-positive disease in gallbladder cancer from three routine histopathological parameters: tumour (T) stage, tumour differentiation, and lymphovascular or perineural invasion (LVPI). Derived from the OMEGA cohort (BJS Open 2025).
Select an option in each category to calculate the score.
Worked example. A T1b tumour scores 11.9% risk of positive nodes if well differentiated without LVPI (score 3), rising to the 33.9–50.0% band with a poorly differentiated tumour and LVPI (score 9).
Scoring (BJS Open 2025). T stage: T1a 0, T1b 3, T2 5, T3 7, T4 10. Differentiation: Well 0, Moderate 1, Poor 2. LVPI: No 0, Yes 4. Maximum score 16. Probability bands are taken directly from Table 3 of Balakrishnan A, et al. Assessment of nodal staging and risk factors for nodal involvement in gallbladder cancer. BJS Open. 2025;9(3):zraf056.
This calculator reproduces a published research model for educational and reference use. It is not a substitute for clinical judgement or multidisciplinary team assessment.
Collaborators
The OMEGA Study Investigators and the collaborating group.
Steering group and lead authors
The study was led by Anita Balakrishnan and colleagues from the Department of HPB Surgery, Cambridge University Hospitals NHS Foundation Trust (Asif Jah, Raaj Praseedom, Emmanuel Huguet, Paul Gibbs, Vasilis Kosmoliaptsis, Simon Harper, Siong Liau, Jack Martin and Bristi Basu), as well as an international panel of experts in gallbladder cancer (Javier Lendoire, Shishir Maithel, Bodil Andersson, Xavier de Aretxabala, Alejandro Brañes, Alejandro Serrablo, Colin Noel and Volkan Adsay). Statistical analysis was led by Petros Barmpounakis and Nikolaos Demiris from the Cambridge Clinical Trials Unit.