Gallbladder cancer is a rare type of biliary tract cancer, with only 12,640 cases diagnosed annually in the United States. Gallbladder cancer is nevertheless a deadly disease, with 4,590 deaths projected for 2026 and an overall survival of 20% at five years for all stages combined. Survival is strongly influenced by stage, however, with early localized disease having a 69% five-year survival and patients with lymph node disease having a drop in survival to 28% at five years. Unfortunately, the survival for patients with distant (metastatic) disease is 3% at five years.1
General approach to management
As an overview, the standard management for resectable gallbladder cancers is a) complete staging, b) upfront oncologic surgery, and c) systemic chemotherapy (if pathologic staging is T1a or greater). Biopsy of gallbladder cancers should be avoided due to a high risk of peritoneal seeding. However, for locally unresectable or metastatic disease, biopsy is necessary to start neoadjuvant or palliative treatment. Oncologic surgical resection for gallbladder cancer is a cholecystectomy with en bloc central liver resection, a portal lymphadenectomy, and resection of the cystic duct stump, if necessary, to achieve negative margins.
Because presentation can occur in a variety of clinical settings, the precise application of this management can change subtly. These clinical algorithms are outlined in great detail in the NCCN Guidelines. However, in brief:
Incidental gallbladder cancer
Gallbladder cancer is often diagnosed as an incidental finding in cholecystectomy specimens performed for other indications (Incidental Gallbladder Cancer, IGBC). Estimates of the incidence of IGBC range from 0.3%-3% of cholecystectomy specimens, and one large institutional series found that up to 47% of gallbladder cancers were diagnosed as IGBCs.2 If the lesion is stage T1a, no suspicious lymph nodes are noted on imaging or pathology, and the cystic duct stump is negative for tumor, the patient can be observed. If, however, a higher stage is noted on pathology or there are any positive margins (liver or cystic duct stump), then an oncologic operation is indicated.
Incidental gallbladder mass on imaging
Alternatively, patients may also present with gallbladder masses or polyps discovered incidentally on imaging done for other reasons. Gallbladder masses and any polyps (greater than 1 cm) should be referred to a surgical oncologist and removed with an oncologic operation (described above) at the initial sitting.
Patients who present with symptoms
Patients may also present with symptoms of right upper abdominal pain, bloating after meals, jaundice, or other more vague symptoms like loss of appetite and weight loss. In these cases, cross-sectional imaging usually identifies a gallbladder mass and sometimes an associated liver mass. Some patients with more challenging diagnostic paths will present with right upper abdominal complaints and are found to have a liver abscess associated with gallbladder inflammation. When the liver is biopsied during placement of a drain, they are found to have gallbladder cancer with local spread to the liver and necrosis of the liver mass.
These patients can be more challenging to manage and usually require a multidisciplinary approach. Nevertheless, after appropriate drainage and abx, if the anatomy appears resectable and no metastatic disease is suspected, the patient can proceed with upfront surgical resection. However, the disease in these cases is often borderline in its resectability, or there may be suspicious nonregional lymph nodes, or the tumor board simply feels that the patient might benefit from neoadjuvant therapy. In these cases, systemic chemo or chemoradiation might be offered first, followed by surgery.
Adjuvant postoperative treatment
Patients with resected gallbladder cancer who have a T stage of T1b or greater (muscle invasive) or who have positive lymph nodes are offered adjuvant capecitabine.3 If the patient has a positive margin that is not amenable to surgical revision, then chemoradiation can be offered, usually in the setting of a multidisciplinary tumor board.
Palliative systemic chemotherapy
With our greater understanding of the natural history of gallbladder cancer and advances in surgical technique, we have been able to cure more patients with localized disease. Unfortunately, many patients will present either with more advanced nonsurgical disease or the disease will recur after surgery. More recent advances in molecular biology have allowed us to understand the genetic changes driving gallbladder cancer, have allowed us to develop better therapeutics and, most importantly, personalize treatment plans based on the genetic findings of the individual’s tumor.
When a patient presents to the clinic, we now send the tissue sample for molecular testing and send the patient’s blood for analysis of circulating tumor DNA. It is also important to have the patient tested for inherited genetic abnormalities that may have made them susceptible to gallbladder cancer. All this information provides detailed genetic data that allows the medical team to develop the most effective treatment plan possible.
The testing will show the tumor’s susceptibility to combination immunotherapy-chemotherapy, antibody-chemotherapy conjugates targeting specific surface markers on cancer cells, or small molecules targeting very specific genetic abnormalities driving cancer growth.
Immunotherapy enables the body’s immune system to identify cancer cells, thereby facilitating its ability to fight cancer. Antibody-chemotherapy drug conjugates act like smart missiles that hone in on the cancer cell, depositing a small dose of chemotherapy into the cancer cell and killing it. The small molecules, which are often pills, target specific genetic abnormalities that are causing cancer growth, shutting the cancer cells down.
Emerging therapies and new data hot-off-the-press
Immunotherapy continues to find uses in more and more cancers, including biliary tract cancers like gallbladder cancer. The TOPAZ-1 study, published in 2022 in the NEJM, showed the efficacy of adding durvalumab to gemcitabine and cisplatin for unresectable or metastatic biliary tract cancers. However, a recent small randomized control trial of 93 patients in JAMA Oncology, the ACCORD study (2025), demonstrated superiority of adjuvant chemoradiation plus immunotherapy (camrelizumab) versus observation for resected extrahepatic and gallbladder biliary tract cancers.4 While this study only compared the immunotherapy arm with observation alone, instead of comparing it to adjuvant capecitabine, this study nevertheless demonstrates the growing excitement over the use of immunotherapy in biliary tract cancers.5
Conclusion
Gallbladder cancer is a rare and deadly cancer with several presenting clinical settings. It is important to consult a surgical oncologist upfront for suspected gallbladder cancer to help guide the management, and it is important to consult a medical oncologist to make sure you are receiving the most up-to-date postsurgery chemo and immunotherapies. Despite the challenging statistics surrounding gallbladder cancer, there remains reason for optimism if treated early and aggressively.
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References:
- American Cancer Society. SEER Database Statistics. Accessed February 12, 2025. https://seer.cancer.gov/statfacts.
- Duffy, A., M. Capanu, G. K. Abou-Alfa, D. Huitzil, W. Jarnagin, Y. Fong, M. D’Angelica, R. P. DeMatteo, L. H. Blumgart, and E. M. O’Reilly. “Gallbladder Cancer (GBC): 10-Year Experience at Memorial Sloan-Kettering Cancer Centre (MSKCC).” Journal of Surgical Oncology 98, no. 6 (2008): 485-89.
- Primrose, John N., et al. “Capecitabine Compared with Observation in Resected Biliary Tract Cancer (BILCAP): A Randomized, Controlled, Multicentre, Phase 3 Study.” The Lancet Oncology 20, no. 5 (2019): 663-73.
- Oh, Do-Youn, et al. “Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer.” NEJM Evidence 1, no. 8 (2022).
- Xiao, Han, et al. “Adjuvant Chemoradiation and Immunotherapy for Extrahepatic Cholangiocarcinoma and Gallbladder Cancer: A Randomized Clinical Trial.” JAMA Oncology 11, no. 9 (September 1, 2025): 1021-1029.
