What is Gallbladder and Bile Duct Cancer?
​Patients with peritoneal metastases from either gallbladder cancer or bile duct cancer (cholangiocarcinoma) typically face a poor prognosis and are usually treated with palliative chemotherapy, immunotherapy, or clinical trials. However, growing interest in cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has shown promise in offering longer survival times compared to standard treatments.
While there is abundant information on more conventional treatments for Gallbladder and Bile Duct Cancer, our focus here will be on the rationale and available data supporting the use of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in these specific cases. It is important to emphasize that evidence regarding the benefit of CRS/HIPEC for Gallbladder Cancer remains limited. Nevertheless, reports suggest potential benefits for certain patients facing Gallbladder Cancer with rare indications for CRS/HIPEC.
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Gallbladder cancer and cholangiocarcinoma (bile duct cancer) are rare and highly invasive cancers that are difficult to treat. Surgical resection offers the only chance for long-term survival; however, early-stage diagnoses are uncommon, with only a small percentage (25%) of patients being diagnosed at a stage where surgery is feasible.[see References: 1] Peritoneal metastases (when cancer that has spread to the peritoneum from other organs) are found in a significant proportion of patients at the time of diagnosis (80%) and are one of the most frequent sites of recurrence (16%).[2, 3]
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Generally, patients with peritoneal metastases from gallbladder cancer or bile duct cancer (often referred to as cholangiocarcinoma) are treated with palliative intent, as the prognosis is generally poor, with median survival often <1 year.[4] Conventional treatment options for these patients typically include systemic chemotherapy (chemotherapy given intravenously), immunotherapy (treatment that uses a person's own immune system to fight cancer), targeted therapy, or participation in clinical trials. Despite this, there has been growing interest among some physicians in the use of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for select cases, drawing on its success in treating other cancers with peritoneal metastases.[5, 6]
The evidence supporting CRS/HIPEC for these cancers is extremely limited, with most data derived from small case reports and retrospective studies. One study showed that, in carefully selected patients, surgical treatment with CRS/HIPEC can offer a significant survival benefit over standard palliative chemotherapy, with a median survival of 21.4 vs 9.3 months.[7] Similarly, another study reported a median survival of 22.4 months after CRS/HIPEC for gallbladder cancer.[8] However, careful patient selection is critical, as factors such as the ability to achieve a complete cytoreduction are strongly linked to prognosis.[9, 10]
While complete cytoreduction is essential, some reports suggest that adding HIPEC can further improve outcomes. One study comparing 35 patients treated with CRS/HIPEC to 43 patients treated with CRS alone found a statistically significant survival advantage in the CRS/HIPEC group, with a median survival of 19 vs 15 months. Notably, postoperative morbidity was similar between groups, indicating that CRS/HIPEC can prolong survival time without increasing complications.[11] A similar study on cholangiocarcinoma also reported a significantly longer median survival in the CRS/HIPEC group (n=51, 25.53 months) compared to the CRS only group (n=61, 11.17 months).[12]
The majority of the studies are for patients with known peritoneal metastases. Additionally, CRS/HIPEC has been proposed as a potential prophylactic treatment for patients with early-stage gallbladder cancer who are at high risk for developing peritoneal metastases, although further research is needed to substantiate this approach.[13]
Finding Specialized Care
Finding a care provider who is knowledgeable with colorectal cancer and how to treat it is critically important. To search for providers who specialize in performing CRS/HIPEC and providers who specialize in colorectal cancer, navigate to our Find a Specialist page.​​
Please note: Our goal is to provide information to help you find a doctor closest to your home that can provide the best quality of care for your diagnosis or your anticipated CRS/HIPEC procedure. The Abdominal Cancers Alliance does not endorse any care provider or medical center over another.
Clinical Trials
Currently, there are many actively recruiting clinical trials for gallbladder cancer and cholangiocarcinoma registered online. Below is a sample of a few of the clinical trials for HIPEC listed on www.ClinicalTrials.gov. Your oncologists (medical, surgical, and radiation) can also help you review clinical trial options and recommendations.
Safety and Feasibility of HIPEC for High-Risk Gallbladder Adenocarcinoma (NCT05430035)
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Status: Recruiting
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This phase I study aims to evaluate the feasibility of incorporating HIPEC into a second look surgery after primary resection of gallbladder cancer with high risk for developing peritoneal metastases
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Inclusion criteria: Gallbladder cancer with intraoperative spillage or high risk pathologic features, able and willing to undergo surgical treatment
Pressurized Intraperitoneal Aerosolized Nab-Paclitaxel in Combination with Gemcitabine and Cisplatin for the Treatment of Biliary Tract Cancer Patients with Peritoneal Metastases (NCT05285358)
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Status: Recruiting
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This phase I study aims to evaluate the feasibility of PIPAC in combination with systemic chemotherapy to help control symptoms and improve the tolerability of treatment in patients with peritoneal metastases from biliary cancer.
- Inclusion criteria: Age ≥18, histologically confirmed cholangiocarcinoma or gallbladder cancer with peritoneal metastases, able to undergo treatment
1. Zhou Y, Yuan K, Yang Y, Ji Z, Zhou D, Ouyang J, Wang Z, Wang F, Liu C, Li Q, Zhang Q, Li Q, Shan X, Zhou J. Gallbladder cancer: current and future treatment options. Front Pharmacol. 2023 May 11;14:1183619. doi: 10.3389/fphar.2023.1183619. PMID: 37251319; PMCID: PMC10213899. 2. SEER: Explorer Application. (2023, November). Seer*Explorer. SEER: Gallbladder Cancer. https://seer.cancer.gov/statistics-network/explorer/application.html?site=38&data_type=1 &graph_type=2&compareBy=sex&chk_sex_1=1&chk_sex_3=3&chk_sex_2=2&rate_ty pe=2&race=1&age_range=1&stage=101&advopt_precision=1&advopt_show_ci=on&hd n_view=0&advopt_show_apc=on&advopt_display=1#resultsRegion0. 3. Margonis GA, Gani F, Buettner S, Amini N, Sasaki K, Andreatos N, Ethun CG, Poultsides G, Tran T, Idrees K, Isom CA, Fields RC, Krasnick B, Weber SM, Salem A, Martin RC, Scoggins C, Shen P, Mogal HD, Schmidt C, Beal E, Hatzaras I, Shenoy R, Maithel SK, Pawlik TM. Rates and patterns of recurrence after curative intent resection for gallbladder cancer: a multi-institution analysis from the US Extra-hepatic Biliary Malignancy Consortium. HPB (Oxford). 2016 Nov;18(11):872-878. doi: 10.1016/j.hpb.2016.05.016. Epub 2016 Aug 13. PMID: 27527802; PMCID: PMC5094487. 4. Rawla P, Sunkara T, Thandra KC, Barsouk A. Epidemiology of gallbladder cancer. Clin Exp Hepatol. 2019 May;5(2):93-102. doi: 10.5114/ceh.2019.85166. Epub 2019 May 23. PMID: 31501784; PMCID: PMC6728871. 5. Goéré D, Passot G, Gelli M, Levine EA, Bartlett DL, Sugarbaker PH, Glehen O. Complete cytoreductive surgery plus HIPEC for peritoneal metastases from unusual cancer sites of origin: results from a worldwide analysis issue of the Peritoneal Surface Oncology Group International (PSOGI). Int J Hyperthermia. 2017 Aug;33(5):520-527. doi: 10.1080/02656736.2017.1301576. PMID: 28540827. 6. Glehen O, Gilly FN, Boutitie F, Bereder JM, Quenet F, Sideris L, Mansvelt B, Lorimier G, Msika S, Elias D; French Surgical Association. Toward curative treatment of peritoneal carcinomatosis from nonovarian origin by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy: a multi-institutional study of 1,290 patients. Cancer. 2010 Dec 15;116(24):5608-18. doi: 10.1002/cncr.25356. Epub 2010 Aug 24. PMID: 20737573. 7. Amblard I, Mercier F, Bartlett DL, Ahrendt SA, Lee KW, Zeh HJ, Levine EA, Baratti D, Deraco M, Piso P, Morris DL, Rau B, Tentes AAK, Tuech JJ, Quenet F, Akaishi E, Pocard M, Yonemura Y, Lorimier G, Delroeux D, Villeneuve L, Glehen O, Passot G; PSOGI and BIG RENAPE working groups. Cytoreductive surgery and HIPEC improve survival compared to palliative chemotherapy for biliary carcinoma with peritoneal metastasis: A multi-institutional cohort from PSOGI and BIG RENAPE groups. Eur J Surg Oncol. 2018 Sep;44(9):1378-1383. doi: 10.1016/j.ejso.2018.04.023. Epub 2018 Jun 19. PMID: 30131104. 8. Randle RW, Levine EA, Clark CJ, Stewart JH, Shen P, Votanopoulos KI. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for gallbladder cancer: a retrospective review. Am Surg. 2014 Jul;80(7):710-3. PMID: 24987905. 9. Leigh N, Solomon D, Pletcher E, Labow DM, Magge DR, Sarpel U, Golas BJ. Is cytoreductive surgery and hyperthermic intraperitoneal chemotherapy indicated in hepatobiliary malignancies? World J Surg Oncol. 2020 Jun 11;18(1):124. doi: 10.1186/s12957-020-01898-5. PMID: 32527272; PMCID: PMC7291534. 10. Huang F, Shamavonian R, Morris DL. Cytoreductive Surgery and HIPEC for Regionally Advanced Gallbladder Cancer: a Case Report. Indian J Surg Oncol. 2023 Jun;14(Suppl 1):127-130. doi: 10.1007/s13193-022-01634-3. Epub 2022 Aug 29. PMID: 37359942; PMCID: PMC10284756. 11. Liu S, Zhong Z, Yi W, Yu Z, Zhang Z, Xia G, Jiang B, Song Y, Peng C. Effect of Hyperthermic Intraperitoneal Perfusion Chemotherapy Combined with Radical Surgery and Capecitabine on Stage III Gallbladder Cancer. Can J Gastroenterol Hepatol. 2021 Oct 8;2021:4006786. doi: 10.1155/2021/4006786. PMID: 34660468; PMCID: PMC8519707. 12. Feng F, Gao Q, Wu Y, Liu C, Yu Y, Li B, Chu K, Yi B, Cheng Q, Jiang X. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy vs. cytoreductive surgery alone for intrahepatic cholangiocarcinoma with peritoneal metastases: A retrospective cohort study. Eur J Surg Oncol. 2021 Sep;47(9):2363-2368. doi: 10.1016/j.ejso.2021.05.014. Epub 2021 May 14. PMID: 34119376. 13. Choi G, Jang S, Choi M, Yang S, Lee C, Kang CM. Curative intent radical cholecystectomy followed by hyperthermic intraperitoneal chemotherapy in ruptured intraductal papillary neoplasm of gallbladder with invasive carcinoma. Ann Hepatobiliary Pancreat Surg. 2022 Feb 28;26(1):113-117. doi: 10.14701/ahbps.21-071. PMID: 34840144; PMCID: PMC8901977.