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Gallbladder Cancer Treatment & Management

  • Author: Mary Denshaw-Burke, MD, FACP; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
Updated: Sep 14, 2015

Medical Care

Although complete surgical resection is the only therapy to afford a chance of cure, en bloc resections of the gallbladder and portal lymph nodes carry a high morbidity and mortality (similar to bile duct carcinoma). Adequate surgical margins may be difficult to achieve. The role of adjuvant radiation therapy is to control microscopic residual deposits of carcinoma in the tumor bed and regional lymph nodes. The rationale for radiation therapy with or without concurrent chemotherapy in patients with unresectable disease is to provide palliation of symptoms. Rarely, it may increase survival.

The role of radiotherapy for carcinoma of the gallbladder is unclear because the available literature is derived from small, single institutional experiences over many years, with a variety of treatment methods used. Complicating this is the fact that only approximately 25% of patients with carcinoma of the gallbladder can undergo curative surgery.

Even large institutions do not accrue more than single-digit numbers of patients per year, and many are not on protocol. Available reports contain small numbers of patients with incomplete reporting of technical treatment data, histological grading, and tumor extent. The literature is strongly biased by patient selection, and interpretation of the reports is difficult. Given these difficulties, the data support the following statements:

Radiotherapy has been delivered in a variety of situations, including after curative resections with close or positive microscopic margins, gross macroscopic residual disease, and palliative debulking with bypass.

Significant increases in survival rates have been reported after curative surgery is attempted and only microscopic residual disease remains. Survival in these patients after surgery alone ranges from 6-7 months and can be prolonged to longer than 12 months with external beam radiotherapy administered as adjuvant therapy. This excludes patients with T1 or stage I disease confined to the mucosa of the gallbladder. Their survival rates are extremely high and they are at very low risk for lymph node metastases.

All patients with tumors beyond the mucosa are candidates for external beam radiotherapy. Patients with curative resection and AJCC stages T2-T4 who have had complete resection who receive radiation have a mean survival of over 16 months. This is compared to less than 6 months mean survival with surgery alone.

5-FU–based chemotherapy is usually given in conjunction with concurrent radiation therapy in the adjuvant setting. Adjuvant chemotherapy can be given with single agent gemcitabine or a fluorpyrimidine-based agent. No evidence-based clinical study exists to demonstrate the benefit of any form of adjuvant therapy in gallbladder cancer. Wherever possible, patients eligible for adjuvant therapy should be entered in a clinical trial. Gemcitabine by itself is an effective agent in the treatment of patients with unresectable recurrent or metastatic disease. The combination of gemcitabine and cisplatin[16] or the combination of gemcitabine and capecitabine may be more effective than gemcitabine alone.

In a randomized, controlled, single institution study from India, Sharma et al compared best supportive care versus 5FU/leucovorin or gemcitabine/oxaliplatin in 81 patients with unresectable gallbladder cancer. The gemcitabine/oxaliplatin treatment arm was statistically superior in terms of overall response rate, median overall survival, and progression-free survival.[17]

In the UK ABC-02 trial,[18] a multicenter, phase III randomized trial, gemcitabine plus cisplatin demonstrated a survival advantage over gemcitabine alone. The median overall survival was11.7 months for those receiving gemcitabine plus cisplatin compared with 8.1 months for those receiving gemcitabine alone; progression-free survival was 8 months in the group receiving gemcitabine plus cisplatin group compared with 5 months in those receiving only gemcitabine.

Because some patients are not able to receive cisplatin-based chemotherapy, Iqbal et al explored gemcitabine plus capecitabine as a possible treatment option in a phase 2 study of 57 patients with advanced or metastatic biliary cancer. This study included both patients with cholangiocarcinoma (67%) and patients with gallbladder cancer (33%). No complete responses were seen. Of the 52 patients who were able to continue the study, a confirmed partial response was seen in 7 patients, and an unconfirmed partial response was seen in 6 patients. Stable disease was seen in 12 patients. Six-month overall survival was 55%, and median survival was 7 months. Of the 51 patients available for toxicity assessment, 6 had grade 4 toxicities. The study concluded that the combination of gemcitabine and capecitabine was well-tolerated.[19]

Because EGFR is overexpressed in a vast majority of biliary tract cancers, trials using EGFR-targeting agents have occurred. The BINGO trial, a phase II clinical trial of 101 patients (24% with gallbladder cancer), compared gemcitabine with oxaliplatin (GEMOX), alone or in combination with cetuximab; an interim analysis demonstrated a benefit for the GEMOX plus cetuximab arm, with a progression-free survival of 5 months compared with 7 months in the other arm.[20]

In support of this, a 30-patient, single-arm, phase II trial also evaluated the role of cetuximab with GEMOX in patients with unresectable advanced or metastatic biliary cancer (10% with gallbladder cancer).[21] An improvement in progression-free survival and overall survival was seen (progression-free survival, 8.8 mo; median overall survival, 15.2 mo). Wild-type KRAS was found in 90% of patients; however, all 3 patients who had tumors with KRAS mutations responded to therapy. Although the data are encouraging, more definitive phase III clinical trials are needed to direct therapy for patients with this particular malignancy.

Selected patients with unresectable disease may be considered for surgical resection after response to chemotherapy. This is based on a retrospective study showing markedly improved survival in a small number of patients who received gemcitabine and cisplatin followed by surgery.[22] More trials are needed to evaluate this benefit.

Patients with a good performance status should be considered for a clinical trial or for treatment with the regimens described in this section. Patients with a poor performance status may be best treated with supportive care.


Surgical Care

Complete surgical resection is the only therapy to offer a chance of cure in this disease. Unfortunately, only a minority of patients present with early-stage disease and are, therefore, considered for curative resection.

Optimistically, 5 year survival rates for gallbladder cancer have increased 5-12% up to 38%. This increase is felt to be related to a trend in standardizing aggressive approaches to locally confined disease.[23] Studies evaluating the significance of tumor involvement of the liver in early T-stage tumors and lymph node metastases on outcomes suggest that a need to standardize minimum requirements for adequate surgical resection and pathological examination of gallbladder cancer resections.[24]

Patients who present with a gallbladder mass or jaundice are evaluated preoperatively for resectability, including chest imaging, abdominal/ pelvic CT scan, or MRI and possibly a staging laparoscopy. Nodal metastases outside of the regional area (ie, porta hepatis, gastrohepatic ligament, retroduodenal area) are not resectable. If the tumor is resectable, the patient should undergo a cholecystectomy, hepatic resection, and regional lymphadenectomy (see the image below). The extent of hepatic resection is currently undefined. However, approximately 25% of T2 tumors have liver involvement. Liver involvement is a prognostic indicator of worse outcome.[24] Bile duct excision may also be necessary, especially if jaundice is present. The operative morbidity and mortality rate increases with the complexity of the operative procedure.

A schematic drawing of the extent of lymphadenecto A schematic drawing of the extent of lymphadenectomy for gallbladder cancer, especially when the extrahepatic biliary tree is resected.

Gallbladder cancer is sometimes an incidental pathology finding after a cholecystectomy is performed for reasons other than cancer. If the tumor is carcinoma in situ (Tis) or only invades the lamina propria (T1a) and the margins of resection are negative, then postoperative observation alone is acceptable. If the tumor is T1b or greater or the margins of resection are positive and if no metastatic disease is present on evaluation (CT or MRI scan and chest radiograph), then a second surgical resection is required. This additional surgery should include partial hepatic resection and regional lymphadenectomy (porta hepatis, gastrohepatic ligament, and retroduodenal lymph nodes). A bile duct resection may also be necessary, depending on tumor size and location. If the original surgery was performed via a laparoscopic approach, then the port sites should also be resected to avoid tumor seeding.

Because of the high incidence of gallbladder cancer in a calcified (porcelain) gallbladder, patients with this finding should be strongly considered for an open cholecystectomy, even if they are asymptomatic. Avoid a laparoscopic cholecystectomy in this setting to avoid the risk of peritoneal seeding if, indeed, gallbladder cancer is present.

Lymph node evaluation is a critical component of radical resections for gallbladder cancer and has been shown to improve survival in a recent retrospective trial.[25] Although no consensus has been reached on the minimum number of lymph nodes required for evaluation for accurate staging, one study demonstrated in a prospectively maintained database that patients with an R0 resection who were determined to be N0 based on total lymph node count (TLNC) of 6 or more had a relapse free (RFS) and disease specific survival (DSS) rates of 70% and 72%, respectively. Patients with an R0 resection who were determined to be N0 based on a TLNC of less than 6 had RFS and DSS rates of 32% and 45%, respectively. This underscores the importance in a thorough lymphadenectomy of the porta hepatis and complete review of the pathological specimens for accurate risk stratification of patients with gallbladder cancer.

The surgical role in treatment of unresectable disease is usually limited to biopsy of the tumor for diagnosis and possible biliary decompression procedures.



A radiation oncologist and medical oncologist should be part of the multidisciplinary team participating in the treatment of patients with gallbladder cancer.

Contributor Information and Disclosures

Mary Denshaw-Burke, MD, FACP Clinical Assistant Professor of Medicine, Jefferson Medical College of Thomas Jefferson University; Clinical Assistant Professor, Affiliated Clinical Faculty of the Lankenau Institute for Medical Research; Program Director of Hematology/Oncology Fellowship, Education Coordinator for Oncology, Lankenau Medical Center

Mary Denshaw-Burke, MD, FACP is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.


Andrew Scott Kennedy, MD Physician-in-Chief, Radiation Oncology

Andrew Scott Kennedy, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American Society for Radiation Oncology, Radiological Society of North America, Americas Hepato-Pancreato-Biliary Association, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Jessica Katz, MD, PhD, FACP Senior Medical Director, Immuno-Oncology, Oncology R&D, GlaxoSmithKline

Jessica Katz, MD, PhD, FACP is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology

Disclosure: for: Currently employed at GSK.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Benjamin Movsas, MD 

Benjamin Movsas, MD is a member of the following medical societies: American College of Radiology, American Radium Society, American Society for Radiation Oncology

Disclosure: Nothing to disclose.

Chief Editor

N Joseph Espat, MD, MS, FACS Harold J Wanebo Professor of Surgery, Assistant Dean of Clinical Affairs, Boston University School of Medicine; Chairman, Department of Surgery, Director, Adele R Decof Cancer Center, Roger Williams Medical Center

N Joseph Espat, MD, MS, FACS is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American College of Surgeons, American Medical Association, American Society for Parenteral and Enteral Nutrition, American Society of Clinical Oncology, Americas Hepato-Pancreato-Biliary Association, Association for Academic Surgery, Central Surgical Association, Chicago Medical Society, International Hepato-Pancreato-Biliary Association, Pancreas Club, Sigma Xi, Society for Leukocyte Biology, Society for Surgery of the Alimentary Tract, Society of American Gastrointestinal and Endoscopic Surgeons, Society of Surgical Oncology, Society of University Surgeons, Southeastern Surgical Congress, Southern Medical Association, Surgical Infection Society

Disclosure: Nothing to disclose.

  1. What are the key statistics about gallbladder cancer?. American Cancer Society. Available at Accessed: August 21, 2013.

  2. National Cancer Institute. Cancer Statistics. SEER Surveillance, Epidemiology, and End Results. Available at Accessed: 2008.

  3. Schottenfeld D and Fraumeni J. Cancer. Epidemiology and Prevention. 3rd. Oxford University Press; 2006. 787-800.

  4. Lowenfels AB, Maisonneuve P, Boyle P, Zatonski WA. Epidemiology of gallbladder cancer. Hepatogastroenterology. 1999 May-Jun. 46(27):1529-32. [Medline].

  5. Bernstein CN, Blanchard JF, Kliewer E, Wajda A. Cancer risk in patients with inflammatory bowel disease: a population-based study. Cancer. 2001 Feb 15. 91(4):854-62. [Medline].

  6. Randi G, Franceschi S, La Vecchia C. Gallbladder cancer worldwide: geographical distribution and risk factors. Int J Cancer. 2006 Apr 1. 118(7):1591-602. [Medline].

  7. Matsukura N, Yokomuro S, Yamada S, Tajiri T, Sundo T, Hadama T, et al. Association between Helicobacter bilis in bile and biliary tract malignancies: H. bilis in bile from Japanese and Thai patients with benign and malignant diseases in the biliary tract. Jpn J Cancer Res. 2002 Jul. 93(7):842-7. [Medline].

  8. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003 Apr 24. 348(17):1625-38. [Medline].

  9. Tsuchiya Y, Sato T, Kiyohara C, Yoshida K, Ogoshi K, Nakamura K. Genetic polymorphisms of cytochrome P450 1A1 and risk of gallbladder cancer. J Exp Clin Cancer Res. 2002 Mar. 21(1):119-24. [Medline].

  10. Singh MK, Pandey UB, Ghoshal UC, Srivenu I, Kapoor VK, Choudhuri G. Apolipoprotein B-100 XbaI gene polymorphism in gallbladder cancer. Hum Genet. 2004 Feb. 114(3):280-3. [Medline].

  11. Wu LC, Chen LT, Tsai YJ, Lin CM, Lin CY, Tian YF, et al. Alpha-methylacyl coenzyme A racemase overexpression in gallbladder carcinoma confers an independent prognostic indicator. J Clin Pathol. 2012 Apr. 65(4):309-14. [Medline].

  12. Benjamin IS. Biliary cystic disease: the risk of cancer. J Hepatobiliary Pancreat Surg. 2003. 10(5):335-9. [Medline].

  13. Hu B, Gong B, Zhou DY. Association of anomalous pancreaticobiliary ductal junction with gallbladder carcinoma in Chinese patients: an ERCP study. Gastrointest Endosc. 2003 Apr. 57(4):541-5. [Medline].

  14. American Joint Committee on Cancer. Staging Resources. AJCC Staging Resources. Available at Accessed: 2008.

  15. Mohandas KM, Swaroop VS, Gullar SU, Dave UR, Jagannath P, DeSouza LJ. Diagnosis of malignant obstructive jaundice by bile cytology: results improved by dilating the bile duct strictures. Gastrointest Endosc. 1994 Mar-Apr. 40(2 Pt 1):150-4. [Medline].

  16. Gupta P, Chitalkar P, Sen A, et al. Combination of gemcite and cisplatin chemotherapy in unresectable gallbladder cancer. J Clin Oncol. ASCO Annual Meeting Proceedings (Post-Meeting Edition). 2007. 25, No18s (June 20 Supplement):15166.

  17. Sharma A, Dwary AD, Mohanti BK, Deo SV, Pal S, Sreenivas V, et al. Best supportive care compared with chemotherapy for unresectable gall bladder cancer: a randomized controlled study. J Clin Oncol. 2010 Oct 20. 28(30):4581-6. [Medline].

  18. Valle JS, Wasan HS, Palmer DD, et al. Gemcitabine with or without cisplatin in patients (pts) with advanced or metastatic biliary tract cancer (ABC): Results of a multicenter, randomized phase III trial (the UK ABC-02 trial). J Clin Oncol. 2009 (suppl; abstr 4503). 27:15s. [Full Text].

  19. Iqbal S, Rankin C, Lenz HJ, et al. A phase II trial of gemcitabine and capecitabine in patients with unresectable or metastatic gallbladder cancer or cholangiocarcinoma: Southwest Oncology Group study S0202. Cancer Chemother Pharmacol. 2011 Dec. 68(6):1595-602. [Medline].

  20. Malka D, Trarbach T, Fartoux L, et al. A multicenter, randomized phase II trial of gemcitabine and oxaliplatin (GEMOX) alone or in combination with biweekly cetuximab in the first-line treatment of advanced biliary cancer: interim analysis of the BINGO trial. J Clin Oncol. 2009. 27(15 Suppl):Abstr 4520.

  21. Gruenberger B, Schueller J, Heubrandtner U, et al. Cetuximab, gemcitabine, and oxaliplatin in patients with unresectable advanced or metastatic biliary tract cancer: a phase 2 study. Lancet Oncol. 2010 Dec. 11(12):1142-8. [Medline].

  22. Gallardo J, Rubio B, Ahumada M, et al. Therapy for advanced gallbladder cancer: Improving survival. J Clin Oncol. 2008 (May 20 suppl; abstr 15566). 26:[Full Text].

  23. Dixon E, Vollmer CM Jr, Sahajpal A, et al. An aggressive surgical approach leads to improved survival in patients with gallbladder cancer: a 12-year study at a North American Center. Ann Surg. 2005 Mar. 241(3):385-94. [Medline]. [Full Text].

  24. Ito H, Ito K, D'Angelica M, Gonen M, Klimstra D, Allen P. Accurate staging for gallbladder cancer: implications for surgical therapy and pathological assessment. Ann Surg. 2011 Aug. 254(2):320-5. [Medline].

  25. Jensen EH, Abraham A, Jarosek S, Habermann EB, Al-Refaie WB, Vickers SA, et al. Lymph node evaluation is associated with improved survival after surgery for early stage gallbladder cancer. Surgery. 2009 Oct. 146(4):706-11; discussion 711-3. [Medline].

  26. Abdalla EK, Vauthey JN. Biliary tract cancer. Curr Opin Gastroenterol. 2001 Sep. 17(5):450-7. [Medline].

  27. American Cancer Society. Facts and Figures. Available at Accessed: March 29, 2008.

  28. Barone JE. Gallbladder Cancer Outcomes May Improve With Radiation. Available at Accessed: August 20, 2013.

  29. Bartlett DL, Ramanathan RK, Ben-Josef E. Cancer of the Biliary Tree. DeVita VT, Lawrence TS, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 8th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2008. 1156-86.

  30. Benson AB, Curley SA, Langnas AN. Hepatobiliary Cancers. NCCN Clinical Practice Guidelines in Oncology. 2005. 1:

  31. Chang BB, Thomas MB, Wolff RA. Pancreatic Cancer and Hepatobiliary Malignancies. Kantarjian HM, Wolff RA, Koller CA. MD Anderson Manual of Medical Oncology. 2nd ed. New York, NY: McGraw-Hill Medical Publishing Division; 2006. 383-393.

  32. Czito BG, Hurwitz HI, Clough RW, Tyler DS, Morse MA, Clary BM. Adjuvant external-beam radiotherapy with concurrent chemotherapy after resection of primary gallbladder carcinoma: a 23-year experience. Int J Radiat Oncol Biol Phys. 2005 Jul 15. 62(4):1030-4. [Medline].

  33. Dawes LG. Gallbladder cancer. Cancer Treat Res. 2001. 109:145-55. [Medline].

  34. Dingle BH, Rumble RB, Brouwers MC,. The role of gemcitabine in the treatment of cholangiocarcinoma and gallbladder cancer: a systematic review. Can J Gastroenterol. 2005 Dec. 19(12):711-6. [Medline].

  35. Douglas HO, Tepper JE, Leichman L. Neoplasms of the Gallbladder. Holland JF, et al, eds. Cancer Medicine. 3rd ed. Philadelphia, Pa: Lea & Febiger; 1993. 1448-1454.

  36. Doval DC, Sekhon JS, Gupta SK, Fuloria J, Shukla VK, Gupta S. A phase II study of gemcitabine and cisplatin in chemotherapy-naive, unresectable gall bladder cancer. Br J Cancer. 2004 Apr 19. 90(8):1516-20. [Medline].

  37. Gallardo JO, Rubio B, Fodor M, Orlandi L, Yanez M, Gamargo C. A phase II study of gemcitabine in gallbladder carcinoma. Ann Oncol. 2001 Oct. 12(10):1403-6. [Medline].

  38. Gunderson LL, Haddock MG, Foo ML, Todoroki T, Nagorney D. Conformal irradiation for hepatobiliary malignancies. Ann Oncol. 1999. 10 Suppl 4:221-5. [Medline].

  39. Gunderson LL, Willett CG. Pancreas and Hepatobiliary Tract. Perez CA, Brady LW, eds. Principles and Practice of Radiation Oncology. 3rd ed. Philadelphia, Pa: Lippincott-Raven; 1997. 1467-1488.

  40. Hawkins WG, DeMatteo RP, Jarnagin WR, Ben-Porat L, Blumgart LH, Fong Y. Jaundice predicts advanced disease and early mortality in patients with gallbladder cancer. Ann Surg Oncol. 2004 Mar. 11(3):310-5. [Medline].

  41. Houry S, Haccart V, Huguier M, Schlienger M. Gallbladder cancer: role of radiation therapy. Hepatogastroenterology. 1999 May-Jun. 46(27):1578-84. [Medline].

  42. Hyder O, Dodson RM, Sachs T, Weiss M, Mayo SC, Choti MA, et al. Impact of adjuvant external beam radiotherapy on survival in surgically resected gallbladder adenocarcinoma: A propensity score-matched Surveillance, Epidemiology, and End Results analysis. Surgery. 2013 Jul 19. [Medline].

  43. Ito H, Matros E, Brooks DC, Osteen RT, Zinner MJ, Swanson RS, et al. Treatment outcomes associated with surgery for gallbladder cancer: a 20-year experience. J Gastrointest Surg. 2004 Feb. 8(2):183-90. [Medline].

  44. Knox JJ, Hedley D, Oza A, Feld R, Siu LL, Chen E. Combining gemcitabine and capecitabine in patients with advanced biliary cancer: a phase II trial. J Clin Oncol. 2005 Apr 1. 23(10):2332-8. [Medline].

  45. Knox JJ, Hedley D, Oza A, Feld R, Siu LL, Chen E. Combining gemcitabine and capecitabine in patients with advanced biliary cancer: a phase II trial. J Clin Oncol. 2005 Apr 1. 23(10):2332-8. [Medline].

  46. Kresl JJ, Schild SE, Henning GT, Gunderson LL, Donohue J, Pitot H. Adjuvant external beam radiation therapy with concurrent chemotherapy in the management of gallbladder carcinoma. Int J Radiat Oncol Biol Phys. 2002 Jan 1. 52(1):167-75. [Medline].

  47. Lillemoe K, Kennedy AS, Picus J. Clinical Management of Carcinoma of the Biliary Tree. Kelsen, et al, eds. Principles and Practice of Gastrointestinal Oncology. Philadelphia, Pa: JB Lippincott Co; 2000. 1:

  48. Lotze MT, Flickinger JC, Carr BI. Hepatobiliary Neoplasms. Devita VT, Hellman S, Rosenberg SA, eds. Principles and Practice of Oncology. 4th ed. Philadelphia, Pa: JB Lippincott Co; 1993. 883-907.

  49. Malik IA, Aziz Z, Zaidi SH, Sethuraman G. Gemcitabine and Cisplatin is a highly effective combination chemotherapy in patients with advanced cancer of the gallbladder. Am J Clin Oncol. 2003 Apr. 26(2):174-7. [Medline].

  50. Malka D, Boige V, Dromain C, Debaere T, Pocard M, Ducreux M. Biliary tract neoplasms: update 2003. Curr Opin Oncol. 2004 Jul. 16(4):364-71. [Medline].

  51. Scheingraber S, Justinger C, Stremovskaia T, et al. The standardized surgical approach improves outcome of gallbladder cancer. World J Surg Oncol. 2007. 5:55. [Medline].

  52. Stuver S, Trichopoulos D. Cancer of the Liver and Biliary Tract. Adami H, Hunter D, Trichopoulos D, eds. Textbook of Cancer Epidemiology. 2nd ed. New York, NY: Oxford University Press; 2008. 308-332/12.

  53. Taner CB, Nagorney DM, Donohue JH. Surgical treatment of gallbladder cancer. J Gastrointest Surg. 2004 Jan. 8(1):83-9; discussion 89. [Medline].

A schematic drawing of the extent of lymphadenectomy for gallbladder cancer, especially when the extrahepatic biliary tree is resected.
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