Adjuvant treatment for localized, resected gallbladder cancer
- Bhoomi Mehrotra, MD
Bhoomi Mehrotra, MD
- Cancer Institute at St. Francis Hospital
- Roslyn, NY
- Tanios Bekaii-Saab, MD
Tanios Bekaii-Saab, MD
- Program Co-Director, GI Cancers, Mayo Clinic Cancer Center
- Senior Associate Consultant , Mayo Clinic, Phoenix AZ
- Professor, Mayo College of Medicine and Science
- Section Editors
- Kenneth K Tanabe, MD
Kenneth K Tanabe, MD
- Section Editor — Gastrointestinal Malignancies
- Professor of Surgery
- Harvard Medical School
- Stanley W Ashley, MD
Stanley W Ashley, MD
- Section Editor — Pancreatic and Hepatobiliary Surgery
- Chief Medical Officer and Senior Vice President for Clinical Affairs
- Brigham and Women’s Hospital
- Frank Sawyer Professor of Surgery
- Harvard Medical School
Gallbladder cancer (GBC) is an uncommon but highly fatal malignancy; fewer than 5000 new cases are diagnosed each year in the United States. Most GBC is found incidentally in patients undergoing exploration for cholelithiasis; a tumor will be found in 1 to 2 percent of such cases [1-4].
Surgery is the only potentially curative therapy for GBC. However, even after complete resection, outcomes are poor, particularly for T3 and/or node-positive disease. High rates of both local and distant recurrence have prompted interest in adjuvant chemotherapy and radiation therapy. (See "Surgical management of gallbladder cancer", section on 'Outcomes' and "Surgical management of gallbladder cancer", section on 'Resectable T3/4 or node positive gallbladder cancer'.)
A high percentage of GBCs are initially unsuspected and detected at the time of laparoscopic cholecystectomy for presumed cholecystitis. The next step for these patients (before adjuvant therapy) is additional surgery to remove lymph nodes and the segments of liver above the gallbladder. (See "Surgical management of gallbladder cancer", section on 'Managing an incidental gallbladder cancer'.)
This topic review will cover adjuvant treatment for localized, resected GBC. The epidemiology, risk factors, clinical features, and diagnostic evaluation, surgical treatment, and treatment for locally advanced unresectable and metastatic GBC are covered separately, as is adjuvant treatment after resection of cholangiocarcinoma. (See "Gallbladder cancer: Epidemiology, risk factors, clinical features, and diagnosis" and "Surgical management of gallbladder cancer" and "Treatment of advanced, unresectable gallbladder cancer" and "Treatment of localized cholangiocarcinoma: Adjuvant and neoadjuvant therapy and prognosis".)
PROGNOSIS AND PATTERNS OF SPREAD
Gallbladder cancer (GBC) has traditionally been associated with a poor prognosis. Observed survival rates from a series of 10,705 cases of GBC collected between 1989 and 1996 in the National Cancer Database (NCDB) and stratified according to stage at diagnosis (using the seventh edition combined American Joint Committee on Cancer [AJCC]/Union for International Cancer Control [UICC] 2010 tumor, node, metastasis [TNM] criteria (table 1) ) are provided (figure 1) .To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Piehler JM, Crichlow RW. Primary carcinoma of the gallbladder. Surg Gynecol Obstet 1978; 147:929.
- Hamrick RE Jr, Liner FJ, Hastings PR, Cohn I Jr. Primary carcinoma of the gallbladder. Ann Surg 1982; 195:270.
- Yamaguchi K, Chijiiwa K, Ichimiya H, et al. Gallbladder carcinoma in the era of laparoscopic cholecystectomy. Arch Surg 1996; 131:981.
- A prospective analysis of 1518 laparoscopic cholecystectomies. The Southern Surgeons Club. N Engl J Med 1991; 324:1073.
- American Joint Committee on Cancer Staging Manual, 7th, Edge SB, Byrd DR, Compton CC, et al (Eds), Springer, New York 2010. p.211.
- Fong Y, Wagman L, Gonen M, et al. Evidence-based gallbladder cancer staging: changing cancer staging by analysis of data from the National Cancer Database. Ann Surg 2006; 243:767.
- Zhu AX, Pawalik TM, Kooby DA, et al.. Gallbladder.. In: AJCC Cancer Staging Manual, 8th, Amin MB (Ed), AJCC, Chicago 2017. p.303.
- Shindoh J, de Aretxabala X, Aloia TA, et al. Tumor location is a strong predictor of tumor progression and survival in T2 gallbladder cancer: an international multicenter study. Ann Surg 2015; 261:733.
- Kondo S, Nimura Y, Kamiya J, et al. Mode of tumor spread and surgical strategy in gallbladder carcinoma. Langenbecks Arch Surg 2002; 387:222.
- Fong Y, Jarnagin W, Blumgart LH. Gallbladder cancer: comparison of patients presenting initially for definitive operation with those presenting after prior noncurative intervention. Ann Surg 2000; 232:557.
- Jarnagin WR, Ruo L, Little SA, et al. Patterns of initial disease recurrence after resection of gallbladder carcinoma and hilar cholangiocarcinoma: implications for adjuvant therapeutic strategies. Cancer 2003; 98:1689.
- Jung SJ, Woo SM, Park HK, et al. Patterns of initial disease recurrence after resection of biliary tract cancer. Oncology 2012; 83:83.
- Barreto SG, Pawar S, Shah S, et al. Patterns of failure and determinants of outcomes following radical re-resection for incidental gallbladder cancer. World J Surg 2014; 38:484.
- Ben-David MA, Griffith KA, Abu-Isa E, et al. External-beam radiotherapy for localized extrahepatic cholangiocarcinoma. Int J Radiat Oncol Biol Phys 2006; 66:772.
- Kim WS, Choi DW, You DD, et al. Risk factors influencing recurrence, patterns of recurrence, and the efficacy of adjuvant therapy after radical resection for gallbladder carcinoma. J Gastrointest Surg 2010; 14:679.
- Ben-Josef E, Guthrie KA, El-Khoueiry AB, et al. SWOG S0809: A Phase II Intergroup Trial of Adjuvant Capecitabine and Gemcitabine Followed by Radiotherapy and Concurrent Capecitabine in Extrahepatic Cholangiocarcinoma and Gallbladder Carcinoma. J Clin Oncol 2015; 33:2617.
- Itoh H, Nishijima K, Kurosaka Y, et al. Magnitude of combination therapy of radical resection and external beam radiotherapy for patients with carcinomas of the extrahepatic bile duct and gallbladder. Dig Dis Sci 2005; 50:2231.
- Park HS, Lim JY, Yoon DS, et al. Outcome of adjuvant therapy for gallbladder cancer. Oncology 2010; 79:168.
- Glazer ES, Liu P, Abdalla EK, et al. Neither neoadjuvant nor adjuvant therapy increases survival after biliary tract cancer resection with wide negative margins. J Gastrointest Surg 2012; 16:1666.
- Nakeeb A, Tran KQ, Black MJ, et al. Improved survival in resected biliary malignancies. Surgery 2002; 132:555.
- Mojica P, Smith D, Ellenhorn J. Adjuvant radiation therapy is associated with improved survival for gallbladder carcinoma with regional metastatic disease. J Surg Oncol 2007; 96:8.
- Gold DG, Miller RC, Haddock MG, et al. Adjuvant therapy for gallbladder carcinoma: the Mayo Clinic Experience. Int J Radiat Oncol Biol Phys 2009; 75:150.
- Todoroki T, Kawamoto T, Takahashi H, et al. Treatment of gallbladder cancer by radical resection. Br J Surg 1999; 86:622.
- Kresl JJ, Schild SE, Henning GT, et al. Adjuvant external beam radiation therapy with concurrent chemotherapy in the management of gallbladder carcinoma. Int J Radiat Oncol Biol Phys 2002; 52:167.
- Czito BG, Hurwitz HI, Clough RW, et al. Adjuvant external-beam radiotherapy with concurrent chemotherapy after resection of primary gallbladder carcinoma: a 23-year experience. Int J Radiat Oncol Biol Phys 2005; 62:1030.
- Cho SY, Kim SH, Park SJ, et al. Adjuvant chemoradiation therapy in gallbladder cancer. J Surg Oncol 2010; 102:87.
- Williams TM, Majithia L, Wang SJ, Thomas CR Jr. Defining the role of adjuvant therapy: cholangiocarcinoma and gall bladder cancer. Semin Radiat Oncol 2014; 24:94.
- González ME, Giannini OH, González P, Saldaña B. Adjuvant radio-chemotherapy after extended or simple cholecystectomy in gallbladder cancer. Clin Transl Oncol 2011; 13:480.
- Kim Y, Amini N, Wilson A, et al. Impact of Chemotherapy and External-Beam Radiation Therapy on Outcomes among Patients with Resected Gallbladder Cancer: A Multi-institutional Analysis. Ann Surg Oncol 2016; 23:2998.
- Kraybill WG, Lee H, Picus J, et al. Multidisciplinary treatment of biliary tract cancers. J Surg Oncol 1994; 55:239.
- Mitin T, Enestvedt CK, Jemal A, Sineshaw HM. Limited Use of Adjuvant Therapy in Patients With Resected Gallbladder Cancer Despite a Strong Association With Survival. J Natl Cancer Inst 2017; 109.
- Todoroki T, Iwasaki Y, Orii K, et al. Resection combined with intraoperative radiation therapy (IORT) for stage IV (TNM) gallbladder carcinoma. World J Surg 1991; 15:357.
- Busse PM, Cady B, Bothe A Jr, et al. Intraoperative radiation therapy for carcinoma of the gallbladder. World J Surg 1991; 15:352.
- Lindell G, Holmin T, Ewers SB, et al. Extended operation with or without intraoperative (IORT) and external (EBRT) radiotherapy for gallbladder carcinoma. Hepatogastroenterology 2003; 50:310.
- Tugba Kos F, Aksoy S, Odabas H, et al. Adjuvant therapy for gallbladder and bile duct cancers: retrospective comparative study. J BUON 2011; 16:464.
- Morrow CE, Sutherland DE, Florack G, et al. Primary gallbladder carcinoma: significance of subserosal lesions and results of aggressive surgical treatment and adjuvant chemotherapy. Surgery 1983; 94:709.
- Oswalt CE, Cruz AB Jr. Effectiveness of chemotherapy in addition to surgery in treating carcinoma of the gallbladder. Rev Surg 1977; 34:436.
- Murakami Y, Uemura K, Sudo T, et al. Adjuvant gemcitabine plus S-1 chemotherapy improves survival after aggressive surgical resection for advanced biliary carcinoma. Ann Surg 2009; 250:950.
- Nakamura M, Nakashima H, Abe T, et al. Gemcitabine-based adjuvant chemotherapy for patients with advanced gallbladder cancer. Anticancer Res 2014; 34:3125.
- Takada T, Amano H, Yasuda H, et al. Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma. Cancer 2002; 95:1685.
- Primrose JN, Fox R, Palmer DH, et al. Adjuvant capecitabine for biliary tract cancer: the BILCAP randomized study (abstract). J Clin Oncol 35, 2017 (suppl; abstr 4006). Abstract available online at http://abstracts.asco.org/199/AbstView_199_186869.html (Accessed on June 29, 2017).
- Edeline J, Bonnetain F, Phelip JM, et al. Gemox versus surveillance following surgery of localized biliary tract cancer: Results of the PRODIGE 12-ACCORD 18 (UNICANCER GI) phase III trial (abstractr). J Clin Oncol 35, 2017 (suppl 4S; abstract 225). http://meetinglibrary.asco.org/content/176861-195 (Accessed on January 27, 2017).
- Wang SJ, Lemieux A, Kalpathy-Cramer J, et al. Nomogram for predicting the benefit of adjuvant chemoradiotherapy for resected gallbladder cancer. J Clin Oncol 2011; 29:4627.
- Mantripragada KC, Hamid F, Shafqat H, Olszewski AJ. Adjuvant Therapy for Resected Gallbladder Cancer: Analysis of the National Cancer Data Base. J Natl Cancer Inst 2017; 109.
- Goetze TO, Al-Batran S-E, Paolucci V, et al. Curative treatment in gallbladder cancer: Adjuvant or multimodal concepts—Evidence from data of 975 cases of The German Registry of Incidental Gallbladder Carcinoma. J Clin Oncol 35, 2017 (suppl 4S; absstract 367). http://meetinglibrary.asco.org/content/175983-195 (Accessed on January 27, 2017).
- Neoptolemos JP, Moore MJ, Cox TF, et al. Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs observation on survival in patients with resected periampullary adenocarcinoma: the ESPAC-3 periampullary cancer randomized trial. JAMA 2012; 308:147.
- Konishi M. Adjuvant chemotherapy for resectable biliary tract cancer: current status and future direction. J Hepatobiliary Pancreat Sci 2012; 19:301.
- Duffy A, Capanu M, Abou-Alfa GK, et al. Gallbladder cancer (GBC): 10-year experience at Memorial Sloan-Kettering Cancer Centre (MSKCC). J Surg Oncol 2008; 98:485.
- Horgan AM, Amir E, Walter T, Knox JJ. Adjuvant therapy in the treatment of biliary tract cancer: a systematic review and meta-analysis. J Clin Oncol 2012; 30:1934.
- http://skynet.ohsu.edu/nomograms (Accessed on November 28, 2011).
- Eckel F, Brunner T, Jelic S, ESMO Guidelines Working Group. Biliary cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2011; 22 Suppl 6:vi40.
- PROGNOSIS AND PATTERNS OF SPREAD
- Patterns of disease recurrence
- ADJUVANT THERAPY
- - Radiation and chemoradiotherapy
- - Adjuvant IORT
- - Chemotherapy alone
- Choice of regimen
- Chemotherapy alone versus chemoradiotherapy
- - Meta-analysis
- - Prediction models
- - Guidelines from expert groups
- POSTTREATMENT SURVEILLANCE
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS