Gallbladder Cancer Guidelines

Updated: Jun 28, 2017
  • Author: Mary Denshaw-Burke, MD, FACP; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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Guidelines

Guidelines Summary

Guidelines Contributor:   Elwyn C Cabebe, MD Physician Partner, Valley Medical Oncology Consultants; Medical Director of Oncology, Clinical Liason Physician, Cancer Care Committee, Good Samaritan Hospital

Diagnosis

According to the National Comprehensive Cancer Network (NCCN) guidelines, gallbladder cancer may be diagnosed as an incidental finding in patients who undergo laparoscopic cholecystectomy, either at surgery or on pathologic review. In such cases, the NCCN recommends postoperative imaging with multiphasic abdominal and pelvic computed tomography (CT) or magnetic resonance imaging (MRI) with intravenous contrast and chest CT with or without contrast. In cases that are an incidental finding on pathologic review, the NCCN also recommmends considering staging laparoscopy. [28]

For cases that present as a mass on an imaging study, the recommended workup includes the following:

  • History and physical examination
  •  Multiphasic abdominal/pelvic CT/MRI with IV contrast
  • Chest CT with or without contrast
  • Liver function tests (LFTs) and assessment of hepatic reserve
  • Surgical consultation
  • Consider carcinoembryonic antigen (CEA) and CA 19-9 testing

For patients who present with jaundice, the recommended workup includes the following:

  • History and physical examination
  • Liver function tests and assessment of hepatic reserve
  • Chest CT with or without contrast
  • Multiphasic abdominal/pelvic CT/MRI with IV contrast
  • Cholangiography (preferably magnetic resonance cholangiopancreatography [MRCP])
  • Surgical consultation
  • Consider CEAl and CA 19-9 testing
  • Consider staging laparoscopy

The European Society of Medical Oncology clinical practice guidelines for biliary cancer published in 2016 recommend diagnosis on the basis of MRI with MRCP contrast-enhanced and diffusion-weighted imaging. CT was deemed less useful. Pathological diagnosis is required before any nonsurgical therapy, but is not critical in patients with characteristic findings of resectable tumors. Endoscopic retrograde cholangiopancreatography (ERCP)–guided biopsies are preferred to biliary brush cytology. [29]

In 2013, the American Society for Gastrointestinal Endoscopy (ASGE) released guidelines for the use of endoscopy in the evaluation of biliary neoplasia. The recommendations for gallbladder polyps included the following [30] :

  • Endoscopic ultrasound (EUS) or fine-needle aspiration (FNA) if the results would change the management
  • Cholecystectomy for symptomatic patients with gallbladder polyps, asymptomatic patients with gallbladder polyps >10 mm, and any patient with gallbladder polyps and primary sclerosing cholangitis
  • Asymptomatic patients with gallbladder polyps ≥6 mm but no other risk factors for gallbladder cancer should receive annual transabdominal ultrasound screening

Staging

Gallbladder cancer staging follows the tumor-node-metastasis (TNM) classification of the American Joint Cancer Committee/Union for International Cancer Control/ (AJCC/UICC) and is classified into four stages based on the depth of invasion into the gallbladder wall and the extent of spread to surrounding organs and lymph nodes. The classification and staging scheme was changed in the 7th edition of the AJCC/UICC manual, published in 2010, to better correlate with the extent of cystic duct and lymph node involvement, resectability of the tumor, and patient outcome. [16]

TNM groupings by stage are as follows:

  • Stage 0- Tis N0 M0
  • Stage I - T1 N0 M0
  • Stage II - T2 N0 M0
  • Stage IIIA - T3 N0 M0
  • Stage IIIB - T1-3 N1 M0
  • Stage IVA - T4 N0-1 M0
  • Stage IVB - Any T N2 M0 any T any N M1

Treatment

The NCCN  guidelines include the following recommendations for resectable disease [28] :

  • Simple cholecystectomy for T1a lesions (limited to the mucosa)
  • Staging laparoscopy, followed immediately (in the same session) by definitive resection; biopsy is not required
  • For patients with T1b or greater lesions, radical cholecystectomy and lymphadenectomy with or without bile duct excision; hepatic resection is performed to obtain clear margins, which usually consists of segments IV B and V but may need to be extended beyond that in some patients
  • For patients with suspicious mass on imaging or with jaundice, cholecystectomy plus en bloc hepatic resection and lymphadenectomy with or without bile duct excision
  • Jaundice that is not amenable to drainage is considered a relative contraindication to surgery; only a portion of those with node-negative disease potentially benefit from complete resection; surgery should only be performed with curative intent
  • Fluoropyrimidine-based chemoradiotherapy, or fluoropyrimidine or gemcitabine chemotherapy alone may be considered for adjuvant treatmen, except for individuals with resected T1a or T1b N0 tumors

The 2016 ESMO guidelines recommendations for resectable disease include the following [29] :

  • Every T-stage above T1a and positivity of any mentioned parameters requires a reoperation and a segment IVb/V liver resection with a ligamentary lymphadenectomy 
  • If the gallbladder was not removed with a bag during laparoscopic resection or the gallbladder perforated (an adverse prognostic factor), the port sites should also be resected 
  • When patients present with jaundice, evaluation of potential resectability is needed 
  • Advanced T-stage (including T4 tumors) is not a contraindication for resection provided they are located in the fundus; these tumors require major liver resection with potential resection of the transverse colon. 
  • Achieving a curative resection of an advanced tumor located at the infundibulum requires the resection of the bile duct, the duodenal bulb and, potentially, the pancreatic head together with a major hepatectomy, especially if right-sided vessels (right hepatic artery, right portal vein) are involved

For management of patients with unresectable or metastatic disease, NCCN makes the following recommendations [28] :

  • Enrollment in clinical trial
  • Fluoropyrimidine or gemcitabine chemotherapy
  • Fluoropyrimidine chemoradiation
  • Supportive care
  • For patients with jaundice, biliary drainage for palliation before instituting chemotherapy