Radiation Oncology: A Question-Based Review

50
Biliary Cancer

Robert C. Susil and Salma Jabbour

image Background


What common condition is linked with increased risk for gallbladder cancer?

Cholelithiasis increases the risk for gallbladder cancer (presumably via chronic inflammation).

What 2 medical conditions are most associated with increased incidence of cholangiocarcinoma?

Pts with primary sclerosing cholangitis or ulcerative colitis have an increased incidence of cholangiocarcinoma.

What is the most common histology for gallbladder cancer?

Most gallbladder cancers are adenocarcinomas.

What pathologic subtype of gallbladder cancer and cholangiocarcinoma is associated with an improved prognosis?

Papillary adenocarcinoma is associated with an improved prognosis compared with other gallbladder adenocarcinomas and cholangiocarcinomas.

What % of gallbladder cancer presents with DM? What 2 sites are most common?

40%–50% of gallbladder cancer presents with DM. Liver and peritoneal involvement is most common.

What % of gallbladder cancer presents with LN mets? What 4 nodal regions are most commonly involved?

45% of gallbladder cancer presents with nodal mets. The cystic, hilar, pericholedochal, and celiac nodes are most commonly involved. Note that the cystic nodes drain to the pericholedocal nodes, which drain to the retropancreaticoduodenal nodes.

What subtype of adenocarcinoma is the most common form of cholangiocarcinoma?

Mucin-producing adenocarcinoma is the most common form of cholangiocarcinoma.

What is the most common route of spread for gallbladder cancer and cholangiocarcinoma?

Gallbladder cancer and cholangiocarcinoma most commonly spread by direct extension (to the liver for gallbladder cancer and along the biliary tree for cholangiocarcinoma).

What are the 3 subsites for cholangiocarcinoma?

Cholangiocarcinoma is divided into intrahepatic, extrahepatic, and hilar (i.e., Klatskin tumors) subsites.

What % of cholangiocarcinomas present with LN mets?

30%–50% of cholangiocarcinomas present with nodal mets.

What % of cholangiocarcinomas present with DM?

30% of cholangiocarcinomas present with DM.

What are the 2 most common presenting Sx for pts with gallbladder cancer or cholangiocarcinoma?

Jaundice and abdominal pain are the 2 most common presenting Sx for pts with gallbladder cancer or cholangiocarcinoma.

Gallbladder cancer is most commonly diagnosed following what procedure?

Gallbladder cancer is most commonly diagnosed following cholecystectomy for presumed benign Dz.

What is the preferred method of tissue Dx for cholangiocarcinoma?

Endoscopic retrograde cholangiopancreatography brushings or CT-guided FNA Bx are preferred methods for tissue Dx of cholangiocarcinoma. However, surgical exploration may be required for Dx in the setting of extensive sclerosis.

During surgical exploration, what type of Bx is preferred for the Dx of cholangiocarcinoma?

During surgical exploration, FNA is preferred over incisional Bx to Dx cholangiocarcinoma (b/c of increased risk of peritoneal failure or wound implant following incisional Bx).

image Workup/Staging


What 2 serum markers should be sent for suspected cholangiocarcinoma?

CEA and CA 19-9 may have value as tumor markers for cholangiocarcinoma.

What 3 imaging studies are typically performed to workup suspected gallbladder cancer or cholangiocarcinoma?

RUQ US, contrast-enhanced CT (preferably multiphase), and magnetic resonance cholangiopancreatography (MRCP) are typically performed for pts with suspected gallbladder cancer or cholangiocarcinoma.

On contrast-enhanced CT of the liver, how can hepatocellular carcinoma and intrahepatic cholangiocarcinoma be distinguished?

On contrast-enhanced CT of the liver, hepatocellular carcinoma usually enhances during the arterial phase, while cholangiocarcinoma may show delayed enhancement.

What is the imaging study of choice for extrahepatic cholangiocarcinoma?

MRCP is the imaging study of choice for extrahepatic cholangiocarcinoma, as it has improved the ability to define tumor extent and LN involvement.

Which suspected cholangiocarcinoma pts are indicated for endoscopic or transhepatic cholangiopancreatography?

Only suspected cholangiocarcinoma pts who require decompression and drainage of the biliary tract require cholangiopancreatography (others should simply have MRCP imaging).

In addition to locoregional imaging, what staging imaging is recommended for gallbladder cancer and cholangiocarcinoma?

In addition to locoregional imaging, staging for gallbladder cancer and cholangiocarcinoma should include chest imaging.

What staging procedure is recommended at the beginning of surgery for gallbladder cancer or cholangiocarcinoma?

Staging laparoscopy is generally recommended at the beginning of surgery for gallbladder cancer or cholangiocarcinoma to r/o peritoneal dissemination.

What is the AJCC 7th edition (2009) T staging for intrahepatic cholangiocarcinoma?

The AJCC staging for intrahepatic cholangiocarcinoma is the same as for primary liver tumors.

How does the new 2009 AJCC staging system for extrahepatic cholangiocarcinoma differ from the 2002 AJCC system?

Perihilar (proximal) and distal bile ducts are separately staged in the new edition.

How should tumors arising from the middle of the common bile duct be staged?

These extrahepatic cholangiocarcinomas are exceedingly rare, but they are staged according to how they are managed, either as a proximal lesion (by combined hepatic and hilar resection) or as distal lesions (by pancreaticoduodenectomy).

What is the AJCC 7th edition (2009) T staging for perihilar cholangiocarcinoma?

1.     Tis: CIS

2.     T1: tumor confined to bile duct, with extension up to muscle layer or fibrous tissue

3.     T2a: tumor invades beyond bile duct wall to surround fat

4.     T2b: tumor invades liver

5.     T3: tumor invades unilat branches of portal vein (right or left) or hepatic artery (right or left)

6.     T4: tumor invades any of the following: main portal vein or bilat branches, common hepatic artery, 2nd-order biliary radicals bilaterally; or unilat 2nd-order biliary radicals with contralat portal vein or hepatic artery involvement

What is the AJCC 7th edition (2009) T staging for distal bile duct cholangiocarcinoma?

1.     Tis: CIS

2.     T1: tumor confined to bile duct histologically

3.     T2: tumor invades beyond bile duct wall

4.     T3: tumor invades liver, gallbladder, pancreas, and/or unilat branches of the portal vein (right or left) or hepatic vein (right or left)

5.     T4: tumor invades celiac axis or superior mesenteric artery (SMA)

What is the AJCC 7th edition (2009) T staging for gallbladder cancer?

The gallbladder and cystic duct are included in this current classification:

1.     Tis: CIS

2.     T1: tumor invades lamina propria (T1a) or muscle layer (T1b)

3.     T2: tumor invades perimuscular connective tissue but not into liver or beyond serosa

4.     T3: tumor perforates serosa and/or directly invades liver and/or invades 1 adjacent organ/structure (stomach, duodenum, colon, pancreas, omentum, or extrahepatic bile ducts)

5.     T4: tumor invades main portal vein, hepatic artery, or multiple extrahepatic organs/structures

What is the AJCC 7th edition (2009) N classification for biliary cancers (gallbladder and perihilar)?

Hilar LNs are distinguished separately from other regional LN mets:

1.     N1 (mets to hilar nodes): nodes of cystic duct, CBD, hepatic artery, and/or portal vein

2.     N2: (mets to regional nodes): periaortic, pericaval, SMA, and/or celiac LNs.

What are the AJCC 7th edition (2009) groupings for biliary cancers (gallbladder and perihilar)?

1.     Stage 0: TisN0

2.     Stage I: T1N0M0

3.     Stage II: T2N0M0

4.     Stage IIIA: T3N0M0

5.     Stage IIIB: T1-3N1M0

6.     Stage IVA: T4N0-1M0

7.     Stage IVB: TXN2M0 or TXNXM1

What AJCC stage grouping do distal bile duct cancers have in common?

Pancreatic cancer, including N staging (N0 or N1), since it is managed with similar approaches.

image Treatment/Prognosis


What % of gallbladder cancer pts have potentially resectable Dz at presentation?

Only 10%–30% of gallbladder cancer pts have potentially resectable Dz at presentation.

Which gallbladder cancer pts do not require a 2nd surgery after adenocarcinoma is discovered following cholecystectomy for presumed benign Dz?

Following cholecystectomy for presumed benign Dz, pts with >T1a (not beyond the lamina propria) gallbladder cancer do not require a 2nd surgery.

What 2nd surgery should be performed after ≥T1b gallbladder adenocarcinoma is discovered on cholecystectomy for presumed benign Dz?

Following cholecystectomy for presumed benign Dz, pts with ≥T1b gallbladder cancer require radical re-resection of the gallbladder bed (2-cm margins), regional nodal dissection, and resection of the port sites.

What is the preferred surgical management for stage T3-T4 gallbladder adenocarcinoma?

Recommended surgical management for stage T3-T4 gallbladder adenocarcinoma includes radical cholecystectomy and regional nodal dissection (porta hepatis, gastrohepatic ligament, and retroduodenal nodes).

What is the preferred surgical management for resectable hilar cholangiocarcinoma? Distal cholangiocarcinoma?

Recommended surgical management for resectable hilar cholangiocarcinoma includes major bile duct resection, Roux-en-Y hepaticojejunostomy, and regional lymphadenectomy. Distal cholangiocarcinomas should be managed with pancreaticoduodenectomy and regional lymphadenectomy.

What is the recommended adj Tx for localized (but >T1a) gallbladder cancer?

Single-institution series suggest that adj 5-FU–based CRT may benefit resected gallbladder cancer pts. (Kresl JJ et al., IJROBP 2002; Yu JB et al., JCO 2008; Gold DJ et al., IJROBP 2009)

What is the recommended definitive Tx for localized, unresectable gallbladder cancer?

Although outcomes are generally very poor, definitive 5-FU–based CRT is an appropriate Tx for unresectable, localized gallbladder cancer. Chemo with 5-FU or gemcitabine is also an appropriate option.

What is the recommended adj Tx for localized, resectable cholangiocarcinoma? Localized, unresectable cholangiocarcinoma?

Single-institution series suggest that 5-FU–based CRT is an appropriate adj Tx for localized resectable cholangiocarcinoma (Hughes MA et al., IJROBP 2007; Nelson JW et al., IJROBP 2009Shinohara T et al., IJROBP 2008). This is also appropriate for unresectable cholangiocarcinoma (Pitt HA et al., Ann Surg 1995).

What are the appropriate targets and doses for adj gallbladder cancer or cholangiocarcinoma RT?

For resected gallbladder cancer or cholangiocarcinoma, the resection bed and regional nodes (porta hepatic, gastrohepatic ligament, retroduodenal, and celiac) should be included in the RT Tx volume. Doses from 45–50 Gy for subclinical Dz and 60–65 Gy for microscopic Dz are appropriate.

What are the appropriate targets and doses for definitive cholangiocarcinoma RT? What are reasonable boost techniques?

For unresectable cholangiocarcinoma, the primary (with 3–5-cm margins along the biliary tract, including possible intrahepatic spread) and regional nodes should be included in the RT Tx volume. Doses from 45–50 Gy should be delivered with EBRT and a boost of 15–20 Gy delivered via intraluminal brachytherapy (prescribed to 0.5–1 cm) or conformal EBRT.

Intrahepatic cholangiocarcinoma is generally managed like what other cancer?

Management for intrahepatic cholangiocarcinoma is generally like that for hepatocellular carcinoma (favoring definitive surgical resection or local ablation therapy).

Is liver transplantation more appropriate for intrahepatic cholangiocarcinoma or for extrahepatic cholangiocarcinoma?

While liver transplantation is generally considered to be contraindicated for intrahepatic cholangiocarcinoma (due to poor outcomes), single-institution studies show promising results for transplantation in well-selected, early-stage, extrahepatic pts. (Rea DJ et al., Ann Surg 2005)

image Toxicity


For issues related to toxicity, please refer to the Hepatocellular Carcinoma section.