Biliary Tract Cancers

Updated: 5 days ago

Gallbladder Cancer

Background:

Most common biliary tract malignancy (~80–95% of all biliary tract cancers) yet it remains relatively rare.
~3 times more common in women
Incidence increases with age (peak 70–75 years)
Symptoms are often indistinguishable from cholelithiasis/cholecystitis.
- ~50% of cases are discovered incidentally on post-cholecystectomy pathologic review
Risk factors:
- Cholelithiasis, obesity chronic Infections (Salmonella typhi, Helicobacter species), chronic cholecystitis, porcelain gallbladder
  - Cholelithiasis is the most strongly associated risk factor, present in 70–90% of gallbladder cancer cases, though only 1–3% of gallstone patients develop cancer.
Survival:
- 5-year survival by stage:
  - Stage I ~87%, Stage II ~73%, Stage IIIA ~32%, Stage IIIB ~24%, Stage IVB ~10%
- If unresectable/metastatic disease:
  - Median OS is ~10–13 months with systemic therapy

Staging:

T1a: lamina propria invasion; T1b: muscular layer invasion
T2a (peritoneal side); T2b (hepatic side, higher rates of nodal involvement and hepatic metastases, inferior survival)
N1 = 1–3 positive nodes; N2 = ≥4 positive nodes
Stage IVB: ≥N2 disease or distant metastases

Treatment:

T1a + negative surgical margins → simple cholecystectomy is curative → observation
- Routine bile duct resection increases morbidity without proven survival benefit; reserve for margin positivity.
T1a + positive surgical margins or T1b or cystic duct LN positive → Re-staging workup (CAP CT scan or staging laparoscopy)
- If resectable:
  - Radical cholecystectomy (hepatic resection + portal lymphadenectomy ± bile duct excision)
- If unresectable or Metastatic cancer:
  - Requires adjuvant therapy:
    - First Line:
      - Capecitabine for 6 months (BILCAP)
      - Capecitabine/Gemcitabine
      - Cisplatin/Gemcitabine + Durvalumab (TOPAZ-1)
    - Second line:
      - FOLFOX/CAPEOX
      - Clinical trial

Cholangiocarcinoma

Risk factors:

Classification:

Intrahepatic cholangiocarcinoma (iCCA)
- Often incidental or found on HCC surveillance in cirrhosis, symptoms (pain, weight loss) signal advanced disease.
- Diagnosis requires core needle biopsy
Extrahepatic cholangiocarcinoma (eCCA)
- Painless jaundice is the most common presentation.
- Work up:
  - MRI/MRCP outperforms CT for biliary invasion (~85% sensitivity and specificity)
  - ERCP allows brushings for cytology + FISH
  - Check serum IgG4 to exclude IgG4-related sclerosing cholangitis.
- Types:
  - Perhilar cholangiocarcinoma (pCCA)
  - Distal cholangiocarcinoma (dCCA)

Tumor Markers:

CEA and CA 19-9 for baseline tests but they should not be used to confirm the diagnosis.
- CA 19-9 is unreliable in obstruction. for jaundiced patients, obtain the baseline CA 19-9 after biliary decompression.
- CA 19-9 >1000 U/mL may suggest metastatic disease.

Treatment:

Non-metastatic disease:

Surgery:
- iCCA:
  - Resection of ≥1 segments + regional lymphadenectomy
    - Fewer than 40% are resectable at diagnosis.
    - Recurrence 50–70%, most within the liver.
    - Surgery contraindications: Decompensated cirrhosis, portal HTN, LN beyond the hepatoduodenal/gastrohepatic ligament
- pCCA:
  - Major hepatectomy (≥3 segments) + caudate lobectomy, extrahepatic bile duct resection, hepaticojejunostomy, portal lymphadenectomy
  - Requires future liver remnant ≥30%
  - Recurrence risk is ~80%
- dCCA:
  - Pancreaticoduodenectomy
Liver transplant:
- Indications:
  - Unresectable pCCA ≤3 cm radial diameter
  - No intra/extrahepatic metastases, node-negative
  - PSC-associated disease (transplant is preferred over resection)
Adjuvant Therapy:
- Capecitabine (category 1) for up to 6 months (BILCAP)
- Gemcitabine
- Gemcitabine/capecitabine
- Cisplatin/gemcitabine
- 5-FU/leucovorin

Metastatic/unresectable disease:

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