What is the management approach for a patient with colorectal cancer (CRC) associated with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC)?

Management of Colorectal Cancer in Patients with Ulcerative Colitis and Primary Sclerosing Cholangitis

Proctocolectomy is the preferred surgical approach for patients with colorectal cancer in the setting of ulcerative colitis and primary sclerosing cholangitis, with ileal pouch-anal anastomosis (IPAA) preferred over ileostomy due to better functional results and lower risk of variceal formation. 1

Risk Assessment and Surveillance

Risk Factors

• Primary sclerosing cholangitis (PSC) significantly increases colorectal cancer risk in ulcerative colitis patients, with an absolute risk up to 31% 2
• Other risk factors include:
  • Disease duration and extent of ulcerative colitis 2
  • More severe or persistent inflammatory activity 2
  • Post-inflammatory polyps 2
  • Family history of colorectal cancer 2

Surveillance Recommendations

• Annual surveillance colonoscopy should be performed in all patients with concurrent PSC following PSC diagnosis, regardless of disease activity, extent, and duration 2
• For patients with UC without PSC, initial screening colonoscopy should be performed 8 years after symptom onset 2
• Surveillance colonoscopy should be performed during disease remission to better discriminate between dysplasia and inflammation 2
• Chromoendoscopy with targeted biopsies is preferred as it increases dysplasia detection rate 2
• Right-sided colon requires particular attention during surveillance as neoplasia in PSC-UC has a predilection for the proximal colon 1

Surgical Management

Surgical Approach

• Proctocolectomy with ileal pouch-anal anastomosis (IPAA) is preferred when feasible 1
• IPAA offers better functional results and lower risk of variceal formation compared to ileostomy 1
• Colectomy is recommended in patients with:
  • High-grade colonic dysplasia or neoplasia
  • Persistent symptomatic colonic inflammatory activity despite optimal medical therapy
  • Confirmed low-grade dysplasia at repeated occasions and/or multiple locations 2

Liver Transplantation Considerations

• Liver transplantation may be necessary before or simultaneously with colorectal surgery if liver function is severely compromised 1
• Consider liver transplantation for:
  • Decompensated cirrhosis
  • Recurrent bacterial cholangitis
  • Severe pruritus or jaundice despite endoscopic and pharmacological therapy
  • High-grade biliary dysplasia 2
• Liver transplantation for early-stage cholangiocarcinoma in PSC can be performed within clinical trials 2

Medical Management

Ulcerative Colitis Treatment

• Treat according to standard inflammatory bowel disease guidelines 1
• Aim for mucosal healing to reduce inflammation and potentially lower cancer risk 2
• Regular 5-aminosalicylic acid (5-ASA) therapy may reduce cancer risk by 75% 3
• Note that UC associated with PSC often has more extensive colitis, higher frequency of rectal sparing, and higher frequency of "backwash ileitis" 1

Chemoprevention

• Ursodeoxycholic acid (UDCA) is not recommended for:
  • Routine treatment of PSC 2
  • Prevention of colorectal cancer or cholangiocarcinoma 2, 1
• Despite some studies showing decreased risk of colorectal dysplasia with UDCA, high-dose UDCA can be problematic in PSC patients 1

Monitoring for Other Malignancies

Cholangiocarcinoma Surveillance

• Suspect cholangiocarcinoma in:
  • Newly diagnosed PSC with high-grade stricture(s)
  • Known PSC with worsening signs/symptoms, progressive stricture(s), or new mass lesion 2
• Diagnostic workup should include:
  • Contrast-enhanced cross-sectional imaging as initial test
  • ERCP with ductal sampling (brush cytology, endobiliary biopsies) for diagnosis and staging 2
  • Serum CA 19-9 assessment (using cutoff of 130 U/mL for symptomatic patients) 1

Gallbladder Surveillance

• Recommend cholecystectomy in PSC patients with:
  • Gallbladder polyps ≥8 mm in size
  • Smaller polyps that are growing in size 2

Post-Treatment Surveillance

• Continue annual surveillance of the ileal pouch after IPAA due to potential risk of dysplasia in the pouch mucosa 1
• For patients who undergo liver transplantation, continue annual surveillance colonoscopy as the risk of colorectal neoplasia remains clinically important post-transplantation 4
• The cumulative incidence of dysplasia post-liver transplantation is approximately 15% at 5 years and 21% at 8 years 4

Pitfalls and Caveats

• Do not delay surveillance colonoscopy beyond 1-2 year intervals as recommended by guidelines 1
• Do not neglect the right side of the colon during surveillance, as up to 76% of colorectal neoplasia in PSC-UC affects the right side 1
• Avoid high-dose UDCA in PSC patients despite potential benefits for colorectal cancer prevention 1
• Do not assume that liver transplantation eliminates the need for continued colorectal cancer surveillance 4