What are the diagnostic markers and treatment options for pancreatic cancer?

Pancreatic Cancer Markers

CA 19-9 is the most useful tumor marker for pancreatic cancer, with elevated levels in approximately 80% of patients with advanced disease, though it should be used primarily for prognosis and monitoring treatment response rather than screening or initial diagnosis. 1

Diagnostic Markers

CA 19-9: The Primary Serum Marker

• CA 19-9 demonstrates 83% sensitivity and serves as the most clinically useful tumor marker for pancreatic cancer, significantly outperforming other markers like CEA 1
• Elevated CA 19-9 (>500 IU/ml) indicates worse prognosis after surgery and should prompt caution regarding immediate surgical intervention 1
• Critical limitation: CA 19-9 is undetectable in patients with Lewis antigen-negative phenotypes (approximately 5-10% of the population), rendering it useless in this subset 1, 2
• CA 19-9 lacks specificity for diagnosis as it can be elevated in benign conditions, particularly cholestasis, making it unreliable as a screening tool 1
• Best clinical use: measuring disease burden and guiding treatment decisions in patients with confirmed pancreatic cancer 1

Other Serum Markers

• CEA (carcinoembryonic antigen) shows considerably lower sensitivity than CA 19-9 and is not recommended as a primary marker 1
• CA 125 has limited utility and is not sufficiently sensitive for pancreatic cancer diagnosis 3

Molecular and Genetic Markers

Recommended Molecular Testing

• KRAS and BRCA testing are generally recommended for all patients with pancreatic cancer 1
• For metastatic disease with KRAS wild-type tumors, assess:
  • Microsatellite instability (MSI) status 1
  • NTRK fusion status 1
  • Other rare fusions that may be actionable 1
• Patients with family history or high-risk features should undergo genetic counseling 1

Actionable Mutations

• BRCA1, BRCA2, or PALB2 mutations indicate potential platinum therapy sensitivity 1
• Rare focal amplifications may contain druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3, PIK3CA) though at low individual prevalence 1

Imaging as Diagnostic "Markers"

First-Line Imaging

• Multiphasic contrast-enhanced CT (including late arterial and portal venous phases) is the first-line imaging modality with >90% positive predictive value for determining unresectability 1, 2
• Perform imaging within 4 weeks before starting treatment 1
• If jaundice is present from obstructive head tumor, obtain imaging BEFORE biliary drainage or stenting to avoid artifacts 1

Complementary Imaging

• Abdominal MRI is recommended when CT is inconclusive, contraindicated, or for evaluating cystic lesions 1, 2
• Hepatic MRI before surgery confirms absence of small liver metastases 1
• EUS-guided biopsy is the preferred method for tissue diagnosis with highest accuracy and lowest risk of tumor seeding 2

Imaging to Avoid

• PET-CT is NOT recommended for diagnosis of primary tumors as it cannot reliably differentiate chronic pancreatitis from cancer 1
• PET-CT may be useful for staging localized tumors or when distant metastases are uncertain (doubtful imaging or high CA 19-9) 1

Clinical Application Algorithm

When to Use CA 19-9

1. Baseline measurement (if no cholestasis present) for prognostic information 1
2. Monitoring during treatment to assess response 1
3. Post-operative surveillance every 3 months for 2 years if preoperatively elevated 4
4. Decision-making for borderline resectable disease: CA 19-9 >500 IU/ml suggests consideration of neoadjuvant therapy before surgery 1

When NOT to Rely on CA 19-9

• Never use for screening in asymptomatic patients 1
• Interpret with extreme caution in presence of jaundice or cholestasis 1
• Do not use as sole diagnostic criterion—always confirm with imaging 2
• Remember it will be falsely negative in Lewis antigen-negative patients 1

Common Pitfalls to Avoid

• Never perform percutaneous biopsy of potentially resectable tumors due to peritoneal seeding risk 2
• Do not delay imaging for biliary stenting in jaundiced patients 1
• Avoid over-interpreting elevated CA 19-9 in the setting of biliary obstruction 1
• Do not use PET scanning for primary diagnosis 1
• Cytology or biopsy proof is mandatory before initiating chemotherapy for localized disease, preferably by EUS guidance 1