What is the recommended workup and treatment for pancreatic cancer?

Pancreatic Cancer Workup

For suspected pancreatic cancer, obtain a pancreatic protocol CT scan of the chest, abdomen, and pelvis as the primary diagnostic imaging study, combined with baseline CA 19-9 measurement (if no cholestasis is present), liver function tests, and family history assessment. 1

Initial Imaging Strategy

Pancreatic protocol CT is the gold standard first-line imaging modality with >90% positive predictive value for determining unresectability and should include late arterial and portal venous phases. 2 This single test often provides sufficient information to proceed directly to surgical consultation if a resectable mass is identified. 1, 3

Key Imaging Considerations:

• Perform imaging within 4 weeks before starting treatment to ensure accuracy of staging 2
• If jaundice is present from an obstructive head tumor, obtain imaging BEFORE biliary drainage or stenting to avoid artifacts that compromise diagnostic quality 2
• Chest CT with contrast (or chest x-ray if CT unavailable) is required to assess for metastatic disease 1
• MRI of the abdomen should be reserved for situations where CT is inconclusive, contraindicated, or when evaluating cystic lesions 2

Laboratory Workup

Baseline Studies:

• Liver function tests are mandatory 1
• CA 19-9 measurement provides prognostic information in approximately 80% of patients with advanced disease 2
  • Sensitivity of 83% makes it the most clinically useful tumor marker 2, 4
  • Critical caveat: CA 19-9 is undetectable in Lewis antigen-negative patients (5-10% of population), rendering it useless in this subset 2
  • Cholestasis falsely elevates CA 19-9, so interpretation must account for biliary obstruction 2, 5
  • CA 19-9 >500 IU/ml indicates worse prognosis and should prompt consideration of neoadjuvant therapy rather than immediate surgery 2

Family History and Genetic Assessment:

• Obtain detailed family history at initial workup 1
• Consider referral for genetic counseling for young patients, those with family history of cancer, or Ashkenazi Jewish ancestry 1
• KRAS and BRCA testing recommended for all patients with confirmed pancreatic cancer 2

Tissue Diagnosis Strategy

The approach to biopsy depends on clinical presentation and treatment intent:

When Biopsy is Required:

• Metastatic disease confirmed on imaging requires biopsy confirmation of the metastatic site before initiating systemic therapy 1
• If microscopic proof will avoid surgery (e.g., unresectable disease, poor surgical candidate), obtain tissue diagnosis 3
• Biliary ductal obstruction present warrants biopsy 1

When Biopsy May Be Deferred:

• Resectable mass on imaging in a surgical candidate can proceed directly to surgery without preoperative biopsy 1, 3
• If helical CT shows a resectable mass in the pancreatic head consistent with clinical suspicion, prepare the patient for surgery 3

Optimal Biopsy Technique:

• EUS-guided fine needle aspiration (EUS-FNA) is the preferred method with highest accuracy (83% sensitivity, 99% specificity) and lowest risk of tumor seeding 2, 4
• Consider EUS to confirm primary site involvement when clinically indicated 1

Additional Diagnostic Studies

When No Mass is Visible on CT:

• ERCP is indicated if clinical suspicion remains high despite negative CT imaging 1, 3
• Endoscopic ultrasonography (EUS) should be considered to evaluate for small lesions not visible on CT 1

Staging Laparoscopy:

• Consider staging laparoscopy to exclude clinically occult intra-abdominal and lymph node metastases, particularly when unresectability appears likely but cannot be confirmed by less invasive methods 1, 3
• This is especially valuable for evaluating resectability in borderline cases 1

Multidisciplinary Review

Multidisciplinary consultation should ideally involve expertise from diagnostic imaging, interventional endoscopy, medical oncology, radiation oncology, surgery, and pathology before finalizing treatment decisions. 1 Consider consultation with a registered dietitian given the high risk of malnutrition. 1

Critical Workup Pitfalls to Avoid

• Do not rely on CA 19-9 alone for diagnosis—it lacks specificity and can be elevated in benign conditions, particularly cholestasis and cholangitis 2, 5
• Do not perform biliary stenting before obtaining diagnostic imaging—this creates artifacts that compromise CT/MRI interpretation 2
• Do not delay imaging beyond 4 weeks before treatment initiation—disease progression may alter staging 2
• Do not assume CA 19-9 is useful in all patients—remember the Lewis antigen-negative population where it provides no information 2
• Do not order unnecessary biopsies in clearly resectable disease—this delays definitive surgical treatment without changing management 3

Molecular Testing for Confirmed Cases

Once pancreatic cancer is confirmed:

• KRAS and BRCA testing for all patients 2
• For metastatic disease with KRAS wild-type tumors, assess MSI status, NTRK fusion status, and other rare actionable fusions 2
• BRCA1, BRCA2, or PALB2 mutations indicate potential platinum therapy sensitivity 2