What is the next step in investigating a patient with suspected pancreatic cancer, high Carbohydrate Antigen 19-9 (CA 19-9) levels, and a negative Endoscopic Ultrasonography (EUS) result after a Computed Tomography (CT) scan?

Next Steps in Investigating Suspected Pancreatic Cancer with Negative EUS

For a patient with suspicion of pancreatic cancer on CT scan, elevated CA 19-9, and a negative EUS, an MRI with MRCP (magnetic resonance cholangiopancreatography) should be performed as the next diagnostic step.

Diagnostic Algorithm for Negative EUS in Suspected Pancreatic Cancer

Rationale for MRI/MRCP

• MRI with MRCP is superior to CT for detecting isoattenuating tumors that may be missed on both CT and EUS 1
• MRI has higher sensitivity than CT for detecting small liver metastases, which is crucial for accurate staging 2
• The European Society for Medical Oncology (ESMO) guidelines recognize MRI as a valuable complementary imaging modality when initial findings are inconclusive 2

When to Consider Repeat EUS-FNA

• If MRI/MRCP is also negative but clinical suspicion remains high:
  • Consider repeat EUS with FNA, which has shown diagnostic accuracy of 61-84% after a failed initial procedure 2
  • Repeat EUS-FNA is particularly valuable when the lesion is in the uncinate process or when there's underlying chronic pancreatitis 2

Additional Considerations

• CA 19-9 elevation alone is insufficient for diagnosis, as it has:

  • Limited specificity (82.8%) with false positives in biliary obstruction 3
  • False negatives in 5-10% of patients with Lewis-negative phenotype 4
  • Sensitivity of only 78.2% for pancreatic cancer 3

• If both MRI and repeat EUS are negative:

  • Consider staging laparoscopy, particularly useful for left-sided tumors or when neoadjuvant treatment is planned 1
  • PET-CT may be considered to help differentiate between benign and malignant lesions in ambiguous cases 2, 1

Important Clinical Considerations

Tissue Diagnosis

• Failure to obtain histological confirmation does not exclude malignancy and should not delay appropriate surgical treatment in highly suspicious cases 2
• If the suspicion of malignancy is very high and the patient is a good surgical candidate with a potentially resectable lesion, surgical exploration may be appropriate even without tissue confirmation 2

Monitoring Approach

• If all imaging studies are negative but clinical suspicion persists:
  • Serial monitoring of CA 19-9 levels is recommended
  • Repeat imaging in 2-3 months
  • Consider alternative diagnoses including autoimmune pancreatitis

Common Pitfalls to Avoid

• Relying solely on CA 19-9 for diagnosis - it has limitations in sensitivity and specificity 2, 4
• Delaying further investigation when EUS is negative but clinical suspicion is high
• Failing to consider that pancreatic cancer can present with normal-appearing pancreatic parenchyma on initial imaging
• Not accounting for the possibility of false-negative EUS results, especially in the setting of chronic pancreatitis or tumors in difficult locations like the uncinate process

The diagnostic approach should be guided by a multidisciplinary team including expertise from diagnostic imaging, interventional endoscopy, medical oncology, and surgery to determine the most appropriate next steps and treatment planning 1.