What is the role of a PET (Positron Emission Tomography) scan in managing a patient with inoperable intrahepatic cholangiocarcinoma on pembrolizumab (pembrolizumab), cisplatin, and gemcitabine with suspected minimal disease progression and stable CA (Cancer Antigen) 199 levels?

Role of PET Scan in Inoperable Intrahepatic Cholangiocarcinoma on Systemic Therapy with Suspected Minimal Progression

PET scan has no established role in monitoring treatment response or detecting minimal disease progression in patients already receiving systemic chemotherapy for inoperable intrahepatic cholangiocarcinoma, and should not be routinely performed in this clinical scenario.

Why PET Scan is Not Indicated for Treatment Monitoring

Limited Evidence for Response Assessment

• PET scanning is explicitly recommended only for initial staging of potentially resectable cholangiocarcinoma to detect occult lymph node and distant metastases, not for monitoring treatment response 1, 2.
• The 2023 EASL-ILCA guidelines identified only a single retrospective study examining PET in recurrent/metastatic cholangiocarcinoma, with no data supporting its use for treatment monitoring in patients already on systemic therapy 1.
• Guidelines consistently recommend CT or MRI for assessing disease progression during treatment, not PET 1.

Specific Limitations in Your Clinical Context

For minimal disease progression assessment:

• PET produces false-negative results in subcentimetric lesions (<1 cm) due to insufficient metabolically active cells for FDG uptake detection 3.
• Infiltrative cholangiocarcinoma subtypes demonstrate poor FDG accumulation even when larger than 1 cm 3.
• PET has low sensitivity (14-47%) for detecting clinically occult metastases, particularly micrometastases 3.

For peritoneal disease detection (critical in cholangiocarcinoma):

• PET has extremely poor sensitivity for peritoneal disease with lesion sizes <5 mm 3.
• 10-20% of cholangiocarcinoma patients have peritoneal metastases that cross-sectional imaging frequently fails to detect 3.
• PET cannot reliably exclude peritoneal disease, which is a common site of progression in cholangiocarcinoma 3.

What Should Be Done Instead

Standard Imaging for Treatment Monitoring

• Contrast-enhanced CT of chest, abdomen, and pelvis remains the standard modality for assessing disease progression during systemic therapy 1.
• MRI is superior to CT for detecting intrahepatic disease progression and should be considered for liver-specific assessment 1.
• Imaging should be performed every 6 weeks during active treatment to assess response per RECIST v1.1 criteria 4.

Clinical Decision Algorithm for Suspected Minimal Progression

When CA 19-9 is stable but minimal radiographic progression is suspected:

1. Obtain high-quality contrast-enhanced MRI of the liver to definitively characterize intrahepatic changes, as MRI is superior to CT for detecting small intrahepatic lesions 1.

2. Perform contrast-enhanced CT of chest, abdomen, and pelvis to assess for extrahepatic progression, particularly lymph nodes and lung metastases 1.

3. Continue current systemic therapy if progression is truly minimal and patient remains clinically stable, as pembrolizumab can be administered beyond RECIST-defined progression if the patient is clinically stable and deriving clinical benefit 4.

4. Do NOT obtain PET scan, as it will not change management and may lead to false-negative results for small-volume disease 3.

Critical Pitfall to Avoid

The most dangerous error would be obtaining a negative PET scan and falsely reassuring yourself that there is no progression. PET's poor sensitivity for small-volume disease means a negative scan does not exclude clinically significant progression, particularly peritoneal or small hepatic metastases 3. This could delay appropriate treatment modifications or consideration of clinical trial enrollment.

When PET Might Rarely Be Considered

The only scenario where PET could potentially add value in your patient would be if you are considering conversion to resectable disease after excellent response to systemic therapy and need to exclude occult distant metastases before surgical consultation 1, 2. However, this does not apply to your patient with inoperable disease and suspected progression.

In summary: Rely on contrast-enhanced CT and MRI for treatment monitoring. PET adds no value and risks false reassurance in this clinical context.