Is the Tempus xF+ (523 gene liquid biopsy panel) test covered for a patient with intrahepatic cholangiocarcinoma and FGFR2 fusion, currently on Pemigatinib (Pemigatinib, Infigratinib is a FGFR inhibitor), with disease progression, who had previous broad molecular profiling?

Coverage of Tempus xF+ Liquid Biopsy in Progressive Intrahepatic Cholangiocarcinoma

This question addresses insurance coverage and medical necessity, not clinical management—the Tempus xF+ liquid biopsy is medically appropriate and guideline-supported for re-evaluating FGFR2 status in this patient with disease progression on pemigatinib, but coverage determination depends on payer-specific policies regarding repeat molecular testing and liquid biopsy panels.

Clinical Context and Medical Necessity

The re-evaluation of FGFR status with liquid biopsy is clinically justified in this scenario for several important reasons:

• Acquired resistance mechanisms are well-documented with FGFR inhibitors, and understanding the molecular basis of progression is critical for selecting subsequent therapy 1, 2
• The patient has already progressed on pemigatinib, making knowledge of current FGFR2 status essential for determining whether to switch to a next-generation FGFR inhibitor (futibatinib) or transition to alternative therapies 1
• Molecular profiling at progression is increasingly recognized as standard practice to identify new actionable alterations or resistance mechanisms that may have emerged 1

Guideline Support for Molecular Testing

The evidence strongly supports comprehensive molecular profiling in advanced cholangiocarcinoma:

• EASL-ILCA guidelines (2023) recommend molecular profiling at diagnosis and emphasize that approximately 30-40% of patients with intrahepatic cholangiocarcinoma harbor potentially actionable molecular aberrations 1
• French Association for the Study of the Liver (AFEF) guidelines (2024) recommend systematic molecular portrait establishment including NGS-based panels to search for actionable alterations 1
• Guidelines specifically note that molecular profiling should be considered in patients at high risk of recurrence or progression to guide treatment decisions 1

Liquid Biopsy Versus Tissue Re-biopsy

Liquid biopsy offers distinct advantages in the progression setting:

• Avoids the risks and logistical challenges of repeat tissue biopsy, which can be particularly difficult in cholangiocarcinoma 1
• Can detect circulating tumor DNA that may represent heterogeneous disease or emerging resistance clones 1
• The 523-gene panel provides comprehensive coverage beyond just FGFR2, potentially identifying alternative actionable targets that have emerged 1

Coverage Considerations

The key coverage issues are:

• Repeat molecular testing: Some payers may consider this "duplicate testing" since the patient had prior broad molecular profiling, though clinical circumstances have changed with disease progression 1
• Liquid biopsy panels: Coverage varies by payer, with some requiring tissue biopsy as first-line unless medically contraindicated 1
• Breadth of panel: A 523-gene panel exceeds what is minimally necessary to assess FGFR2 status alone, though it aligns with guideline recommendations for comprehensive profiling 1

Medical Necessity Arguments

To support coverage, the following points are relevant:

• Disease progression on targeted therapy creates new clinical context that justifies repeat molecular assessment to guide subsequent treatment selection 1
• Multiple FDA-approved targeted therapies exist for cholangiocarcinoma beyond FGFR inhibitors (IDH1 inhibitors, HER2-directed therapy, MSI-H immunotherapy), making comprehensive profiling clinically actionable 1
• Next-generation FGFR inhibitors like futibatinib may overcome certain resistance mechanisms, but understanding the specific resistance pattern is important 1
• The patient is considering locoregional therapy, and molecular profiling may identify systemic therapy options that could be combined with or sequenced after hepatic artery infusion 1

Common Pitfalls

Important caveats regarding this testing:

• Prior authorization is typically required for comprehensive genomic profiling panels, and denial rates can be high for repeat testing 1
• The timing of testing matters: If the patient proceeds immediately to locoregional therapy without plans for subsequent systemic therapy, the urgency of molecular testing may be questioned 1
• FGFR2 alterations other than fusions/rearrangements (such as amplifications or point mutations) show minimal benefit from current FGFR inhibitors, so the specific alteration type matters 1, 3
• Some payers may require documentation that tissue biopsy is not feasible before approving liquid biopsy 1

Practical Recommendation

The oncology team should:

• Submit prior authorization with clear documentation of disease progression on pemigatinib and the clinical need to assess for resistance mechanisms 1
• Emphasize that results will directly impact treatment selection between next-generation FGFR inhibitors, alternative targeted therapies, or chemotherapy 1
• Include guideline references supporting molecular profiling in progressive disease 1
• If denied, consider appealing with peer-to-peer review, as the clinical rationale is strong even if payer policies are restrictive 1