Appeal type: Medical necessity
Decision: Upheld

Diagnosis: Colon Cancer

Treatment: Comprehensive molecular profile test

The insurer denied coverage for comprehensive molecular profile test

The denial is upheld

This is a patient that has been diagnosed the patient with colon cancer. The treating provider has requested Foundation One Liquid CDx provided, which is under review.

The use of next-generation sequencing (NGS) panel testing as a means to select anti-cancer therapy in advanced cancer remains an area of active research with ongoing studies of thermoplastic polyurethanes (TPUR) and Molecular Analysis for Therapy Choice (MATCH). The concept of this approach is that all cancers are unique, and each cancer has a specific individual molecular driver which can be identified using this testing. Once identified, specific therapy can be given to the patient directly treating their tumor. The majority of studies of this approach are fraught with methodological design issues such as lack of randomization and inclusion of large numbers of patients with established molecular drivers (such as breast cancer with er and her2) and then claiming that the identification and targeting of said known drivers contributes to benefit. There has been only one well-designed trial of this approach, simulated highways for intelligent vehicle algorithms (SHIVA), which demonstrated that this testing approach does not improve clinical outcomes for patients with advanced cancer.  

Standard testing for colon cancer would include Kirsten rat sarcoma viral oncogene (KRAS), neuroblastoma ras viral oncogene homolog (NRAS), V-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAF) and does not require this panel to perform. There are smaller panels and more direct testing available that can be used.

Le Tourneau, C., et al. (2015), "The use of molecularly targeted agents outside their indications does not improve progression-free survival compared with treatment at physician's choice in heavily pretreated patients with cancer. Off-label use of molecularly targeted agents should be discouraged, but enrolment in clinical trials should be encouraged to assess predictive biomarkers of efficacy."

"Although these results are preliminary, significant discordance also has been noted between reports comparing tissue-based next-generation sequencing tests and, in a recent report, between results from F1 and G360 testing. Our findings indicate that in-depth comparisons of next-generation sequencing tests across larger numbers of patients with cancer are needed to improve concordance and clinical utility" (Kuderer, N. M. et al. 2017).

"Use of such testing has rapidly increased, with further growth anticipated. Mutations identified on tumor sequencing may be acquired somatically, caused by postzygotic mosaicism, or inherited through the germline. Identification of germline mutations potentially influences treatment of the current cancer, may provide prognostic information about the potential development of future cancers, and has important implications for family members in terms of risk and prevention of disease. However, guidelines on both how to determine which somatic findings may be potentially germline and the optimal clinical practice for referral and germline testing of patients undergoing tumor sequencing are not widely available, and there is no established standard of care" (Clark, D. F. et al. 2019).   

Based on the above, the insurer's denial must be upheld. The health care plan did act reasonably and with sound medical judgment and in the best interest of the patient. 

The medical necessity for comprehensive molecular profile test provided is not substantiated.