Molecular pathology tests that identify pathogenic mutations and cytogenetic translocations help us define the molecular subtypes of common cancers. Because several of these acquired mutations/translocations may predict response to specific therapies, screening tests for “targetable” mutations are now commonly available in clinical laboratory improvement amendments (CLIA)-approved clinical labs. It is unclear whether these test results can also serve as independent prognostic factors. This review aims to clarify the value of certain molecular pathology tests for improving our estimates of prognosis for common cancers (breast, lung, colon, urinary bladder) affecting Medicare beneficiaries. The main purpose of this review is to determine whether these tests improve estimation of prognosis (for recurrence), affect physician decision making, and/or improve clinical outcomes when compared with traditional assessment of prognosis of recurrence. These genetic tests are used in two different contexts. In one, the tests are used in a specific context of a diagnostic/therapy combination, where the diagnostic test is being used to predict response to a very specific treatment. In the second context, the genetic tests are used to estimate the patient’s prognosis, and physicians use this prognostic information to choose from a variety of different treatment options. CMS requested this report to evaluate the second context. Therefore, studies that evaluate specific diagnostic/therapy combinations are excluded from this report
The following tests are under consideration for this assessment and apply to all Key Questions (KQs): microsatellite instability (MSI) for colorectal cancer (CRC), MLH1 promoter methylation for CRC, KRAS mutations for CRC, BRAF mutations for CRC, Oncotype DX Colon mRNA expression for CRC, Oncotype DX Breast mRNA expression for breast cancer, MammaPrint mRNA expression for breast cancer, ALK cytogenetics for lung cancer, EGFR mutations for lung cancer, KRAS mutations for lung cancer, and UroVysion cytogenetics for urinary bladder cancer.