Shift to Gene Panels to Assess Hereditary Cancer Risk Forges Ahead Despite Reimbursement Hurdles and Concerns About Clinical Utility

A virtually unlimited number of genes tied to hereditary cancer risk can be simultaneously assessed in commercially available tests given both advances in technology and the Supreme Court's two-year old ruling overturning gene patents. By screening multiple genes in parallel, research has shown that diagnostic yields are on the rise and time to results are down, with the added benefit of not adding much incremental cost for delivery of additional information.

As a result of all of these factors, there has been a noticeable uptick in clinical adoption of multigene panels to assess hereditary cancer risk. Yet, despite research heralding the effectiveness of these multigene panels' appearing in the literature, some clinicians are asking whether adoption is occurring prematurely, before there is a good understanding of the consequences of panel-based testing on clinical management of the patient and other potentially affected relatives.

"Many cancer genetics experts have again urged caution, characterizing the use of multigene testing in the clinical setting as premature. Yet thousands of women and their physicians are ignoring this advice, ordering a wide selection of multiplex tests daily," writes Elizabeth Swisher, M.D., from University of Washington, Seattle in an editorial in JAMA Oncology on Aug. 13. "The train has left the station and is unlikely to return. It is therefore critical that we assess the clinical utility of such testing."

While some appreciate the potential future importance of collection of more genetic data (as it can be reanalyzed as genetic understanding evolves), others view mega-panels that include low- to moderate-risk genes mutations as actually complicating clinical decision-making, since the clinical actionability of these results is less defined. Given the questions over the clinical utility of test results, it is no surprise that insurers often balk at paying for panel-based tests. While the industry is well aware of the need to generate evidence of clinical utility, there remains scant evidence as to the cost effectiveness of panel-based testing.

Insurers, including the Centers for Medicare and Medicaid Services (CMS), are not yet convinced of the benefit of paying for panel-based testing, according to a research note published May 28 by senior research analyst William Quirk at Piper Jaffray & Co. CMS published preliminary gap fill rates for sequencing-based panels well below current reimbursement levels calculated using stacking of Current Procedural Terminology (CPT) codes. Of the 21 next-generation sequencing-related CPT codes, which were designed to improve transparency in reimbursement, only four were priced using preliminary gap fill payment. Of the four priced tests, targeted sequencing panels (of five to 50 genes) were priced by only a single Medicare administrative contractor. Quirk called the pricing for the panel "surprising." Quirk cites industry sources saying that there is "little reimbursement traction from private payers" as well, with most tests billed under the new codes denied payment.

Yet, industry watchers are hopeful that momentum is gaining for reimbursing these multigene panels. In mid-August a multi-stakeholder group convened by the Center for Medical Technology Policy (CMTP, Baltimore, Md.) recommended coverage for sequencing panels of 5-50 genomes if they include a subset of constituent genes that are considered to be standard-of-care and medically necessary for the patient. The groups says such reimbursement is necessary to advance personalized medicine for cancer. CMTP focuses on comparative effectiveness and patient-centered outcomes research. The group, which included sequencing testing and technology companies, medical professional societies, patient advocacy groups, and leading health plans, also recommended that payers rely on the College of American Pathologists accreditation program and proficiency testing to assure the analytic validity of sequencing tests, as well as a proposal for payers to cover larger, even more comprehensive panels with preauthorization under circumstances of "extenuating medical need." Additionally, the group's recommendations call for proposals to incentivize laboratory and clinician sharing of data, to promote patient participation in clinical trials and registries.

Takeaway: Despite reimbursement hurdles and the need to study the effect panel-based testing has on clinical care, panel-based testing for heritable cancer risk will continue to gain momentum.