Response to Comments for MolDX: Genomic Health™ Oncotype DX® Prostate Cancer Assay

Include Coverage for NCCN/AUA Intermediate Risk Patients Comment: A commenter submitted anecdotal information regarding his personal use of this assay. He said that “maturing date shows that Gleason 3+4=7 carcinoma do well on active surveillance and carry a similar cancer specific survival to those of Gleason 3+3=6. While AS (active surveillance) may not be appropriate for all intermediates, the assay (aka Genomic Prostate Score – GPS) provides my patients with the additional information needed to better understand if AS is an appropriate consideration. I strongly urge the reconsideration of approval for NCCN intermediate risk patients.” A number of other commenters also expressed coverage for intermediate risk patients. Another commenter writes “patients with Gleason sum 3+4 intermediate risk prostate cancer can have clinical outcomes indistinguishable from low risk disease (Raldow JAMA Oncol 2015) and recent studies indicates that between 8-16% of intermediate risk patients use AS as their primary management strategy (Shelton AUA 2015, Loeb AUA 2015).” This commenter notes that accurate risk stratification remains a challenge and believes this GPS provides an independent measure of aggressiveness. Response: Accurate prostate cancer risk stratification remains a challenge. The GPS assay validation studies showed that incorporation of GPS results with clinical assessment more accurately identified very low- and low risk biological potential, and thus, appropriate candidates for AS. Despite limited data from the validation studies that suggested some intermediate patients with a low GPS benefit from AS, the NCCN and other medical groups do not recommend this approach. Prospective clinical studies are ongoing by the test manufacturer aimed at addressing the clinical utility of GPS for intermediate risk patient. The results of these studies may allow Medicare coverage of intermediate risk patients in the future. Life Expectancy of 10-20 Years Comment: A commenter disagrees with the coverage requirement of 10-20 years. He indicates that “life expectancy should not limit the opportunity to utilize this important piece of data that will impact shared decision making at the time of diagnosis.” He also indicates “by accepting patients of all life expectancy, we can avoid any bias in our utilization and offer the same resources to all patients. Another commenter writes that “a life expectancy of = 10 years makes much more sense as it falls in line with NCCN guidelines and with the usual clinical approach to life expectancy assessments.” He indicated that capping life expectancy at 20 years does not make intuitive or clinical sense stating “Why would a patient whose life expectancy is = 20 years not qualify for risk stratification with this assay?” Response: Since coverage is predicated on prospective longitudinal data which for prostate cancer may require 10-20 years, little to no data would be forthcoming if the assay was used for patients with significantly shorter life expectancies. The purpose of this policy is to provide Medicare coverage for an assay with very limited clinical utility (assay results in improved patient outcomes) that would not otherwise be covered due to very limited prospective utility. The life expectancy criteria has been changed to = 10 years. CTR (Certification and Training Registry) Program Comment: CTR appears to be a valid concept to ensure the proper utilization and tracking of outcomes. The commenter states that “the reality though is that this type of program will impact and prove excessive burden on myself and office staff to complete this additional data capture.” The commenter suggests that the detail of the CTR be reconsidered. Response: The data capture consists of requisite patient information on the test requisition and biennial (2x/yr) submission of prostate cancer-related morbidity or mortality, (if any). This does not constitute an excessively burdensome requirement for coverage. Prevent Unnecessary Harms of Definitive Treatment Comment: One commenter said that patients are often scared when they are first diagnosed with prostate cancer and are wary of the concept of AS. He indicates that use of this assay has provided reassurance to these newly-diagnosed patients because they can easily comprehend why it is safe to intentionally delay treatment and are even provided a numerical, quantitated risk result. He also indicates that an elevated assay result can reinforce when patients who met criteria for low risk NCCN prostate cancer need to be treated. Response: The purpose of this Coverage with Data Development policy is to provide limited coverage for an assay with limited clinical utility (assay results in improved patient outcomes) as currently documented in existing publications. This policy support the opportunity to develop that data within the limited scope of the policy’s parameters that would not otherwise be eligible for coverage as reasonable and necessary. Patient Registry Requirements Comment: A commenter indicates that many of the patient registry requirements are being met in an ongoing, prospective observational trial of 1200 newly diagnosed prostate cancer patients that is being conducted by Genomic Health. The commenter hopes that the data collection will supplement the data collection under this policy to allow full coverage without data collection and CTR requirements. Response: Unconditional coverage predicated on solid scientific data for low and intermediate risk prostate cancer patients is desired by both Genomic Health and Palmetto GBA. Correction of CGS and MolDx contractor Error Commenter: The current policy incorrectly states “To ensure that physicians understand the limitation of the test based on its validation through retrospective non-US based standards of care studies.” Response: CGS and the MolDx contractor apologizes for the incorrect statement and recognizes that Genomic Health validations studies were all US based and used contemporary standards of care. The incorrect statement in the policy has been corrected to read: “To ensure that physicians understand the limitation of the test based on its validation.”