Response to Comments: MolDX DecisionDX Uveal Melanoma

I use this gene expression profile test as part of my routine work-up for uveal melanoma patients, and I believe that the result is an important component of their patient care. Knowing their DecisionDx Class allows me to adjust their imaging schedule so that it is appropriate for their metastatic risk. I also work closely with a medical oncologist at Duke, who sees my Class 1B and Class 2 patients due to their higher risk of disease spread.

Supportive comments noted. No comments against coverage of this assay.

This test has been validated in numerous studies for its ability to accurately predict metastatic potential in patients with uveal melanoma. This is allowed tailored screening for high-risk patients. Additionally, tailored screening allows referral to oncology services at an earlier stage and gives patients the ability to understand their risk of metastasis and potentially allows earlier intervention for metastatic disease.

Supportive comments noted. No comments against coverage of this assay.

At our center, the multidisciplinary melanoma team recommends bi-annual systemic surveillance for patients at intermediate or high risk for metastatic disease (class 1B and 2 patients), with MRI liver and CT chest, whereas for low risk class 1A patients, liver ultrasound and chest x-ray is preferred. Furthermore, a Class 2 patient would also see our melanoma medical oncologist. It is important in this rare disease setting to have as much information about a patient’s risk as possible and this test is a critical component of that risk assessment.

Supportive comments noted. No comments against coverage of this assay.

I have presented my own series of more than 200 patients that confirmed the clinical performance of the test. The draft local coverage determination for DecisionDx-UM that you have issued is important for Medicare patients, as this test helps us decide what the best follow-up plan is with imaging, liver function testing, and the appropriate frequency of these tests based on metastatic risk.

Supportive comments noted. No comments against coverage of this assay.

The clinical utility of the test is to determine which patients are high-risk and should receive close, frequent screening in an effort to detect metastatic disease as early as possible but also to prevent low-risk patients from getting frequent imaging that they will likely not benefit from. I also send my intermediate (Class 1B) and high risk (Class 2) patients to see a medical oncologist so that they have a pre-existing relationship if they ultimately experience metastasis.

Supportive comments noted. No comments against coverage of this assay.

I participated in the original prospective validation of the test and since then several studies have confirmed that the test is accurate in predicting metastatic risk. Therefore, the test result can be used to inform a metastatic screening plan that matches the biological risk of the patient, with Class 1 patients having less frequent screening compared to Class 2 patients, who need more frequent screening and may also be eligible for an adjuvant therapy trial.

Supportive comments noted. No comments against coverage of this assay.

I offer this test to my uveal melanoma patients and then subsequently use the results to guide how frequently the patient has metastatic screening. I also encourage all of my Class 2 patients to see a medical oncologist who specializes in uveal melanoma and has access to an adjuvant clinical trial if they should want adjuvant treatment. Although not all Class 2 patients will have the means or desire to travel to see a medical oncologist, I do recommend this and as an alternative, their primary care physician or myself can perform their surveillance locally to monitor for metastasis.

Supportive comments noted. No comments against coverage of this assay.

The most important impact of the test result is that it helps to guide the post-treatment surveillance of the patient with increased surveillance (i.e. more frequent imaging) for Class 2 patients and lessened surveillance for Class 1 patients. I prefer that all my patients see a medical oncologist to manage their surveillance, while I focus on their eye care follow-up. However, given that I see some patients who are traveling long distances for their medical care and/or are among underserved patient populations, if they cannot feasibly see a medical oncologist, I will then prescribe their surveillance myself or work directly with their primary care physician to do so. Either way, the surveillance the patient receives reflects the risk associated with their DecisionDx-UM result.

Supportive comments noted. No comments against coverage of this assay.

I use DecisionDx-UM routinely for my uveal melanoma patients and the test results are critical for determining surveillance intensity, which is usually managed by a medical oncologist or, in rare cases where the patient cannot realistically see a medical oncologist due to geographic location, by me. In either case, Class 2 patients receive higher intensity surveillance while Class 1 patients receive lower intensity surveillance. The test results are also beneficial for Class 2 patients who are seeking clinical trials, as there are two trials currently enrolling for adjuvant treatment based on a Class 2 result.

Supportive comments noted. No comments against coverage of this assay.

Comments 10 - 12, summarizes the comments Noridian received for Draft Local Coverage Determinations DL37070 (JE)/DL37072 (JF) MolDX: DecisionDx-UM (Uveal Melanoma). A. It is reassuring to see the draft local coverage determination for DecisionDx-UM. This test is widely used in the United States for newly diagnosed uveal melanoma patients. I used it routinely in my prior practice at Duke University and will continue to use it in my new position at Stanford University, so I am glad to see that the test will be covered for Medicare patients. I participated in the original prospective validation of the test and since then several studies have confirmed that the test is accurate in predicting metastatic risk. Therefore, the test result can be used to inform a metastatic screening plan that matches the biological risk of the patient, with Class 1 patients having less frequent screening compared to Class 2 patients, who need more frequent screening and may also be eligible for an adjuvant therapy trial. Thank you for providing coverage for this important test, and I hope that longer term coverage will be considered given its importance in prognostication for uveal melanoma. B. I was encouraged after reading the draft LCD for DecisionDx-UM for Medicare patients. I use gene expression profiling regularly at the Casey Eye Institute/OHSU to guide decisions regarding systemic surveillance for metastatic disease after the patient’s eye is treated. At our center, the multidisciplinary melanoma team recommends bi-annual systemic surveillance for patients at intermediate or high risk for metastatic disease (class 1B and 2 patients), with MRI liver and CT chest, whereas for low risk class 1A patients, liver ultrasound and chest x-ray is preferred. Furthermore, a Class 2 patient would also see our melanoma medical oncologist. It is important in this rare disease setting to have as much information about a patient’s risk as possible and this test is a critical component of that risk assessment. Thank you for your coverage of this test and I hope that coverage will be extended. C. I would like to comment on the Draft LCD for DecisionDx-UM gene expression profiling for uveal melanoma. I am happy to see that the test will be covered for Medicare patients, and I would encourage Palmetto to consider long-term coverage of the test as well. The clinical utility of the test is to determine which patients are high-risk and should receive close, frequent screening in an effort to detect metastatic disease as early as possible but also to prevent low-risk patients from getting frequent imaging that they will likely not benefit from. I also send my intermediate (Class 1B) and high risk (Class 2) patients to see a medical oncologist so that they have a pre-existing relationship if they ultimately experience metastasis. However, there may be cases where I may need to provide the follow up management of these patients and would appreciate if that option be made available the final LCD. The LCD policy is reassuring to me that my patients will continue to be able to have this test as part of their routine care. D. In effect, it is very encouraging that the test is viewed as important and will be covered. I hope that you will also consider its long-term coverage based on its utility in my practice that I have described. E. At the University of Michigan, I use DecisionDx-UM routinely for prognostication in my patients with uveal melanoma, and I have presented my own series of more than 200 patients that confirmed the clinical performance of the test. The draft local coverage determination for DecisionDx-UM that you have issued is important for Medicare patients, as this test helps us decide what the best follow-up plan is with imaging, liver function testing, and the appropriate frequency of these tests based on metastatic risk. Considering that numerous physicians, including myself, have utilized this test for several years and consider it standard-of-care, I recommend that the test should be covered in the future as well. F. I was pleased to hear that you are considering coverage for the decision DX uveal melanoma test. This test has been validated in numerous studies for its ability to accurately predict metastatic potential in patients with uveal melanoma. This is allowed tailored screening for high-risk patients. Additionally, tailored screening allows referral to oncology services at an earlier stage and gives patients the ability to understand their risk of metastasis and potentially allows earlier intervention for metastatic disease. This test is a vital portion of the care given to my patients with uveal melanoma. I sincerely hope that you will approve coverage for this necessary test. G. I am writing to comment on the Draft Local Coverage Determination for DecisionDx-UM. It is very encouraging to see that this gene expression test for uveal melanoma will be covered for Medicare patients. I use DecisionDx-UM routinely for my uveal melanoma patients and the test results are critical for determining surveillance intensity, which is usually managed by a medical oncologist or, in rare cases where the patient cannot realistically see a medical oncologist due to geographic location, by me. In either case, Class 2 patients receive higher intensity surveillance while Class 1 patients receive lower intensity surveillance. The test results are also beneficial for Class 2 patients who are seeking clinical trials, as there are two trials currently enrolling for adjuvant treatment based on a Class 2 result.

Noridian appreciates the input.

• Coverage indications and guidelines, limitations, and/or Medical Necessity (page 2)
• Text in draft LCD states: “…This test is intended for the determination of metastatic risk and to guide surveillance and referral to medical oncology…” Based on feedback from the physician specialists who routinely care for uveal melanoma patients (who order and utilize the test results), they do frequently refer to medical oncology, but occasionally there may be medical or logistical reasons why a referral may not be optimal. Therefore, we would suggest adding the opportunity for ophthalmology physicians who specialize in treating patients with uveal melanoma to have the option to continue managing these patients if referral to medical oncology is not the optimal approach. Please note that these physicians who specialize in treating patients with uveal melanoma often manage metastatic surveillance plans if a patient is not able to be managed by medical oncology for surveillance. The suggested language would read as follows:
• Suggested text: …This test is intended for the determination of metastatic risk and to guide surveillance and referral to medical oncology or continued management by an ophthalmologist with experience in the management of uveal melanoma.
• Clinical Performance Utility (page 6)
• Text in draft LCD states: “…Continued coverage is dependent on the publication and/or presentation of clinical utility data demonstrating, for example, that at least 80% of class 2 patients are referred to medical oncology for management…” We would also suggest that based on input from physician specialists who treat this disease that the referral percentage be adjusted to 70%.

Suggested text: …Continued coverage is dependent on the publication and/or presentation of clinical utility data demonstrating, for example, that at least 70% of class 2 patients are referred to medical oncology. ICD-10 Codes (Page 8)

• The draft LCD excluded three ICD-10 codes that are also used by ophthalmologists who specialize in treating patients with uveal melanoma. We request inclusion of all appropriate ICD-10 codes that are currently used to bill this test and other uveal melanoma related procedures to both Medicare and private insurers. These are:

C69.30 Malignant neoplasm of unspecified choroid C69.31 Malignant neoplasm of right choroid C69.32 Malignant neoplasm of left choroid C69.40 Malignant neoplasm of unspecified ciliary body C69.41 Malignant neoplasm of right ciliary body C69.42 Malignant neoplasm of left ciliary body C69.90 Malignant neoplasm of unspecified site of unspecified eye C69.91 Malignant neoplasm of unspecified site of right eye C69.92 Malignant neoplasm of unspecified site of left eye CPT Code (Page 7) We request a change of the billing CPT code from 81599 (Unlisted Multianalyte Assay with Algorithmic Analysis) to 84999 (Miscellaneous Chemistry), which is the code outlined in the Noridian DecisionDx-UM billing guideline (effective January 1, 2017). References (Page 6) We provide the following references which appear in the Clinical Performance: Utility table, but are not listed in the reference section. Aaberg, T.M., Jr., et al., Current clinical practice: differential management of uveal melanoma in the era of molecular tumor analyses. Clin Ophthalmol, 2014. 8: p. 2449-60. Plasseraud, K.M., et al., Clinical Performance and Management Outcomes with the DecisionDx-UM Gene Expression Profile Test in a Prospective Multicenter Study. Journal of Oncology, 2016. 2016: p. 1-9. We commend this LCD, which guarantees that Medicare beneficiaries who are diagnosed with Uveal Melanoma will have access to this important, standard of care test, that informs patient management, and appreciate your consideration of these suggested modifications.

Medical oncologist: The following has been added to the DecisionDx-Um Test Description and Intended Use: “In rare cases where the patient cannot realistically see a medical oncologist due to geographic location (long distance to travel), and/or are among underserved patient populations, if they cannot feasibly see a medical oncologist, surveillance testing for class 2 patients can be directed by the ophthalmologist physician who specialize in treating patients with uveal melanoma or work directly with their primary care physician to do so.” Clinical Utility: This contractor recognizes that patient variables may contribute to less than 100% compliance with referral to a medical oncologist. Eighty percent (80%) is a generally accepted level of compliance for class 2 patients. It is a desired goal, not an absolute cutoff. ICD-10 codes: C69.30 Malignant neoplasm of unspecified choroid, C69.40 Malignant neoplasm of unspecified ciliary body, and C69.90 Malignant neoplasm of unspecified site of unspecified eye are non-specific and will not be added to the policy. The purpose of ICD-10 is to provide diagnosis specificity. References: The following references were inadvertently omitted from the reference list and have been added to the policy: Aaberg, T.M., Jr., et al., Current clinical practice: differential management of uveal melanoma in the era of molecular tumor analyses. Clin Ophthalmol, 2014. 8: p. 2449-60. Plasseraud, K.M., et al., Clinical Performance and Management Outcomes with the DecisionDx-UM Gene Expression Profile Test in a Prospective Multicenter Study. Journal of Oncology, 2016. 2016: p. 1-9.

The draft LCD for DecisionDx-UM is important for Medicare patients with uveal melanoma who benefit from this prognostic test. I would like to give my support for this LCD, because I offer this test to my uveal melanoma patients and then subsequently use the results to guide how frequently the patient has metastatic screening. I also encourage all of my Class 2 patients to see a medical oncologist who specializes in uveal melanoma and has access to an adjuvant clinical trial if they should want adjuvant treatment. Although not all Class 2 patients will have the means or desire to travel to see a medical oncologist, I do recommend this and as an alternative, their primary care physician or myself can perform their surveillance locally to monitor for metastasis. It will be very beneficial for Medicare patients to have this test covered so that we have this important piece of information to use develop their follow-up plan.

In the DecisionDx-UM Test Description and Intended Use, the following has been added to the policy: In rare cases where the patient cannot realistically see a medical oncologist due to geographic location (long distance to travel), and/or are among underserved patient populations, if they cannot feasibly see a medical oncologist, surveillance testing for class 2 patients can be directed by the ophthalmologist physician who specialize in treating patients with uveal melanoma or work directly with their primary care physician to do so.