Pacific Edge : Comment on Novitas LCD DL39365

Dear Dr. Mann,

We are writing in response to your open request for comment on DL39365. This letter also addresses the draft LCD from First Coast Service Options. We have numerous concerns regarding the LCD, but most critically, the evidentiary review associated with the non-coverage determination of Cxbladder products.

EXECUTIVE SUMMARY:

• This letter contains Pacific Edge's response to the LCD for our Cxbladder Triage (0363U) and Detect (0012M) tests which are indicated for the hematuria evaluation in patients with no prior diagnosis of urothelial carcinoma (UC) as well as the Cxbladder Monitor test (0013M) which is indicated for surveillance of patients diagnosed with non-muscle invasive bladder cancer (NMIBC).
• We maintain that our published clinical data supports the inclusion of Cxbladder Triage and Detect for specific patient populations in the clinical pathway for hematuria evaluation, and the published clinical data supports the inclusion of Cxbladder Monitor into the clinical pathway for surveillance of patients diagnosed with non-muscle invasive bladder cancer(1-4).
• The letter also references three Cxbladder tests (Cxbladder Resolve, Enhanced Detect, and Enhanced Triage) referenced in the LCD that are in development and not commercially available and therefore are not appropriate for an evidentiary review or inclusion/exclusion from coverage(5).
• We share our medical rebuttal to many of the points made in the evidentiary review on the LCD that we believe do not reflect the clinical value of the tests and the substantial clinical evidence developed to validate them.
• Pacific Edge respectfully makes the following requests for changes to the LCD.

REQUESTS

1. We request Cxbladder Triage, Detect, and Monitor be included as covered tests in the final LCD language for the specific patient populations outlined below. The published clinical evidence and the demonstrated real world clinical value of these tests with high negative predictive value affirms the need for continued access of these tests to the Medicare population (see appendix for specific evidence).
2. If Novitas does not support the request above:
3. 1. We request that all tests in the hematuria evaluation pathway be completely removed from this LCD as they do not fit the inclusion criteria which requires an

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established diagnosis or significant suspicion of cancer. This removal would include Cxbladder Triage and Detect.

1. We request that once removed from LCD DL39365, Cxbladder Triage and Detect continue to be covered per the guide and documentation requirements of LCA 58917 as currently covered when the tests are documented as medically necessary by the treating physician.
2. We request that Novitas convene a Contractor Advisory Committee session to determine if urinary biomarkers should be included in an existing or new LCD.

3. We request that all mentions of Enhanced Cxbladder Detect, Resolve or Enhanced Cxbladder Triage be removed from the LCD as these tests are not available for clinical use. The data supporting the analytic validity, clinical validity, and clinical utility of these tests is still under development.

SUPPORT FOR REQUESTS:

Support for Request #1

We request Cxbladder Triage, Detect, and Monitor be included as covered tests in the final LCD language for the specific patient populations outlined below. The published clinical evidence and the demonstrated real world clinical value of these tests with high negative predictive value affirms the continued access of these tests to the Medicare population.

Rationale:

Cxbladder Detect

Clinical Scenario and Patient Population

Cxbladder Detect is intended for use with patients presenting with any microhematuria to risk stratify those patients into low, intermediate, and high risk of bladder cancer. This stratification can reduce the burden of investigations for the low and intermediate risk patients after shared decision making with the patient and prioritize those with high risk for full investigation. The test can also be used to adjudicate diagnostic dilemmas when cytology is equivocal, or cystoscopy is un-informative in both microscopic and gross hematuria patients.

There are approximately 7 million patients in the US that present annually with hematuria, of which 75% present with microhematuria (defined as ≥3 RBC/HPF and with no visible blood in urine).

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These patients are risk stratified by AUA guidelines into low, intermediate, and high risk microhematuria based on clinical and demographic factors with the approximate percentages being 5%, 12%, and 83% respectively(6).

Studies have shown that most of these patients do not have UC, with prevalence data showing approximately 5% of patients having UC(6).

The current standard of care for those patients is dependent on their risk stratification, where only low risk patients are counseled to return in 6-8 months for another urine analysis (UA) to determine if they need a full workup. Intermediate and high-risk patients on the other hand are provided a full workup, including a cystoscopy, to assess the bladder and CT (Computerized Tomography) urography to assess the upper tract. The risks associated with this standard of care are those associated with any invasive procedure including infections, urethral damage, and any allergic reactions to contrast agents used for CT urography to name a few.

The clinical utility of Detect is driven by the high negative predictive value that identifies the patients that present with microhematuria that are at significantly lower risk of currently having UC so that they can be given lower intensity diagnostic evaluations. The value to the Medicare population of adopting Detect prior to cystoscopy is the reduction of unnecessary cystoscopy and imaging procedures for patients who do not need it, while simultaneously improving the yield of cancer diagnoses within the patients that do receive the full workup.

Proposed Eligibility Criteria for Cxbladder Detect

• Microhematuria (MH) patients referred to the urology office for evaluation. o MH is defined as ≥3 RBC/HPF with no visible blood in urine.
  o Gross hematuria for adjudication of diagnostic dilemmas.
• Non-malignantor gynecologic causes ruled out by urologist prior to ordering the test. o UTI (urinary tract infections), kidney stones, etc..., ruled out.

The diagram below illustrates the two clinical pathways for Cxbladder Detect:

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Conclusion

Cxbladder Detect should be a covered benefit for Medicare patients under the LCD because:

• It has demonstrated analytical validity, clinical validity, and clinical utility in published studies (see appendix for specific studies).
• The current standard of care drives significant overuse of diagnostic procedures, specifically invasive and unpleasant cystoscopy. For lower risk patients, this has a

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disproportionate impact on the elderly given the higher rates of complications in patients with multiple co-morbidities.

The clinical value of expanded use of tests with high negative predictive value also benefits patients as it reduces the financial burden on the health care system by removing patients from unnecessary procedures with no impact on patient outcomes.

Cxbladder Triage

Clinical Scenario and Patient Population

Triage is indicated to risk stratify and identify lower-risk hematuria patients to reduce the burden of unnecessary investigations. It is intended for use by primary care physicians or at the urology office to prioritize patients and manage unnecessary referrals for more invasive evaluation at the urology office.

The clinical utility of Triage is to identify the patients that present with microhematuria that have significantly lower risk of currently having UC so that they can be managed according to the low risk AUA guidelines recommendation rather than given a full workup that is unnecessary for those patients.

The value to the Medicare population of adopting Triage prior to cystoscopy is reduction of unnecessary cystoscopy and imaging procedures for patients at lower risk, while simultaneously improving the yield of cancer diagnoses within the patients that do receive the full workup.

Proposed Eligibility Criteria for Cxbladder Triage

• Microhematuria (MH) patients at the Primary care office, or low risk patients referred to the urology office.
• MH is defined as ≥3- 25 RBC/HPF with no previous incidence of gross hematuria.
• Non-malignantor gynecologic causes ruled out by urologist prior to ordering the test.

1. UTI, kidney stones, etc..., ruled out.

Conclusion

Cxbladder Triage should be a covered benefit for Medicare patients under the LCD because:

• It has demonstrated analytical validity, clinical validity, and clinical in published studies
  (see appendix for specific studies).
• The current standard of care drives significant overuse of diagnostic procedures, specifically invasive and unpleasant cystoscopy. For lower risk patients, this has a disproportionate impact on elderly patients given the higher rates of complications in patients with multiple co-morbidities.

The clinical value of expanded use of tests with high negative predictive value also benefits patients as it reduces the financial burden on the health care system by removing patients from unnecessary procedures with no impact on patient outcomes.

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