LCD Reference Article Response To Comments Article

Response to Comments: MolDX: Prognostic and Predictive Molecular Classifiers for Bladder Cancer

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Response to Comments: MolDX: Prognostic and Predictive Molecular Classifiers for Bladder Cancer
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The comment period for the MolDX: Prognostic and Predictive Molecular Classifiers for Bladder Cancer DL38576 Local Coverage Determination (LCD) began on 04/23/20 and ended on 07/07/20. The notice period for L38576 begins on 06/03/2021 and will become effective on 07/18/2021. The comments below were received from the provider community.

Response To Comments

Number Comment Response
1

The following comment was submitted to multiple contractors (Noridian, WPS and Palmetto GBA).

On behalf of the Association for Molecular Pathology (AMP) and the College of American Pathologists (CAP), we thank you for the opportunity to review and comment on the proposed policy for MolDX: Prognostic and Predictive Molecular Classifiers for Bladder Cancer.

The AMP is an international medical and professional association representing approximately 2,500 physicians, doctoral scientists, and medical technologists who perform or are involved with laboratory testing based on knowledge derived from molecular biology, genetics, and genomics. Membership includes professionals from academic medicine, hospital-based and private clinical laboratories, the government and the in vitro diagnostics industry.

The CAP is the world’s largest organization of board-certified pathologists and leading provider of laboratory accreditation and proficiency testing programs. The CAP serves patients, pathologists, and the public by fostering and advocating excellence in the practice of pathology and laboratory medicine worldwide.

We are submitting joint comments because currently our organizations share the same position regard this draft LCD.

Both AMP and CAP appreciate the MAC’s approach to proposing coverage for tests that demonstrate valuable information when used to make significant clinical decisions for cancer patients, rather than providing recommendations regarding use of a specific drug or treatment. The policy parameters support coverage needed to help manage bladder cancer patients and this approach to coverage will help to facilitate the development of better tests in the future for bladder cancer and other tumors by accelerating their market introduction and reducing clinical uncertainty.

After reviewing the proposed policy’s coverage criteria, we ask that the MAC consider the following recommendations.

Coverage Indications, Limitations, and/or Medical Necessity

1. The second coverage criteria (#2) requires that “The beneficiary is within the population and has the indication for which the test was developed and is covered. The lab providing the test is responsible for clearly indicating to treating clinicians the population and indication for test use.”

The AMP and CAP are concerned about Laboratories being held responsible for verifying that a patient meets a coverage policy’s criteria. Laboratories do not keep patient medical records, nor do they always have access to them. The treating physician, and not the laboratory, must take responsibility for the medical necessity of a test because only the treating physician, not the laboratory, will have the necessary information to make that determination. For this reason, it would not be reasonable to hold the laboratory responsible for substantiating the medical necessity of a test. This is especially pertinent as there are many tests for which there is no FDA-approved alternative, and under CLIA, it is the laboratory’s responsibility to only document the validity of the test for the analyte it purports to assay.

Recommend: We recommend the MAC remove the last sentence in criteria #2 making labs responsible for the appropriate beneficiary population and indications for test usage by treating clinicians, for the aforementioned reasons. Alternatively, amend the proposed policy language to state that the lab will make available the appropriate indications of the test to the ordering physician.

2. Number seven (#7) of the coverage criteria states that a test must successfully complete a technical assessment that will ensure that analytical and clinical validity criteria are met to establish the test as reasonable and necessary. The Molecular Diagnostic Services (MolDX) Technical Assessment (TA) has been a well-established requirement of the MolDX program since 2011. Since that time, laboratory developed tests or tests with undefined or unproven clinical utility have had to undergo a TA to ensure coverage. The TA process is detailed on the MAC’s website and is a coverage requirement that applies to all molecular diagnostic tests covered under MolDX, and therefore, does not need to be reiterated in individual LCDs.

Recommend: Remove the requirement that a test must successfully complete a TA, as it is redundant and unnecessary.

Thank you again for the opportunity to review and comment on this proposed policy. We are happy to be of assistance in providing additional clinical or other information to assist you with this draft LCD.

 

Thank you for your comments. The Technical Assessment process is an integral part of the MolDX program validation process as you clearly discuss. While redundant in the policy it emphasizes the importance of this process for coverage decisions. As far as the lab responsibility, we determine that the indications should be made clear to the ordering physician. The responsibility for a test being reasonable and necessary is to be documented by the ordering physician.

2

The following comment was submitted to Noridian.

I strongly support the proposed LCD for Prognostic and Predictive Molecular Classifiers for Bladder Cancer. As a urologist who actively treats bladder cancer patients, I have seen firsthand both the significant side effects as well as the life extending interventions we provide, regardless whether the intervention is surgery, chemotherapy or radiation. Balancing the intensity of therapeutic interventions, with the side effects that they bring is one of greatest clinical challenges we, as urologists, face in treating bladder cancer. Over the last few years, I have been increasingly interested in the Decipher Bladder Cancer Test which stratifies patients into molecular subtypes. There is significant utility in use of molecular subtypes as a biomarker for stratifying patients to treatments of increasing intensity. As such, the Decipher subtypes have provided me with additional information which I have considered in my decision making for balancing the intensity of therapies to maximize patient outcomes and wellness.

There is a great importance in adopting biomarkers for improving patient outcomes, which is critically important given the complexity of cancer care and the observed response rates for patients with bladder cancer. In my role as an educator and trainer of the next generation of urologic oncologists, I see the necessity of expanding the role of biomarkers and precision oncology applied to therapeutic interventions. Historically, our bladder cancer patients have not benefitted from these innovations due to the lower incidence of the disease. However, we are now at a point where testing and clinical data support the use of these test more broadly. Therefore, I support this coverage decision in enabling my Medicare covered patients in gaining access to important molecular tests, like the Decipher test.

Finally, as I contrast the access to molecular tools that I have available to me in my role as a clinical trialist versus what patients can afford outside of clinical trials, we see a disparity of care when we limit the access of valuable tests, especially in the case of bladder cancer where have an abundance of retired, fixed-income patients who cannot afford significant out-of-pocket costs. Thank you for your consideration and role in improving cancer care.

Thank you for your support of the policy.

3

The following comment was submitted to multiple contractors (Noridian and Palmetto GBA).

Director at the Dana Farber Cancer Institute, an affiliate of Harvard Medical School. At Dana-Farber, he leads multiple cutting-edge clinical trials studying novel immunotherapy and targeted drugs to cure bladder cancer. He is also the national or international Principal Investigator of multiple clinical trials for bladder cancer patients. Additionally, he is on the steering committees of several major clinical trials attempting to improve outcomes and change the standard of care of bladder cancer patients. He has also led translational projects and developed prognostic classifications and clinical endpoints focused on bladder cancer. He is a member of Southwest Oncology Group (SWOG) and Bladder Cancer Task Force of the U.S. NCI GU Steering Committee.

The clinical management of patients with muscle-invasive bladder cancer is complex. Current standard of care is neoadjuvant cisplatin-based combination chemotherapy, followed by radical cystectomy. However, with even with cisplatin-based chemotherapy only 30–35% of patients achieve a pathological complete response, resulting in improved outcomes; meaning new and more effective therapies and / or better means of stratifying patients to chemotherapy are needed. As a result of this unmet need, multiple PD-1 / PD-L1 inhibitors have been approved, although these approvals are limited to the metastatic space, many trials are underway, both as single agent and in combination with cisplatin, in the neoadjuvant space. Early results from these trials suggests similar pathological response rates to neoadjuvant chemotherapy, again suggesting patient stratification will be essential for maximum treatment efficacy.

It is important to recognize that no single variable provides all the information required for clinical decision making with respect to neoadjuvant therapy. As such, additional tools, such as biomarkers are required to help inform patient management. Molecular subtyping models, such as the Decipher Bladder test, represent promising new biomarkers which may provide insight into the underlying biology of a patient tumor, which in turn could help identify tumor sensitivities to different therapies. For example, in a recent publication it was found that the Decipher claudin-low subtype had an excellent progression free survival with neoadjuvant pembrolizumab, where standard biomarkers such as TMB and PD-L1 staining did not distinguish patients based on outcome. Therefore, the Decipher bladder test may represent a very promising tool to identify patients suitable for checkpoint therapy.

In the neoadjuvant chemotherapy setting the molecular subtyping has also shown that luminal tumors may benefit less from chemotherapy, while basal tumors may receive greater benefit. Interestingly, luminal tumors are more likely to be organ confined and basal tumors, non-organ confined. Benefit from neoadjuvant chemotherapy has also been shown to be particularly good for non-organ confined patients, suggesting a strong correlation between the biology (subtype) and clinical behavior (stage) of a patient tumor. Given clinical staging is also problematic in bladder cancer, subtyping may help identify patients who would benefit from chemotherapy but may not otherwise be offered this as a treatment option.

Personalized patient care and patient experience may be improved with molecular testing of bladder cancer tumors. These types of tests may help clinicians identify patients who would be candidates for trials, especially in the immune therapy setting, which may offer additional hope to cure this often deadly disease.

Thank you for your comments and support of the policy.

4

The following comment was submitted to multiple contractors (Noridian and Palmetto GBA).

I am writing a letter to support the draft bladder cancer LCD. I am an Assistant Professor of Medicine at Case Western Reserve University and staff radiation oncologist at the Cleveland Clinic. My clinical practice and research are focused on genitourinary malignancies. My laboratory in the Cleveland Clinic Lerner Research Institute studies the genetic and epigenetic characteristics of aggressive subtypes of bladder cancer including the neuroendocrine, small cell subtype.

There exists a significant need for reliable biomarkers, both predictive and prognostic, to better select patients for tailored treatments in both localized and metastatic bladder cancer. This is particularly true in the era of personalized therapy, where response rates and outcomes depend on selecting the right patients for newer targeted therapies. For example, our work suggests molecular classifiers may better select patients for organ preserving therapies which maximize both cancer control and quality of life (e.g., bladder preservation with combined chemotherapy and radiation). Another example is neoadjuvant chemotherapy, where response rates and survival benefit (approx. 40% and 5%, respectively) could be improved with better patient stratification to identify which patients benefit and which patients can be spared the toxicity of treatment.

Molecular subtyping holds a great deal of promise for filling the unmet need for clinically actionable biomarkers. In recent years, advances in molecular subtyping have shown potential to directly impact patient management across many treatment modalities. The Decipher Bladder test is a perfect example, where the subtyping results could provide additional supporting information to help guide patient management. The Decipher Bladder classifier determines whether a patient is basal, claudin-low, luminal, luminal infiltrated or neuroendocrine-like (more details below). Here, the basal tumors appear to have better outcomes with platinum-chemotherapy, but poor outcomes with checkpoint inhibitors, while the opposite proved true for claudin-low tumors. The luminal tumors, on the other hand, were more likely to be organ confined, and concordantly, received less benefit from chemotherapy.

The neuroendocrine-like tumors are quite unique and require special attention. Histological small cell / neuroendocrine bladder cancer is a rare disease entity accounting for approximately 1% of bladder cancer tumors. This disease entity is highly aggressive, presenting with significant morbidity and very poor prognosis. At present, treatment of small cell bladder cancer derived from data from small cell lung cancer, typically consisting of an etoposide and platinum-based regimen.

Recent work has identified an occult (hidden) subset of bladder tumors that present as conventional urothelial carcinoma but have a gene expression profile and clinical presentation that is extremely consistent with histological small cell bladder. The neuroendocrine-like subtype is part of the Decipher Bladder molecular test and has been rigorously evaluated across numerous cohorts. As identifying these tumors would be unlikely as part of routine pathological screening (as they appear urothelial), molecular testing would help identify these patients who may require additional or different therapy. In our own work, we have found that novel targeted therapies may be appropriate (e.g., DLL3 ADC, Koshkin et al) or multimodality therapy (chemoradiation, NCCN, Batista da Costa et al, CCR, 2018).

In summary, stratifying patients by molecular subtyping provides additional clinically relevant information that can be combined with conventional clinical tools to improve patient selection for existing standard of care, as well as new emerging therapies. It is my sincere belief that the Decipher Classifier for Bladder Cancer will have a profound and sustained positive impact on the clinical management of bladder cancer and I urge you move forward with approval in the most expeditious manner possible.

Thank you for your comments and support of the policy.

5

The following comment was submitted to Noridian.

I would like to offer my support for coverage of the Decipher Bladder test for bladder cancer patients.

While many urine tests have being evaluated for detection and surveillance of patients with non-muscle invasive bladder cancer, very little headway has been made with respect to tissue markers. This is particularly important in the management of muscle-invasive bladder cancer.

The Decipher Bladder test offers important insight into the biology of bladder cancer which is critical for patient management. The focus of the test is to classify bladder cancer into different molecular subtypes based on RNA expression. Each subtype has different implications for therapy.

We know that the luminal subtype has the best prognosis and the lowest risk of upstaging at the time of radical cystectomy. There is evidence to suggest that this subtype does not respond as well to chemotherapy. Together this means that these patients will benefit little from neoadjuvant chemotherapy and instead are best served by primary cystectomy.

On the other hand, the basal subtype does particularly poorly with surgery alone and appears to benefit most from neoadjuvant cisplatin-based chemotherapy. These patients should be prioritized for pre-operative chemotherapy. The luminal infiltrated subtype does relatively poorly with each strategy and should prioritized for clinical trials to test new treatments. More recently the claudin-low subtype has been demonstrated to have excellent outcomes with neoadjuvant checkpoint inhibitors, suggesting these patients may best treated with this therapy.

The neuroendocrine-like subtype of bladder cancer is a particular high-risk patient group and it is important to recognize these a priori. These tumors are histologically the same as conventional urothelial carcinoma but have the biology of high-risk neuroendocrine disease. There is some indication that these patients might do better with immunotherapy, although this remains to be evaluated more thoroughly.

Another important aspect in treating muscle-invasive bladder cancer is the relative underutilization of bladder-preserving strategies, primarily in the form of chemoradiation. The Decipher Bladder test is able to identify a subset of patients with high expression of inflammatory genes that have particular favorable outcomes after radiation therapy, although the same signature is not prognostic for patients undergoing cystectomy. This could help select patients for primary radiation.

In summary, the Decipher Bladder test can aid in guiding treatment for patients with muscle invasive bladder cancer. It has important clinical implications and would be a valuable tool in the armamentarium of the urologists, radiation oncologists and medical oncologists treating these patients.

 

Thank you for your comments and support of the policy.

6

The following comment was submitted to Noridian.

I am writing this letter in support of the new proposed LCD for Prognostic and Predictive Molecular Classifiers for Bladder Cancer. I am the Chief of the Division of Urology, Associate Professor (Tenured), Robert Earl Cone Endowed Professorship, Director of Urologic Oncology, Director of Urologic Research and Co-Director for the Department of Surgery Clinical Outcomes Research Program at the University of Texas Medical Branch (UTMB) at Galveston. I have also been appointed the Medical Director for High Value Care at UTMB Health System. My academic, clinical and research expertise is focused in bladder cancer. I direct a federally funded bladder cancer research program dedicated to identifying at risk bladder cancer patients to inform targeted interventions to improve survival. Our team has presented at the Institute of Medicine and published in several high impact journals. I serve as the Section Editor in Bladder Cancer for the British Journal of Urology International.

There is a striking discordance between the clinical staging of a patient with bladder cancer and the pathological staging, which is determined at surgery. Current reports indicate pathological upstaging from occurs in about 40% of patients, with the majority being upstaged from organ confined (OC) to non-organ confined (NOC) disease. Despite the current clinical variables used estimate to estimate bladder tumor aggressiveness, these error rates persist.

While neoadjuvant chemotherapy (NAC) prior to radical cystectomy is highly under-utilized in the US (as our group has published only 13% receive NAC), this treatment has been shown to have a significant survival benefit in patients with muscle-invasive bladder cancer. Underuse has been attributed to NAC toxicity combined with providers uncertain which patients may benefit most from NAC. Cisplatin-based NAC has been shown to greatly improve the outcomes of patients with cT2-T4 disease, especially for patients with NOC disease (pT3+ or N+). If a patient is inaccurately staged at the time of diagnosis and receives an immediate radical cystectomy only to find NOC disease, then this patient can no longer be afforded the benefits of NAC. Identification of patients at higher risk of upstaging is therefore critical to reducing treatment morbidity, minimizing treatment costs and improving patient outcomes.

There are few available clinical tools which have been shown to improve the accuracy of clinical staging in patients with bladder cancer. Molecular classifiers are becoming an increasingly promising tool to help address clinical challenges, including risk of upstaging. The Decipher Bladder test is a whole transcriptome-based assay which determines the underlying biology of a patient tumor to categorize the patient tumor into one of five molecular subtypes: luminal, luminal infiltrated, basal, claudin-low and neuroendocrine-like. Of note, this test helps identify luminal tumors which are not only more likely to have organ confined disease and lack nodal disease, but also have similar outcomes, regardless of receipt of neoadjuvant chemotherapy. The advantage of this stratification is the opposite is also true, where non-luminal patients (one of the other four subtypes) are more likely to have NOC and therefore would be candidates for NAC. Taken together, the Decipher Bladder test provides another level of information to inform patient treatment.

The Decipher Bladder also identifies patients who have neuroendocrine-like disease, which may benefit from more aggressive interventions or claudin-low tumors, which have recently been shown to have superior outcomes with immune checkpoint therapies. Informing multiple treatment options is an added benefit to other biomarkers, which tend to provide a ‘yes/no’ answer with regards to whether a patient could be a candidate for a given treatment. Overall, this molecular test could help inform treatment decisions for many patients with bladder cancer.

 

Thank you for your comments and support of the policy.

7

The following comment was submitted to Palmetto GBA.

We would like to thank MolDX for proposing the new coverage policy for prognostic and predictive molecular classifiers for patients with bladder cancer. We are in support of the policy and respectfully submit for consideration, for the purpose of clarification, the following requested changes:

  • In the section titled “Coverage Indications, Limitations, and/or Medical Necessity”
    • In the coverage criterion 4.a, as worded, it is not clear that “ordered intensity” refers to treatment options that have varied or increasing levels of intensity. We request that the phrase “an ordered intensity” be changed to “varied or increasing levels of intensity”.
    • In the coverage criterion 7, we suggest that demonstration that the technical assessment should also require that the test meets criterion 6, and be changed to “The test successfully completes a technical assessment that ensures the test is reasonable and necessary when used as described in 4. and validated as described in 5. and 6. above.”
  • In the section titled “Summary of Evidence”:
    • In the second sentence of the second paragraph, we request that “adenomcarcinoma of the bladder“ be changed to “adenocarcinoma of the bladder”.

Further, after careful review of the policy, we submit that the Decipher Bladder test meets the criteria for coverage, as follows:

  • Decipher Bladder is a genomic test indicated for patients diagnosed with high grade non-muscle invasive (clinical stage cT1), muscle-invasive (cT2-T4) and locally advanced (cT3-T4) bladder cancer. It is performed on transurethral resection of bladder tumor (TURBT) specimens from patients who have not yet had a cystectomy. Decipher Bladder identifies the intrinsic biology of the tumor based on a 209-gene expression classifier that subtypes tumors as Luminal, Luminal-Infiltrated, Basal, Claudin-low and Neuroendocrine-like subtypes of bladder cancer (Sjödahli, Choiii, Robertsoniii, Kamouniv). Decipher Bladder is used to assist physicians and their patients in making treatment decisions around the utilization of neoadjuvant chemotherapy or immunotherapy prior to radical cystectomy.
  • As referenced in the draft LCD, Decipher Bladder has been validated as a predictor of pathological and survival outcomes (Seiler (proposed LCD ref 8), Lotan (proposed LCD ref 9), Batista da Costa (proposed LCD ref 10), Efstathiouv, Grivasvi, Necchivii) in the intended use population. The test is used by physicians to help prioritize patients who are candidates for multiple potential treatments, which have an ordered (i.e. varied or increasing levels of) intensity based on consensus guidelines. Decipher Bladder is used to help select from among multiple potential treatments. For example, patients with tumors of a non-luminal subtype have a higher probability of harboring non-organ confined disease at diagnosis who may be undertreated with radical cystectomy alone (Lotan). Similarly, Decipher Bladder facilitates neoadjuvant therapy decisions as a patient with a basal tumor may be prioritized to neoadjuvant cisplatin-based chemotherapy (Lotan, Seiler) or a Decipher Bladder claudin low subtype patient to neoadjuvant immunotherapy (Necchi) prior to radical cystectomy. Patients with a Decipher Bladder neuroendocrine-like subtype may be selected for an intensified chemotherapy regimen adding etoposide to cisplatin (Batista da Costa, Grivas) as recommended in current NCCN guidelines for neuroendocrine bladder cancer. These uses of Decipher Bladder are examples of the test being used to decide among treatment options of varied or increasing levels of intensity as required in criterion 4.a. of the proposed LCD.
  • In addition to the clinical validation studies referenced above, extensive analytical validation studies have been performed to ensure Decipher Bladder accurately stratifies patients into one of five subtypes, helping the physician and patient decide among multiple treatment options as described above.
  • Since it appears that studies based on Decipher Bladder formed the basis for this coverage decision, we assume that MolDX is in agreement that Decipher Bladder should be covered under this policy, but if not, we would like to know when and how we may go about submitting our assay for technical assessment to be covered.

Based on the above, we request coverage for Decipher Bladder for patients with bladder cancer with:

  • High grade, stage T1 non-muscle invasive bladder cancer, or
  • Any grade, stage T2-T4 muscle invasive bladder cancer, or
  • Any grade, locally advanced stage T3-T4 bladder cancer

We thank you for your consideration.

 

Thank you for your comments and support of the policy. We have clarified the coverage criteria using your comments.

8

The following comment was submitted to Palmetto GBA.

For the coverage of molecular diagnostic tests in bladder cancer, we recommend the deletion of coverage condition #3, “The patient has not had a cystectomy.” This condition is not necessary, as a valid molecular test may also inform treatment decisions post cystectomy should such treatment options enter into the consensus guidelines. Coverage condition #4 is well-stated and sufficient enough to achieve what is intended with condition #3, while keeping the LCD broad enough to anticipate future FDA approvals and adoption into guidelines of new treatments post cystectomy, as well as the associated molecular tests that may inform such treatment decisions.

Thank you for your comments. We will revise the policy based on your suggestion.

9

The following comment was submitted to Palmetto GBA.

I am writing with respect to the recently released proposed LCD Prognostic and Predictive Molecular Classifiers for Bladder Cancer for which I am in strong support.

As a medical oncologist who actively treats patients with bladder cancer, I routinely treat patients with neoadjuvant chemotherapy prior to radical cystectomy. Unfortunately, this approach is not effective in everyone.

lmmunotherapy has dramatically changed the way we treat metastatic bladder cancer, particularly considering there has been a lack of novel therapies for treating bladder cancer over the past forty years. However, it results in modest responses of around 20%. Emerging clinical trials, including BLASST-1 (Bladder Cancer Signal Seeking Trial) led by me show promising activity with immunotherapy and chemotherapy in neoadjuvant setting, but lack of predictive biomarkers limits our ability to accurately select which patients need chemotherapy or immunotherapy or both. There is an unmet need to do a much better job in identifying patients who would not respond to avoid disease progression and financial toxicity.

I have been exploring the use of the Decipher Bladder subtyping test as a promising new tool which may help guide treatment in my clinical practice. This test has shown promising utility for predicting benefit from neoadjuvant chemotherapy, and more recently also from immunotherapy / checkpoint inhibitors, and suggests a more efficient identification of immunotherapy responsive patients than the recently FDA approved and CMS reimbursed TMB assay, which has not performed well in bladder cancer.

Having commercial access to the Decipher Bladder subtyping test can improve how I decide on systemic therapies and the sequencing of those systemic therapies for patients with bladder cancer. Utilizing the test, I believe the Decipher Bladder test has great potential to improve the clinical management and quality of life for patients with bladder cancer. I therefore am in strong support of the proposed Medicare coverage decision.

Thank you for your comments and support of the policy.

10

The following comment was submitted to Palmetto GBA.

I am writing to give my strong support of the new coverage policy for prognostic and predictive molecular classifiers for patients with bladder cancer on behalf of myself as a urologic oncologist, as well as the patients that I care for and treat. Currently, the gold standard of treatment with patients who have muscle invasive bladder cancer is neoadjuvant chemotherapy followed by radical cystectomy (based on level 1 evidence that shows an improvement in survival). Unfortunately, our gold standard does not uniformly benefit all patients as our current ability to accurately stage patient is poor. For example, in large prospective and retrospective multi- institutional cohorts approximately ¼ of patients with clinical T1 disease and ½ of patients with clinical T2 disease had pathologic T3+ disease at time of cystectomy and would have benefitted from chemotherapy. Conversely, those with truly organ confined disease (cT1/T2 that is pT1/T2) can avoid the side effects of chemotherapy and achieve a cure with cystectomy alone. Thus, neoadjuvant chemotherapy is not widely used in the US and our current paradigm has failed our patients via undertreating some, while over-treating others.

Molecular classification that subtypes tumors as Luminal, Luminal-Infiltrated, Basal, Claudin-low and Neuroendocrine-like have emerged as valuable predictors of bladder cancer biology by 1) improving staging by identifying which tumors are organ confined 2) informing response to systemic therapy (chemotherapy and immunotherapy). This has been discovered and validated across numerous studies using Decipher Bladder, a genomic test that uses a 209-gene expression classifier, that performed on TURBT specimens from patients with cT1-T4 bladder cancer who have not yet had a cystectomy (Seiler et al, Lotan et al, Batista da Costa et al, Efstathiou et al, Grivas et al, and most recently Necchi et al). Thus, molecular classification by Decipher Bladder could identify patients who were high-risk and would respond to systemic therapy prospectively – getting the right treatment to the right patient at the right time. Downstream effects would be improved outcomes and reduce cost (both to the patient by avoiding toxicity and to the health care system).

Speaking as a scientist, the current published studies support the use of molecular classification in our clinical paradigm by improving staging accuracy and predicting response to treatments. Speaking as a clinician, these types of tests are critical in selecting appropriate treatments and doing everything in our power to improve the outcomes and reduce the burden on our patients in their battle against bladder cancer.

Thank you for your comments and support of the policy.

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Keywords

  • Bladder Cancer