Multiple LCDs: MolDX: Molecular Assays for the Diagnosis of Cutaneous Melanoma; MolDX: Prognostic and Predictive Molecular Classifiers for Bladder Cancer Open Public Meeting - August 11, 2022 - JF Part B

Jocelyn Fernandez:
Before we begin the meeting, I would like to make the following announcements: This meeting will be recorded. The audio recording, and written transcript will be posted to our website following today's meeting. All lines are currently being muted and will remain muted throughout the meeting. Only registered presenters will be allowed to comment today. For their presenters, you are being allotted 10 minutes to make comments. Your line will be opened when it is your turn to speak. Make sure you are not on mute within your system, or we will not be able to hear your comments. You should be prepared to begin your presentation immediately when called upon and will hear the moderators voice when one-minute remains.

By signing in today, you are giving consent to the use of your recorded voice and your comments. Please be mindful of sharing any personal health information during your presentation.

In addition to comments that are made today, all comments should also be submitted in writing. All written comments received will be recorded in the response to comments article.

Last item, we will be projecting your slides, so let us know when to move forward.

I will now turn the meeting over to Dr. Anitra Graves.

Dr. Graves, you may begin.

Dr. Graves:
Thank you, Jocelyn, and good afternoon, everyone. Welcome to the Virtual Open Public Meeting, my name is Dr. Anitra Graves. I am a Medical Director with the Noridian Healthcare Solutions representing Medicare AB Jurisdictions, JE and JF. We are looking forward to comments and are very appreciative of the time you committed to preparing them.

The LCDs that we are looking at today are MolDX: Prognostic and Predictive Molecular Classifiers for Bladder Cancer, with the Policy Numbers DL38647 for JE, and DL38649 JF.

The second LCD is MolDX: Molecular Assays for the Diagnosis of Cutaneous Melanoma. Those policy numbers are DL39373 for JE and DL39375 for JF.

So, we'll begin with the Prognostic and Predictive Molecular Classifiers for Bladder Cancer policy. It appears that we have no presenters for this policy. This is a MAC-initiated reconsiderations, provide updated guidance and clarification regarding reasonable and necessary criteria for prognostic and predictive molecular testing for bladder cancer. We look forward to any written comments that may be submitted during the comment period.

Next slide

The next policy is a stakeholder-initiated policy request.

Documentation of the original request is posted online on the Medicare Coverage Database and can be located in the accompanying tracking sheet, which will appear automatically upon searching for the specific LCD ID.

DL39373 and DL39375 outlines limited coverage for molecular testing for the diagnosis of continuous melanoma, with specific details pertaining to coverage indications, limitations, and medical necessity.

We do have three presenters for this policy: The first commenter is Dr. Alexander Witkowski.

Please, I apologize if I butcher your name. Dr. Witkowski is from Oregon Health and Sciences University.

Jocelyn?

Jocelyn Fernandez:
Dr. Witkowski, your line is open. Dr. Witkowski?

Dr. Witkowski:
Yes, thank you. There's a slight delay. Thank you very much for the introduction. I appreciate that. And then, I'm Dr. Alexander Witkowski I'm a Clinical Dermatologist.

Dr. Cockerell:
This is Dr. Cockerell speaking, I'm not hearing any sound from your end, if you can hear me, but I need to be able to hear so I know when you are queuing me up to talk.

Dr. Witkowski:
I can hear Dr. Cockerell. Can everybody hear me clearly?

Jocelyn Fernandez:
This is Jocelyn, yes, I can hear you, Dr. Cockerell and Dr. Witkowski

Dr. Witkowski:
Thank you, may, I proceed?

Jocelyn Fernandez:
Yes, please.

Dr. Witkowski:
OK, thank you. So, just starting again, I'm Dr. Alexander Witkowski. I'm a Clinical Dermatologist in Portland, Oregon, at an academic institution at the Oregon Health and Sciences University Department of Dermatology, and I am the co-director of the Skin Imaging and Technology Center. If you could, please advance the slide.

These are my current disclosures and today I am representing myself only and I am not being compensated for my time present today. Please advance to the next slide.

So, today, I'm going to briefly speak in regard to the draft LCD MolDX Molecular Assays for diagnosis of Cutaneous Melanoma. I fundamentally agree with the position that both test the 23 GEP and the 35 GEP test, commercially known as MyPath and DecisionDX-DiffDX, should be available for Medicare beneficiaries under a single LCD.

I think that this draft policy establishes appropriate coverage for these two GEP tests broadly. I am here today specifically because I have a single refinement or a recommended suggestion that I believe MolDX should consider as this draft policy moves towards a final LCD. I believe that dermatologists, like myself, are inadvertently left out of the current wording of this draft policy. And I believe that this is a mistake because dermatologists are the primary point of care and the experts for diagnosis and treatment of melanocytic neoplasms. Dermatologists, like myself, work closely with our pathology colleagues and there are other dermatologists in our community who actually read their own pathology slides in order other relevant ancillary tests, as they may be appropriate. And this work is actually reimbursed by CMS.

Both interpreting Pathologists and dermatology treating clinicians should be able to order these tests and are capable of determining which patient will benefit from GEP testing, diagnostic GEP testing, and when the test is medically reasonable and necessary for their patients. Next slide, please.

So, this slide briefly highlights the different tools that I'm using in my clinical practice as a Clinical dermatologist and starting with visual inspection I augment that with their dermoscopy, and in certain cases possibly a 2-GPA adhesive patch, and in some cases I also use a tool, as you can see called the reflectance confocal microscope. All of these tools allow me to evaluate, skin lesion before my decision to make a biopsy and I, as a dermatologist, I'm an expert to when I'm using these tools and choosing them correctly and knowing when they're necessary, in order to guide my practice and provide precision medicine to my patients. After the biopsy is done in a specimen is finally center pathology. The 23 GEP or the 35 GEP tests can be ordered to guide the correct diagnosis for melanoma versus nevus by the interpreting pathologists, I believe that the need for these tests can be appropriately identified by a dermatologist treating the patients in the setting of an equivocal or uncertain biopsy report rendered to the patient.

Next slide, please.

So just a very brief background. So advanced imaging tools may aid in prebiopsy decision making, but however, there is a broad consensus that advanced imaging does not benefit, biopsy decision making and lesions with an obviously clear clinical diagnosis and you can see here a benign nevus is on the left and an obvious melanoma on the right.

Next slide, please.

And on the contrary, there's also a broad consensus that advanced imaging does benefit biopsy decision making and lesions with equivocal, or uncertain clinical diagnostic criteria. So, in lesions such as the melanocytic proliferations in these two photos, additional imaging modalities, such as dermoscopy or confocal microscopy, could be beneficial to inform decision making around the need for biopsy. As the dermatologists I am trained to know when these ancillary clinical decision-making tools are appropriate and when they are not appropriate.

Next slide, please.

So, in this schematic, you can see that the figure shows how a dermatologist use clinical tools to evaluate melanocytic neoplasms before biopsy and then on the right side of this yellow bar, dermatopathologists, pathologists, and dermatologists are all involved in the interpretation of the resulting skin biopsies to inform the management decisions for their patients. I want to highlight for this presentation and audience that dermatologists have a key input into the diagnosis of melanocytic lesions before the biopsy and after the biopsy. Yet, the draft LCD in its current form only allows dermatopathologists to use GEP testing for uncertain equivocal, melanocytic neoplasms.

Next slide, please.

Here, I'm giving comments specifically about the draft LCD which does appropriately cover dermatopathologists ordering both these diagnostic GEP test the 23 and 35 GEP. But I do think that there's an opportunity to allow other skin cancer specialists to also have access to these GEP test when there is significant clinical ambiguity. Clinical ambiguity occurs when the diagnosis between melanoma and non-melanoma remains uncertain or equivocal, after the pathology review. And this can also lead to overtreatment or undertreatment by the dermatology treating provider who uses the pathology report for guidance. Benign melanocytic neoplasms, for example, mild or moderately dysplastic nevi do not necessitate re-excision.

So, in that sense, clinical ambiguity frequently results, and patients managed with surgical excision for non-melanomas, because the treating dermatologist has a significant concern for missing a malignant melanoma. This is why we see that 65% of physicians re-excising mildly moderately dysplastic nevi published studies like this one from 2014. This compares with literature published and cited in this draft LCD that shows how GEP testing with 23 or 35 GEP can reduce surgical management decisions. Again, avoiding unnecessary re-excisions, when dermatology treating clinician obtain a benign or a negative diagnostic GEP result.

Accurate diagnosis has an inherent clinical utility to dermatologist and as a definitive diagnosis and forms patient management decisions and GEP testing for ambiguous wanted sort of lesions, reduces this clinical ambiguity, and can help safely avoid unnecessary re-excisions.

Next slide, please.

In the interest of time, this utility data for dramatic pathologists and dermatologists has already been approved appropriately cited in the draft LCD. Could you please advance to the next slide?

So, to illustrate my perspective, I think a case is the most efficient way to demonstrate where 25 and 35 GEP testing fits in the clinical management of patients seen by a dermatologist. This clinical image on the slide is of a patient who I saw in consultation for a concerning pigmented skin, lesion on her left, posterior shoulder.

If you could advance to the next slide, please.

I use a variety of different advanced imaging modalities in my clinical practice as I mentioned before and, in this example, you can see a high definition dermascopic Image of the same concerning lesion on the patient's shoulder here. You can see a blue-white veil, 50% of the surface area asymmetry with a typical network and round structures all highlighted with the arrows. These particular dermascopic features, for, which every dermatologist and dermatology provider in the United States is trained to use this tool, raises clinical concern for malignant melanoma or a severely dysplastic nevis.

Please advance to, thank you. In my practice I know I have an opportunity to use very high precision tools in an academic setting and here's an example of what the confocal microscope that I use daily actually looks like.

Next slide please.

So, I use the confocal microscope in cases like this because it provides me with complimentary information on, top of the actual dermascopic image of concern. In this particular case we can see in high resolution the dermal - epidermal junction with the presence high numerosity of atypical cells with nuclear pleomorphism and non-edge papillae, these are all confocal terminology.

Next slide please.

This slide just highlighting with the red circles we can see distinct individual populations of these atypical melanocytes. And in the context of all those features I mentioned previously very high concern for melanoma, based on clinical, dermascopic and confocal microscopy features.

Next slide please.

So, this is the actual pathology report, from this case, that I received after the initial biopsy for which I performed a complete sampling of the skin. Dermatologists receive clinically ambiguous reports, and they design. We have the advanced training to recognize cases like this, one with diagnostic and treatment uncertainty. And when you can see here from this report, that's highlighted in yellow, I actually reported exactly what concerned me. But you can see a critical mismatch between my clinical dermascopic confocal features suggestive of melanoma and then the initial benign topline diagnosis of a compound nevis. Still the pathologist clarifies a lesion is atypical, has features of atypia but does not specify, what type of clinical follow-up of the areas recommended. Just to give the audience perspective, this could be naked eye observation, clinical photography, dermascopic photography, deep-shaped biopsy, wedge biopsy, or an excision biopsy, and so ultimately, I have to make that decision as the provider and I need a very clear, distinct, definitive, pathology diagnosis, and recommendation for which I did not receive.

Next slide, please.

So, I ordered the 23 and 35 GEP tests for diagnostic purposes, and you can see that, I, it came back positive suggestive of a malignant neoplasm. I received this result from my patient to add this objective data point based on genetic expression profiling to help achieve clinical pathologic correlation and informs subsequent management for the patient.

Next slide, please.

After integrating my clinical data and re-review with the Pathologist, you can see that they changed their diagnosis to the correct one, which was melanoma inside two, and this has a big influence on the way we treat the patient with a local wide excision. And, of course, more frequent follow-up of that particular patient. So, this clinical critical, sorry, this clinical critical mass match occurred when I received the pathology report that had an initial topline diagnosis as a benign compound nevis with atypical features and ultimately it was truly a melanoma.

Next slide, please.

I want to emphasize that the clinical impact this has on the patient's actual correct treatment. So, she had a melanoma. It needed to be excised with a wider margin excision, and she also needed to be converted instead of having an annual, overall suggested visit to having a, you know, every three months visit for the next two years due to a new onset history of melanoma.

Next slide, please.

This is a very brief synopsis of a workflow that we developed implementing the use of the 23 and 35 GEP tests at our academic center, and you can see that importantly GEP testing's position, in the schematic for lesions with uncertain malignant potential, with different actionable patient management plans that follow a malignant or positive GEP result or a benign GEP result.

As it relates to this current workflow, it is important to note that the draft policy as written will appropriately ensure coverage for both of these tasks. When one is ordered by a board certified or board eligible, dermatopathologist. However, in my humble opinion, the draft policy is just missing the ability for a dermatology treating clinicians to also submit appropriate GEP orders for these assays and the case that I presented here.

Next slide, please.

Moving towards the end of my presentation, the draft LCD does set out appropriate guardrails to avoid over testing. I do advocate to include as ordering providers, pathologists, dermatopathologists as is, and also, consideration to include dermatologists all of whom are specialists trained to identify lesions that meet the criteria set out by this LCD. To ensure appropriate testing the LCD should keep the existing draft language regarding coverage of GEP tests ordered by dermatologists. dermatopathologists, excuse me, I won't read it here. But I do agree with the limitations set out in the draft policy about the types of lesions in clinical moments when this testing is appropriate. I could imagine adding criteria that a dermatologist would need to meet in order to identify lesions that have significant clinical concern, potentially from clinical history or dermascopic imaging or criteria, which may not be known by the pathologist interpreting the slides.

Next slide, please.

On this last slide and in conclusion, Medicare already entrust dermatologist to pick tests before the biopsy. I believe that dermatologists can also be trusted to identify appropriate lesions for these GEP tests, as I do in my daily clinical practice, especially after the biopsy report is made as well. The draft LCD appropriately covers both MyPath and Diff-DX Medicare beneficiaries based on published clinical validity and clinical utility data and this aligns with the ordering flow at our own institution. The only area where I'm actually voicing my critique is that restricting coverage only to dermatopathologist misses a subset of expert training clinicians, specifically dermatologists that should also have access to GEP testing, to guide patient management decisions, since we are ultimately responsible for doing that to the patient and explaining to them why we're doing that.

Fundamentally, lesions that are appropriate for GEP testing should be accessible to and reimburse for pathologist, dermatopathologists and dermatologist alike. This test is clearly beneficial for Medicare patients, including my own, for whom I use this test to help correctly diagnose and manage their cutaneous melanocytic neoplasms with an equivocal or uncertain diagnosis.

Next slide please.

And with that, I want to thank everybody for your attention, the opportunity to share my comment today and I addressed and recommend everybody if you're interested in melanoma, to look at the resources that we offer for both patients and providers in a public forum and with that, thank you very much for your time.

Dr. Graves:
Thank you, Dr. Witkowski, really appreciate those comments and please make sure you submit these comments in writing, so that we can properly consider them for this comment period.

Our next presenter is Dr. Clay Cockerell, he is from the Cockerell Dermpatopathology Group and Dermpath on Demand as well. Welcome, Dr. Cockerell.

Dr. Cockerell:
Thank you very much. Yes, I'm happy to appreciate you giving me the opportunity to do. So, the next slide would also have had academic appointments at New York University Medical Center and Baylor Medical Center. So, not only those laboratory affiliations. Similar to what Dr. Witkoski has, I am a dermatopathologist so, I am using this test routinely now in my practice, and we've been using it now for a number of years.

Go to the next slide, and this has been a very, as with Dr. Witkoski, I have not received any compensation, I do consult with Castle Biosciences, but do not receive and compensation for this presentation.

Next slide, please.

So, basically, we are in favor of the way that this LCD is written in general. You understand the value of this. It's been used now in clinical practice.

But I can tell you, my own personal experiences has been a practice paradigm shift if you will. Many of these ambiguous (unrecognizable/unable to hear)

Jocelyn Fernandez:
Dr. Cockerell, it seems like your audio is better now, So, um, you can continue.

Dr. Cockerell:
OK, OK, good. Well, as I was saying, we are by far the most frequent users of these tests but as you heard Dr. Witkowski say here are certain settings where it's very important dermatopathologists are involved in decision making and even in some settings, surgical pathologists.

Let's go to the next slide.

So, basically, as you heard, any clinician should really theoretically have the ability to be involved in the ordering of this test. I don't think any of us here are thinking that this should be something that just about anybody should order willy-nilly, it should be used in a very rational fashion. When a clinician may have a situation where they really truly picks up and is a melanoma, the biopsy maybe result comes back ambiguous or comes back as a benign process when the clinician really thinks its cancer.

I think it's very important for the clinician to have the ability to intervene in that situation and say, "Hey, this is something we need a better diagnosis on a more definitive diagnosis, we need to get this test ordered". so that's really what we're kind of, advocating for here is situations, where someone other than the dermatopathologist would be the one to order to test. The next slide.

So, this is a challenging area, and it's been challenging for us for many years. It goes back to the 1970s and 1980s and we struggled with this for years. When I was in training on the basis of sorting things out as basically an atypical (unrecognizable) sometimes even recognize a liquid biopsy and follow-up with patients. Today, we have this test available to us to give us an objective bit of information to add to what we see under the microscope it is actually the objective as opposed to subjective test, such as FISH which are not as valuable or not as useful as this and we do appreciate the fact that this LCD recognizes that, we're just trying to say that they're setting for people other than me, be the ones that might be involved in the decision making and ordering this test. Go to the next slide.

So, there are two tests available, one is the original test that was developed by Myriad and acquired be Castle, a number of years ago. MyPath Melanoma with 23 genes, this gives a result of either benign, intermediate, or malignant. Next slide.

And if there's an intermediate result, it reflexed to the next test, which is the DiffDX 35 gene expression profile, and these tests are complimentary.

So, it actually increases the sensitivity and specificity of diagnosis when using the two tests together so very complimentary.

Next slide.

And both of these tests have been validated in multiple studies. For the clinical validity, I won't go through all of these now, but you can see the sensitivity and specificity are very high.

Next slide

And also valid for the clinical utility of dermatopathologists and dermatologists using them in practice and these were helpful producing diagnoses basically reducing rescissions when it's a benign region, et cetera.

Next slide.

Then, of course, here, also, talking about similar performance to that, of MyPath 35 tested, to more recent tested forms, as well as the first-generation test.

Next slide.

And these tests have been (unrecognizable) verified, and they've actually been endorsed, if you will, by a number of different national organizations. Again, NCNN now understands the validity and values using the testing. American Academy of Dermatology recognizes the use of the GEP testing. Recently, the American Society for Dermatopathology, which is our subspecialty organizations recognize this as invaluable and so there's, there's a consensus among major organizations out there that this is useful and helps him rendering diagnoses and I think the LCD reflects that. We are mainly just talking about looking at scope of faculty use and all these different say.

Next slide.

In some situations, there just isn't a board-certified/board-eligible dermatopathologist available. I grew up in West Texas, which is pretty far from here and they didn't have any dermatopathologists in that area at all. So, if there's an ambiguous diagnosis, it would have to be sent to consultation and the access to consultation is not always available by some insurance plans, and payers do not allow for consultation/second opinion, there are situations where the pathologist really doesn't want to send the specimen all for one reason, rather, maybe, or this disincentivized by doing so. It's not always, you don't always have access to a dermatopathologist. So, by mandating that, that can decrease appropriate access in certain situations. Many cases, the person that's really on the front end of the situation, making the diagnoses is the clinical dermatologist, like Dr. Witkowski, he is seeing the patient, he looks at the lesion that looks like the melanoma to him and he has other tests that he does on it and then it gets back with an appropriate diagnosis on it and then let's say, has to send the biopsy not to even a board certified dermatopathologist, it's a corporation.

Will then, he's going to need to be able to intervene in that in order to get a more accurate diagnosis. In some settings, there are surgical pathologists that are not board certified/board eligible. Maybe in a rural setting or something, they have to deal with a lot melanocytic neoplasms, most of them don't really choose to do that without board, training, in dermatopathology, but in some cases, they'll get pretty good at it and they're using FISH, they're using immunochemistry, and so, they're already use another test and it is certainly reasonable to allow those individual very select, small number of individuals that have access to this expertise if they're actually diagnosing the ambiguous lesions and they're not sending them all out to people like me to do this on a routine basis.

So, there are situations where it's valuable to others, and just for them, out of a biologist ordering this test, the next slide.

And, just like Dr. Witkowski had a nice case, I've got one here for you, as well. This was a 69-year-old man he went to a dermatologist for a concerning lesion on the left mid-upper back and receive a biopsy to rule out atypical melanocytic process. The pathologist said that it was difficult to diagnose. He wasn't really sure, but it was that it wasn't diagnostic of malignancy.

Then the dermatologist requested that the pathologist wasn't a dermatopathologist and ordered the GED test to clarify the diagnosis.

So, this is where we have a non-board-certified dermatopathologist, a clinical dermatologist who says, I'm really worried about this lesion and let's get this test on it. So, they did submit the test and get it done. The next slide demonstrates the result of this show features of a malignancy. And so, at this point, they were able to do a definitive diagnosis the nevoid melanoma as relevant to thin, the patient obviously had a good prognosis with this lesion.

But this is something that if it had been diagnosed in that way or maybe not even the diagnosed of cancer might not have been treated appropriately, progressed, and ultimately caused more harm to the patient.

So, without having the best available, it really wouldn't have been possible to get a definitive diagnosis of this specific person who was a Medicare patient.

Next slide.

This is my final slide. So, just in general, you know, these tests are well proven and well accepted, the accepted by large organizations, like the Academy of Dermatology, NCCN and others and so letting this access to be expanded to people that aren't just purely board certified and board eligible dermatopathologists and done in a rational, intelligent way, it's something that certainly can help patients and to be added to the armamentarium of people that are dealing with these lesions and I think it can be done in a way that's not necessarily that is going to cause and overutilization of that and nobody wants that.

We do want to have the ability to have permissions users in the proper setting, to deliver the best diagnoses for the patients.

So, if we can remove this specialization/specialty restriction that can help everyone (unrecognizable).

So, thank you very much for your attention and we'll get this information to you in writing so you'll have that for people would want to look at this.

Dr. Graves:
Thank you, Dr. Cockerell. We really appreciate your time, and we will definitely be looking forward to those written comments once they are submitted, we are having just a little bit of technical difficulty. So please, bear with us.

Our third speaker is Dr. Matthew Goldberg. He is here representing Castle Biosciences and also happens to be the requester for this policy. Dr. Goldberg?

Dr. Goldberg
Yes, I think I've unmuted myself. Can you all hear me?

Jocelyn Fernandez:
Yes.

Dr. Goldberg
Great.

Well, thank you for the opportunity to present here during the reading open meeting for the proposed LCD molecular assays for diagnosis of cutaneous melanomas. Thank you for the introduction. My name is Dr. Matthew Goldberg. I'm a board-certified dermatologist and dermatopathologist and an Assistant Clinical Professor of Dermatology at the Icon School of Medicine at Mount Sinai. By relevant disclosures that I'm the Medical Director or CastleBiosciences where I'm an employee and stockholder.

Next slide please.

For background, Castle has significant expertise in the field of cutaneous oncology. And today I'll be focusing on the two diagnostic ancillary gene expression profile tests or GEP tests, MyPath melanoma, and Decision DX, DiffDX melanoma that I'll refer to as MyPath and DiffDX during this presentation.

Next slide, please.

At a high level, Castle agrees with the draftable foundational policy, as it will continue to provide Medicare coverage for diagnostic ancillary GEP tests for primary cutaneous malign acidic neoplasms which the diagnosis is equivocal. Certain policy and associated billing encoding article designate that both Mypath and DiffDX coverage criteria according to the policy. And designate both GEP tested that medical reasonableness and necessity criteria for Medicare.

Next slide, please.

In the draft LCD, MolDX has appropriately reviewed and published evidence supporting the clinical validity and clinical utility of these assays, and highlights how GEP testing provides a much-needed objective ancillary diagnostic test that can complement the other subjective tools available to pathologists, such as immunochemistry, FISH, or second opinion consultation.

It's also important to highlight those limitations on Billing one GEP test for a single lesion is consistent with Castle Biosciences billing policy and further coverage and DL39373, and DL39375 is appropriately limited to specimens of uncertain molecular potential, and clinical scenarios, when GEP results will influence clinical management interventions.

So, in the setting of this broad agreement, with the draft LCD, Castle was recommending one revision to the draft coverage guidance to include board certified and board eligible pathologists and dermatologists as these two additional types of clinicians manage patients with these types of lesions today.

Next slide, please.

The draft LCD appropriately recognizes the unmet clinical need addressed by GEP testing of melanocytic neoplasms that has been well described in the literature and was alluded to by Dr. Cockerell just minutes ago. Importantly, diagnostic uncertainty can lead to clinical management uncertainty, and it can be impactful for for avoiding over and under treatment of these lesions.

Next slide, please.

The graphic on this slide highlights the peer reviewed published manuscripts that prospectively support the clinical validity and utility of Mypath, and DiffDX and the evidence supporting each test is strong and is appropriately referenced in the draft LCD.

Next slide please.

In every stage of their work-up on a case, pathologists interpreting skin, biopsies endeavor to correctly classify melanocytic neoplasms as a benign nevis for melanocytic melanoma and GEP correctly considered as an objective diagnostic ancillary test that can inform this distinction seen here on the right side of this figure.

Next slide, please.

The draft LCD contains clear appropriate language limiting GEP testing to primary cutaneous melanocytic neoplasms for which the diagnosis is equivocal are uncertain, and for which patients may be subjected to additional clinical interventions.

This language highlighted in the red box here helps to ensure that lesions appropriate for GEP testing are in fact, the lesions being tested and that align with the intended uses both Mypath and DiffDX.

Next slide, please.

For the LCD language itself, the stated purpose of GEP testing is to assist dermatopathologists to arrive at the correct diagnosis of melanoma versus non melanoma, when examining skin biopsies. However, there are other well qualified specialists who currently diagnose and manage these lesions. Specifically anatomic pathologists routinely receive and diagnose skin biopsies and, in some instances, function as dermatopathologists. This is even more acute in rural areas where access to dermatopathologists is limited.

Dermatologists routinely integrate pathology reports into patient management plans, and, in some instances, also function as dermatopathologists. We believe that these clinicians should be able to submit Mypath or DiffDX orders that meet the Medicare criteria, as they are both highly trained specialists involved in the diagnosis and management of patients with these lesions and they are currently able to order and do order other diagnostic ancillary tests, such as immunohistochemistry and FISH.

Next slide, please.

So, the schematic displayed on this slide depicts the process of clinical pathologic correlation. That is consolidating the pathologist and treating dermatologists impressions of the lesions into a clinical diagnosis to ensure that a final pathology report makes sense within the clinical context of the patient.

This process highlights two points in the patient's journey where diagnostic GEP can aid in this process. First in the interpretation of equivocal histopathology by the pathologists reviewing the slides under a microscope and second, in rendering a clinical diagnosis at the bedside as the treating clinician incorporates the histologic diagnosis with other clinical information to establish the patient management plans that follow.

Importantly, different providers lead these two diagnostic steps, and GEP can be incorporated by both the treating pathologist who provides the diagnostic interpretation and the treating clinician who incorporates the pathology report into actual management plans.

So, taking a step back, dermatopathologists are not operating alone in their role to sign out challenging melanocytic neoplasms. There's clear collaboration between the clinician treating the patient and the pathologist interpreting the patient's skin biopsy to obtain clinical pathologic correlation that ultimately inform patient management decisions such as additional surgeries and (unrecognizable) biopsies when appropriate.

So, for the next several slides, I'll walk through the rationale to add pathologists and dermatologists as covered ordering clinicians for these GEP tests. First, I will discuss anatomic pathologists.

Please advance 1 more slide.

While most skin biopsies are interpreted by dramatic theologists, there are pathologists who regularly interpret skin biopsies, who can order other relevant ancillary tasks and who can benefit from the clinical utility of GEP testing cited in the LCD.

There are regional variations in the number of dermatopathologists available to a particular community or group of patients. For example, rural areas have access to fewer dermatopathologists than urban centers. But the main point here is that there are pathologists who have developed significant expertise and interpreting skin biopsies. and when signing out cases for equivocal melanocytic neoplasms, these pathologists are functioning as dermatopathologists.

Next slide, please.

The figure on this slide, maps out the clinical pathologic correlation process and the white plus sign is where pathologist currently interpret skin biopsies and order diagnostic ancillary tests. However, the LCD doesn't fully reflect this real-world workflow because pathologists are not listed as covered clinicians. Given this fact, we support the inclusion of board certified and board eligible anatomic pathologists and dermatopathologists, as ordering clinicians for GEP testing in the final LCD.

Switching gears now to discuss the inclusion of dermatologists as ordering clinicians.

Please advance 1 more slide.

The draft LCD sites clinical utility publications, for both dermatopathologist and dermatologists, and the study showed that dermatologists can incorporate a benign GEP result into patient management plans to reduce unnecessary excisions, and this constitutes a clear utility for the treating dermatology clinician.

Next slide, please.

Returning to this, schematic, dermatologists are central members of the diagnostic team responsible for integrating pathology reports into clinical diagnoses that inform management decisions and if the treating dermatologist as ultimately responsible for planning, definitive surgical versus non-surgical management, it stands to reason that they should be able to have diagnostic GEP orders covered by Medicare. In addition, dermatologists are trained to be able to interpret their own skin biopsies noted here about the second white plus sign.

Today, a treating dermatologist can complete a pathology report for a particular lesion and order other ancillary tests. So, when dermatologists are essentially functioning as dermatopathologists, we believe that they should also be able to have GEP orders covered by Medicare.

Next slide, please.

So, to summarize: Castle is supportive of a minor revision to the draft LCD because board certified and board eligible dermatopathologists, pathologists, and dermatologists alike are all skilled treating clinician as it should have access to ancillary diagnostic, GEP testing, to improve diagnosis and management decisions for Medicare beneficiaries. Fundamentally, Castle does not believe that if a patient has a lesion interpreted by a non dermatopathologist, they should be restricted from covered GEP testing.

This could have unintended consequences that may result in disparate impact on patients living in rural areas and may result in both overtreatment of benign lesions and missed melanoma diagnoses. As such, adding pathologists and dermatologists to the LCD is beneficial for patients and will support appropriate testing.

Next slide, please.

So, in conclusion, on this last slide here, Castle supports the draft foundational LCD DL39373 and DL39375 and the inclusion and coverage of both MyPath and DiffDX based on a comprehensive literature review and level of published evidence supporting the subjective diagnostic tests. The draft LCDs limitations of billing one GEP tests for single lesion are consistent with Castle Biosciences billing policy and the draft LCD coverage guidance on specimen inclusion and intended use language already restrict use of this test to specialists capable of determining when testing is appropriate.

Therefore, we recommend treating board certified and board eligible dermatopathologists, pathologists, and dermatologists, as covered ordering clinicians and the final LCD as these specialists currently diagnose and manage these patients and this reality is not wholly reflected in the draft policy.

Overall, Castle believes that the inclusion specialists will support appropriate testing within the intended use of both MyPath and DiffDX.

Specific text suggestions will fall in our written comments prior to the close of the open comment period and that comment will also submit examples of LCDs that have less narrow restrictions on the ordering subspecialty which we believe could be seen as instructive guidepost to allow for the entire team treating patients with these equivocal or uncertain melanocytic neoplasms to be able to order these GEP tests appropriately.

Once again, thank you for the opportunity to present during this open meeting.

Dr. Graves:
Thank you very much, Dr. Goldberg, we really appreciated that presentation, and again, we are very, very much appreciative of the time you have all committed in providing their comments, and we certainly look forward to receiving those in writing, so that we may respond accordingly in the response to comment article.

This concludes the presentation portion of today's meeting. We will now move on to closing on next steps. Thank you, Jocelyn.

Jocelyn Fernandez:
In closing we would like to communicate the next steps in the policy development process.

The comment period for the proposed LCDs will remain open until August 20, 2022. All comments to be considered by our medical directors for the proposed LCDs must be submitted in writing. Written comments can be e-mailed to policydraft@noridian.com or mailed to the address on your screen. More information on our proposed LCDs are located on our website at noridianmedicare.com

Upon review of the comments are, medical directors will either finalize or retired the proposed LCDs. Responses to comments will be viewable in the response to comments article.

Please monitor our website or register for listserv notifications to be informed of actions taken on our proposed LCDs. I will now turn the meeting back to Dr. Graves for final remarks.

Dr. Graves:
Thank you Jocelyn, and thank you all for attending this Noridian virtual open public meeting as you realize, we have essentially gone to this format in the era of Covid, we hope that you were able to receive information that's necessary, and we do look forward to written comments, should you see fit to do so in response to the proposed policy, please enjoy the rest of your afternoon, and hopefully we will be seeing you for future virtual open meetings, with Noridian.

Thank you.