Reimagining Melanoma Diagnosis with Genomic Analysis

As melanoma remains the condition responsible for the most skin cancer deaths annually, early diagnosis is a critical, yet difficult-to-achieve, goal. Early melanomas-in-situ and thin melanomas can be very hard to detect but offer high survival rates (around 99 percent) with appropriate treatment. With time, though, these tumors become thicker and more invasive, and the mortality rate quickly rises. Typically, melanoma is diagnosed by biopsy, which has numerous issues. First, a patient must find a dermatologist, often facing long wait times. Then, the visit to the office, the subsequent biopsy or biopsies, and the waiting game afterwards can be quite daunting. Finally, recent evidence has called into question the reliability of traditional modalities for diagnosing melanomas.

A novel modality, encompassing smart sticker technology from DermTech, has greatly improved dermatologists’ ability to non-invasively test nevi for genetic aberrations found in melanoma. By combining a non-invasive technology with the science behind drivers of melanoma, this pathway offers an improved likelihood of diagnosis and subsequent timely, effective treatment, all while offering the best cosmetic outcomes since no initial biopsy for a benign lesion is needed. Furthermore, in an era of telehealth, DermTech’s Pigmented Lesion Assay (PLA) stands alone in being able to accurately manage suspicious moles for patients at home. Additionally, with patients for whom the prospect of physically getting to a dermatologists’ practice puts a prohibitive burden on access to care, this offers a safe and easy alternative. Integrating DermTech’s technology into their practices may help dermatologists be prepared for the future of both dermatologic care and skin cancer detection beyond biopsies.

Innovating Non-Invasive Testing through Genomics

The smart sticker technology is novel, as gathering DNA and RNA from an adhesive patch presents a wide range of opportunities and applications for future study. Over the past two years of utilizing the PLA in my practice, I have not had a single sample rejected for insufficient data collected during in-person or virtual visits, which speaks to the user-friendliness of the technology at both the practitioner and patient level. In developing the PLA, a robust database of genetic markers was used to identify several genes that, together, are highly sensitive toward diagnosing melanoma, with a Negative Predictive Value of 99 percent. In comparison, for the traditional biopsy modality, only one melanoma is identified for every 25 surgical biopsies performed. Up to 17 percent of early-stage melanomas are missed altogether, leading to both potential undertreatment and inaccurate data that are being used to guide health care system decisions. The DermTech Melanoma Test (PLAplus) examines LINC, PRAME, and TERT genetic markers, which are common mutations found in cutaneous melanoma. The LINC, PRAME and TERT indicators are present in 84 percent, 83 percent and 73 percent of melanomas, respectively. Combining these together allows for more accurate diagnoses to guide procedural decisions; even for a malignant lesion, this can better help decide whether to take a shave biopsy—which may risk missing the depth of a lesion—or an excisional biopsy. This technology can improve dermatologists’ chances of diagnosing melanoma at an early stage, which leads to better cure rates and patient survival.

Augmenting Telehealth with At-Home Testing

In the era of telehealth, especially amidst a global pandemic, DermTech’s Melanoma Test is a lifeline for patients who are concerned about a changing mole but are unable to visit a dermatologist’s office due to fear of risks associated with COVID-19. While serious safety and health concerns preventing patients from coming to dermatologists’ offices were valid, the decline in dermatology visits due to COVID-19 had a serious impact on melanoma diagnosis. Research from the Global Coalition for Melanoma Patient Advocacy estimates that approximately 14,944 early-stage melanomas went undiagnosed in the United States, in part due to missed skin check visits. While telehealth presents a variety of positive opportunities throughout healthcare, it is difficult to implement in dermatology when diagnosis depends on a clear image of skin lesions. Between a potentially blurry video call with the patient or issues sending photographs due to the telehealth platform, online options fail to replace the effectiveness of an in-person visit. The status quo for most dermatologists in this case is to either ban lesion/mole checks from telehealth visits or to have the patient come in for all but a minority of situations where there is a very obvious benign lesion (such as a cherry angioma), thus largely obviating the purpose for a telehealth visit in the first place. DermTech’s Pigmented Lesion Assay completely changes this dynamic, though, by offering dermatologists the ability to oversee the patient’s collection of a suspicious lesion’s DNA and receive results that clearly offers guidance as to whether lesions are high risk or benign.

Expanding Access to Accurate Evaluation of Nevi

Beyond the growing shift to telehealth sparked by the pandemic, at-home testing is a motivating option for patients who lack physical access to dermatology services. Outside of metropolitan areas, rural patients are most likely to be far removed from general health care providers, let alone dermatologists. This may lead to a delay in diagnosis until the lesion appears extremely abnormal, at which point the risks of invasion and metastasis could be significantly elevated. For example, a study in the Journal of Investigative Dermatology examined late-stage melanoma cases from 1995 to 2016 and found that decreased access to health systems was related to an increased proportion of late-stage melanoma among diagnosed cases. Telehealth options that we have put into place allow patients in distant areas (sometimes up to hundreds of miles away) to gain access to care for a broader range of concerns, ranging from common skin issues to more complex inflammatory skin diseases, and finally, suspicious moles for which we had no good option previously. As the PLA testing is covered by Medicare and DermTech accepts all commercial insurance, this also offers a cost-effective testing solution.

Reducing Scarring in Cosmetic Areas

A common patient concern arises when considering biopsies of lesions located in cosmetically sensitive areas. Often, patients come in after years of repeated biopsies and are frustrated by extensive scarring, especially when nothing malignant had been found previously. When considering a non-invasive test such as the PLA, patients can get the reassurance they are looking for without any scarring; alternatively, patients will get clear evidence that a biopsy is necessary. Dermatologists can unobtrusively test for melanoma in highly sensitive locations and reserve biopsies only for lesions that are at higher risk based on genomic data. We have had patients who have gone through getting three biopsies per year for as long as they remember, who are much happier with a non-invasive option and even promote this discovery to their friends and social network, which is great for patient satisfaction as well.

Integrating DermTech Into Your Practice

As medical technology evolves, it is critical for dermatologists to continue updating their practices to provide patients with up-to-date care. Integrating new technology into existing workplace processes often appears tedious but is easier than it seems. While the PLA may take some getting used to (as any new workflow does), once familiar with it, there is not a significant difference from a biopsy—and there is no bleeding to deal with! While we do still have to explain the test to our patients, the concept is rather compelling and, as such, DermTech is fully integrated into our practice and readily available in our examination rooms or for ordering online via telemedicine. For patients at home, the test is easy to use, with all required materials (namely, a gauze pad and a permanent marker) included in the kit. Patients simply identify the lesion(s) of concern, rub with gauze, press the smart sticker on top, trace the outline of the lesion with a pen, lift the sticker and press it onto the collection strip. This process is completed four times to ensure thorough data collection. From a practical standpoint, we generally schedule up to three visits for the testing, all relatively quick and easy, for the whole process. First, we meet with the patient via telehealth to discuss the lesion(s) of concern and decide if a PLA is appropriate. If it is, the patient has the choice of setting up another remote visit once the kit is received to supervise data collection. Finally, we have another visit to discuss the test results and next steps, depending on the test’s outcome. Patients have responded very positively to being offered these options and seem truly grateful that we are trying to think outside of the box to deliver care to wherever they are.

Reimagining Dermatology Beyond Biopsies

When determining whether or not to perform a biopsy, it is important to consider the risks and benefits of the various options. In a lesion with a strong suspicion for malignant melanoma, an immediate excisional biopsy is, of course, the gold standard. But most cases involve lesions that have some atypia; we are just not sure what it represents. So, we are left with the choice of biopsy or serial monitoring with dermoscopic images. I have often wondered about the medicolegal ramifications of the latter approach, but now we have a non-invasive, easy option in the form of the PLA. We thus avoid the conversation about risk of infection, bleeding, scarring and the risks of letting a potentially malignant lesion develop for a few months. Importantly, there is also no threshold of time when it is too early to utilize the PLA. As soon as patients mention a concerning lesion that is not clearly benign by exam and/or dermoscopy, dermatologists can order the test and use the results to determine if further procedures are needed. This seems to be a better approach than serial monitoring, as it removes both the risks of the procedure and the potential risk of waiting while the patient has a malignant lesion that is progressing.

Aside from these practical concerns, the most important information dermatologists should consider is the accuracy of PLA in identifying melanoma in comparison to current methodologies. In a study done by the Dutch Melanoma Working Party, researchers presented an expert panel of dermatopathologists with previously read biopsy slides and asked them to issue a diagnosis. Underdiagnosis (reported benign but upgraded to melanoma) was found in up to 25 percent of cases reported as malignant lesions, while overdiagnosis (reported melanoma, but actually a benign nevus) was present in about a third of previously reported benign lesions. There is significant uncertainty that arises from sampling error (owing to a small proportion of a specimen that is actually visualized by the dermatopathologist) or discordance in the exact criteria that define dysplastic nevi, melanoma-in-situ, and invasive melanoma. In melanoma research and treatment, the overall goal is to reduce the overall number of deaths caused by this disease, and inaccurate diagnosis is a major problem. With genomic information available via an easy, non-invasive test and defined, consistent risk rates for specific lesions, we should see this as an improvement on the paradigm of how we approach pigmented lesions in practice. This has the potential to transform our ability to diagnose melanoma accurately and quickly, and we can build on this evidence to better refine our treatment approaches to specific lesions harboring different mutations.

With a great deal of attention and concern being directed at the cost of evaluating for melanomas in dermatologic care as a whole, it is important to consider a cost-effective, innovative technology such as the PLA. Over time, this may ultimately help get more patients timely treatment and reduce the mortality burden of malignant melanoma.