Melanoma Awareness Month: Pecora’s Insights on Prevention and Treatment

Andrew Pecora, MD

For Melanoma Awareness Month, Andrew Pecora, MD, discussed melanoma prevention and treatment. Pecora emphasized the importance of lifelong UV protection, regular skin exams, and early detection.

“[Anyone] can have melanoma. Although the likelihood of some [individuals] getting melanoma is less, it is not zero,” Pecora, chief of the skin and sarcoma division at John Theurer Cancer Center, and professor of medicine and oncology of Georgetown University Medical Center, told Targeted Oncology^TM in an interview. “[Oncologists] have to understand the patient in front of [them] and their unique risk. It is not only their behavior, but their disposition.”

In the interview, Pecora debunked common misconceptions about melanoma, highlighting its occurrence in non-sun-exposed areas and in people of all ages, detailed advancements in targeted therapies and immunotherapies, which have significantly improved survival rates, and stressed the need for oncologists to educate patients on skin exams.

Targeted Oncology^TM: Given that Melanoma Awareness Month is crucial for education, what are the key updates in melanoma prevention and early detection that are important for oncologists to know?

Pecora: Melanoma is a potentially preventable skin cancer, and given how severe it is capable of being, anything that one can do to prevent it from occurring, or if it does occur, to catch it as early as possible, is a benefit to that patient. The methods of preventing melanoma start in childhood, because it is a lifelong accumulation of ultraviolet radiation, damage to your skin that significantly increases the risk of most melanomas. Avoidance of excess sun exposure, use of sunscreens, avoidance of unnecessary ultraviolet radiation such as tanning beds are all important. Wearing protective clothing is important, and it is a lifelong effort that will allow you, as you get older, to have your skin stay healthy.

In addition to that, even with those protective mechanisms, you still may get a melanoma. Some [patients] are genetically more predisposed to get melanoma than others. If you are found to have a melanoma, it is in your interest to catch it as early as possible, so therefore self-exams, along with good dermatologic examinations, are important. As you get older, having those on a regular basis are critical, so that a qualified professional can screen your skin and look for suspicious changes. We always say that the most important thing for people to be aware of is that if they notice a change in a mole, if it changes in color, if it changes in size, if it changes in character, that should never be ignored, and they should seek an appointment with their dermatologist to have an appropriate assessment and, if necessary, a biopsy.

What are some common misconceptions about melanoma that you frequently encounter? How can oncologists dispel these myths within their practices?

There are several myths. Number 1, melanoma can occur in your skin, in a spot where you never had a mole before. I think a lot of people think, “Oh, it is a mole I have had all my life, and that changes, and that is where the only place melanoma can come from.” While it can come from a mole you have had your entire life, it doesn't have to. It can come from anywhere.

The second thing is melanoma can present and then regress. In other words, your own immune system can attack it and remove it so that you may show up with an enlarged lymph node under your arm or in your groin, or even worse, show up with melanoma somewhere in your body, like your liver or your lung, and have no history of a of a skin melanoma. That can happen, and I see that not infrequently.

Medical animation of melanoma cancer cells: © vitanovski - stock.adobe.com

The other thing is that melanoma can occur in non-sun-exposed parts of your body. It can occur on the bottom of your feet, in your nail beds, in your mouth, and in the other mucus membranes of your body, so it does not have to occur only in sun-exposed areas.

The last thing is that people, unfortunately, believe melanoma only occurs in older people. While the likelihood of melanoma occurring goes up as age increases. I have seen children and young teenagers with melanoma. Anyone, regardless of age, should always be aware that if they notice a change, either a new lesion that they never saw before, or a change in the size, shape, color, or character of a mole that they've had for a few years, they should seek immediate medical attention.

From your perspective, what are the latest advancements in melanoma treatment, and how do you see these impacting patient care at different community oncology settings?

A decade ago, or a little more than that, melanoma was a disease that you could only treat with surgery. There were some other treatments, such as interferon and interleukin, that had very marginal benefit with a lot of [adverse events], and unfortunately, [most patients] who had melanoma that had spread to their organs died of that melanoma within a year or 2, most within a year. That has fundamentally changed.

Two major discoveries of which our cancer center and I have been involved with from the beginning are targeted therapies, wherein about 50% of [patients] who have melanoma, their melanoma has a mutation in the melanoma DNA called a BRAF mutation. If there is a mutation in the BRAF gene, then there are drugs that have been FDA-approved that, when given, can not only regress an advanced melanoma, but actually make it completely go away. If you have locally advanced melanoma, such as stage II or stage III melanoma, after your surgery you get one of these drugs, it has been proven that these drugs being taken for 1 year increases your chances of living without melanoma ever coming back. It actually increases your chances of living.

The other major advance is immunotherapy. What we learned was that our own T cells are capable of recognizing and killing tumor associated proteins, and in the case of melanoma, those proteins expressed on the surface of the melanoma cell that say to your own body, “Hey, this is not a normal cell, and this is something that could hurt me, and it needs to be destroyed.” Our immune systems are capable of recognizing and destroying those cancer cells. In the case of melanoma, we learned that the tumor cells had the ability to shut off the T cells. T cells have an off switch called checkpoints, and tumor cells would engage a checkpoint and turn it off, like turning the light switch off. What a number of people discovered—one of which was James P. Allison, PhD, who I had the pleasure of working with at Memorial Sloan Kettering [Cancer Center] when I was there years ago doing research, and who went on and win the Nobel Prize because he figured it out—if I can cover up the off switch with an antibody, and they call that a checkpoint inhibitor, I can prevent the cancer cell from turning off the T cell, and the T cell can then go on and kill the cancer cell. In fact, what we have found is a variety of immunotherapies are all effective in not just eliminating advanced melanoma or metastatic melanoma or preventing it from coming back. They are capable of curing [patients]. Even [patients that] have melanoma that has spread to their brain.

So, where we are today is either with targeted therapy or with immunotherapy. On average, we can cure about half of the patients. Unfortunately, the other half of the patients we cannot cure, and there are a variety of reasons why we cannot. We are now entering the next phase of developing therapies that will hopefully let us cure the other half, so no one ever dies of melanoma again. We are doing this with amazing technology.

What we learned with the COVID pandemic is you can take RNA and put it in a little packet, and it creates a vaccine. In the case of COVID, they took RNA from the COVID virus, and they put it in a little packet, injected it in our arms, and we made T cells and gave us immunity against the COVID virus. Well, using that same technology, what we do now is we send a piece of the melanoma to a laboratory. The laboratory sequences the DNA of a healthy cell, your healthy cell, and then it sequences the DNA of the cancer cell, and it looks where [the] cancer cell [is] different. So, there are 6 or 7 areas where the cancer cells DNA has been mutated. That is what's making it melanoma. They then snip those abnormal pieces of DNA out, and they have a cell make RNA from that mutated DNA, and they put it in a little packet, a little lipid packet, and they send it back to me and other people who are doing this research, and we inject it in your arm like a vaccine. In addition to getting the checkpoint inhibitor I spoke about previously, patients are also getting RNA from their own melanoma that is being presented to your lymphocytes that then make melanoma proteins to super-stimulate their T cells, so that you enhance the army of T cells out to kill your cancer. We hope it is going to increase the cure rate from 52% to a much higher number, and that is the cutting edge of where melanoma is right now.

What advice do you have for oncologists on educating their patients about the importance of regular skin exams and some of the effective strategies for promoting this in practice?

I think every cancer doctor wishes that their patients never needed them and they never got cancer. The single best way to treat cancer is to prevent it. I believe all oncologists are dedicated to teaching their patients strategies to prevent preventable cancers. Not every cancer is preventable, but the ones that are preventable, like preventing lung cancer by stopping smoking, preventing skin cancer, melanoma, squamous cell carcinoma, Merkel cell tumors by avoiding excess UV radiation, and on and on, are important things to do, and I think most oncologists understand that, but always should be encouraged to continue to do it.

Melanoma can present differently across various patient populations. What are some unique challenges or considerations when diagnosing or treating melanoma in diverse communities?

[Anyone] can have melanoma. Although the likelihood of some [individuals] getting melanoma is less, it is not zero. Diagnosing melanoma in someone who has very dark skin can be a challenge, so you need to be hypervigilant. Certain populations have a predisposition more than others to a variety of cancers, of which melanoma is one. [For example,] genes like BRCA1 and BRCA2 are more common in the Jewish population. Melanoma is one of the cancers that has a higher likelihood. So ,you just have to understand the [patient] in front of you and their unique risk. It is not only their behavior, but their disposition, and then the case of skin cancer, their pigmentation, that you have to factor into how you are going to evaluate them and how you are going to follow them up.

Looking ahead, what are some of the most promising areas of research that have potential to significantly improve patient outcomes?

The advancement of targeted therapies, immunotherapies, and cellular therapies like tumor-infiltrating lymphocytes, where we actually take T cells from a person with advanced melanoma and put them in a laboratory to grow the T cells up into a massive army of T cells and putting them back in—it's the combination of those things, and then also enhancing the immunity of preexisting tumors that have become resistant to immunotherapy. That's the future of where we are. It's very bright, and I do see a day when no one will die of melanoma.