Data Show Melanoma Site to Be Independent High-Risk Factor for Recurrence, Poor Outcomes

In 2022, approximately 3.3 million individuals in the United States received a diagnosis of melanoma, according to Scott Soefje, PharmD, MBA, BCOP, FCCP, FHOPA, director of pharmacy cancer care services and an assistant professor at Mayo Clinic in Rochester, Minnesota. Furthermore, basal cell carcinoma is the most common skin cancer, with approximately 80% of patients with skin cancer receiving this diagnosis, and squamous cell carcinoma (SCC) is the second most common.

Soefje further explained that incidence of melanoma is increasing. For many cancers, the population is increasing whereas incidence is decreasing. But melanoma is unique in that it’s the other way around: Incidence is increasing over time. Soefje noted this may indicate that melanoma will be a more significant burden than it is today.

“Generally, [melanomas are] curable if they’re caught early. And our surgeons are really good about removing them. However, when they advance to locally advanced disease or they become metastatic, that’s when we have to start thinking about systemic therapies, and pharmacy gets involved,” Soefje said.

Additionally, with the recurrence of melanoma, surgery can lead to disfigurement, especially after repeated treatments. Soefje noted that when he worked as a specialty resident in oncology pharmacy at South Texas Veterans Health Care System in San Antonio, he treated patients with SCC who required multiple surgeries and experienced significant disfigurement.

“It is a significant problem and it’s something that all pharmacists should know about,” Soefje said. “I think most of us probably know the risk factors [of] sunlight [and] radiation exposure. But we’ve also had experiments in Japan and Chernobyl [in Ukraine] into radiation exposure, and skin cancers have become common there as well. So it’s 1 of those things that [are] primarily [caused by] UV radiation, but there are other types of radiation.

Additionally, some skin cancers occur in patients who have received radiation therapy for breast cancer or Hodgkin disease, according to Soefje. Sun exposure is not the only risk factor; all forms of radiation pose a risk for skin cancer.

“This is what I teach residents: It’s chemicals, radiation, viruses, and [genetics]. So there [is] some genetic pathway signaling, particularly with PTCH1, that leads to the nevoid basal cell carcinoma syndromes, but albinism is [also] associated with it,” Soefje said.

Soefje explained that during management of other tumor types, SCC shows up as an adverse effect of some of the therapies, with location of the tumor site being a risk factor. Locations where the risk of developing SCC increases include the ears, lips, hands, face, and feet.

“Also, when you start looking at pathology, the risk factors for recurrence include poorly differentiated aggressive growth patterns and whether there’s perineural involvement,” Soefje said. “Prior history of radiotherapy and prior history of skin cancer are risk factor[s] for it recurring. Lastly, immunosuppression is a risk factor [as well].”

Joanna Walker, MD, director of the Rare and Advanced Skin Cancer Clinic and assistant professor of clinical dermatology at the University of Pennsylvania in Philadelphia, explained that some high-risk sites for patients developing locally advanced or metastatic disease include genitalia and the scalp. “There’s new research from the Penn group showing the scalp as an independent high risk for recurrence and poor outcomes. And [that is] even when controlling for same stage,” Walker said. “We don’t know [whether] it’s something about the rich vascular or lymphatic region that [disease is] coming up in or [whether] it’s simply in a tough area and someone’s under[managing] it, [which means] there’s a higher risk for it recurring.”

Walker further explained that when assessing whether surgery is the best option available, her team looks to National Comprehensive Cancer Network (NCCN) guidelines. “The NCCN guidelines have, for both basal cell and squamous cell [carcinoma], risks and stratification into low- and high-risk tumors, depending on the site, the histology, the size of the tumor. And there’s appropriate use criteria for when something has a better outcome when it’s [managed] with Mohs micrographic sur gical treatment,” Walker said. “Low-risk, small, superficial tumors can be scraped, they can be frozen, they can be [managed] with topicals. But things that are larger or in higherrisk anatomic sites can and should be [managed] with surgery, particularly with microscopically controlled surgery.”

Soefje noted that in his experience, he has found the cosmetic aspect of treatment options affects patients’ decisions about whether to opt for surgery. “We’ve had patients decline surgery because they were afraid of the cosmetic impacts,” Soefje said. “I suspect the scalp is difficult to [perform] surgery on.”

Walker responded by explaining that although it’s easy to remove skin cancer tumors on the scalp, the healing process can be difficult and the wound more difficult to suture. For that purpose, she noted her team has used grafts, which is a more challenging procedure.