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  • New Options for Avoiding/Treating Skin Cancer

    Vigilance regarding sun safety becomes even more important during the summer months, although limiting skin exposure to damaging ultraviolet (UV) radiation is necessary during every season. Beyond the cosmetic damages that patients may notice, there can be severe consequences for patients who do not protect their skin from the potential harm in overexposure. These consequences can include the multiple types of cancers that originate in the skin: basal cell carcinoma, squamous cell carcinoma, neuroendocrine carcinoma, and melanoma—which has the potential to be the most serious. The most prevalent form of skin cancer in the US is nonmelanoma; it represents most common malignancies, but accounts for less than 0.1% of patient deaths caused by cancer. In 2012, an estimated >2M new cases occurred, and there were approximately less than 1,000 deaths. Statistics suggest yearly increases in incidence rates, some of which may be due to heighted skin cancer awareness and the resulting increase of investigation and biopsy of skin lesions.

    Various factors contribute to an individual patient’s risk for developing skin cancer. For example, cumulative and/or intermittent acute exposure to UV radiation (leading to sunburn), and an individual’s sensitivity to UV radiation can each play a role. Individuals who have light complexions and substantial exposure to sunlight may be at a heightened risk, though regardless of skin color, everyone is potentially susceptible to sunburn and other harmful effects of exposure to UV radiation. Other contributing risk factors include geographic location, arsenic exposure, and having the human papilloma virus infection. Individuals with organ transplants who are receiving immunosuppressive drugs are also at increased risk.

    The most malignant form of skin cancer is melanoma. We define primary cutaneous melanoma as any primary melanoma lesion, regardless of tumor thickness, in patients without clinical or histologic evidence of regional or distant metastatic disease (stage 0-IIC). The incidence of melanoma has been increasing for the last four decades and is responsible for most deaths related to skin cancer. This year, the estimates are 76,690 new cases and 9,480 deaths in the US. However, treatment is nearly always curative with early disease detection. For a lesion that is clinically suspicious for cutaneous melanoma, the preferred approach in diagnosis is a narrow excisional biopsy encompassing the lesion’s full breadth, with clinically negative margins to a depth sufficient to ensure the lesion is not transected. A 1- to 3-mm margin surrounding the lesion is the suggested requirement. In order to allow for microstaging, an experienced pathologist should examine the specimen, and a second review by an independent qualified pathologist is prudent. Prognosis is determined by the anatomic location of the lesion and by clinical and histological factors. The spread of the tumor, either by local extension (through lymphatics) or by hematogenous routes to distant sites, is the basis for clinical staging. The lungs and liver are common sites for metastases, but any organ may be involved. Even after surgery or alternative treatment, relapse is possible.

    Visual examination is the only widely proposed screening procedure for skin cancer. Patients can perform such examinations themselves in addition to professional clinical examinations we conduct. When melanoma is confirmed after a screening and subsequent biopsy, surgery is not always the only treatment option. Though the primary treatment modality for cutaneous melanoma is surgical excision, we also have a growing list of oncology treatments that may be appropriate alternatives. We may consider these when surgery is not reasonable due to patient comorbidities or preferences. FDA-approved nonsurgical therapies for melanoma include DTIC-Dome (dacarbazine), Proleukin (aldesleukin), Yervoy (ipilimumab), Zelboraf (vemurafenib), and the newly approved Tafinlar (dabrafenib) and Mekinist (trametinib).

    The FDA approved Tafinlar and Mekinist in May 2013 for the treatment of advanced or unresectable melanoma. Tafinlar, a BRAF inhibitor, received approval for use as a treatment for patients with melanoma whose tumors express the BRAF V600E gene mutation. Mekinist, a MEK inhibitor, was approved to treat patients whose tumors express the BRAF V600E or V600K gene mutations. Approximately half of melanomas arising in the skin have a BRAF gene mutation. Tafinlar and Mekinist were approved as single agents, not as a combination treatment. The FDA approved Tafinlar and Mekinist with a genetic test called the THxID BRAF test, a companion diagnostic that will help determine if a patient’s melanoma cells have the V600E or V600K mutation in the BRAF gene.

    PDR Network can be a useful resource for information on cancer drugs, as well as other drug types, offering alerts and specific product labeling. Keep current with information on products like those used to treat skin cancer by using PDR.net. If you use an electronic health record (EHR), please ensure that it includes the PDR drug data feeds, including PDR BRIEF, which delivers updated drug information, full labeling, and safety warnings integrated into your electronic prescribing system. Drug information in EHRs is often months out of date, which is why PDR BRIEF is available at no cost to providers and EHR vendors.

    Salvatore Volpe, MD, FAAP, FACP, CHCQM
    Chief Medical Officer
    PDR Network

    Bichakjian C, Halpern A, Johnson T, et al. Guidelines of care for the management of primary cutaneous melanoma. J Am Acad Dermatol. 2011; 65(5):1032-1047.
    U.S. Food and Drug Administration. FDA approves two drugs, companion diagnostic test for advanced skin cancer. May 29, 2013. Online content.
    http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm354199.htm. Accessed June 25, 2013.
    National Cancer Institute. Cancer Topics: Skin Cancer web page. http://www.cancer.gov/cancertopics/types/skin. Accessed June 25, 2013.