Treatments for melanoma and non-melanoma skin cancers include surgery, radiation therapy, topical and systemic drugs. The treatment choice depends on the cancer staging, risk of recurrence, and risk of metastasis. Tumors with high-risk behavior (based on location and size, well-defined versus ill-defined borders, primary versus recurrent disease, immunosuppression status, sites of prior radiotherapy, invasion into local nerves, evidence of chronic inflammation or rapid growth) are placed on high-risk treatment pathways (Kim 2012). Cure rates of non-melanoma skin cancers can reach 96-99% but are associated with high rates of recurrence. Five-year recurrence rates as high as 50% have been reported by some authors (Nguyen 2002; Firnhaber 2012), although lower rates have also been reported and vary by treatment type (Kim 2012).
Electrodessication and Curettage
Electrodessication and curettage (ED&C) is one of the most widely used treatments for squamous and basal cell carcinomas. It uses high voltage current to destroy the tumor and surrounding healthy tissue, which is removed by scraping with a special instrument (curette). The process is repeated until the tumor is removed. Low-risk areas (the trunk and extremities) are ideal locations for treatment by ED&C (Galiczynski 2011). Five-year tumor recurrence rates following ED&C are 7.7% (Kim 2012).
Cryosurgery has been used for both benign and malignant dermatological lesions. A cryogen (usually liquid nitrogen) is applied to the lesion with an applicator device, lowering the tissue temperature to -50°C to -60°C. This causes necrosis (death) of tumor cells and local healthy tissue. Cryosurgery is not suitable for aggressive tumors, those with ill-defined borders, or those that extend deeper than 10 mm (Galiczynski 2011). Five-year tumor recurrence rates following cryosurgery are 7.5% for non-melanoma skin cancers (Kim 2012).
Surgical excision is the standard option for surgical management of most non-melanoma skin cancers. The objective of surgical excision is to remove the entire tumor in addition to several millimeters of healthy tissue around the lesion as a safety margin. The size of excision margins varies by the size and aggressiveness of the tumor, with squamous cell carcinoma tumors over 2 cm in size requiring at least 10 mm of healthy tissue to be excised around the tumor. Taking sufficient margins during excision increases the probability that all of the tumor has been removed; this can be verified by microscopic evaluation of the excision margins. Surgical excision of basal cell carcinoma on the head, neck, trunk, and extremities has a five-year cure rate >95%, although the resultant surgical wounds can have cosmetic or functional impacts for the patient (Lazareth 2013).
Mohs microsurgery is the preferred method of treatment for all non-melanoma high-risk tumors based on reported efficacy, with five-year tumor recurrence rates for basal cell carcinoma of 1-3.3% (Lazareth 2013; Kim 2012; Paoli 2011; Rowe 1989). It also offers significant advantages for surgical excision of melanoma (Hui 2012). In the Mohs technique, the tumor is excised with a very thin margin, and the excised tumor is immediately analyzed for the presence of any malignant cells within the margins of the excision. If malignant cells are found, these are mapped back onto the skin incision so the surgeon may precisely remove the additional cancerous tissue. The process is repeated until all surgical margins are clear of cancer cells. Mohs microsurgery presents the best cure rates, lowest recurrence rates, and leaves the smallest surgical wounds. The major disadvantages are expense and limited access to surgeons trained in the technique (Lazareth 2013; Larson 2013). Patients can locate physicians trained in Mohs surgery through the Surgeon Finder resource on the website of the American College of Mohs Surgery (http://acms.execinc.com/edibo/SurgeonFinder).
Radiation can be an effective therapy for non-melanoma skin cancers up to 15 mm in diameter located in high-risk areas (Kim 2012). It offers reasonable cosmetic as well as functional outcomes and is a consideration for some types of cancerous lesions arising on or near the eyelids, nose, ears, and lips (Lazareth 2013). Superficial radiation therapy delivers low voltage (orthovoltage) X-ray radiation that rapidly loses its strength as it penetrates tissues to treat superficial cancers. Cancerous lesions up to about 6 cm deep require treatment by higher energy (megavoltage) electron beam radiation generated by linear accelerators to adequately penetrate tissues. A third type of radiotherapy, brachytherapy or interstitial therapy, delivers small beads of radioactive material directly into the cancerous lesion. Because the intensity of brachytherapy radiation decreases rapidly with distance, it allows a very high radiation dose to be delivered right at the source of the malignancy, while sparing noncancerous surrounding tissue (Hulyalkar 2011). Radiotherapy is a useful adjunct therapy for incompletely excised tumors, or those that have spread to local or distant lymph nodes (Lazareth 2013). Five-year tumor recurrence rates for basal cell carcinoma following radiotherapy are 8.7% (Kim 2012). Because of the potential to cause DNA damage and induce additional tumor formation in the treated area, radiotherapy is not a preferred option in young or immunocompromised individuals (Lazareth 2013).
Topical therapies have been used either alone (monotherapy) or as an adjunct to other therapies for the treatment of non-melanoma skin cancers (Amini 2010). They are convenient, can generally preserve skin appearance and integrity, and can be used to treat large areas. The immunomodulating agent imiquimod (Aldara®) and the DNA synthesis inhibitor 5-fluorouracil (5-FU) are among the two most commonly used topical agents (Desai 2012; MacFarlane 2010). Imiquimod is approved by the Food and Drug Administration (FDA) for treatment of superficial basal cell carcinoma <2 cm in diameter. 5-FU has been used as a treatment for other solid tumors (breast and colorectal) when given intravenously and is indicated for the topical treatment of pre-cancerous skin lesions (actinic keratosis) as well as squamous cell carcinoma in situ (Galiczynski 2011). Few randomized trials compared the efficacy of topical treatment of squamous or basal cell carcinomas to that of surgery or radiation (Kim 2012), and the evidence of their use as monotherapy is limited. Use of topical imiquimod or 5-FU may be more appropriate for patients with small tumors in low-risk areas who are unwilling to undergo better-established therapies (Firnhaber 2012).