Nontraditional Management of Basal Cell Carcinoma

May 2013 | Volume 12 | Issue 5 | Original Article | 525 | Copyright © 2013

Nina Botto MD and Gary Rogers MD

Department of Dermatology, Tufts Medical Center, Boston, MA

Abstract

This review discusses nontraditional modalities available for the treatment of basal cell carcinoma along with the existing evidence to support their respective uses in varying clinical situations. By definition, these modalities are nonsurgical, and in many cases, are not approved by the US Food and Drug Administration as treatments for basal cell carcinoma, including topical chemotherapies, photodynamic therapy, oral therapies, and complementary therapies. Nonetheless, as the population of patients with skin cancer increases at epidemic proportions, many of these modalities are, and will become, increasingly relevant in the dermatologist’s armamentarium.

J Drugs Dermatol. 2013;12(5):525-533.

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BACKGROUND

Skin cancer is increasing at epidemic proportions in the United States. More than 3.5 million nonmelanoma skin cancers (NMSCs)1 are diagnosed in the United States annually, with basal cell carcinoma (BCC) being the most common, accounting for more than one-third of all adult cancers.2 Ultraviolet (UV) light exposure is the most modifiable risk factor associated with development of BCC.3

Surgery (excisional and destructive) and radiation therapy4 are the mainstays of treatment of BCC. Surgical modalities, including electrodessication and curettage (EDC), excision, cryosurgery, and Mohs micrographic surgery (MMS) (Table 1), are traditionally employed in the management of BCC.5 These are all accepted means of treatment with associated risks, including functional impairment, scarring, disfigurement, and other morbidities. In addition, there are significant financial and quality of life costs associated with some of these modalities. In elderly patients, those with poor baseline functional status, or those on chronic therapy with immunosuppressive agents, the use of nonstandard therapies may be justified. Similarly, patients who have failed standard interventions, those with large or multifocal tumors, and patients with multiple primary BCCs may require nonstandard therapies to control their disease. Figure 1 highlights the pathogenesis of BCC and the importance of the hedgehog pathway in the development of BCC, as well as showing how inhibitors of the pathway can stop tumor progression.

Many studies exist in the literature comparing surgical treatment modalities; however, there are few controlled trials with significant (5-year) follow-up time to truly assess efficacy. The varying aggressiveness of BCC subtypes, primary vs recurrent status of a given tumor, and the anatomic site all render comparisons difficult.

Photodynamic Therapy

Photodynamic therapy (PDT) using topical photosensitizer 5-aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) is used to treat actinic keratoses (AKs), Bowen’s disease, superficial and nodular BCC, and as a preventive method for NMSC. MAL-PDT, used in Europe, Australia, and New Zealand, is approved for the treatment of both superficial and nodular BCC. In the United States, ALA is approved for the treatment of AK and is used off-label in the treatment of BCC. MAL is reported to be a more lipophilic, deeper-penetrating, less charged preparation, 6 which may account for its use in nodular BCC. However, one small pilot study randomizing treatment of nodular BCC to an ALA arm vs an MAL arm showed no statistically significant difference in outcomes between the 2 photosensitizers, and only an increase in cost with treatment using MAL.7

There are a variety of light sources that can be used in PDT, including intense pulsed light, lasers, and incoherent wave light sources, which all have different properties and thus range in their respective absorption spectra of protoporphyrin, and in short, can show great disparity in their efficacies.8

When used to treat BCC, PDT has shown to be a noninvasive treatment option with good cosmetic results. Five-year follow-up data from clinical trials using both ALA and MAL are variable, but overall, PDT is inferior to surgical excision (Table 2).9 In a retrospective study of 147 superficial BCCs and 189 nodular BCCs treated with MAL-PDT, 91% and 89% of superficial and nodular BCCs were clear at 3 months, with a 9% and 21% recurrence rate, respectively, at 35-month follow-up.10 An open-label, multicenter study using MAL-PDT and red light on “difficult to treat” superficial and nodular BCCs (large and H-zone lesions) found 3-month clearance rates between 93% and 94% and 2-year recurrence rates ranging from 18% to 30%.11 Another open-label study evaluating clinical and histologic clearance rates of large superficial and nodular BCC at high risk for scarring, recurrence, or disfigurement with conventional treatments found recurrence rates at 60 months to be 38% for superficial BCC and 18% for nodular BCC.12 In addition, in both of these studies, “good or excellent” cosmetic outcomes were reported in 84% to 94% of lesions.11,12

PDT has been reported to be superior to cryosurgery with regard to postsurgical scarring, keloids, immunosuppresion, poor wound

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