Photodynamic therapy with photosensitizers is used in the management of a wide spectrum of superficial epithelial tumors. A topical photosensitizing agent such as 5-aminolevulinic acid or methyl aminolevulinate is applied to the tumor, followed by exposure to a specific wavelength of light (whether laser or broad band), depending upon the absorption characteristics of the photosensitizer. In the case of multiple BCCs, short-acting systemic (intravenous) photosensitizers such as verteporfin have been used investigationally. Upon light activation, the photosensitizer reacts with oxygen in the tissue to form singlet oxygen species, resulting in local cell destruction.
In case series, PDT has been associated with high initial CR rates. However, substantial regrowth rates of up to 50% have been reported with long-term follow-up. A randomized trial of PDT versus excision is summarized in the section on simple excision above. Two small trials, one reported in abstract form only, comparing PDT with cryosurgery are summarized in the cryosurgery section above, showing similar antitumor efficacy but better cosmesis with PDT.[17,18,19]
Topical fluorouracil (5-FU)
Topical 5-FU, as a 5% cream, may be useful in specific limited circumstances. It is a Food and Drug Administration (FDA)-approved treatment for superficial BCCs in patients for whom conventional methods are impractical, such as individuals with multiple lesions or difficult treatment sites. Safety and efficacy in other indications have not been established.[22,23][Level of evidence: 3iiiDiv] Given the superficial nature of its effects, nonvisible dermal involvement may persist, giving a false impression of treatment success. In addition, the brisk accompanying inflammatory reaction may cause substantial skin toxicity and discomfort in a large proportion of patients.
Imiquimod topical therapy
Imiquimod is an agonist for the toll-like receptor 7 and/or 8, inducing a helper T-cell cytokine cascade and interferon production. It purportedly acts as an immunomodulator. It is available as a 5% cream and is used in schedules ranging from twice weekly to twice daily over 5 to 15 weeks. Most of the experience is limited to case series of BCCs that are less than 2 cm2 in area and that are not in high-risk locations (i.e., within 1 cm of the hairline, eyes, nose, mouth, ear; or in the anogenital, hand, or foot regions). Follow-up times have also been generally short. Reported CR rates vary widely, from about 40% to 100%.[Level of evidence 3iiiDiv]
There have been a number of randomized trials of imiquimod.[24,25,26,27,28,29] However, the designs of all of them make interpretation of long-term efficacy impossible. Most were industry-sponsored dose-finding studies, with small numbers of patients on any given regimen; and patients were only followed for 6 to 12 weeks, with excision at that time to determine histologic response.[Level of evidence 1iDiv] Therefore, although imiquimod is an FDA-approved treatment for superficial BCCs, some investigators in the field do not recommend it for initial monotherapy for BCC; some reserve it for patients with small lesions in low-risk sites who cannot undergo treatment with more established therapies.