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Dovepress Photodynamic therapy in dermatology Studies on the treatment of actinic keratoses are notori- ously difficult to perform. Quantitation of actinic keratoses before and after treatment is hindered by the fact that actinic keratoses can appear and disappear spontaneously. The literature on PDT for actinic keratoses is daunting, but convincingly, ALA-PDT is an effective treatment for actinic keratoses, with an excellent cosmetic outcome, especially compared with 5-fluorouracil and cryotherapy.57 One recent meta-analysis, which included 32 publications, found that ALA-PDT (blue light: relative risk [RR] 6.22, red light: RR 5.94,) or MAL-PDT (red light: RR 4.46,) was superior to placebo-PDT for treatment of individual lesions. Based on participant-observed complete clearance in eight interven- tions, efficacy from most effective to least effective was 5-fluorouracil . ALA-PDT ∼ imiquimod ∼ ingenol mebu- tate ∼ MAL-PDT . cryotherapy . diclofenac . placebo.58 ALA-PDT with blue light is the standard for treatment of actinic keratosis, but multiple protocols exist. At our institution, ALA is applied for a one-hour incubation under occlusion prior to blue light exposure (10 J/cm2). The use of a 5-ALA self-adhesive patch may eliminate discrepancies in ALA application. Red light has also been used for the treat- ment of actinic keratoses. One randomized controlled study found that complete clearance of actinic keratoses 8 weeks after treatment occurred with 4-hour incubation of the self- adhesive ALA patch (86% of actinic keratosis lesions) and red light therapy. Shorter incubation times at 2 hours (73%), one hour (72%), and half an hour (51%) proved to be subpar.59 In one Phase III study, the 5-ALA patch-PDT without crust removal proved superior (82% and 89%) to placebo-PDT (19% and 29%, P,0.001) and cryosurgery (77%) in improve- ment of actinic keratosis lesions on the scalp.60 Use of PDT has evolved from its application as mono- therapy to an adjunct with other treatments. The value of sequential treatment with MAL-PDT and imiquimod was investigated in a randomized trial (n=105). Better response rates were seen for combination treatment than for either monotherapy; however, the difference in response was statisti- cally significant only for the comparison between combina- tion therapy and MAL-PDT monotherapy.61 Squamous cell carcinoma Management of SCC is categorized by metastatic potential, ie, low-risk cutaneous SCC or high-risk (aggressive) cutane- ous SCC, where surgical excision is the gold standard for the latter. Current therapies for SCC include surgical excision (Mohs surgery), cryotherapy, electrosurgery, topical treat- ments (5-fluorouracil and imiquimod), radiation therapy, Clinical, Cosmetic and Investigational Dermatology 2014:7 and PDT. PDT is only recommended for treatment of SCC in situ, and not for the treatment of invasive SCC.5,62 PDT demonstrated superior efficacy and less scarring in the treatment of SCC in situ when compared with cryo- therapy or 5-fluorouracil in a Cochrane review (n=363).63 In particular, ALA-PDT appeared to have greater efficacy than 5-fluorouracil but MAL-PDT was not demonstrated to be superior over 5-fluorouracil. Also, there was no difference in recurrence rates at 12 months with either MAL-PDT or ALA-PDT when compared with 5-fluorouracil.64 There are no randomized controlled trials directly comparing treatment with ALA-PDT versus MAL-PDT. The efficacy of PDT for SCC in situ was illustrated by a trial in which 225 patients were randomly assigned to two treatments of MAL-PDT (160 mg/g) with red light (570–670 nm, 75 J/cm2), PDT using a placebo, or conventional treatment (either cryotherapy or topical 5-fluorouracil). The lesion complete response rate at 12 months showed that MAL-PDT was superior to cryotherapy (80% versus 67%; odds ratio 1.77) and also bet- ter than 5-fluorouracil (80% versus 69%; odds ratio 1.64). Cosmesis at follow-up was excellent in 94% of patients treated with MAL-PDT versus 66% with cryotherapy and 76% with 5-fluorouracil. However, lesion recurrence rates at 12 months were similar with MAL-PDT, cryotherapy, and topical 5-fluorouracil (15%, 21%, and 17%, respectively).65 There was also no significant difference in efficacy between MAL-PDT and 5-fluorouracil in the treatment of SCC in situ in immunosuppressed individuals.66 Several studies have looked at varying light sources. An observational study (n=53), using MAL-PDT, occlusion for 3 hours, and red light (630 nm, 38 J/cm2, 7.5 minutes) demonstrated that 76% of the lesions achieved a complete response after two sessions with a medium follow-up of 16.6 months.62 There appears to be no superiority of ALA- PDT with two-fold illumination (light treated at 4 and 6 hours with 20 and 80 J/cm2) versus single illumination (light treated at 4 hours with 75 J/cm2).67,68 There was also no statistically significant difference between ALA-PDT with red light or green light regarding clearance of lesions, but there were significantly fewer recurrences at 12 months of lesions treated with red light. In summary, PDT can be considered for treatment of SCC and SCC in situ when there are multiple lesions, in an area where multiple surgeries would result in morbidity (for example, the lower extremities), or when lesions are known to be noninvasive. For optimal treatment, red light should be utilized. MAL-PDT achieves better penetration and has been shown to be more effective than ALA-PDT. submit your manuscript | www.dovepress.com Dovepress 149PDF Image | applications of photodynamic therapy dermatology
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