Can photodynamic therapy reverse the signs of photoageing and field cancerization?

Abstract

ORIGINAL ARTICLE, 150 Topical photodynamic therapy (PDT) is an effective and now widely approved therapy for actinic keratosis (AK), squamous cell carcinoma (SCC) in situ and certain basal cell carcinomas (BCC).1 As the photosensitizer can be applied to lesional and surrounding skin, with large area LED light sources available, PDT is increasingly used to treat field cancerization, the presence of multiple nonmelanoma skin cancers and precursor lesions including dysplastic keratinocytes in photoexposed sites.2 Several studies, predominantly in organ transplant recipients on long-term immunosuppressants, observed that field PDT can delay and reduce the development of a number of new nonmelanoma skin cancer lesions.3 Although a single treatment was shown to prevent AK, BCC and SCC during a 1-year follow-up study, other studies suggest repeated PDT sessions are necessary, with the current consensus that PDT can prevent AK, and potentially SCC, in transplant recipients.4 The development of multiple AK is also common against a background of severe photodamage in immunocompetent patients. A significant delay in the development of new AK has recently been observed in a split-face, placebo-controlled study of field PDT in photodamaged skin.5 Several clinical studies show that PDT can also improve other aspects of photodamage, with improvement in wrinkles, tactile roughness, sallowness and mottled pigmentation.6 Can PDT therefore achieve reversal of signs of photoageing and field cancerization? Beyond clinical observation, do we have evidence that PDT does anything more than treat emerging as well as visible superficial skin cancers, with a favourable healing profile? A recent study showed the potential for PDT to reduce the histological features of actinic damage and elastosis, and significantly decrease expression of Ki-67 and TP53, although expression of cyclin D1 remained stable following biopsies taken from lesional skin.7 Evidence that a single PDT session was insufficient to clear the early oncogenic markers supports clinical experience that multiple treatments are required to optimize the preventive effect of PDT. In this issue of BJD, Szeimies et al. report on the clinical, histological and immunohistochemical effect of three consecutive monthly treatments with PDT using methyl aminolaevulinate (MAL) on photodamaged skin with multiple AK.8 In addition to clearing 90% of visible AKs, a significant decrease in keratinocyte atypia (following biopsy from clinically normal skin) was reported, in addition to an increase in collagen deposition and improvement in solar elastosis. A decrease in TP53 expression using nonspecific staining was not significant but a smaller change might be anticipated pre- to post-PDT given that clinically normal skin was sampled. We are therefore accumulating evidence that PDT has the potential to reduce the carcinogenic potential in areas of field cancerization and promote improvement in certain aspects of photoageing. More studies please! None declared.