Long-term Follow-up and Histological Changes of Superficial Nonmelanoma Skin Cancers Treated With Topical δ-Aminolevulinic Acid Photodynamic Therapy

Abstract

To investigate the immediate and longterm effects of photodynamic therapy with ␦-aminolevulinic acid (ALA-PDT) on superficial basal cell carcinomas (BCC) and superficial squamous cell carcinomas (SCC).Design: Retrospective study with 60 months of maximal follow-up.Setting: University-based hospital in Graz, Austria.Patients: Forty-seven subjects with a total of 95 superficial BCC and 35 superficial SCC.Interventions: A compound of 20% ␦-aminolevulinic acid was topically applied under an occlusive and lightshielding dressing before exposure to either UV-A or different wave bands of polychromatic visible light (fullspectrum visible light, Ͼ515, Ͼ570, or Ͼ610 nm).Main Outcome Measures: Primary tumor responses and recurrence rates in the long-term follow-up, as well as histological changes associated with ALA-PDT, were studied.Results: The complete primary response rate for all wave bands of light was 86% (82/95) for superficial BCC and 54% (19/35) for superficial SCC. There was no statisti-cally significant difference among the response rates to the different wave bands of light. After a median follow-up of 19 months (range, 3-60 months) for BCC and 8 months (range, 3-47 months) for SCC, the overall recurrence rate was 44% (36/81) and 69% (11/16), respectively. At 36 months after therapy, the projected disease-free rate was 50% (95% confidence interval, 43%-57%) for BCC vs 8% (95% confidence interval, 7%-9%) for SCC (PϽ.001, log-rank test). Histopathologic studies revealed a significant increase of fibrosis in the dermis after ALA-PDT and appearance of a sharp border between fibrotic and nonfibrotic tissue. In 15 of 16 BCC examined, the border between fibrotic and nonfibrotic tissue was deeper in the dermis than the maximum tumor thickness before therapy (PϽ.001, Wilcoxon signed rank test). Similar histopathologic observations were made in SCC. Conclusions:Our study revealed poor long-term cure rates for superficial BCC and SCC treated with topical ALA-PDT and visible light. The histopathologic observations showing remarkable fibrosis in the dermis indicated that the effect of ALA-PDT reached deeper than the initial depth of invasiveness of the neoplastic tissue, suggesting in turn that the poor long-term results of ALA-PDT cannot be explained by insufficient penetration of the therapy effect.

A programme of research to set priorities and reduce uncertainties for the prevention and treatment of skin disease

“…By year 3, 74% of areas were graded as having good appearance and the remainder were acceptable. Fink-Puches 1998 623 Kübler 1999 632 Baptista 2006 Most of the observed effects in this study occurred in the first few days post radiation, most commonly reactive hyperaemia, oedema and slight soreness which were mild in severity and transient. No systemic adverse events were noted.…”

“…There were 14 small prospective studies (comprising 297 patients) which evaluated the response of SCCs to photodynamic therapy [619][620][621][622][623][624][625][626][627][628][629][630][631][632] (see Appendix 13). Three studies separated SCCs according to level or depth of invasion 619,622,625 and one was a non-randomised two-arm comparison of topical photodynamic therapy either with or without a 5% glycolic acid penetration enhancer.…”

“…620,622,629,631,632 In eight of the included studies, SCCs that had apparently completely responded to photodynamic therapy initially were observed for recurrence. [621][622][623]625,[629][630][631][632] Pooled recurrence data from these studies (119 SCCs) gave an odds of recurrence of 26.4% (95% CI 12.3% to 43.7%; I 2 = 72%) ( Figure 48). The results are summarised in Appendix 13.…”

“…621 Separate SCC data for adverse events were not available from the included studies. Fink-Puches 1998 623 Lui 1995 620 Harth 1998 628 Fritsch 1998 …”

Basal Cell Carcinoma

“…In addition to damaging target cells directly, PDT, through upregulated cytokine production, enhances the innate and adaptive immune responses in immunocompetent individuals (Oseroff, 2006). In a study of 95 patients with sBCC, the primary response rate with ALA PDT was 86%, with a 44% recurrence rate after a median follow up of 19 months and a projected diseasefree rate of only 50% (Fink-Puches et al, 1998). In a long-term study of 350 sBCC and nBCC lesions treated with methyl 5-ALA PDT, 89% of lesions cleared with an overall cure rate of 79% after a mean follow-up of 35 months (Soler et al, 2001).…”