Long-term follow-up and histological changes of superficial nonmelanoma skin cancers treated with topical δ-aminolevulinic acid photodynamic therapy

Objective: To investigate the immediate and longterm effects of photodynamic therapy with delta-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% delta-aminolevulinic acid was topically applied under an occlusive and light-shielding dressing before exposure to either UV-A or different wave bands of polychromatic visible light (full-spectrum visible light, >515, >570, or >610 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 statistically 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 (P<.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 (P<.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 AW-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.