Photodynamic therapy using aminolaevulinic acid for patients with nonhyperkeratotic actinic keratoses of the face and scalp: phase IV multicentre clinical trial with 12-month follow up.

BACKGROUND: Actinic keratoses (AKs) are the most common epithelial precancerous lesions, especially among individuals with light complexions. AKs are believed to progress to in situ squamous cell carcinoma (SCC) and potentially, to invasive SCC. AKs and invasive SCCs share certain histopathological features and both share genetic tumour markers and p53 mutations. Given these facts, the treatment and management of AKs are integral components to quality dermatological health care.
OBJECTIVES: Topical aminolaevulinic acid-based photodynamic therapy (ALA-PDT) has been extensively studied over the last several years. This study seeks to characterize further the efficacy and safety of ALA-PDT by extending previous work to: (i) assess the long-term recurrence rate of AKs that have resolved after ALA-PDT; (ii) to characterize the histopathology of treated AK lesions that do not completely respond to ALA-PDT or recur in long-term follow up; (iii) to characterize the histopathology of untreated clinically diagnosed AK lesions in the study population at baseline; and (iv) to evaluate ALA-PDT in darker skin types than previously studied.
METHODS: Patients enrolled in this study had six to 12 discrete AK lesions, either on the face or the scalp. Individual AK lesions designated for treatment were graded as either grade 1 (lesions slightly palpable and more easily felt than seen) or grade 2 (moderately thick AKs, easily seen and felt). Patients with grade 3 (very thick and/or hyperkeratotic) lesions were excluded. For each subject, two lesions at baseline were randomized to biopsy, and were not followed as part of the study while the remaining lesions (target lesions) were treated with ALA-PDT (baseline and month 2, if required) and followed for 12 months.
RESULTS: Of the 110 patients enrolled, 101 completed the study. The target AK lesions in the per-protocol population clearing completely in the first and second months following a single ALA-PDT treatment (baseline) were 76% and 72%, respectively. Sixty per cent of the patients received a second ALA-PDT treatment, limited to the target AKs still present at month 2. The percentage of treated target lesions that cleared completely peaked at 86% at month 4 then decreased gradually over time to 78% at month 12. The overall recurrence rate for all lesions that were noted to be cleared at some visit during the 12-month period was 24% (162/688). Of the 162 recurrent lesions 16 were lost to follow up, seven spontaneously cleared and 139 were biopsied. With respect to the lesions biopsied, 91% (127/139) were diagnosed histopathologically as AK, with the balance of lesions being SCC (nine of 139: 7%), basal cell carcinoma (one of 139: 0.7%) and other non-AK diagnoses (two of 139: 1%). The recurrence rate for histologically confirmed AKs was 19%. The clinical diagnosis of AK by investigators appeared to be accurate, with 91% (200/220) of the untreated clinically diagnosed AK lesions being histopathologically confirmed to be AK (AK, 142/220: 65%; advanced AK, 29/220: 13%; macular AK, 29/220: 13%). Despite concentrated efforts to recruit patients with Fitzpatrick skin types IV-VI, the distribution was as follows: I, 11%; II, 36%; III, 41%; IV, 11%; V, 2%. The demographics of this study population are typical of a patient population with AK.
CONCLUSIONS: ALA-PDT was shown to be an effective and safe therapy for the treatment of AKs of the face and scalp in skin types I-V, with an acceptable rate of recurrence over 12 months of histologically confirmed AKs of 19%. Phototoxicity reactions were all expected, nonserious and had essentially resolved after 1 month post-treatment independent of skin type.

RCT Entities:   Population Interventions Outcomes