A European multicentre randomised prospective study compared MAL-PDT and cryosurgery for AK. A total of 193 patients with 699 lesions received either a single treatment with MAL-PDT (repeated after 1 week in 8 % of cases) or a double freeze-thaw course of liquid nitrogen cryosurgery. The overall complete response (CR) rates after 3 months were not significantly different: 69 % with MAL-PDT and 75 % with cryosurgery. However, the cosmetic outcomes were deemed excellent (no scarring or hypopigmentation) in 96 % of patients treated with MAL-PDT and in 81 % of those treated with cryosurgery, and the difference was statistically significant [7].

A higher overall complete response rate after 3 months was observed with MAL-PDT (91 %) in 204 Australian patients who received another treatment session after 1 week (Table 25.1). CRs with a single treatment session of cryosurgery (68 %) and placebo (30 %) were significantly lower. Cosmetic outcome was rated excellent in 81 % of MAL-PDT patients versus 51 % of patients treated with cryosurgery [11].

Similar results (89 % CR) were found in 80 American AK patients treated with two sessions of MAL-PDT in a multicentre, randomised, double-blind, placebo-controlled study. The cosmetic outcome was scored good to excellent in more than 90 % of patients [12].

In an open prospective study, 211 patients with 413 thin to moderately thick AKs were randomised to undergo either a single treatment with MAL-PDT (regimen I; n  =  105) or 2 treatments at weekly intervals (regimen II; n  =  106). Thirty-seven lesions (19 %) showing an incomplete response 3 months after a single treatment were retreated. All patients were followed up 3 months after the last treatment. The complete response rate for thin lesions after a single treatment was 93 %, which was similar to 89 % after repeated treatment. Response rates were lower for thicker lesions: 70 % versus 84 %, respectively. However, the overall response rate in patients randomised for the single treatment improved after the second treatment: 88 %. The conclusion of this study was that a single MAL-PDT session is effective for thin AK and repeated treatments are recommended for thicker or non-responding lesions [13].

In a randomised multicentre trial using a side-by-side design, 119 patients with 1,501 lesions were treated with MAL-PDT or cryotherapy [14]. Twenty-four weeks after treatment, no significant difference of complete remission rates (MAL-PDT, 89.1 %; cryotherapy, 86.1 %) was seen but patients had a significant better cosmetic result with PDT.

Transplant patients have an increased propensity to develop multiple AKs and an increased transformation rate into invasive squamous cell carcinoma (SCC). Seventeen transplant recipients with a total number of 129 mild to moderate AKs were enrolled in a prospective, randomised, double-blind, placebo-controlled study. Two lesional areas of a patient were randomised for MAL-PDT or placebo cream plus light exposure. MAL-PDT cleared lesional areas in 13 of 17 patients, whereas placebo did not improve treated areas [15]. In an open trial from the same group, 20 transplant recipients and 20 controls with AK or BD underwent either a single or two consecutive treatments of 20 % ALA-PDT [16] and showed similar cure rates after 4 weeks. However, the rates were significantly lower in immunosuppressed patients after 12 and 48 weeks [15, 16]. Table 25.1 summarises the results obtained in the aforementioned studies.

A few multicentre, randomised, prospective and controlled studies of MAL-PDT of both superficial and nodular BCC have been done in the USA, Australia and Europe (Table 25.2). In 59 patients with 350 superficial (thickness <2 mm) BCCs, the complete-clearance response rate was 89 % after 3 months and 79 % after a follow-up of 24–48 months (median, 35 months). Cosmetic outcome was reported as excellent or good in 98 % of cases [17].