Treatment of superficial basal cell carcinoma by topical photodynamic therapy with fractionated 5-aminolaevulinic acid 20% vs. two-stage topical methyl aminolaevulinate: results of a randomized controlled trial.

BACKGROUND: Basal cell carcinoma (BCC) is the most common type of skin cancer and incidence rates are increasing. Photodynamic therapy (PDT) is a frequently used treatment, especially for superficial BCC (sBCC). Two topical photosensitizing agents are currently used to treat sBCC, namely 5-aminolaevulinic acid (ALA) and its ester, methyl aminolaevulinate (MAL). Previous research showed a high efficacy for ALA-PDT using a twofold fractionated illumination scheme in which two light fractions of 20 J cm-2 and 80 J cm-2 were delivered 4 h and 6 h after ALA application. OBJECTIVES: To evaluate whether twofold ALA-PDT is superior to conventional MAL-PDT for sBCC. METHODS: We performed a single-blind, randomized, multicentre trial in the Netherlands. RESULTS: Overall, 162 patients were randomized either to conventional MAL-PDT or twofold ALA-PDT. After 12 months, a total of six treatment failures occurred following ALA-PDT and 13 treatment failures occurred following MAL-PDT. The 12-month cumulative probability of remaining free from treatment failure was 92·3% [95% confidence interval (CI) (83·7-96·5)] for ALA-PDT and 83·4% (95% CI 73·1-90·0) for MAL-PDT (P = 0·091). CONCLUSIONS: The twofold ALA-PDT scheme resulted in fewer recurrences, although the difference between both treatment groups was not statistically significant. However, ALA-PDT resulted in higher pain scores and more post-treatment side-effects compared with MAL-PDT.

Photodynamic therapy vs. topical imiquimod for treatment of superficial basal cell carcinoma: a subgroup analysis within a noninferiority randomized controlled trial.

BACKGROUND: A recent noninferiority randomized controlled trial (RCT) indicated that imiquimod can be considered as superior to methylaminolevulinate photodynamic therapy (MAL-PDT) in the treatment of superficial basal cell carcinoma (sBCC). Knowledge of treatment effectiveness in subgroups of patients is of great value in clinical practice to select the most effective treatment for an individual patient with sBCC. OBJECTIVES: To explore whether the relative treatment effect of MAL-PDT and imiquimod is consistent across subgroups defined by patient and tumour characteristics. METHODS: Data were derived from a single-blinded, noninferiority, multicentre RCT comparing MAL-PDT, topical imiquimod and fluorouracil (ISRCTN79701845). Treatment success was defined as free of tumour recurrence at 12-month follow-up. Subgroup analyses were performed for subgroups defined by sex, age, tumour location and tumour size. RESULTS: Two hundred and two patients received MAL-PDT and 198 received imiquimod. The superiority of imiquimod vs. MAL-PDT was observed in subgroups of females, sBCC on the trunk and large tumours with risk differences in favour of imiquimod of 18·4% [95% confidence interval (CI) 7·8-29·0%], 21·0% (95% CI 10·9-31·1%) and 18·9% (95% CI 7·1-30·7%), respectively. Higher probability of treatment success for imiquimod vs. MAL-PDT was consistently found in all other subgroups with the exception of sBCC localized on the lower extremities in older patients. In the latter subgroup, the risk difference at the expense of imiquimod was -57·3% (95% CI -81·7% to -32·9%). CONCLUSIONS: Imiquimod remains the first-choice treatment for sBCC in terms of effectiveness. In older patients with sBCC on the lower extremities MAL-PDT might be preferred. Results should be interpreted carefully as subgroup analyses were exploratory and not driven by prior hypotheses.

Agreement between histological subtype on punch biopsy and surgical excision in primary basal cell carcinoma.

BACKGROUND: Diagnosis of clinically suspected basal cell carcinoma (BCC) by histological confirmation with punch biopsy has been recommended before treatment. Even shave biopsy has been proposed as useful to predict the correct subtype in primary BCC in 76-81%, whereas the agreement between histological BCC subtype on punch biopsy and subsequent excision specimens in recurrent BCC is 67.1%. However, no large studies on the agreement between histological BCC subtype seen on punch biopsy and the following surgical excision are performed in primary BCC. OBJECTIVE: The aims of this study were (i) to establish the agreement between histological BCC subtype on punch biopsy and the subsequent surgical excision of primary BCC and; (ii) to investigate the proportion of primary BCCs in which punch biopsy enables identification of the most aggressive growth pattern. METHODS: Retrospective analyses of 243 primary BCCs with both punch biopsy and subsequent surgical excision. Analyses were based on the most aggressive histological subtype of the tumour. RESULTS: The agreement between BCC subtype on punch biopsy and the subsequent surgical excision of primary BCCs was 60.9%. A punch biopsy can predict the most aggressive growth pattern of primary BCCs in 84.4%. Seventy-four percentage of all primary BCCs consisted of more than one histological subtype. CONCLUSION: Dermatologists and other physicians have to be aware of the limited diagnostic value of a punch biopsy to determine the histological BCC subtype of the whole lesion. Misdiagnosis of the subtype will lead to undertreatment in one of six primary BCCs.

Overall treatment success after treatment of primary superficial basal cell carcinoma: a systematic review and meta-analysis of randomized and nonrandomized trials.

BACKGROUND: Several noninvasive treatment modalities are available for superficial basal cell carcinoma (sBCC). OBJECTIVES: This systematic review aims to determine residue, recurrence and tumour-free survival probabilities of patients with primary sBCC treated with the currently most frequently used therapies. METHODS: The PubMed (January 1946 to October 2010), EMBASE (January 1989 to October 2010) and Cochrane (January 1993 to October 2010) databases, and reference lists were searched without date restriction. Inclusion criteria were studies that included primary, histologically proven sBCCs, that reported on residue and/or recurrence probabilities after treatment, and had a minimum follow-up period of 12 weeks. Both randomized and nonrandomized studies were included. The primary and secondary outcomes were the probability of complete response and tumour-free survival, respectively. Two independent reviewers selected 36 studies (14 randomized and 22 nonrandomized), and extracted residue, cumulative recurrence and tumour-free survival probabilities. RESULTS: Pooled estimates of percentages of sBCC with complete response at 12 weeks post-treatment, derived from 28 studies, were 86.2% [95% confidence interval (CI) 82-90%] for imiquimod treatment, and 79.0% (95% CI 71-87%) for photodynamic therapy (PDT). With respect to tumour-free survival at 1 year, the pooled estimates derived from 23 studies were 87.3% for imiquimod (95% CI 84-91%) and 84.0% for PDT (95% CI 78-90%). Only a small number of studies reported on the results of sBCC treatment with 5-fluorouracil (one), surgical excision (one) and cryotherapy (two). CONCLUSIONS: Pooled estimates from randomized and nonrandomized studies showed similar tumour-free survival at 1 year for imiquimod and PDT. The PDT tumour-free survival was higher in studies with repeated treatments. However, these results were largely derived from nonrandomized studies, and randomized studies with head-to-head comparison of imiquimod and PDT are lacking. There is a need for head-to-head comparison studies between PDT, imiquimod and other treatments with long-term follow-up to enable better recommendations for optimal sBCC treatment.