Conventional and combination topical photodynamic therapy for basal cell carcinoma:systematic review and meta-analysis

Background: Topical photodynamic therapy (PDT) is an established treatment option for low-risk basal cell carcinoma (BCC).Objectives: To compare efficacy, cosmesis and tolerability of PDT for BCC with alternative treatments.Methods: MEDLINE, PubMed, Embase and CENTRAL databases were searched from inception until 1 September 2017. Included studies were randomized controlled trials (RCTs) of PDT for nodular (n) and superficial (s) BCC reporting at least one of the following outcomes: clearance at 3 months and sustained at 1 or 5 years; recurrence at ≥ 1 year; cosmesis; adverse events; tolerability.Results: From 2331 search results, 15 RCTs (2327 patients; 3509 BCCs) were included. PDT efficacy (5-year sustained clearance) was high but inferior to excisional surgery [nBCC pooled risk ratio (RR) 0·76; 95% confidence interval (CI) 0·63–0·91], and without re-treatment of partially responding lesions, was modestly inferior to imiquimod (sBCC: RR 0·81; 95% CI 0·70–0·95) and similar to fluorouracil (sBCC: RR 0·88; 95% CI 0·75–1·04). Five-year sustained clearance was inferior with conventional vs. fractionated PDT (sBCC: RR 0·76; 95% CI 0·68–0·84). PDT cosmesis was superior to surgery (sBCC: RR 1·68, 95% CI 1·32–2·14; nBCC: RR 1·82, 95% CI 1·19–2·80) and cryosurgery (BCC: RR 3·73, 95% CI 1·96–7·07), and without re-treatment of partially responding lesions was similar to imiquimod (sBCC: RR 1·01, 95% CI 0·85–1·19) and fluorouracil (sBCC: RR 1·04, 95% CI 0·88–1·24). Peak pain was higher but of shorter duration with PDT than topical treatments. Serious adverse reactions were rarer with PDT than imiquimod (sBCC: RR 0·05, 95% CI 0·00–0·84) and fluorouracil (sBCC: RR 0·11, 95% CI 0·01–2·04). Combination PDT regimens demonstrated reduced recurrence and improved cosmesis; however, results from these small studies were often nonsignificant.Conclusions: PDT is an effective treatment for low-risk BCC, with excellent cosmesis and safety. Imiquimod has higher efficacy than single-cycle PDT but more adverse effects. Highest efficacy is with excisional surgery. Fractionated and combination PDT options warrant further study.