5-aminolevulinic acid photodynamic therapy for the treatment of basal and squamous cell carcinoma: A systematic review

• Efficacy and safety of ALA-PDT was systematically reviewed for BCC, SCC, and BD. • Fifty-eight studies were assessed, including 40 for BCC, 9 for SCC, and 27 for BD. • ALA-PDT achieves favorable outcomes with high clearance rates and good cosmetics. • Response rates vary by lesion type, with relatively high recurrence rates for SCC. • Further trials are needed to optimize ALA-PDT protocols for the management of NMSC. 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is used off-label in the US to treat basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and Bowen disease (BD). We performed a systematic review to assess the efficacy and safety of published ALA-PDT protocols for these conditions. A PubMed search was conducted through August 8, 2024, to identify studies evaluating 10% or 20% ALA-PDT in BCC, SCC, and BD. Randomized controlled trials, observational studies, and case series with >5 patients were included. Quality assessment was performed using the Grading of Recommendations Assessment, Development, and Evaluation approach. Fifty-eight studies were included in the analysis (BCC, n = 40; SCC, n = 9, BD, n = 27). Considerable heterogeneity was observed in ALA concentration, light sources, incubation times, and pretreatment strategies, precluding a standardized synthesis of outcomes. ALA-PDT achieved high clearance rates for superficial BCC and BD, with superior cosmetic outcomes compared to surgery or cryosurgery. Studies of ALA-PDT for SCC were limited with short follow-up times. Nodular BCC and SCC lesions demonstrated lower response rates, particularly with ALA-PDT monotherapy. Recurrence rates varied widely and were highest in patients with SCC. The most frequent adverse events were erythema, pain, and scaling. This review provides a comprehensive summary of evidence-based ALA-PDT protocols for BCC, BD, and SCC, but published protocols are heterogeneous without a clear consensus. While ALA-PDT is effective, safe, and cosmetically favorable for less invasive tumors, protocol variability underscores the need for further randomized controlled trials to determine optimal treatment parameters.