Conventional and Combination Topical Photodynamic Therapy for Basal Cell Carcinoma

Systematic Review and Meta-analysis

N.J. Collier; A.K. Haylett; T.H. Wong; C.A. Morton; S.H. Ibbotson; K.E. McKenna; R. Mallipeddi; H. Moseley; D. Seukeran; K.A. Ward; M.F. Mohd Mustapa; L.S. Exton; A.C. Green; L.E. Rhodes

Disclosures

The British Journal of Dermatology. 2018;179(6):1277-1296. 

In This Article

Abstract and Introduction

Abstract

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.

Introduction

Basal cell carcinoma (BCC) is the most common cancer worldwide, with reported incidence increasing.[1] BCCs form a substantial and growing proportion of a dermatologist's workload and are a large burden to Western health services.[2] An effective treatment armamentarium is required, alongside prevention strategies. This systematic review examines randomized controlled trials (RCTs) comparing conventional topical photodynamic therapy (PDT) with alternative treatments, including fractionated PDT and combination regimens.

Mortality from BCC is low and BCCs almost never metastasize. However, advanced tumours cause considerable morbidity through local tissue destruction, leading to disfigurement and functional compromise.[3] The risk of morbidity depends on tumour location and subtype. The majority of BCCs are low risk, i.e. less aggressive subtypes, superficial BCC (sBCC) and nodular BCC (nBCC), located in anatomical areas that allow uncomplicated resection without substantially impairing function or cosmesis.[4]

Surgical excision allows unparalleled cure rates, but the cosmetic outcome depends on BCC size and location, reconstruction method and expertise.[4–6] One of several nonsurgical treatments available for nBCC and sBCC is topical PDT with 5-aminolaevulinic acid (ALA) or methyl aminolaevulinate (MAL).[7–9] The licensed MAL-PDT protocol uses a cycle of two treatments, 1 week apart, with outcome reviewed at 3 months, where it is usual practice to re-treat partially responding lesions.[10] High clearance rate (although lower for nBCC than sBCC), excellent cosmesis and a low adverse event (AE) rate are reported.[9]

The objective of this systematic review and meta-analysis of RCTs was to evaluate PDT as a treatment for BCC. Treatment choice is based not only on efficacy, but also tailored to patients' preferences with respect to cosmesis and AEs.[11,12] This review aims to provide clinicians with comprehensive, up-to-date evidence regarding these outcomes from a review of all available published RCTs of PDT and comparator topical, surgical and combination treatments for low-risk BCC. A further purpose of this work was to inform the development of the updated British Association of Dermatologists and British Photodermatology Group guidelines for topical PDT (2018).

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