NICE (IPG 155) supports the use of PDT for superficial basal cell carcinoma but does not make recommendations for alternative topical treatment options. In their 2008 guidance, the British Association of Dermatologists recommends PDT and topical imiquimod (amongst other treatment options) for the treatment of primary small superficial basal cell carcinoma. The guidance did not address the use of topical fluorouracil.
This single blind, non-inferiority, randomised controlled multicentre trial assessed the effectiveness of the alternative treatment options, imiquimod and fluorouracil cream, versus PDT in Dutch patients with histologically proven superficial basal-cell carcinoma.
Patients were randomised to PDT (two sessions with an interval of 1 week; N=202), imiquimod cream (once daily, five times a week for 6 weeks; N=198), or fluorouracil cream (twice daily for 4 weeks; N=201). The proportion of patients tumour-free at both 3 and 12 month follow-up (primary endpoint) was 72•8% (95% CI 66•8—79•4) for PDT, 83•4% (78•2—88•9) for imiquimod cream, and 80•1% (74•7—85•9) for fluorouracil cream. The difference between imiquimod and PDT was 10•6% (95% CI 1•5—19•5; p=0•021) and 7•3% (—1•9 to 16•5; p=0•120) between fluorouracil and PDT, and between fluorouracil and imiquimod was −3•3% (—11•6 to 5•0; p=0•435.
Patients treated with PDT, reported moderate to severe pain and burning sensation most often during the actual session. Local skin redness was most often reported as moderate or severe in all treatment groups. Patients treated with creams more often reported moderate to severe local swelling, erosion, crust formation, and itching of the skin than patients treated with PDT. In the PDT group no serious adverse events were reported. One patient treated with imiquimod and two patients treated with fluorouracil developed a local wound infection and needed additional treatment in the outpatient setting.
Overall the authors concluded that topical fluorouracil was non-inferior to imiquimod and both were superior to PDT for treatment of superficial basal-cell carcinoma. However they note that consideration of other aspects that have effect on selection of therapy, such as aesthetic outcome, compliance, and adverse reaction, could necessitate alternative treatment in individual patients.
A supporting commentary notes that the study was well designed and adequately powered. However, limitations include the short follow up, no histological confirmation of cure; and the study did not investigate cryosurgery, which may be viewed as another cost-effective treatment option.