Treatment of post-transplant premalignant skin disease: a randomized intrapatient comparative study of 5-fluorouracil cream and topical photodynamic therapy

Abstract

Background: Organ transplant recipients (OTR) are at high risk of developing nonmelanoma skin cancer and premalignant epidermal dysplasia (carcinoma in situ/ Bowen's disease and actinic keratoses). Epidermal dysplasia is often widespread and there are few comparative studies of available treatments.

Objectives: To compare topical methylaminolaevulinate (MAL) photodynamic therapy (PDT) with topical 5% fluorouracil (5-FU) cream in the treatment of post-transplant epidermal dysplasia.

Methods: Eight OTRs with epidermal dysplasia were recruited to an open-label, single-centre, randomized, intrapatient comparative study. Treatment with two cycles of topical MAL PDT 1 week apart was randomly assigned to one area of epidermal dysplasia, and 5-FU cream was applied twice daily for 3 weeks to a clinically and histologically comparable area. Patients were reviewed at 1, 3 and 6 months after treatment. The main outcome measures were complete resolution rate (CRR), overall reduction in lesional area, treatment-associated pain and erythema, cosmetic outcome and global patient preference.

Results: At all time points evaluated after completion of treatment, PDT was more effective than 5-FU in achieving complete resolution: eight of nine lesional areas cleared with PDT (CRR 89%, 95% CI: 0.52-0.99), compared with one of nine lesional areas treated with 5-FU (CRR 11%, 95% CI: 0.003-0.48) (P = 0.02). The mean lesional area reduction was also proportionately greater with PDT than with 5-FU (100% vs. 79% respectively). Cosmetic outcome and patient preference were also superior in the PDT-treated group.

Conclusions: Compared with topical 5-FU, MAL PDT was a more effective and cosmetically acceptable treatment for epidermal dysplasia in OTRs and was preferred by patients. Further studies are now required to confirm these results and to examine the effect of treating epidermal dysplasia with PDT on subsequent development of squamous cell carcinoma in this high risk population.

Fig 1

Complete resolution rate (CRR) for topical photodynamic therapy (PDT) and topical 5-fluorouracil (5-FU) at 1, 3 and 6 months of follow up.

Fig 2

(a) Actinic keratoses on dorsum of left hand prior to treatment with 5-fluorouracil cream. (b) Complete resolution of actinic keratoses at 6 months following treatment.

Fig 3

Mean lesional area before and 6 months after treatment with 5-fluorouracil (5FU) and photodynamic therapy (PDT).

Fig 4

Carcinoma in situ (a) before and (b) 6 months after topical treatment with photodynamic therapy with methylaminolaevulinate.

Fig 5

Overall cosmetic outcome following treatment with photodynamic therapy (PDT) vs. 5-fluorouracil (5-FU).

Fig 6

Mean daily pain scores for lesions treated with topical photodynamic therapy (PDT, dashed line) and 5-fluorouracil (5FU, solid line) based on a four-point visual analogue scale (0-3).

Fig 7

Mean daily erythema scores for lesions treated with topical photodynamic therapy (PDT, dashed line) and 5-fluorouracil (5FU, solid line) based on a four-point visual analogue scale (0-3).