Treatment of post-transplant premalignant skin disease: a randomized intrapatient comparative study of 5-fluorouracil cream and topical photodynamic therapy. Fractionated illumination improves the outcome in the treatment of precancerous lesions with photodynamic therapy. Response of Bowen disease to ALA-PDT using a single and a 2-fold illumination scheme. Comparison of topical methyl aminolevulinate photodynamic therapy with cryotherapy or Fluorouracil for treatment of squamous cell carcinoma in situ: Results of a multicenter randomized trial. Comparison of red and green light in the treatment of Bowen's disease by photodynamic therapy. Comparison of photodynamic therapy with cryotherapy in the treatment of Bowen's disease. Imiquimod 5% cream monotherapy for cutaneous squamous cell carcinoma in situ (Bowen's disease): a randomized, double-blind, placebo-controlled trial. Photodynamic therapy of multiple nonmelanoma skin cancers with verteporfin and red light-emitting diodes: two-year results evaluating tumor response and cosmetic outcomes.
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.
                To compare topical methylaminolaevulinate (MAL) photodynamic therapy (PDT) with topical 5% fluorouracil (5-FU) cream in the treatment of post-transplant epidermal dysplasia.
                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.
                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.
                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. Photodynamic therapy (PDT) is a noninvasive therapy for non-melanoma skin cancer. The aim of this study was comparison of efficacy between fractioned versus single dose illumination in photodynamic therapy (PDT) of actinic keratosis (AK) and Bowen's disease (BD). Fifty-one patients (36 AK and 15 BD) were treated with PDT They were randomly arranged in two treatment groups. Group one included 26 patients (20 AK and 6 BD) that, after five hours of incubation with 20% 5-ALA, were treated with a single illumination of 100 Jcm(-2) at fluence rate of 30 mWcm(-2). Group two included 25 patients (16 AK and 9 BD) that, after 16 hours of incubation with 20% 5-ALA, were treated with two light fractions (50 plus 50 Jcm(-2)) at same fluence rate with dark interval of two hours between fractions. Twenty-four weeks later, a treated area was incubated for four hours again with 5-ALA in order to detect occult areas of abnormal skin with possible remaining tumor tissue. In case of fluorescence, histological examination was performed. In the group one, fluorescence at the end of the session was absent in 19 (73%) or very weak in 7 (27%). Residual tumor was found in 15 (75%) AK and in 4 (66.6%) BD. In the group two, fluorescence at the end of second session was more intense; in one patient (4%) was absent, very weak in 5 (20%) and weak in 19 (76%) of patients. In this group histology revealed remaining tumor tissue in only 2 (12.5%) AK and 2 (22.2%) BD. Among the patients in the first group, the remaining tumor tissue was significantly bigger (p=0.005). The treatment response with clearing of tumor tissue was significantly higher in fractionated illumination than in a single dose illumination group. Fractionated illumination scheme with 16 hours of incubation separated by two hours dark interval significantly improves the therapeutic outcome in tumor eradication. nan To compare the efficacy, tolerability, and cosmetic outcome of photodynamic therapy (PDT) using topical methyl aminolevulinate with cryotherapy or topical fluorouracil for treatment of squamous cell carcinoma in situ.
                Randomized, placebo-controlled study, with follow-up at 3 and 12 months after last treatment.
                Forty outpatient dermatology centers in 11 European countries.
                Random sample of 225 patients with histologically confirmed squamous cell carcinoma in situ (lesion size, 6-40 mm) and no evidence of progression.
                Treatment with PDT with methyl aminolevulinate (160 mg/g; n = 96) or matching placebo cream (n = 17), cryotherapy (n = 82), or topical fluorouracil (5% cream; n = 30). Methyl aminolevulinate or placebo cream was applied for 3 hours before illumination with broadband red light (75 J/cm2, 570-670 nm). Treatment was repeated 1 week later. Cryotherapy was performed with liquid nitrogen spray. Fluorouracil was applied for 4 weeks. Lesions with a partial response at 3 months were re-treated.
                Clinically verified complete response of lesions; blinded and on-site assessment of cosmetic outcome (4-point rating scale).
                At 12 months, the estimated sustained lesion complete response rate with methyl aminolevulinate PDT was superior to that with cryotherapy (80% vs 67%; odds ratio, 1.77; 95% confidence interval, 1.01-3.12; P = .047), and better than that with fluorouracil (80% vs 69%; odds ratio, 1.64; 95% confidence interval, 0.78-3.45; P = .19). Cosmetic outcome at 3 months was good or excellent in 94% of patients treated with methyl aminolevulinate PDT vs 66% with cryotherapy and 76% with fluorouracil, and was maintained at 12 months.
                Methyl aminolevulinate PDT is an effective treatment option for squamous cell carcinoma in situ, with excellent cosmesis. A variety of protocols exist for the treatment of Bowen's disease by photodynamic therapy (PDT) using topical 5-aminolaevulinic acid (5-ALA).
                To determine the optimal wavelength (red or green light) for this treatment.
                A randomized comparison study of ALA-PDT using red (630 +/- 15 nm) or green (540 +/- 15 nm) light in the treatment of Bowen's disease.
                The initial clearance rate for lesions treated by red light was 94% (30 of 32) in comparison with 72% (21 of 29) for those lesions receiving green light (P = 0.002). Over the following 12 months, there were two recurrences in the red light group and seven in the green light group reducing the clearance rates to 88% and 48%, respectively. The frequency and severity of pain experienced were similar between the two treatment groups. No hyperthermia, nor significant difference in lesional temperatures, was observed between the wavelengths studied.
                Green light is less effective than red light, at a theoretically equivalent dose, in the treatment of Bowen's disease by topical ALA-PDT. The efficacy and suitability of photodynamic therapy (PDT) was compared with that of cryotherapy in the treatment of 40 lesions of Bowen's disease. Lesions were randomized to receive either cryotherapy with liquid nitrogen, or PDT using a portable desktop lamp incorporating a 300 W xenon short arc discharge source. A porphyrin precursor, 5-aminolaevulinic acid (5-ALA), was applied topically 4 h before irradiation in the PDT group. Each lesion received 125 J/cm2 at a fluence rate of 70 mW/cm2. All patients were reviewed at 2-monthly intervals and treatments repeated if required. Cryotherapy produced clearance in 10 of 20 lesions after one treatment, the remaining 10 lesions requiring two or three treatment applications. PDT resulted in clearance of 15 of 20 lesions after one treatment and of the remaining five lesions after a second treatment. The probability that a lesion cleared after one treatment was greater with PDT than cryotherapy (P < 0.01). Cryotherapy was associated with ulceration (five of 20), infection (two of 20) and recurrent disease (two of 20); no such complications occurred following PDT. PDT using a non-laser light source and topical 5-ALA appears to be at least as effective as cryotherapy in the treatment of Bowen's disease with fewer adverse effects. We conducted a double-blind, placebo-controlled, randomized trial to evaluate the preliminary efficacy and safety of imiquimod 5% cream treatment for cutaneous squamous cell carcinoma (SCC) in situ.
                In all, 31 patients with biopsy-proven cutaneous SCC in situ were randomly assigned to placebo (vehicle) (n = 16) or imiquimod 5% cream (n = 15) daily for 16 weeks. Patients were assessed at week 28 for the primary end point, resolution of cutaneous SCC in situ.
                Of the 31 patients enrolled, 3 dropped out. Intention-to-treat analysis revealed 11 of the 15 patients (73%) in the imiquimod group achieved resolution of cutaneous SCC in situ, with no relapse during the 9-month follow-up period; none in the placebo group achieved resolution (P < .001). Imiquimod 5% cream was generally well tolerated and there were no serious adverse events.
                Topical imiquimod 5% cream has proven to be an effective treatment for cutaneous SCC in situ. However, studies to define the ideal dosing regimen and cost-effectiveness are required before it can be accepted as a recognized therapy.
                In this controlled trial, patients with cutaneous SCC in situ receiving topical imiquimod 5% cream as monotherapy experienced a high degree of clinical benefit compared with placebo. Efficient treatment of patients with multiple synchronous nonmelanoma skin cancers represents a therapeutic challenge.
                To study the safety and efficacy of photodynamic therapy (PDT) with verteporfin and red light in the treatment of multiple nonmelanoma skin cancers.
                Open-label, randomized, multicenter, dose-ranging phase 2 study conducted at 4 North American university-based dermatology clinics.
                Fifty-four patients with 421 multiple nonmelanoma skin cancers including superficial and nodular basal cell carcinoma and squamous cell carcinoma in situ (Bowen disease).
                A single intravenous infusion of 14 mg/m(2) of verteporfin followed 1 to 3 hours later by exposure of tumors to 60, 120, or 180 J/cm(2) of red light (688 +/- 10 nm) from a light-emitting diode panel.
                Pathologic response of treated sites was assessed at 6 months. Clinical and cosmetic responses were assessed and graded at 6 weeks, 3 months, and 6 months after verteporfin PDT, with optional follow-up visits at 12, 18, and 24 months.
                The histopathologic response, defined as absence of tumor on biopsy specimens 6 months after verteporfin PDT, ranged from 69% at 60 J/cm(2) to 93% at 180 J/cm(2). At 24 months of follow-up (276 tumors in 31 patients), the clinical complete response rate ranged from 51% at 60 J/cm(2) to 95% at 180 J/cm(2). No significant systemic adverse events were observed; most events occurred at the treated tumor sites and included events such as pain. Overall, 65% (95% confidence interval, 58%-71%) of tumors were judged to have good to excellent cosmesis at 24 months.
                A single course of verteporfin PDT showed treatment benefit for patients with multiple nonmelanoma skin cancers.
Overall, there has been very little good-quality research on treatments for Bowen's disease. There is limited evidence from single studies to suggest MAL-PDT is an effective treatment. Although cosmetic outcomes appear favourable with PDT, five-year follow-up data are needed. Significantly more lesions cleared with MAL-PDT compared to cryotherapy. No significant difference in clearance was seen when MAL-PDT was compared with 5-FU, but one study found a significant difference in clearance in favour of ALA-PDT when compared to 5-FU. There was no significant difference in clearance when cryotherapy was compared to 5-FU.
The lack of quality data for surgery and topical cream therapies has limited the scope of this review to one largely about PDT studies. The age group, number, and size of lesions and site(s) affected may all influence therapeutic choice; however, there was not enough evidence available to provide guidance on this. More studies are required in the immunosuppressed populations as different therapeutic options may be preferable. Specific recommendations cannot be made from the data in this review, so we cannot give firm conclusions about the comparative effectiveness of treatments.