Interventions for cutaneous Bowen's disease
Bowen's disease is the clinical term for in situ squamous cell carcinoma of the skin. Cutaneous lesions present as largely asymptomatic, well‐defined, scaly erythematous patches on sun‐exposed skin. In general, people with Bowen's disease have an excellent prognosis because the disease is typically slow‐growing and responds favourably to treatment. Lesions are persistent and can be progressive, with a small potential (estimated to be 3%) to develop into invasive squamous cell carcinoma. The relative effectiveness of the available treatments is not known for Bowen's disease, and this review attempts to address which is the most effective intervention, with the least side‐effects, for cutaneous Bowen's disease.
To assess the effects of therapeutic interventions for cutaneous Bowen's disease.
We searched the following databases up to September 2012: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2012, Issue 9), MEDLINE (from 1946), EMBASE (from 1974), PsycINFO (from 1806), and LILACS (from 1982). We also searched online trials registers. We checked the bibliographies of included and excluded studies and reviews, for further references to relevant randomised controlled trials (RCTs).
We included all randomised controlled trials assessing interventions used in Bowen's disease, preferably histologically proven.
Data collection and analysis
Two authors independently carried out study selection and assessment of methodological quality.
The primary outcome measures were complete clearance of lesions after the first treatment cycle and recurrence rate at 12 months. Our secondary outcomes included the number of lesions that cleared after each treatment cycle, the number of treatment cycles needed to achieve clearance, the recurrence rates at > 12 months, cosmetic outcome, quality of life assessment, and adverse outcomes as reported by both participant and clinician.
We included 9 studies, with a total of 363 participants. One study demonstrated statistically significantly greater clearance of lesions of Bowen's disease with MAL‐PDT (methyl aminolevulinate with photodynamic therapy) when compared with placebo‐PDT (RR (risk ratio) 1.68, 95% CI (confidence interval) 1.12 to 2.52; n = 148) or cryotherapy (RR 1.17, 95% CI 1.01 to 1.37; n = 215), but there was no significant difference when MAL‐PDT was compared to 5‐FU (5‐fluorouracil). One study demonstrated statistically significantly greater clearance of lesions with ALA‐PDT (5‐aminolevulinic acid with photodynamic therapy) versus 5‐FU (RR 1.83, 95% CI 1.10 to 3.06; n = 66), but no statistically significant difference in recurrence rates at 12 months (RR 0.33, 95% CI 0.07 to 1.53).
Cryotherapy showed no statistically significant difference in clearance rates (RR 0.99, 95% CI 0.78 to 1.26) or recurrences at 1 year (RR 1.48, 95% CI 0.53 to 4.17) when compared to 5‐FU in 1 study of 127 participants.
One study compared imiquimod to placebo and demonstrated statistically significantly greater clearance rates in the imiquimod group (9/15 lesions) compared to placebo (0/16) (Fisher's Exact P value < 0.001). The imiquimod group did not report any recurrences at 12 months, but at 18 months, 2/16 participants in the placebo group had developed early invasive squamous cell carcinoma.
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.
Fiona J Bath‐Hextall, Rubeta N Matin, David Wilkinson, Jo Leonardi‐Bee
Plain language summary
Treatments for cutaneous Bowen's disease
Bowen's disease is the clinical term for a particular precancerous skin lesion. These lesions rarely cause patients any symptoms, but appear as well‐defined scaly patches on sun‐exposed skin, commonly in those over 60 years. They occur more in women and most frequently involve the lower legs of those affected in the UK. It is not known why, but the body sites most commonly affected vary across different countries. In general, people with Bowen's disease have an excellent prognosis because the disease is typically slow to develop and responds favourably to treatment. Lesions are usually slow‐growing, and although they are not life‐threatening, there is a small risk of progression to a skin cancer (estimated to be 3%) known as invasive squamous cell carcinoma.
This review attempted to find which is the most effective treatment for cutaneous Bowen's disease, with the least side‐effects.
There are a range of treatment options including the following: topical therapies, such as 5‐fluorouracil (5‐FU) and imiquimod creams; surgical interventions, such as excision and Mohs micrographic surgery; destructive therapies, such as cryotherapy (freezing); and light‐based therapies, such as photodynamic therapy (where a light‐sensitive cream is used in combination with visible light).
We included 9 randomised controlled trials, with a total of 363 participants. No studies examined surgical methods.
Photodynamic therapy appears to be an effective treatment and has the benefit of minimal scarring compared with cryotherapy or 5‐fluorouracil. Cryotherapy is convenient and less expensive, but does not appear to be as effective as photodynamic therapy and results in more scarring; 5‐aminolevulinic acid with photodynamic therapy (ALA‐PDT) appears to be more effective than 5‐fluorouracil, whereas methyl aminolevulinate with photodynamic therapy (MAL‐PDT) does not appear to be as good as 5‐fluorouracil. One study demonstrated benefit with imiquimod cream.
Specific recommendations cannot be made from these data, so this review cannot give firm conclusions about the comparative effectiveness of treatments. There is a clear need for future research to focus on a range of different studies comparing various therapies with each other, and in particular to surgical treatments to provide high‐quality evidence to guide clinical practice. The age group, number and size of lesions, sites affected, and immunological status may all influence therapeutic choices. Longer‐term follow up (up to 10 years) is needed to determine the effect of treatments on risk of progression of lesions of Bowen's disease to squamous cell carcinoma.
Fiona J Bath‐Hextall, Rubeta N Matin, David Wilkinson, Jo Leonardi‐Bee
Implications for practice
There is only limited quality data available to guide clinical practice. Clinicians need to carefully consider the needs of individuals, characteristics, sites of the lesions, and any comorbidities. Some people may not require any treatment at al; others will benefit from either surgical excision, other destructive treatments, cryotherapy, or topical treatments such as 5‐fluorouracil or photodynamic therapy. Photodynamic therapy appears to be an effective and safe non‐scarring treatment, which should be considered if available. The limited data suggest that 5‐fluorouracil is as effective as PDT, that cryotherapy is possibly less effective than PDT, and that imiquimod is also effective, but has not been compared with PDT. Cost, likely adverse events, and patient preference will all play a part in the choice of treatment.
Implications for research
The lack of good‐quality research on common treatments for Bowen's disease has influenced this review towards PDT studies. There is a clear need for a range of different studies comparing various therapies with each other and potentially with placebo, in order to provide high‐quality evidence to guide clinical practice. In particular, studies comparing interventions to surgical treatments are lacking, for example, quality RCTs comparing surgery with topical treatments, topical treatments with each other, e.g. 5‐fluorouracil with imiquimod, and topical treatments versus PDT, e.g. imiquimod with PDT.
Although there is evidence that imiquimod is an effective treatment, studies comparing this intervention to other standard therapies are needed. With these data, we have been unable to stratify treatments according to lesion size, site, or number because of the small numbers of participants. Larger studies are therefore required to better provide guidance to clinicians. Finally, one study reported increased development of squamous cell carcinoma (SCC) in the placebo‐treated group suggesting that treatment may reduce the risk of progression from Bowen's disease. None of the other studies attempted to assess impact of the intervention on progression to SCC, and future studies should consider this as a clinically important outcome.