An evidence based approach towards optimising the management of patients with squamous cell carcinoma of the skin

• Main Author: Lansbury, Louise E.
• Published: University of Nottingham 2014
• Subjects: 616.99; WR Dermatology
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.639914

Cutaneous squamous cell carcinoma (SCC) is a common cancer yet its treatment is under-researched. The objective of this thesis was to develop a proposal for a randomised controlled trial (RCT) to address uncertainties relating to the management of the condition, and to ultimately improve the management of affected patients. Two systematic reviews were initially conducted to appraise the current evidence base for SCC treatments. Only one RCT was eligible for inclusion in the Cochrane systematic review; a small study which found no significant difference in time to recurrence between patients treated with post-operative 13-cis retinoic acid and interferon, and those not receiving adjuvant treatment. Systematic review and meta-analysis of observational studies included 118 studies. Pooled estimates of recurrence were lowest after cryotherapy and curettage and electrodesiccation, although lesions treated by these modalities were mostly small and low-risk. Although pooled recurrence after Mohs surgery appeared lower than after conventional excision or radiotherapy, the differences were not significant with overlapping 95% confidence intervals. For photodynamic therapy, pooled recurrence after apparently successful initial treatment was particularly high (26%). Evidence relating to the effectiveness of topical and systemic treatments was very limited. Estimates of recurrence were used to inform the sample size calculation for the proposed RCT. A survey of healthcare professionals was conducted to establish research priorities and identify clinically important management uncertainties from which initial trial scenarios were formulated. High-risk SCCs were identified as a research priority, with optimal surgical management and the role of adjuvant radiotherapy being key areas of uncertainty. Through multi-disciplinary collaboration, a proposal for a two-stage RCT has been developed; in the first stage, locoregional recurrence after conventional surgery with a controlled excision margin will be compared with Mohs surgery, and in the second stage locoregional recurrence will be compared between patients treated with adjuvant radiotherapy versus those receiving no adjuvant treatment. Feasibility work conducted during the development of the trial has involved: a) A retrospective analysis of SCCs treated over twelve-months to determine the number of patients and types of SCCs potentially eligible for recruitment into the proposed trial and to further inform the sample size calculation. Within five years of treatment 6% of 357 patients experienced local recurrence, 3% had regional recurrence and 1.5% died of their SCC. Comparison of the most recent American Joint Cancer Council (AJCC7) and an alternative Brigham and Women’s Hospital (BWH) classification showed that approximately 50% of SCCs were T2 in both schemes and eligible for entry into the first stage of the proposed trial. However, an additional BHW T2b substage better stratified outcomes dependent on the number of risk features, and indicated that 19% of all SCCs would potentially be also eligible for the second stage of the trial. b) A questionnaire and focus group study to assess the acceptability of the RCT and to identify possible barriers to recruitment. Participants had a desire to be better informed about SCC, wanting information relating to the trial to be provided in a variety of formats. 71% of participants were hypothetically willing to be randomised into the surgical stage of the proposed trial but had more concerns about the second stage involving adjuvant radiotherapy. Lack of equipoise and confusion about the concept of randomisation will need to be carefully addressed when presenting the trial to participants. The proposed trial will be the first to directly compare treatments for the types of SCC seen commonly in clinical practice. For the trial to be adequately powered, an estimated 5400 participants will need to be recruited, so a multi-centre, multi-disciplinary approach will be necessary.