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Interventions for non-metastatic squamous cell carcinoma of the skin: systematic review and pooled analysis of observational studies

BMJ 2013; 347 doi: (Published 04 November 2013) Cite this as: BMJ 2013;347:f6153
  1. Louise Lansbury, research associate1,
  2. Fiona Bath-Hextall, reader in evidence based healthcare12,
  3. William Perkins, consultant dermatologist3,
  4. Wendy Stanton, librarian4,
  5. Jo Leonardi-Bee, associate professor in medical statistics5
  1. 1Centre of Evidence Based Dermatology, University of Nottingham, Nottingham NG7 2NR, UK
  2. 2School of Health Sciences, University of Nottingham, Nottingham, UK
  3. 3Department of Dermatology, Nottingham University Hospitals NHS Trust, Queen’s Medical Centre, Nottingham, UK
  4. 4Greenfield Medical Library, Nottingham Education Centre, University of Nottingham, UK
  5. 5Division of Epidemiology and Public Health, University of Nottingham, Nottingham City Hospital, Nottingham, UK
  1. Correspondence to: L Lansbury Louise.Lansbury{at}
  • Accepted 11 September 2013


Objectives To assess the effects of treatments for non-metastatic invasive squamous cell carcinoma (SCC) of the skin using evidence from observational studies, given the paucity of evidence from randomised controlled trials.

Design Systematic review of observational studies.

Data sources Medline, Embase, to December 2012.

Review methods Observational studies of interventions for primary, non-metastatic, invasive, SCC of the skin that reported recurrence during follow-up, quality of life, initial response to treatment, adverse events, cosmetic appearance, or death from disease. Studies were excluded if data for primary cutaneous SCC was not separable from other data. Data were extracted independently by two reviewers. Meta-analysis was performed where appropriate using a random effects model to estimate the pooled proportion of an event with 95% confidence intervals.

Results 118 publications were included, covering seven treatment modalities. Pooled estimates of recurrence of SCCs were lowest after cryotherapy (0.8% (95% confidence interval 0.1% to 2%)) and curettage and electrodesiccation (1.7% (0.5% to 3.4%)), but most treated SCCs were small, low risk lesions. After Mohs micrographic surgery, the pooled estimate of local recurrence during variable follow-up periods from 10 studies was 3.0% (2.2% to 3.9%), which was non-significantly lower than the pooled average local recurrence of 5.4% (2.5% to 9.1%) after standard surgical excision (12 studies), and 6.4% (3.0% to 11.0%) after external radiotherapy (7 studies). After an apparently successful initial response of SCCs to photodynamic therapy, pooled average recurrence of 26.4% (12.3% to 43.7%; 8 studies) was significantly higher than other treatments. Evidence was limited for laser treatment (1 study) and for topical and systemic treatments (mostly single case reports or small non-comparative series with limited follow-up).

Conclusions Many observational studies have looked at different treatment modalities for SCC, but the evidence base for the effectiveness of these interventions is poor. Comparison of outcomes after different treatments should be interpreted cautiously owing to biases inherent in the types of study included, and lack of direct comparisons to enable the estimation of relative treatment effect. Further evidence is needed to develop a prognostic model and stratify individuals at high risk of developing SCC, to improve the evidence base for this common cancer and to optimise clinical management.

Protocol registration International Prospective Register of Systematic Reviews (PROSPERO) registration number CRD42011001450.


  • We thank Alemayehu Amberbir (AA) and Joanna Browne (JB) who assisted with data extraction.

  • Contributors: LL, FB-H, WP, and JL-B contributed to the development of the review questions. WS and LL designed the searches. LL, FB-H, and JL-B assessed the eligibility of studies for inclusion, extracted data, and assessed risk of bias and quality of reporting. JL-B developed the statistical analysis. LL, FB-H, WP, and JL-B contributed to the analysis and interpretation of data. LL drafted the article and all other authors approved the final version, had full access to the data, and take responsibility for the integrity of the data and accuracy of the analysis. LL is the guarantor.

  • Funding: This systematic review presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research funding scheme (RP-PG-0407-10177).

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare: LL, FBH, WP, and JLB received support from the NIHR for the submitted work; all authors declare no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: None required.

  • Data sharing: Statistical code and dataset are available from the corresponding author at Louise.Lansbury{at}

  • The lead author (the manuscript’s guarantor) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:

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