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

Abstract

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.

Fig 1 PRISMA flowchart of studies. BCC=basal cell carcinoma

Fig 2 Risk of bias assessment of included studies. Percentage indicates proportion of studies

Fig 3 Local recurrence of SCCs after surgical excision

Fig 4 Local recurrence of SCCs in ear locations after surgical excision

Fig 5 Local recurrence of SCCs in non-ear locations after surgical excision

Fig 6 Regional recurrence of SCCs after surgical excision

Fig 7 Regional recurrence of SCCs in ear locations after surgical excision

Fig 8 Regional recurrence of SCCs in non-ear locations after surgical excision

Fig 9 Deaths attributable to disease after surgical excision

Fig 10 Incomplete excision of SCCs after surgical excision

Fig 11 Local recurrence of SCCs after Mohs micrographic surgery

Fig 12 Regional recurrence of SCCs after Mohs micrographic surgery

Fig13 Unspecified recurrence of SCCs after Mohs micrographic surgery

Fig 14 Deaths attributable to disease after Mohs micrographic surgery

Fig 15 Local recurrence of SCCs after external radiotherapy

Fig 16 Regional recurrence of SCCs after external radiotherapy

Fig 17 Unspecified recurrence of SCCs after external radiotherapy

Fig 18 Deaths attributed to disease after external radiotherapy

Fig 19 Local recurrence of SCCs after brachytherapy

Fig 20 Unspecified recurrence of SCCs after curettage and electrodesiccation

Fig 21 Unspecified recurrence of SCCs after cryotherapy

Fig 22 Apparent complete response of SCCs after photodynamic therapy. (1) “elevated” SCCs; (2) “early invasive” SCCs; (3) “nodular” SCCs; (4) “superficial” SCCs; (5) no glycolic acid added to photodynamic therapy; (6) photodynamic therapy plus glycolic acid; (7) “invasive” SCCs; (8) “microinvasive” SCCs

Fig 23 Recurrence after apparent complete response of SCCs following photodynamic therapy. (1) “superficial” SCCs; (2) “nodular” SCCs; (3) “microinvasive” SCCs; (4) “invasive” SCCs