Clinical and Incidental Perineural Invasion of Cutaneous Squamous Cell Carcinoma: A Systematic Review and Pooled Analysis of Outcomes Data | Dermatology | JAMA Dermatology | JAMA Network
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Original Investigation
August 2017

Clinical and Incidental Perineural Invasion of Cutaneous Squamous Cell Carcinoma: A Systematic Review and Pooled Analysis of Outcomes Data

Author Affiliations
  • 1Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  • 2Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
JAMA Dermatol. 2017;153(8):781-788. doi:10.1001/jamadermatol.2017.1680
Key Points

Question  Is there a risk difference in disease-related outcomes between patients with cutaneous squamous cell carcinoma and clinical perineural invasion vs patients with cutaneous squamous cell carcinoma and incidental perineural invasion?

Finding  In this systematic review and pooled analysis, outcomes data from the current literature were compared among patients with cutaneous squamous cell carcinoma and clinical perineural invasion or incidental perineural invasion. Patients with cutaneous squamous cell carcinoma and clinical perineural invasion had a significantly higher risk of local recurrence and death from disease than did patients with cutaneous squamous cell carcinoma and incidental perineural invasion.

Meaning  Patients with cutaneous squamous cell carcinoma and clinical perineural invasion are at a greater risk of poor outcomes compared with those with cutaneous squamous cell carcinoma and incidental perineural invasion and may benefit from enhanced long-term surveillance.

Abstract

Importance  Perineural invasion (PNI) in cutaneous squamous cell carcinoma (CSCC) has been associated with an increased risk of poor outcomes. Patients with PNI may present with clinical symptoms and/or radiologic evidence of PNI (clinical PNI [CPNI]), yet most patients are asymptomatic and PNI is often found on histologic examination (incidental PNI [IPNI]). Evidence-based estimates of the risks of disease-related outcomes comparing IPNI and CPNI are limited in the dermatology literature.

Objectives  To review and synthesize outcomes data for patients with CSCC and CPNI or IPNI.

Data Sources  A systematic review was conducted in MEDLINE and EMBASE for English-language articles published since inception to November 11, 2016.

Study Selection  All studies that reported a disease-related outcome (local recurrence, nodal metastasis, distant metastasis, or disease-specific death) of CSCCs with CPNI and IPNI were included.

Data Extraction and Synthesis  Articles were screened for eligibility, and any possible discrepancies in this screening were resolved. Data extracted included study characteristics, tumor characteristics, treatments performed, and disease-related outcomes. Overall risks of disease-related outcomes were generated by pooling patients from eligible studies. χ2 Statistics and Fisher exact tests were used to evaluate differences in disease-related outcomes.

Main Outcomes and Measures  Risks of disease-related outcomes and 5-year recurrence-free, disease-specific, and overall survival.

Results  A total of 12 studies containing 241 patients with CPNI and 381 patients with IPNI were included in the systematic review and analysis. The overall risks of local recurrence and disease-specific death were significantly higher in patients with CSCC and CPNI compared with those with CSCC and IPNI (local recurrence, 37% vs 17%; P < .001; disease-specific death, 27% vs 6%; P < .001). The risks of nodal metastasis and distant metastasis did not differ significantly by PNI classification. Patients with CSCC and CPNI had poorer mean 5-year recurrence-free survival and disease-specific survival compared with patients with IPNI (recurrence-free survival, 61% vs 76%; P = .009; disease-specific survival, 70% vs 88%; P = .002).

Conclusions and Relevance  Patients with CSCC and CPNI are at an increased risk of local recurrence and disease-specific death compared with patients with CSCC and IPNI and have a 30% risk of death. Patients with PNI may benefit from increased long-term surveillance. Further studies are needed to establish standardized guidelines on follow-up and dermatologic surveillance in this high-risk patient population.

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