Content » Vol 100, September

Clinical Report

Risk Factors and Prognosis for Metastatic Cutaneous Squamous Cell Carcinoma: A Cohort Study

Jaakko S. Knuutila, Pilvi Riihilä, Samu Kurki, Liisa Nissinen, Veli-Matti Kähäri
DOI: 10.2340/00015555-3628


Cutaneous squamous cell carcinoma (cSCC) has metastatic potential. The aims of this study were to identify the risk factors for metastasis of primary cSCC and for poor prognosis in metastatic cSCC. Retrospective primary tumour cohorts of metastatic cSCCs (n = 85) and non-metastatic cSCCs (n = 218) were analysed. The mean annual rate of metastasis for primary cSCCs was 2.28%. In 49.4% of patients with metastatic cSCC, metastasis was detected within 6 months of diagnosis of the primary cSCC. There was no prior history of cSCC in 84.7% of metastatic cSCCs. Risk factors for metastasis included Clark’s level 5, tumour diameter 20–29.9 mm, age at diagnosis < 50 or 70–79 years, and location on lower lip or forehead. A reduced risk of metastasis correlated with: isosorbide mono-/di-nitrate and/or aspirin use; comorbidity with actinic keratosis or basal cell carcinoma; and actinic keratosis or cSCC in situ as part of, or confirmedly preceding, primary cSCC. Poor prognosis in metastatic cSCC correlated significantly with ≥3 nodal metastases and extranodal extension of metastasis. These results characterize new risk factors for metastatic cSCC.


The incidence of cutaneous squamous cell carcinoma is increasing worldwide. Cutaneous squamous cell carcinoma has metastatic potential and causes mortality. However, clinical assessment of the risk of metastasis is challenging, and the risk factors have not been established. This study shows that metastasis of primary cutaneous squamous cell carcinoma occurs early, and that there is no prior history of cutaneous squamous cell carcinoma in the majority of cases. The presence of previous cutaneous squamous cell carcinoma precursors and basal cell carcinoma reduces the risk of metastasis. This study provides novel evidence that use of aspirin and/or isosorbide mono-/di-nitrate correlates significantly with a lower risk of metastasis. These findings provide new risk and prognostic factors for metastatic cutaneous squamous cell carcinoma at the patient and tumour level.

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