Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer. In this retrospective cohort study we have defined factors associated with the risk of metastasis of primary cSCCs. By automated screenings and manual review cohorts of metastatic primary cSCCs (mcSCC) (n=85) and non-metastatic primary cSCCs (n=238) treated at a tertiary care center in Finland were generated for comparison. The rate of metastasis was determined utilizing statistics from Finnish Cancer Registry. Mean rate of metastasis of primary cSCC in the study region was 2.4%. In 85% of cases metastasis was diagnosed within 2 years of the primary tumor diagnosis. The overall 1-, 2- and 5-year survival estimate from the diagnosis of metastasis was 67%, 43% and 31%, respectively. Significant risk factors for metastasis with odds ratios (OR) exceeding 10 were Clark’s level 5 (OR 33.3; 95% confidence interval (CI) 14.5-76.4), tumor diameter 20-29.9 mm (OR 17.3; 95% CI 6.8 44.0), invasion beyond fat (OR 16.1; 95% CI 8.3-31.3), tumor diameter ≥30mm (OR 13.4; 95% CI 5.7-31.6), and location on lower lip (OR 11.5; 95% CI 2.4- 54.8). Significant risk reducing factors for metastasis included primary tumor location on cheek (excluding preauricular region) (OR 0.2; 95% CI 0.1-0.9), co-location with actinic keratosis or cSCC in situ (OR 0.4; 95% CI 0.2-0.7), preceding use of isosorbide mono-/dinitrate (OR 0.3; 95% CI 0.1-0.8) or aspirin (OR 0.5; 95% CI 0.2-0.8). Use of isosorbide mono-/dinitrate and aspirin in combination further lowered the risk of metastasis (OR 0.1; CI 0.0-0.7). These results show the poor prognosis of metastatic cSCC in preimmunotherapy era and suggest Clark’s level as applicable risk factor for metastasis in stratification of primary cSCCs. In addition, the results indicate that isosorbide mono-/dinitrate and aspirin especially in combination lower the risk of metastasis of primary cSCC.

Risk factors for metastasis of cutaneous squamous cell carcinoma: a single-institution cohort study