Importance: Although most cases of cutaneous squamous cell carcinoma (CSCC) are easily cured with surgery or ablation, a subset of these tumors recur, metastasize, and cause death. We conducted the largest study of CSCC outcomes since 1968. Objective: To identify risk factors independently associated with poor outcomes in primary CSCC. Design: A 10-year retrospective cohort study. Setting: An academic hospital in Boston. Participants: Nine hundred eighty-five patients with 1832 tumors. Main Outcomes and Measures: Subhazard ratios for local recurrence, nodal metastasis, disease-specific death, and all-cause death adjusted for presence of known prognostic risk factors. Results: The median follow-up was 50 (range, 2-142) months. Local recurrence occurred in 45 patients (4.6%) during the study period; 36 (3.7%) developed nodal metastases; and 21 (2.1%) died of CSCC. In multivariate competing risk analyses, independent predictors for nodal metastasis and disease-specific death were a tumor diameter of at least 2 cm (subhazard ratios, 7.0 [95% CI, 2.2-21.6] and 15.9 [4.8-52.3], respectively), poor differentiation (6.1 [2.5-14.9] and 6.7 [2.7-16.5], respectively), invasion beyond fat (9.3 [2.8-31.1] and 13.0 [4.3-40.0], respectively), and ear or temple location (3.8 [1.1-13.4] and 5.9 [1.3-26.7], respectively). Perineural invasion was also associated with disease-specific death (subhazard ratio, 3.6 [95% CI, 1.1-12.0]), as was anogenital location, but few cases were anogenital. Overall death was associated with poor differentiation (subhazard ratio, 1.3 [95% CI, 1.1-1.6]) and invasion beyond fat (1.7 [1.1-2.8]). Conclusions and Relevance: Cutaneous squamous cell carcinoma carries a low but significant risk of metastasis and death. In this study, patients with CSCC had a 3.7% risk of metastasis and 2.1% risk of disease-specific death. Tumor diameter of at least 2 cm, invasion beyond fat, poor differentiation, perineural invasion, and ear, temple, or anogenital location were risk factors associated with poor outcomes. Accurate risk estimation of outcomes from population-based data and clinical trials proving the utility of disease-staging modalities and adjuvant therapy is needed.
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