Factors Predictive of Recurrence and Death From Cutaneous Squamous Cell Carcinoma: A 10-Year, Single-Institution Cohort Study

TLDR: 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 in primary cutaneous squamous cell carcinoma.

Abstract: 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.