Enhanced metastatic risk stratification for cutaneous squamous cell carcinoma by combining clinical guidelines with the Erasmus MC model: Results from 2 nationwide nested case-control studies

Background: Reliably assessing metastatic risk in cutaneous squamous cell carcinoma remains clinically challenging despite established guidelines. Objective: To assess whether a clinicopathologic risk prediction model (Erasmus MC model) can enhance the identification of high-risk metastatic patients within the current European and National Comprehensive Cancer Network guidelines for cutaneous squamous cell carcinoma. Methods: A Dutch nested case-control cohort (n = 390 derived from N = 12,325), was first stratified by guideline-defined risk groups. Each high-risk group was further stratified using thresholds for the risk estimated by the Erasmus MC model. The performance was assessed in an independent English nested case-control cohort (n = 696, derived from N = 31,981). Results: The European guideline-defined high-risk group had a 3-year metastatic risk of 3.8% (95% CI 2.4% to 5.2%). Within this group, 18.2% of the patients were identified with a higher 3-year risk of 10.1% (95% CI 6.7% to 13.5%). For the National Comprehensive Cancer Network-defined very high-risk group, the overall 3-year risk was 7.4% (95% CI 2.0% to 9.2%). Of these, 34.5% of the patients had an even greater risk of 14.0% (95% CI 8.3% to 19.6%). Limitations: Routinely collected health care data often lacks detailed clinical information. Conclusion: The Erasmus MC model improves metastatic risk stratification by identifying higher risk groups within the frameworks of current European and National Comprehensive Cancer Network cutaneous squamous cell carcinoma guidelines.