A Sensitivity Meta-Analysis of Disease-Specific Death in Localized Cutaneous Squamous Cell Carcinoma

Background: Patients with localized cutaneous squamous cell carcinoma (cSCC) have different risk for disease-specific death (DSD) from patients with metastatic cSCC. Patients and Methods: We conducted a sensitivity meta-analysis to identify the risk factors associated with DSD, in patients with localized cSCC at initial diagnosis (without locoregional or distant metastasis). Results: Nine studies, with 5,205 patients, were included. Median follow-up ranged from 18 to 81 months. The number of deaths due to cSCC ranged from 3 to 40. Patients with immunosuppression were almost 2 times more likely to die from cSCC compared to immunocompetent patients (risk ratio: 1.85, 95% CI: 1.32-2.61). There was a positive but nonsignificant overall association with DSD for depth beyond fat, tumor diameter, presence of perineural invasion, location, and thickness. These results should be interpreted with caution, as there was limited evidence-based data on DSD in localized cSCC, due to the small number of studies reporting DSD, the absence of reporting the margin status, the variability of selected risk factors across studies, and the variability of definition of risk factors. Conclusions: In our meta-analysis, in localized cSCC at initial diagnosis, patients with immunosuppression were at significantly higher risk to die from cSCC. Our findings further highlight the need for a standardized set of risk factors to be included in studies on prognosis of cSCC and for including margin status and DSD among the studied outcomes.