Immunosuppression as an Independent Risk Factor for Poor Outcomes in Cutaneous Squamous Cell Carcinoma: A Prospective Study.

Abstract

Background: The impact of immunosuppression on poor outcomes in cutaneous squamous cell carcinoma (cSCC) remains unclear.

Objective: To quantify the effect of immunosuppression on poor outcomes in cSCC and compare its prognostic value to currently accepted high-risk features.

Methods: Single-center, prospective study conducted between January 1, 2014, and December 31, 2021. Outcomes of interest included recurrence, nodal involvement, metastasis, and cSCC-specific mortality. Multivariate logistic regression was performed to identify independent predictors of the grouped dependent variable: poor outcomes.

Results: One thousand four hundred unique cases of cSCC were identified among 929 patients, of which 156 (16.8%) were immunosuppressed. Immunosuppressed patients were more likely to develop Brigham and Women's Hospital T2b/T3 tumors (p < .0001) and experience poor outcomes (p < .0001). Immunosuppression was independently associated with poor outcomes (AOR: 3.44; p = .011), when controlling for differentiation, depth of invasion, perineural invasion (PNI), and size. Immunosuppression outperformed clinical size ≥2 cm (AOR:2.45; p = .021), PNI (AOR:2.81; p = .54), and deep invasion (AOR:6.61; p = .07) in predicting poor outcomes.

Conclusion: The authors demonstrate that immunosuppression is a significant independent predictor of poor outcomes in cSCC and outperforms currently accepted high-risk features. This analysis suggests that cSCC in immunosuppressed patients may have a distinct, more aggressive tumor biology that is not fully captured by traditional staging systems.