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

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

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

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.

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.

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.