Diagnostic Modalities and Nodal Staging in High-Risk Cutaneous Squamous Cell Carcinoma.

Abstract

Early detection of nodal metastases in high-risk cutaneous squamous cell carcinoma (cSCC) is crucial, yet the optimal baseline staging approach remains uncertain. To compare the diagnostic performance of physical examination, ultrasonography, and contrast-enhanced computed tomography (CT) in detecting nodal metastases at baseline staging of high-risk cSCC, both overall and stratified by patients' immune status. This was a prospective, multicenter, paired diagnostic study conducted from January 2022 to April 2025 across 13 tertiary dermato-oncology centers in Spain. The study included patients with histologically confirmed high-risk cSCC (stage T2b/T3 or T2a with additional high-risk features). Data were analyzed from July to September 2025. Sensitivity, specificity, predictive values, and area under the receiver operating characteristic curve (AUROC) of each diagnostic modality, benchmarked against histology or short-term clinical follow-up as reference standard. The analysis included 155 patients (median [IQR] age, 80.3 [74.4-85.5] years; 34 [21.9%] female and 121 [78.1%] male; 64 [41.3%] immunosuppressed), of whom 12 patients (7.7%; 95% CI, 4.3%-13.4%) developed nodal metastases within 3 months after surgery. Ultrasonography results showed the highest overall sensitivity (63.6%; 95% CI, 30.8%-89.1%), followed by CT (54.5%; 95% CI, 23.4%-83.3%) and physical examination (8.3%; 95% CI, 0.2%-38.5%). Specificities were 95.6% (95% CI, 90.6%-98.4%), 95.0% (95% CI, 90.0%-98.0%), and 99.3% (95% CI, 96.2%-100%), respectively. Ultrasonography and CT demonstrated almost perfect agreement (κ = 0.87; 95% CI, 0.72-1.00), whereas concordance with physical examination was poor. Subgroup analysis by immune status revealed marked disparities in diagnostic performance. In patients with immunocompetence, both ultrasonography and CT achieved 100% sensitivity (95% CI, 54.1%-100% and 47.8%-100%, respectively) and excellent AUROC (0.98; 95% CI, 0.96-1.00 for both). In contrast, sensitivity declined markedly among patients who were immunosuppressed (20.0% [95% CI, 0.5%-71.6%] for ultrasonography and 16.7% [95% CI, 0.4%-64.1%] for CT; AUROCs, 0.57 ([95% CI, 0.37-0.77] and 0.55 [95% CI, 0.38-0.72], respectively), with metastases often emerging abruptly during follow-up despite negative baseline staging. This diagnostic study found that ultrasonography and CT significantly outperformed physical examination for detecting baseline nodal metastases in high-risk cSCC and can be used interchangeably depending on clinical context and resource availability. However, their poor performance in patients with immunosuppression reveals a need for tailored recommendations in future clinical practice guidelines and emphasizes the importance of close clinical follow-up in this subgroup.