Background: Cutaneous squamous cell carcinoma (cSCC) of the head and neck is treated primarily with surgical excision. Poor prognostic indicators in high-risk cSCC are largely extrapolated from mucosal literature and are highly variable in single-institution studies. In addition, the impact of adjuvant therapy remains unclear. There is especially a paucity of data for chemotherapy in the adjuvant setting.
Objective: To review the oncologic outcomes of patients with advanced/high-risk cSCC of the head and neck treated with definitive surgery and to identify risk factors for treatment failure. Our hypothesis was that 1) adjuvant systemic therapy in combination with radiation after definitive surgery provides a survival benefit, and that 2) aggressive pathologic features (perineural invasion [PNI], lymphovascular invasion, positive margins) and extracapsular extension of metastatic nodal disease (ECE) portend a worse prognosis in cSCC of the head and neck.
Methods: A retrospective chart review was performed on all patients with cSCC treated definitively with surgery requiring parotidectomy and neck dissection at the University of Miami between 2011 and 2017. Demographics, surgical and pathologic details, and treatment information were recorded. The primary outcome was progression-free survival (PFS). Survival data were analyzed by the Kaplan-Meier method. Univariable analysis using a Cox proportional hazards model was performed to determine each risk factor’s effect on PFS. Factors reaching statistical significance and predetermined aggressive pathologic features were included in multivariable analyses.
Results: One hundred four patients with a median age of 68 years (range 42-91 years) were reviewed. Twenty-one patients were treated with surgery alone, 45 patients underwent adjuvant radiotherapy and 38 patients underwent adjuvant chemoradiotherapy. The 2- and 5-year PFS for the entire cohort was 63.6% and 48.6%, respectively. Pathologic factors associated with decreased PFS on univariable analysis were positive margins (Hazard Ratio [HR]=2.10, p=0.041), lymphovascular space invasion (HR=2.33, p=0.047), and PNI (HR=2.48, p=0.022). There was no effect for ECE of nodal disease (HR=0.81, p=0.57). On multivariable analysis, when accounting for the effect of these factors and for differences in adjuvant treatment, only PNI remained an independent risk factor for worse PFS (HR=2.55, p=0.044). Increasing tumor size was also a strong independent risk factor for disease recurrence (Likelihood Ratio=8.14) that remained significant on multivariable analysis, especially when tumor size was greater than 2 cm (HR=8.04, p=0.006). The use of adjuvant chemotherapy was not associated with improved PFS on Cox analysis (HR=1.29, p=0.43) and did not portend a survival benefit on Kaplan-Meier analysis when looking at the whole cohort of patients (p=0.70), nor when compared with adjuvant radiation alone for high-risk patients (p=0.15).
Conclusions: Cutaneous squamous cell carcinoma necessitating surgical treatment with parotidectomy and neck dissection has a high recurrence rate despite the use of adjuvant therapy. In our series, increasing tumor size was a strong independent risk factor for disease recurrence. Of the traditional pathologic risk factors for decreased survival, only PNI was associated with worse PFS on multivariable analysis. The presence of advanced nodal disease and ECE did not lead to a higher recurrence rate. There was no benefit for chemotherapy in this setting.