Association of Positive Initial Margins With Survival Among Patients With Squamous Cell Carcinoma Treated With Total Laryngectomy

Abstract

Importance: Frozen-section analysis of margin status is routinely performed during total laryngectomy for squamous cell carcinoma; in the case of positive initial frozen margins, re-resection to negative margins can often be accomplished. Some evidence suggests that positive initial margins may be associated with worse survival among patients with head and neck cancer even when final margins are negative, but the significance of positive initial frozen margins in total laryngectomy is poorly understood.

Objective: To determine the association between disease-free survival and positive initial margins among patients treated with total laryngectomy for squamous cell carcinoma.

Design, setting, and participants: In this retrospective cohort study conducted at a tertiary care center, records of 237 consecutive patients treated with total laryngectomy for squamous cell carcinoma from February 2008 to July 2016 were reviewed for demographic characteristics, disease staging, pathologic markers, and outcomes. Margins were considered to be positive if they contained invasive carcinoma, carcinoma in situ, or severe dysplasia. Data analysis was performed from March to June 2018.

Interventions: All patients had undergone total laryngectomy for squamous cell carcinoma.

Main outcomes and measures: Variables associated with disease-free survival were analyzed using a univariable and multivariable Cox proportional hazards model.

Results: Among all 225 patients (184 [92%] male; mean age, 63.9 years; range, 30-92 years) who underwent total laryngectomy and had negative final margins, 127 patients underwent primary total laryngectomy and 98 underwent salvage total laryngectomy, with mean (SEM) follow-up of 29.3 (1.8) months. Initial frozen margins were positive in 40 of 225 patients (18%); positive initial margins occurred in 21 of 127 patients who underwent primary total laryngectomy (17%) and in 19 of 98 patients who underwent salvage total laryngectomy (19%). On multivariable analysis, only salvage laryngectomy was associated with significantly worse disease-free survival (hazard ratio [HR], 3.35; 95% CI, 1.76-6.36). Among 98 patients who underwent salvage total laryngectomy, positive lymph nodes, lymphovascular invasion, extracapsular nodal extension, and adjuvant therapy were associated with worse disease-free survival on univariable analysis, but no factors remained significant on multivariable analysis. Among 127 patients who underwent primary total laryngectomy, positive nodes, lymphovascular invasion, extracapsular nodal extension, and positive initial margins were associated with worse disease-free survival; however, only positive initial margins were associated with significantly worse disease-free survival on multivariable analysis (HR, 5.01; 95% CI, 1.55-16.2).

Conclusions and relevance: In this study, positive initial margins were associated with worse disease-free survival among patients who underwent primary total laryngectomy despite negative margins on final pathologic examination. This finding may indicate aggressive tumor behavior in the context of primary laryngeal squamous cell carcinoma.

Figure 1.. Kaplan-Meier Curve and Univariable Cox Proportional Hazards Analysis of Disease-Free Survival According to Margin Status

Figure 2.. Kaplan-Meier Curves of Disease-Free Survival Among Patients Who Underwent Primary Total Laryngectomy and Salvage Total Laryngectomy According to Initial Margin Status

Figure 3.. Cumulative Incidence Survival Curves for Patients Who Underwent Primary Total Laryngectomy Stratified by Initial Margin Status