Outcome Disparities in Patients with Early-Stage Laryngeal Cancer Depending on Localization, Tobacco Consumption, and Treatment Modality

<b>Background/Objectives:</b> Laryngeal squamous cell carcinoma (LSCC) is among most frequent malignancies of the head and neck. Recent oncologic research focusses on advanced rather than on early stages. Thus, we aimed to improve the knowledge concerning prognostic factors and survival in early glottic (GC) and supraglottic cancer (SGC). <b>Methods:</b> We retrospectively investigated patients diagnosed in 2007 to 2020 with stage I or II GC (ICD-10-C32.0) or SGC (ICD-10-C32.1, C32.8 or C32.9). For precise discrimination of GC and SGC, pathology reports about biopsy and definitive excision were closely examined and information on clinical characteristics and risk factors were collected before analyzing patterns of risk factors for overall survival (OS) in multivariate Cox regression analyses (mvCox). <b>Results:</b> The cohort included 220 patients with early GC (<i>n</i> = 183) and SGC (<i>n</i> = 37). The GC patients showed significantly improved 5-year OS compared to SGC patients (83.6% vs. 64.9%; <i>p</i> = 0.004), whereas survival according to UICC stage (I vs. II) was not different (<i>p</i> = 0.177). Surgical resection was superior to definitive radiotherapy (RT) for 5-year OS (<i>p</i> < 0.001). Cumulative tobacco consumption of greater than 10 pack years drastically impaired OS (<i>p</i> = 0.024), especially in patients receiving RT (<i>p</i> < 0.001). Supraglottic localization, smoking, and re-resection after initial R1 status consistently were independent prognostic factors in mvCox. <b>Conclusions:</b> Our cohort of early LSCC patients demonstrates significant negative impact of supraglottic localization, older age, tobacco consumption, poor tumor differentiation, and re-resection on OS. Further research is required as there is still lack of evidence on optimal decision-making and therapeutic strategies.