Outcomes and Risk Factors in Young Patients with Head-and-Neck Cancer: A Multi-Center Retrospective Analysis

Background and Objectives: Head and neck cancer in patients aged 40 years or younger represents a rare and heterogeneous entity with conflicting data regarding prognosis and risk factors. This study aimed to evaluate oncological outcomes and independent prognostic factors in young patients treated with radio(chemo)therapy. Materials and Methods: This retrospective multi-center analysis included patients aged ≤ 40 years with histologically confirmed HNC who received definitive or adjuvant radio(chemo)therapy between 2002 and 2023 at the University Hospital Regensburg and affiliated partner hospitals. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method. Independent prognostic factors were identified by Cox proportional hazard regression with backward stepwise elimination. Results: A total of 88 patients were included. The median age at diagnosis was 38.2 years (IQR 35.8–39.8). Median OS was 91.0 months in the adjuvant and 23.7 months in the definitive treatment group. In multivariate analysis, four independent predictors of OS were identified: nicotine abuse (HR 2.887; p = 0.004), pre-existing comorbidities (HR 2.871; p = 0.005), absence of complete remission 12 weeks after radiotherapy (HR 25.676; p < 0.001), and locoregional recurrence or distant metastases (HR 8.183; p < 0.001). Failure to achieve complete remission was the sole independent predictor of PFS (HR 4.479; p < 0.001). Conclusions: In young HNC patients, early treatment response and disease recurrence are the strongest determinants of survival, alongside modifiable lifestyle factors and comorbidity burden. These findings support the need for intensified response monitoring and tailored follow-up strategies in this patient population.