Surgery followed by adjuvant radiotherapy versus definitive radiotherapy for locally advanced squamous cell carcinoma of the pharynx and larynx: a propensity score-matched analysis.

Aim: Locally advanced squamous cell carcinoma (SCC) of the pharynx and larynx is commonly treated with either primary surgery followed by adjuvant radiotherapy (RT) or definitive RT with or without concurrent systemic therapy. Comparative outcome data between these treatment strategies remain limited because retrospective analyses are frequently affected by treatment-selection bias. This study compared oncologic outcomes between primary surgery followed by adjuvant RT and definitive RT using propensity score matching to reduce baseline confounding. Methods: A retrospective analysis was performed on 309 patients with locally advanced SCC of the oropharynx, hypopharynx, or larynx treated at our center. Propensity scores were generated using a multivariable logistic regression model including T stage, N stage, and age at diagnosis. One-to-one nearest-neighbor matching with a caliper of 2% resulted in 61 matched patient pairs treated with primary surgery followed by adjuvant RT or definitive RT. Survival outcomes were analyzed using the Kaplan-Meier method and compared using log-rank tests. Multivariable Cox regression analyses were performed to account for imbalances in previous malignancies after matching. Results: After propensity score matching, 61 patients treated with primary surgery followed by adjuvant RT and 61 patients treated with definitive RT were included, with improved balanced baseline characteristics for the matching variables. Median OS was 81 months in the surgery followed by adjuvant RT group and was not reached in the definitive RT group, with no statistically significant difference between groups (p = 0.70). Numerical differences favored adjuvant RT for progression-free survival (median PFS: 81.0 vs. 43.4 months; p = 0.09) and loco-regional recurrence-free survival (p = 0.08), although these differences were not statistically significant. Lymphedema was the only toxicity significantly more frequent in the adjuvant RT cohort (33% vs. 13%, p = 0.017), while rates of other treatment-related toxicities were comparable. Multivariable analyses adjusted for previous malignancies confirmed the absence of significant associations between treatment modality and survivals. Conclusion: Primary surgery followed by adjuvant RT and definitive RT achieved comparable overall survival in patients with locally advanced SCC of the pharynx and larynx after propensity score matching. However, the surgery plus adjuvant RT strategy demonstrated trends toward improved disease control and local control. These findings support individualized multidisciplinary treatment selection while prospective comparative studies remain warranted.