Impact of postoperative radiotherapy on combined local SCC events and survival in non-metastatic oral and pharyngeal squamous cell carcinoma

Whether postoperative radiotherapy (PORT) reduces post-treatment malignant events in oral and pharyngeal squamous cell carcinoma (SCC) remains uncertain, particularly in population-based settings where true recurrence cannot be distinguished from second primary tumors (SPTs). Using SEER data (1975–2021), we evaluated the association between PORT and combined local SCC events—subsequent SCCs of identical morphology occurring within C00–C14—and assessed its impact on overall survival (OS). A retrospective cohort of 26,953 patients with first primary non-metastatic oral/pharyngeal SCC who underwent surgery was identified. PORT was defined as postoperative external-beam radiotherapy. The primary endpoint was combined local SCC events, reflecting SEER-captured recurrence- or SPT-like occurrences. Fine–Gray competing-risk models estimated subdistribution hazard ratios (sHRs), treating non-cancer death as the competing event. Poisson regression evaluated calendar-year trends. OS was assessed using Kaplan–Meier analysis with 1:1 propensity score matching (PSM) to adjust for baseline imbalances. Sensitivity analyses restricted to classical oral cavity SCC (C00–C06) and excluded all pharyngeal subsites. Among 26,953 patients, 8,355 (31.0%) received PORT. PORT recipients had more adverse disease characteristics, including higher rates of regional-stage disease and high-grade morphology. During follow-up, 146 patients (0.54%) developed combined local SCC events, with lower incidence in the PORT group (0.7% vs. 0.2%, P < 0.001). PORT independently reduced the risk of combined events (sHR 0.34, 95% CI 0.20–0.59). Results were consistent across all subgroups and sensitivity analyses. After PSM, OS did not differ significantly between PORT and non-PORT groups (HR 0.97, 95% CI 0.89–1.12). Among patients who developed combined SCC events, OS likewise remained comparable. In this large, population-based study, PORT was associated with a substantially lower risk of registry-captured local SCC events across oral and pharyngeal subsites, although no adjusted survival advantage was observed. These findings underscore PORT’s role in improving local disease control while highlighting the need for recurrence-specific datasets to refine patient selection.This study provides real-world evidence on PORT effectiveness using a SEER-based composite endpoint tailored for registries lacking recurrence data.