Background/purpose
Tegafur-uracil (UFUR) is widely prescribed as metronomic adjuvant chemotherapy for oral squamous cell carcinoma (OSCC) in East Asia, though its long-term benefit remains unclear. This study aimed to evaluate the oncologic and pathological impact of adjuvant UFUR in a large real-world OSCC cohort spanning three decades.
Materials and methods
This retrospective, single-institution cohort included 2048 patients with histopathologically confirmed OSCC treated at a tertiary medical center in Taiwan (1990–2020). All underwent curative-intent surgery with or without postoperative radiotherapy or concurrent chemoradiotherapy (CCRT). Among them, 878 patients received adjuvant metronomic UFUR for ≥12 months. Survival outcomes were analyzed using Kaplan–Meier and Cox proportional hazards models, and clinicopathologic associations were assessed using chi-square and Wilcoxon tests.
Results
Adjuvant UFUR did not improve disease-free survival (DFS) across cancer stages and was associated with significantly poorer DFS in early-stage diseases. Hazard ratios (HRs) for DFS in stages I–III were 1.523, 1.616, and 1.441, respectively (all P < 0.01). UFUR-treated patients also exhibited higher rates of recurrence, earlier onset of second primary cancers, and more frequent spindle-cell transformation, particularly among poorly-differentiated OSCCs.
Conclusion
Adjuvant metronomic UFUR provided no survival advantage and was associated with unfavorable histopathologic evolution in OSCCs. These findings warrant re-evaluation of UFUR as routine adjuvant therapy and support risk-adapted, molecularly guided postoperative strategies in oral cancer management.
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