Impact of Adjuvant Tegafur-Uracil on Oral Squamous Cell Carcinoma: A 30-Year Retrospective Study

Purpose The long-term benefit of metronomic Tegafur-Uracil as adjuvant chemotherapy for oral squamous cell carcinoma (OSCC) following curative surgery, with postoperative radiotherapy or concurrent chemoradiotherapy when clinically indicated, remains uncertain. Methods We retrospectively analyzed 2,048 OSCC patients treated at a tertiary medical center in Taiwan between 1990 and 2020. The impact of adjuvant Tegafur-Uracil on disease-free survival (DFS), recurrence rates, second primary cancers, and spindle-cell transformation was assessed using Kaplan-Meier and Cox proportional hazards models. Results Of the 2,048 patients, 341 (14.10%) had stage I, 364 (15.05%) had stage II, 342 (13.40%) had stage III, and 1,398 (57.44%) had stage IV disease. A total of 878 patients received metronomic Tegafur-Uracil therapy. Among stage I and II OSCC patients, those who did not receive Tegafur-Uracil had significantly better DFS when treated with surgery alone, while no survival benefit was observed with the addition of Tegafur-Uracil in all treatment modalities. Tegafur-Uracil treatment was associated with a slight delay in recurrence, but also with earlier occurrence of second primary cancers and higher recurrence rates in early-stage patients. Notably, Tegafur-Uracil was linked to an increased incidence of spindle-cell transformation, particularly in poorly differentiated tumors. Conclusion In this retrospective cohort of OSCC patients, adjuvant metronomic Tegafur-Uracil therapy did not confer a benefit of DFS, even among early-stage patients with adverse pathological features for whom adjuvant chemotherapy is conventionally indicated. These findings suggest caution in the routine use of Tegafur-Uracil in OSCC and emphasize the need for individualized patient selection.