5‑Fluorouracil‑based adjuvant chemotherapy improves the clinical outcomes of patients with lymphovascular invasion of upper urinary tract cancer and low expression of dihydropyrimidine dehydrogenase

: Lymphovascular invasion (LVI) by urothelial carcinoma of the upper urinary tract (UC-UUT) is associated with an unfavorable prognosis. However, a high proportion of patients with UC-UUT are unable to receive the recommended doses of cisplatin-based adjuvant chemotherapy due to advanced age or renal dysfunction resulting from nephroureterectomy. Tegafur-uracil is an oral form of 5-fluorouracil whose efficacy is influenced by the activities of enzymes associated with its metabolism, such as dihydropyrimidine dehydrogenase (DPD), orotatephosphoribosyltransferase (OPRT) and thymidylate synthase (TS). The aim of the present study was to investigate the efficacy of adjuvant 5-fluorouracil chemotherapy for UC-UUT with LVI, and to assess the expression of enzymes associated with 5-fluorouracil metabolism as promising biomarkers of therapy efficacy. The present study retrospectively investigated 52 cases of UC-UUT. Following nephroureterectomy, tegafur-uracil was administered to 15 out of 30 patients with LVI who were not eligible for cisplatin-based adjuvant chemotherapy. Levels of DPD, OPRT and TS expression in tumor specimens were determined by reverse transcription-quantitative polymerase chain reaction, and their associations with the efficacy of adjuvant 5-fluorouracil chemotherapy were analyzed. The levels of DPD, OPRT and TS expression were not associated with pathological factors or outcome, although a higher expression of TS was associated with a poorer outcome. Adjuvant 5-fluorouracil chemotherapy significantly improved the outcome of patients with lower DPD expression. However, the levels of OPRT and TS expression did not influence therapeutic efficacy. Adjuvant 5-fluorouracil chemotherapy appears to be effective for lymphovascular-invasive UC-UUT in patients with lower DPD expression.