Oncological Outcomes of Neoadjuvant Chemotherapy in High‐Risk UTUC : A Multicenter Study

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Abstract
Objectives: To evaluate the effect of neoadjuvant chemotherapy (NAC) on pathological response and oncologic outcomes in patients with high‐risk upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU) in a real‐world multicenter setting. Methods: We retrospectively analyzed data from 184 patients with high‐risk UTUC who underwent RNU across six institutions and were divided into NAC and non‐NAC groups. The primary endpoint was pathological downstaging. Secondary endpoints were non‐urinary‐tract recurrence‐free survival (NUT‐RFS) and overall survival (OS). We also compared the NAC group with the combined non‐NAC and adjuvant chemotherapy (AC) group. Propensity score matching (PSM) was performed to adjust for baseline differences. Results: 34.2% and 14.1% of 184 patients (median age, 75 years; men, 70.7%) received NAC and AC, respectively. NAC was not significantly associated with pathological downstaging. On multivariable analysis, positive urine cytology (bladder) was independently associated with a lower likelihood of downstaging, whereas a higher baseline eGFR was independently associated with a higher likelihood of downstaging. Neither NUT‐RFS nor OS differed significantly between the NAC and non‐NAC groups or between the NAC and non‐NAC plus AC groups, either in the overall cohort or after PSM. Conclusions: In this real‐world cohort, NAC did not significantly improve pathological or survival outcomes in patients with high‐risk UTUC. Oncological outcomes did not differ significantly between NAC and AC administered after pathological confirmation of risk, although this comparison is susceptible to selection and guarantee‐time bias. Pathology‐guided AC may be a reasonable perioperative strategy, but its relative benefit remains uncertain and warrants prospective validation.

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