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

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.

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.

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.

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.