Adjuvant Systemic Therapy Improved Survival After Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma

Background: The purpose of this study was to test for survival differences according to adjuvant chemotherapy (AC) status in radical nephroureterectomy (RNU) patients with pT2–T4 and/or N1–2 upper tract urothelial carcinoma (UTUC). Patients and Methods: Within the Surveillance, Epidemiology, and End Results database (SEER, 2007–2020), patients with UTUC treated with AC versus RNU alone were identified. Kaplan–Meier plots and multivariable Cox regression models addressed cancer-specific mortality (CSM). Results: Of 1995 patients with UTUC, 804 (40%) underwent AC versus 1191 (60%) RNU alone. AC rates increased from 36.1 to 57.0% over time in the overall cohort [estimated annual percentage changes (EAPC) ± 4.5%, p < 0.001]. The increase was from 28.8 to 50.0% in TanyN0 patients (EAPC ± 7.8%, p < 0.001) versus 50.0–70.9% in TanyN1–2 patients (EAPC ± 2.3%, p = 0.002). Within 698 patients harboring TanyN1–2 stage, median CSM was 31 months after AC versus 16 months in RNU alone (Δ = 15 months, p < 0.0001) and AC independently predicted lower CSM [hazard ratio (HR) 0.64; p < 0.001]. Similarly, within subgroup analyses according to stage, relative to RNU alone, AC independently predicted lower CSM in T2N1–2 (HR 0.49; p = 0.04), in T3N1–2 (HR 0.72; p = 0.015), and in T4N1–2 (HR 0.49, p < 0.001) patients. Conversely, in all TanyN0 as well as in all stage-specific subgroup analyses addressing N0 patients, AC did not affect CSM rates (all p > 0.05). Conclusions: In RNU patients, AC use is associated with significantly lower CSM in lymph-node-positive (N1–2) patients but not in lymph-node-negative patients (N0). The distinction between N1–2 and N0 regarding the effect of AC on CSM applied across all T stages from T2 to T4, inclusively.