Adjuvant chemotherapy vs. observation for locally advanced upper tract urothelial carcinoma following radical nephroureterectomy

Authors

  • Sina Monfared Division of Urologic Surgery, Beth Israel Deaconess Medical Center, Boston, MA
  • Sumedh Kaul Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA
  • Jamil Almohtasib Division of Urologic Surgery, Beth Israel Deaconess Medical Center, Boston, MA
  • Aaron Fleishman Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA
  • Agustin Perez-Londoño Division of Urologic Surgery, Beth Israel Deaconess Medical Center, Boston, MA
  • Ruslan Korets Division of Urologic Surgery, Beth Israel Deaconess Medical Center, Boston, MA
  • Peter Chang Division of Urologic Surgery, Beth Israel Deaconess Medical Center, Boston, MA
  • Andrew Wagner Division of Urologic Surgery, Beth Israel Deaconess Medical Center, Boston, MA
  • Simon Kim Division of Urology, University of Colorado Anschutz Medical Center, Aurora, CO
  • Joaquim Bellmunt Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
  • Nima Aghdam Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, MA
  • Aria F. Olumi Division of Urologic Surgery, Beth Israel Deaconess Medical Center, Boston, MA
  • Boris Gershman Division of Urologic Surgery, Beth Israel Deaconess Medical Center, Boston, MA

DOI:

https://doi.org/10.5489/cuaj.9678

Keywords:

locally advanced upper tract urothelial carcinoma, radical nephroureterectomy, adjuvant chemotherapy

Abstract

Introduction: Although a single randomized trial demonstrated improved survival with adjuvant chemotherapy (AC) for locally advanced (pT2-4 or N+) upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU), this survival benefit was not observed in pT2 or N+ patients, and real-world data are lacking. We therefore emulated the completed POUT trial using a large, nationwide cancer registry.

Methods: We identified patients aged 50−79 years with pT2−4 or pN+, non-metastatic UTUC treated with RNU from 2006−2020 in the National Cancer Database (NCDB). A propensity score for receipt of multiagent AC within three months of RNU was estimated using logistic regression, and the associations of AC with overall survival (OS) were evaluated after reweighting by stabilized inverse probability of treatment weights (sIPW).

Results: The study cohort comprised 3206 patients, of whom 802 (25%) received AC. pT stage was £pT2 in 954 (30%) patients, and 167 (5%) patients had pN+ disease. Median followup was 47.0 (interquartile range 24.0−86.0) months. After IPW-reweighting, AC was not associated with improved OS compared to observation, with five-year OS of 60% vs. 58%, respectively (hazard ratio 0.92, 95% confidence interval 0.79−1.08, p=0.30). When examining treatment effects across baseline characteristics, AC was not associated with improved survival for any pT or pN category.

Conclusions: In analyses designed to emulate the POUT trial, we did not observe improved OS with AC in the overall cohort, nor in specific pT or pN categories. These findings suggest the need to examine the real-world comparative effectiveness of AC in locally advanced UTUC in further studies.

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Published

2026-08-20

How to Cite

Monfared, S., Kaul, S., Almohtasib, J., Fleishman, A., Perez-Londoño, A., Korets, R., … Gershman, B. (2026). Adjuvant chemotherapy vs. observation for locally advanced upper tract urothelial carcinoma following radical nephroureterectomy. Canadian Urological Association Journal, 20(12). https://doi.org/10.5489/cuaj.9678

Issue

Vol. 20 No. 12 (2026): CUAJ December

Section

Original Research

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