Oncologic Outcomes in Patients with Residual Upper Tract Urothelial Carcinoma Following Neoadjuvant Chemotherapy

Sean A Fletcher; Maximilian Pallauf; Emelia K Watts; Kara A Lombardo; Jack A Campbell; Michael E Rezaee; Morgan Rouprêt; Stephen A Boorjian; Aaron M Potretzke; M Reza Roshandel; Guillaume Ploussard; Hooman Djaladat; Alireza Ghoreifi; Andrea Mari; Riccardo Campi; Zine-Eddine Khene; Jay D Raman; Eiji Kikuchi; Michael Rink; Firas Abdollah; Joost L Boormans; Kazutoshi Fujita; David D'Andrea; Francesco Soria; Alberto Breda; Jean Hoffman-Censits; David J McConkey; Shahrokh F Shariat; Benjamin Pradere; Nirmish Singla

doi:10.1016/j.euo.2024.01.010

Oncologic Outcomes in Patients with Residual Upper Tract Urothelial Carcinoma Following Neoadjuvant Chemotherapy

Eur Urol Oncol. 2024 Jan 22:S2588-9311(24)00035-X. doi: 10.1016/j.euo.2024.01.010. Online ahead of print.

Authors

Sean A Fletcher¹, Maximilian Pallauf², Emelia K Watts³, Kara A Lombardo¹, Jack A Campbell¹, Michael E Rezaee¹, Morgan Rouprêt⁴, Stephen A Boorjian⁵, Aaron M Potretzke⁵, M Reza Roshandel⁶, Guillaume Ploussard⁷, Hooman Djaladat⁸, Alireza Ghoreifi⁸, Andrea Mari⁹, Riccardo Campi⁹, Zine-Eddine Khene¹⁰, Jay D Raman¹¹, Eiji Kikuchi¹², Michael Rink¹³, Firas Abdollah¹⁴, Joost L Boormans¹⁵, Kazutoshi Fujita¹⁶, David D'Andrea¹⁷, Francesco Soria¹⁸, Alberto Breda¹⁹, Jean Hoffman-Censits²⁰, David J McConkey²⁰, Shahrokh F Shariat¹⁷, Benjamin Pradere⁷, Nirmish Singla²¹

Affiliations

¹ The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Urology, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria.
³ Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, USA.
⁴ GRC 5 Predictive Onco-Uro, Sorbonne University, Department of Urology, Pitie-Salpetriere Hospital, AP-HP, Paris, France.
⁵ Department of Urology, Mayo Clinic, Rochester, MN, USA.
⁶ Department of Urology, Mayo Clinic, Rochester, MN, USA; Department of Urology, Westchester County Medical Center, Valhalla, NY, USA.
⁷ Department of Urology, La Croix du Sud Hôpital, Quint Fonsegrives, France.
⁸ Institute of Urology, University of Southern California, Los Angeles, CA, USA.
⁹ Department of Urology, Careggi Hospital, Florence, Italy.
¹⁰ Department of Urology, Rennes University Hospital, Rennes, France.
¹¹ Department of Urology, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA.
¹² Department of Urology, St. Marianna University School of Medicine, Kanagawa, Japan.
¹³ Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹⁴ Department of Urology, Vattikuti Urology Institute, Henry Ford Hospital, Detroit, MI, USA.
¹⁵ Department of Urology, Erasmus University Medical Center Rotterdam, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
¹⁶ Department of Urology, Kindai University Faculty of Medicine, Osaka, Japan.
¹⁷ Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
¹⁸ Division of Urology, Department of Surgical Sciences, San Giovanni Battista Hospital, University of Studies of Torino, Turin, Italy.
¹⁹ Department of Urology, Fundació Puigvert, Autonomous University of Barcelona, Barcelona, Spain.
²⁰ The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
²¹ The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA. Electronic address: nsingla2@jhmi.edu.

PMID: 38262800
DOI: 10.1016/j.euo.2024.01.010

Abstract

Background and objective: Growing evidence supports the use of neoadjuvant chemotherapy (NAC) for upper tract urothelial carcinoma (UTUC). However, the implications of residual UTUC at radical nephroureterectomy (RNU) after NAC are not well characterized. Our objective was to compare oncologic outcomes for pathologic risk-matched patients who underwent RNU for UTUC who either received NAC or were chemotherapy-naïve.

Methods: We retrospectively identified 1993 patients (including 112 NAC recipients) who underwent RNU for nonmetastatic, high-grade UTUC between 1985 and 2022 in a large, international, multicenter cohort. We divided the cohort into low-risk and high-risk groups defined according to pathologic findings of muscle invasion and lymph node involvement at RNU. Recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS) estimates were calculated using the Kaplan-Meier method. Multivariable analyses were performed to determine clinical and demographic factors associated with these outcomes.

Key findings and limitations: Among patients with low-risk pathology at RNU, RFS, OS, and CSS were similar between the NAC and chemotherapy-naïve groups. Among patients with high-risk pathology at RNU, the NAC group had poorer RFS (hazard ratio [HR] 3.07, 95% confidence interval [CI] 2.10-4.48), OS (HR 2.06, 95% CI 1.33-3.20), and CSS (subdistribution HR 2.54, 95% CI 1.37-4.69) in comparison to the pathologic risk-matched, chemotherapy-naïve group. Limitations include the lack of centralized pathologic review.

Conclusions and clinical implications: Patients with residual invasive disease at RNU after NAC represent a uniquely high-risk population with respect to oncologic outcomes. There is a critical need to determine an optimal adjuvant approach for these patients.

Patient summary: We studied a large, international group of patients with cancer of the upper urinary tract who underwent surgery either with or without receiving chemotherapy beforehand. We identified a high-risk subgroup of patients with residual aggressive cancer after chemotherapy and surgery who should be prioritized for clinical trials and drug development.

Keywords: Neoadjuvant chemotherapy; Oncologic outcomes; Upper tract urothelial carcinoma.