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

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^*

^*Corresponding author for this work

Urology

Johns Hopkins University
Nova Southeastern University
Sorbonne Université
Mayo Clinic Rochester, MN
Quint Fonsegrives
University of Southern California
Azienda Ospedaliera Careggi
CHU de Rennes
Penn State Heart and Vascular Institute
St. Marianna University School of Medicine
University Medical Center Hamburg-Eppendorf
Henry Ford Health System
Kindai University
Medical University of Vienna
University of Turin
Autonomous University of Barcelona

Research output: Contribution to journal › Article › Academic › peer-review

9 Citations (Scopus)

32 Downloads (Pure)

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.

Original language	English
Pages (from-to)	1061-1068
Number of pages	8
Journal	European urology oncology
Volume	7
Issue number	5
DOIs	https://doi.org/10.1016/j.euo.2024.01.010
Publication status	Published - 1 Oct 2024

Bibliographical note

Publisher Copyright:
Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.

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10.1016/j.euo.2024.01.010

Oncologic Outcomes in Patients with Residual Upper Tract Urothelial Carcinoma Following Neoadjuvant ChemotherapyFinal published version, 1.41 MBLicence: Article 25fa Dutch Copyright Act

Cite this

Fletcher, S. A., Pallauf, M., Watts, E. K., Lombardo, K. A., Campbell, J. A., Rezaee, M. E., Rouprêt, M., Boorjian, S. A., Potretzke, A. M., Roshandel, M. R., Ploussard, G., Djaladat, H., Ghoreifi, A., Mari, A., Campi, R., Khene, Z. E., Raman, J. D., Kikuchi, E., Rink, M., ... Singla, N. (2024). Oncologic Outcomes in Patients with Residual Upper Tract Urothelial Carcinoma Following Neoadjuvant Chemotherapy. European urology oncology, 7(5), 1061-1068. https://doi.org/10.1016/j.euo.2024.01.010

@article{201686212a6a4741a75f3e4b5f807014,

title = "Oncologic Outcomes in Patients with Residual Upper Tract Urothelial Carcinoma Following Neoadjuvant Chemotherapy",

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-na{\"i}ve. 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-na{\"i}ve 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-na{\"i}ve 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.",

author = "Fletcher, \{Sean A.\} and Maximilian Pallauf and Watts, \{Emelia K.\} and Lombardo, \{Kara A.\} and Campbell, \{Jack A.\} and Rezaee, \{Michael E.\} and Morgan Roupr{\^e}t and Boorjian, \{Stephen A.\} and Potretzke, \{Aaron M.\} and Roshandel, \{M. Reza\} and Guillaume Ploussard and Hooman Djaladat and Alireza Ghoreifi and Andrea Mari and Riccardo Campi and Khene, \{Zine Eddine\} and Raman, \{Jay D.\} and Eiji Kikuchi and Michael Rink and Firas Abdollah and Boormans, \{Joost L.\} and Kazutoshi Fujita and David D'Andrea and Francesco Soria and Alberto Breda and Jean Hoffman-Censits and McConkey, \{David J.\} and Shariat, \{Shahrokh F.\} and Benjamin Pradere and Nirmish Singla",

year = "2024",

month = oct,

day = "1",

doi = "10.1016/j.euo.2024.01.010",

language = "English",

volume = "7",

pages = "1061--1068",

journal = "European urology oncology",

issn = "2588-9311",

publisher = "Elsevier",

number = "5",

}

Fletcher, SA, Pallauf, M, Watts, EK, Lombardo, KA, Campbell, JA, Rezaee, ME, Rouprêt, M, Boorjian, SA, Potretzke, AM, Roshandel, MR, Ploussard, G, Djaladat, H, Ghoreifi, A, Mari, A, Campi, R, Khene, ZE, Raman, JD, Kikuchi, E, Rink, M, Abdollah, F, Boormans, JL, Fujita, K, D'Andrea, D, Soria, F, Breda, A, Hoffman-Censits, J, McConkey, DJ, Shariat, SF, Pradere, B & Singla, N 2024, 'Oncologic Outcomes in Patients with Residual Upper Tract Urothelial Carcinoma Following Neoadjuvant Chemotherapy', European urology oncology, vol. 7, no. 5, pp. 1061-1068. https://doi.org/10.1016/j.euo.2024.01.010

TY - JOUR

T1 - Oncologic Outcomes in Patients with Residual Upper Tract Urothelial Carcinoma Following Neoadjuvant Chemotherapy

AU - Fletcher, Sean A.

AU - Pallauf, Maximilian

AU - Watts, Emelia K.

AU - Lombardo, Kara A.

AU - Campbell, Jack A.

AU - Rezaee, Michael E.

AU - Rouprêt, Morgan

AU - Boorjian, Stephen A.

AU - Potretzke, Aaron M.

AU - Roshandel, M. Reza

AU - Ploussard, Guillaume

AU - Djaladat, Hooman

AU - Ghoreifi, Alireza

AU - Mari, Andrea

AU - Campi, Riccardo

AU - Khene, Zine Eddine

AU - Raman, Jay D.

AU - Kikuchi, Eiji

AU - Rink, Michael

AU - Abdollah, Firas

AU - Boormans, Joost L.

AU - Fujita, Kazutoshi

AU - D'Andrea, David

AU - Soria, Francesco

AU - Breda, Alberto

AU - Hoffman-Censits, Jean

AU - McConkey, David J.

AU - Shariat, Shahrokh F.

AU - Pradere, Benjamin

AU - Singla, Nirmish

PY - 2024/10/1

Y1 - 2024/10/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85205275241

U2 - 10.1016/j.euo.2024.01.010

DO - 10.1016/j.euo.2024.01.010

M3 - Article

C2 - 38262800

AN - SCOPUS:85205275241

SN - 2588-9311

VL - 7

SP - 1061

EP - 1068

JO - European urology oncology

JF - European urology oncology

IS - 5

ER -

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

Abstract

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