Neoadjuvant chemotherapy prior to radical nephroureterectomy: Survival outcomes and recurrence patterns by pathologic node status

Farshad Sheybaee Moghaddam; Rashid K Sayyid; Alireza Ghoreifi; Antonio Franco; Zhenjie Wu; Linhui Wang; Alessandro Antonelli; Francesco Ditonno; Firas Abdollah; Marco Finati; Giuseppe Simone; Gabriele Tuderti; Emma Helstrom; Andres F Correa; Ottavio De Cobelli; Matteo Ferro; Francesco Porpiglia; Daniele Amparore; Antonio Tufano; Sisto Perdonà; Stephan Brönimann; Nirmish Singla; Margaret F Meagher; Ithaar H Derweesh; Dinno F Mendiola; Mark L Gonzalgo; Reuben Ben-David; Reza Mehrazin; Sol C Moon; Soroush Rais-Bahrami; Courtney Yong; Chandru P Sundaram; Raj Bhanvadia; Vitaly Margulis; Riccardo Autorino; Hooman Djaladat

doi:10.1016/j.urolonc.2025.03.001

Neoadjuvant chemotherapy prior to radical nephroureterectomy: Survival outcomes and recurrence patterns by pathologic node status

Farshad Sheybaee Moghaddam, Rashid K Sayyid, Alireza Ghoreifi, Antonio Franco, Zhenjie Wu, Linhui Wang, Alessandro Antonelli, Francesco Ditonno, Firas Abdollah, Marco Finati, Giuseppe Simone, Gabriele Tuderti, Emma Helstrom, Andres F Correa, Ottavio De Cobelli, Matteo Ferro, Francesco Porpiglia, Daniele Amparore, Antonio Tufano, Sisto PerdonàStephan Brönimann, Nirmish Singla, Margaret F Meagher, Ithaar H Derweesh, Dinno F Mendiola, Mark L Gonzalgo, Reuben Ben-David, Reza Mehrazin, Sol C Moon, Soroush Rais-Bahrami, Courtney Yong, Chandru P Sundaram, Raj Bhanvadia, Vitaly Margulis, Riccardo Autorino, Hooman Djaladat

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

Abstract

PURPOSE: To evaluate survival outcomes and recurrence patterns by pathologic nodal status in upper tract urothelial carcinoma (UTUC) patients receiving neoadjuvant chemotherapy (NAC) prior to radical nephroureterectomy (RNU) and lymph node dissection (LND).

MATERIALS AND METHODS: Using the international ROBUUST 2.0 database, a retrospective analysis of UTUC patients who underwent robotic/laparoscopic RNU+LND±NAC was performed. Patients were stratified by NAC and pathologic nodal status into pN0, ypN0, pN+, and ypN+ subgroups. Overall (OS), metastasis-free (MFS), and urothelial recurrence-free survivals (RFS) were compared using Kaplan-Meier curves and multivariable Cox regression modeling.

RESULTS: The cohort included 883 patients (15% received NAC). 212 (24%) patients had (y)pN+ disease. Median follow-up was 19 months. Compared to pN+ patients, ypN+ patients had significantly worse 1- (64% vs. 72%), 3- (40% vs. 54%), and 5-year (20% vs. 31%) OS rates. Node-negative patients had similar OS, irrespective of NAC treatment (1-year: 94%; 3-year: 77%-82%). At 1 year, all ypN+ patients had metastases, while 13% of pN+ patients remained metastasis-free. Among ypN+ patients, 89% experienced nodal/regional or distant metastases as the site of initial recurrence, compared to 39% of pN+ patients. Initial nodal/regional or distant metastases occurred in 42% and 18% of ypN0 and pN0 patients, respectively.

CONCLUSION: ypN+ patients have worse survival compared to pN+ patients. Recurrence patterns differ by nodal and NAC status, with ypN+ patients having a significantly higher incidence of nodal/regional or distant metastases as the initial site of recurrence. These survival outcomes and recurrence patterns differences may have important surveillance and treatment implications.

Original language	English
Pages (from-to)	441.e19-441.e27
Journal	Urologic oncology
Volume	43
Issue number	7
Early online date	Mar 24 2025
DOIs	https://doi.org/10.1016/j.urolonc.2025.03.001
State	Published - Jul 2025

Keywords

Ureteral neoplasm
Nephroureterectomy
Laparoscopy
Drug therapy
Survival
Lymph Node Excision
Ureteral Neoplasms/pathology
Humans
Middle Aged
Male
Survival Rate
Treatment Outcome
Lymphatic Metastasis
Neoplasm Recurrence, Local/pathology
Carcinoma, Transitional Cell/drug therapy
Kidney Neoplasms/pathology
Female
Retrospective Studies
Aged
Nephroureterectomy/methods
Chemotherapy, Adjuvant
Neoadjuvant Therapy/methods

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10.1016/j.urolonc.2025.03.001

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Sheybaee Moghaddam, F., Sayyid, R. K., Ghoreifi, A., Franco, A., Wu, Z., Wang, L., Antonelli, A., Ditonno, F., Abdollah, F., Finati, M., Simone, G., Tuderti, G., Helstrom, E., Correa, A. F., De Cobelli, O., Ferro, M., Porpiglia, F., Amparore, D., Tufano, A., ... Djaladat, H. (2025). Neoadjuvant chemotherapy prior to radical nephroureterectomy: Survival outcomes and recurrence patterns by pathologic node status. Urologic oncology, 43(7), 441.e19-441.e27. https://doi.org/10.1016/j.urolonc.2025.03.001

@article{9f24af046a9c4189bd3f4a3566c6682f,

title = "Neoadjuvant chemotherapy prior to radical nephroureterectomy: Survival outcomes and recurrence patterns by pathologic node status",

abstract = "PURPOSE: To evaluate survival outcomes and recurrence patterns by pathologic nodal status in upper tract urothelial carcinoma (UTUC) patients receiving neoadjuvant chemotherapy (NAC) prior to radical nephroureterectomy (RNU) and lymph node dissection (LND).MATERIALS AND METHODS: Using the international ROBUUST 2.0 database, a retrospective analysis of UTUC patients who underwent robotic/laparoscopic RNU+LND±NAC was performed. Patients were stratified by NAC and pathologic nodal status into pN0, ypN0, pN+, and ypN+ subgroups. Overall (OS), metastasis-free (MFS), and urothelial recurrence-free survivals (RFS) were compared using Kaplan-Meier curves and multivariable Cox regression modeling.RESULTS: The cohort included 883 patients (15\% received NAC). 212 (24\%) patients had (y)pN+ disease. Median follow-up was 19 months. Compared to pN+ patients, ypN+ patients had significantly worse 1- (64\% vs. 72\%), 3- (40\% vs. 54\%), and 5-year (20\% vs. 31\%) OS rates. Node-negative patients had similar OS, irrespective of NAC treatment (1-year: 94\%; 3-year: 77\%-82\%). At 1 year, all ypN+ patients had metastases, while 13\% of pN+ patients remained metastasis-free. Among ypN+ patients, 89\% experienced nodal/regional or distant metastases as the site of initial recurrence, compared to 39\% of pN+ patients. Initial nodal/regional or distant metastases occurred in 42\% and 18\% of ypN0 and pN0 patients, respectively.CONCLUSION: ypN+ patients have worse survival compared to pN+ patients. Recurrence patterns differ by nodal and NAC status, with ypN+ patients having a significantly higher incidence of nodal/regional or distant metastases as the initial site of recurrence. These survival outcomes and recurrence patterns differences may have important surveillance and treatment implications.",

keywords = "Ureteral neoplasm, Nephroureterectomy, Laparoscopy, Drug therapy, Survival, Lymph Node Excision, Ureteral Neoplasms/pathology, Humans, Middle Aged, Male, Survival Rate, Treatment Outcome, Lymphatic Metastasis, Neoplasm Recurrence, Local/pathology, Carcinoma, Transitional Cell/drug therapy, Kidney Neoplasms/pathology, Female, Retrospective Studies, Aged, Nephroureterectomy/methods, Chemotherapy, Adjuvant, Neoadjuvant Therapy/methods",

author = "\{Sheybaee Moghaddam\}, Farshad and Sayyid, \{Rashid K\} and Alireza Ghoreifi and Antonio Franco and Zhenjie Wu and Linhui Wang and Alessandro Antonelli and Francesco Ditonno and Firas Abdollah and Marco Finati and Giuseppe Simone and Gabriele Tuderti and Emma Helstrom and Correa, \{Andres F\} and \{De Cobelli\}, Ottavio and Matteo Ferro and Francesco Porpiglia and Daniele Amparore and Antonio Tufano and Sisto Perdon{\`a} and Stephan Br{\"o}nimann and Nirmish Singla and Meagher, \{Margaret F\} and Derweesh, \{Ithaar H\} and Mendiola, \{Dinno F\} and Gonzalgo, \{Mark L\} and Reuben Ben-David and Reza Mehrazin and Moon, \{Sol C\} and Soroush Rais-Bahrami and Courtney Yong and Sundaram, \{Chandru P\} and Raj Bhanvadia and Vitaly Margulis and Riccardo Autorino and Hooman Djaladat",

note = "Publisher Copyright: {\textcopyright} 2025 Elsevier Inc.",

year = "2025",

month = jul,

doi = "10.1016/j.urolonc.2025.03.001",

language = "English",

volume = "43",

pages = "441.e19--441.e27",

journal = "Urologic oncology",

issn = "1078-1439",

publisher = "Elsevier Inc.",

number = "7",

}

Sheybaee Moghaddam, F, Sayyid, RK, Ghoreifi, A, Franco, A, Wu, Z, Wang, L, Antonelli, A, Ditonno, F, Abdollah, F, Finati, M, Simone, G, Tuderti, G, Helstrom, E, Correa, AF, De Cobelli, O, Ferro, M, Porpiglia, F, Amparore, D, Tufano, A, Perdonà, S, Brönimann, S, Singla, N, Meagher, MF, Derweesh, IH, Mendiola, DF, Gonzalgo, ML, Ben-David, R, Mehrazin, R, Moon, SC, Rais-Bahrami, S, Yong, C, Sundaram, CP, Bhanvadia, R, Margulis, V, Autorino, R & Djaladat, H 2025, 'Neoadjuvant chemotherapy prior to radical nephroureterectomy: Survival outcomes and recurrence patterns by pathologic node status', Urologic oncology, vol. 43, no. 7, pp. 441.e19-441.e27. https://doi.org/10.1016/j.urolonc.2025.03.001

TY - JOUR

T1 - Neoadjuvant chemotherapy prior to radical nephroureterectomy

T2 - Survival outcomes and recurrence patterns by pathologic node status

AU - Sheybaee Moghaddam, Farshad

AU - Sayyid, Rashid K

AU - Ghoreifi, Alireza

AU - Franco, Antonio

AU - Wu, Zhenjie

AU - Wang, Linhui

AU - Antonelli, Alessandro

AU - Ditonno, Francesco

AU - Abdollah, Firas

AU - Finati, Marco

AU - Simone, Giuseppe

AU - Tuderti, Gabriele

AU - Helstrom, Emma

AU - Correa, Andres F

AU - De Cobelli, Ottavio

AU - Ferro, Matteo

AU - Porpiglia, Francesco

AU - Amparore, Daniele

AU - Tufano, Antonio

AU - Perdonà, Sisto

AU - Brönimann, Stephan

AU - Singla, Nirmish

AU - Meagher, Margaret F

AU - Derweesh, Ithaar H

AU - Mendiola, Dinno F

AU - Gonzalgo, Mark L

AU - Ben-David, Reuben

AU - Mehrazin, Reza

AU - Moon, Sol C

AU - Rais-Bahrami, Soroush

AU - Yong, Courtney

AU - Sundaram, Chandru P

AU - Bhanvadia, Raj

AU - Margulis, Vitaly

AU - Autorino, Riccardo

AU - Djaladat, Hooman

PY - 2025/7

Y1 - 2025/7

N2 - PURPOSE: To evaluate survival outcomes and recurrence patterns by pathologic nodal status in upper tract urothelial carcinoma (UTUC) patients receiving neoadjuvant chemotherapy (NAC) prior to radical nephroureterectomy (RNU) and lymph node dissection (LND).MATERIALS AND METHODS: Using the international ROBUUST 2.0 database, a retrospective analysis of UTUC patients who underwent robotic/laparoscopic RNU+LND±NAC was performed. Patients were stratified by NAC and pathologic nodal status into pN0, ypN0, pN+, and ypN+ subgroups. Overall (OS), metastasis-free (MFS), and urothelial recurrence-free survivals (RFS) were compared using Kaplan-Meier curves and multivariable Cox regression modeling.RESULTS: The cohort included 883 patients (15% received NAC). 212 (24%) patients had (y)pN+ disease. Median follow-up was 19 months. Compared to pN+ patients, ypN+ patients had significantly worse 1- (64% vs. 72%), 3- (40% vs. 54%), and 5-year (20% vs. 31%) OS rates. Node-negative patients had similar OS, irrespective of NAC treatment (1-year: 94%; 3-year: 77%-82%). At 1 year, all ypN+ patients had metastases, while 13% of pN+ patients remained metastasis-free. Among ypN+ patients, 89% experienced nodal/regional or distant metastases as the site of initial recurrence, compared to 39% of pN+ patients. Initial nodal/regional or distant metastases occurred in 42% and 18% of ypN0 and pN0 patients, respectively.CONCLUSION: ypN+ patients have worse survival compared to pN+ patients. Recurrence patterns differ by nodal and NAC status, with ypN+ patients having a significantly higher incidence of nodal/regional or distant metastases as the initial site of recurrence. These survival outcomes and recurrence patterns differences may have important surveillance and treatment implications.

AB - PURPOSE: To evaluate survival outcomes and recurrence patterns by pathologic nodal status in upper tract urothelial carcinoma (UTUC) patients receiving neoadjuvant chemotherapy (NAC) prior to radical nephroureterectomy (RNU) and lymph node dissection (LND).MATERIALS AND METHODS: Using the international ROBUUST 2.0 database, a retrospective analysis of UTUC patients who underwent robotic/laparoscopic RNU+LND±NAC was performed. Patients were stratified by NAC and pathologic nodal status into pN0, ypN0, pN+, and ypN+ subgroups. Overall (OS), metastasis-free (MFS), and urothelial recurrence-free survivals (RFS) were compared using Kaplan-Meier curves and multivariable Cox regression modeling.RESULTS: The cohort included 883 patients (15% received NAC). 212 (24%) patients had (y)pN+ disease. Median follow-up was 19 months. Compared to pN+ patients, ypN+ patients had significantly worse 1- (64% vs. 72%), 3- (40% vs. 54%), and 5-year (20% vs. 31%) OS rates. Node-negative patients had similar OS, irrespective of NAC treatment (1-year: 94%; 3-year: 77%-82%). At 1 year, all ypN+ patients had metastases, while 13% of pN+ patients remained metastasis-free. Among ypN+ patients, 89% experienced nodal/regional or distant metastases as the site of initial recurrence, compared to 39% of pN+ patients. Initial nodal/regional or distant metastases occurred in 42% and 18% of ypN0 and pN0 patients, respectively.CONCLUSION: ypN+ patients have worse survival compared to pN+ patients. Recurrence patterns differ by nodal and NAC status, with ypN+ patients having a significantly higher incidence of nodal/regional or distant metastases as the initial site of recurrence. These survival outcomes and recurrence patterns differences may have important surveillance and treatment implications.

KW - Ureteral neoplasm

KW - Nephroureterectomy

KW - Laparoscopy

KW - Drug therapy

KW - Survival

KW - Lymph Node Excision

KW - Ureteral Neoplasms/pathology

KW - Humans

KW - Middle Aged

KW - Male

KW - Survival Rate

KW - Treatment Outcome

KW - Lymphatic Metastasis

KW - Neoplasm Recurrence, Local/pathology

KW - Carcinoma, Transitional Cell/drug therapy

KW - Kidney Neoplasms/pathology

KW - Female

KW - Retrospective Studies

KW - Aged

KW - Nephroureterectomy/methods

KW - Chemotherapy, Adjuvant

KW - Neoadjuvant Therapy/methods

UR - https://www.scopus.com/pages/publications/105001022636

U2 - 10.1016/j.urolonc.2025.03.001

DO - 10.1016/j.urolonc.2025.03.001

M3 - Article

C2 - 40133182

SN - 1078-1439

VL - 43

SP - 441.e19-441.e27

JO - Urologic oncology

JF - Urologic oncology

IS - 7

ER -

Neoadjuvant chemotherapy prior to radical nephroureterectomy: Survival outcomes and recurrence patterns by pathologic node status

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