Survival in Responders and Nonresponders of Neoadjuvant and Induction Chemotherapy in Invasive Urothelial Carcinoma of the Urinary Bladder: A Clinical and Pathological Stage-Matched Analysis

Daan J. Reesink; Charlotte S. Voskuilen; Ewoudt M.W. van de Garde; Kees Hendricksen; Simon Horenblas; Harm H.E. van Melick; Bas W.G. van Rhijn

doi:10.1016/j.clgc.2025.102319

Survival in Responders and Nonresponders of Neoadjuvant and Induction Chemotherapy in Invasive Urothelial Carcinoma of the Urinary Bladder: A Clinical and Pathological Stage-Matched Analysis

Daan J. Reesink^*
, Charlotte S. Voskuilen
, Ewoudt M.W. van de Garde
, Kees Hendricksen
, Simon Horenblas
, Harm H.E. van Melick
, Bas W.G. van Rhijn

^*Corresponding author for this work

St. Antonius Ziekenhuis
The Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital
University of Regensburg

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

Abstract

Introduction/Background: A recent study reported that patients with residual urothelial carcinoma of the bladder subsequent to neoadjuvant/induction chemotherapy (NAIC) prior to RC exhibited inferior oncological outcomes in comparison to pathological stage-matched patients who underwent upfront RC. Our hypothesis is that this may be ascribed to variations in preoperative CT-stage rather than the impact of chemotherapy. Patients and Methods: This retrospective multicentre study included 513 patients who underwent RC for cT2-4N0-3M0 disease between 2010 and 2017. Patients were categorized based on pathological outcomes: pathological complete response (pCR, (y)pT0N0), complete downstaging (pCD, (y)pT0/is/a/1N0) and residual muscle-invasive and/or node positive disease (rMIBC, (y)pT2-4N0 and/or (y)pN1-3). Results: Of the total cohort, 175 (34.1%) patients underwent NAIC+RC, while 338 (65.9%) underwent upfront RC. NAIC+RC patients exhibited lower age and CCI-scores, along with higher cT&N-stage (all P-values < .001). The mOS was 60.5 months for NAIC+RC and 49.4 months for upfront RC (P-value = .171). In patients with rMIBC, survival was inferior after NAIC+RC compared to upfront RC. However, the clinical stage distribution between NAIC+RC and upfront RC was imbalanced, with 3% versus 49% cT2N0 patients and 47% versus 9% cT4b and/or N+ patients, respectively. Following adjustments for cT & N-stage, age, and CCI-scores in multivariable Cox proportional-hazards analysis, worse OS was associated with upfront RC (HR 1.52, [95% CI, 1.11-2.10], P-value = .009). Conclusion: The observed inferior survival in cT2-4N0-3M0 patients with rMIBC after NAIC+RC compared to those undergoing upfront RC resulted from worse preoperative characteristics, including clinical stage. The representation of clinical disease stage should not be overlooked in survival analyses.

Original language	English
Article number	102319
Number of pages	14
Journal	Clinical Genitourinary Cancer
Volume	23
Issue number	3
Early online date	21 Feb 2025
DOIs	https://doi.org/10.1016/j.clgc.2025.102319
Publication status	Published - Jun 2025

Bibliographical note

Publisher Copyright:
© 2025 Elsevier Inc.

Funding

The authors thank the registration team of the Netherlands Comprehensive Cancer Organisation (IKNL) for the collection of data for the Netherlands Cancer Registry as well as IKNL staff for scientific advice. The authors thank Roche Nederland B.V. for funding for this research project. This research received a grant from Roche Nederland B.V. to perform this study (Grant number: ML40374).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Bladder carcinoma
Invasive bladder cancer
Muscle invasive
Radical cystectomy
Systemic therapy response

Access to Document

10.1016/j.clgc.2025.102319

Survival in Responders and Nonresponders of Neoadjuvant and Induction Chemotherapy in Invasive Urothelial Carcinoma of the Urinary Bladder: A Clinical and Pathological Stage-Matched AnalysisFinal published version, 1.76 MBLicence: Taverne

Cite this

Reesink, D. J., Voskuilen, C. S., van de Garde, E. M. W., Hendricksen, K., Horenblas, S., van Melick, H. H. E., & van Rhijn, B. W. G. (2025). Survival in Responders and Nonresponders of Neoadjuvant and Induction Chemotherapy in Invasive Urothelial Carcinoma of the Urinary Bladder: A Clinical and Pathological Stage-Matched Analysis. Clinical Genitourinary Cancer, 23(3), Article 102319. https://doi.org/10.1016/j.clgc.2025.102319

@article{496157999a994708a960fa35eb96c845,

title = "Survival in Responders and Nonresponders of Neoadjuvant and Induction Chemotherapy in Invasive Urothelial Carcinoma of the Urinary Bladder: A Clinical and Pathological Stage-Matched Analysis",

abstract = "Introduction/Background: A recent study reported that patients with residual urothelial carcinoma of the bladder subsequent to neoadjuvant/induction chemotherapy (NAIC) prior to RC exhibited inferior oncological outcomes in comparison to pathological stage-matched patients who underwent upfront RC. Our hypothesis is that this may be ascribed to variations in preoperative CT-stage rather than the impact of chemotherapy. Patients and Methods: This retrospective multicentre study included 513 patients who underwent RC for cT2-4N0-3M0 disease between 2010 and 2017. Patients were categorized based on pathological outcomes: pathological complete response (pCR, (y)pT0N0), complete downstaging (pCD, (y)pT0/is/a/1N0) and residual muscle-invasive and/or node positive disease (rMIBC, (y)pT2-4N0 and/or (y)pN1-3). Results: Of the total cohort, 175 (34.1\%) patients underwent NAIC+RC, while 338 (65.9\%) underwent upfront RC. NAIC+RC patients exhibited lower age and CCI-scores, along with higher cT\&N-stage (all P-values < .001). The mOS was 60.5 months for NAIC+RC and 49.4 months for upfront RC (P-value = .171). In patients with rMIBC, survival was inferior after NAIC+RC compared to upfront RC. However, the clinical stage distribution between NAIC+RC and upfront RC was imbalanced, with 3\% versus 49\% cT2N0 patients and 47\% versus 9\% cT4b and/or N+ patients, respectively. Following adjustments for cT \& N-stage, age, and CCI-scores in multivariable Cox proportional-hazards analysis, worse OS was associated with upfront RC (HR 1.52, [95\% CI, 1.11-2.10], P-value = .009). Conclusion: The observed inferior survival in cT2-4N0-3M0 patients with rMIBC after NAIC+RC compared to those undergoing upfront RC resulted from worse preoperative characteristics, including clinical stage. The representation of clinical disease stage should not be overlooked in survival analyses.",

keywords = "Bladder carcinoma, Invasive bladder cancer, Muscle invasive, Radical cystectomy, Systemic therapy response",

author = "Reesink, \{Daan J.\} and Voskuilen, \{Charlotte S.\} and \{van de Garde\}, \{Ewoudt M.W.\} and Kees Hendricksen and Simon Horenblas and \{van Melick\}, \{Harm H.E.\} and \{van Rhijn\}, \{Bas W.G.\}",

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

year = "2025",

month = jun,

doi = "10.1016/j.clgc.2025.102319",

language = "English",

volume = "23",

journal = "Clinical Genitourinary Cancer",

issn = "1558-7673",

publisher = "Elsevier Inc.",

number = "3",

}

Reesink, DJ, Voskuilen, CS, van de Garde, EMW, Hendricksen, K, Horenblas, S, van Melick, HHE & van Rhijn, BWG 2025, 'Survival in Responders and Nonresponders of Neoadjuvant and Induction Chemotherapy in Invasive Urothelial Carcinoma of the Urinary Bladder: A Clinical and Pathological Stage-Matched Analysis', Clinical Genitourinary Cancer, vol. 23, no. 3, 102319. https://doi.org/10.1016/j.clgc.2025.102319

Survival in Responders and Nonresponders of Neoadjuvant and Induction Chemotherapy in Invasive Urothelial Carcinoma of the Urinary Bladder: A Clinical and Pathological Stage-Matched Analysis. / Reesink, Daan J.; Voskuilen, Charlotte S.; van de Garde, Ewoudt M.W. et al.
In: Clinical Genitourinary Cancer, Vol. 23, No. 3, 102319, 06.2025.

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

TY - JOUR

T1 - Survival in Responders and Nonresponders of Neoadjuvant and Induction Chemotherapy in Invasive Urothelial Carcinoma of the Urinary Bladder

T2 - A Clinical and Pathological Stage-Matched Analysis

AU - Reesink, Daan J.

AU - Voskuilen, Charlotte S.

AU - van de Garde, Ewoudt M.W.

AU - Hendricksen, Kees

AU - Horenblas, Simon

AU - van Melick, Harm H.E.

AU - van Rhijn, Bas W.G.

PY - 2025/6

Y1 - 2025/6

N2 - Introduction/Background: A recent study reported that patients with residual urothelial carcinoma of the bladder subsequent to neoadjuvant/induction chemotherapy (NAIC) prior to RC exhibited inferior oncological outcomes in comparison to pathological stage-matched patients who underwent upfront RC. Our hypothesis is that this may be ascribed to variations in preoperative CT-stage rather than the impact of chemotherapy. Patients and Methods: This retrospective multicentre study included 513 patients who underwent RC for cT2-4N0-3M0 disease between 2010 and 2017. Patients were categorized based on pathological outcomes: pathological complete response (pCR, (y)pT0N0), complete downstaging (pCD, (y)pT0/is/a/1N0) and residual muscle-invasive and/or node positive disease (rMIBC, (y)pT2-4N0 and/or (y)pN1-3). Results: Of the total cohort, 175 (34.1%) patients underwent NAIC+RC, while 338 (65.9%) underwent upfront RC. NAIC+RC patients exhibited lower age and CCI-scores, along with higher cT&N-stage (all P-values < .001). The mOS was 60.5 months for NAIC+RC and 49.4 months for upfront RC (P-value = .171). In patients with rMIBC, survival was inferior after NAIC+RC compared to upfront RC. However, the clinical stage distribution between NAIC+RC and upfront RC was imbalanced, with 3% versus 49% cT2N0 patients and 47% versus 9% cT4b and/or N+ patients, respectively. Following adjustments for cT & N-stage, age, and CCI-scores in multivariable Cox proportional-hazards analysis, worse OS was associated with upfront RC (HR 1.52, [95% CI, 1.11-2.10], P-value = .009). Conclusion: The observed inferior survival in cT2-4N0-3M0 patients with rMIBC after NAIC+RC compared to those undergoing upfront RC resulted from worse preoperative characteristics, including clinical stage. The representation of clinical disease stage should not be overlooked in survival analyses.

AB - Introduction/Background: A recent study reported that patients with residual urothelial carcinoma of the bladder subsequent to neoadjuvant/induction chemotherapy (NAIC) prior to RC exhibited inferior oncological outcomes in comparison to pathological stage-matched patients who underwent upfront RC. Our hypothesis is that this may be ascribed to variations in preoperative CT-stage rather than the impact of chemotherapy. Patients and Methods: This retrospective multicentre study included 513 patients who underwent RC for cT2-4N0-3M0 disease between 2010 and 2017. Patients were categorized based on pathological outcomes: pathological complete response (pCR, (y)pT0N0), complete downstaging (pCD, (y)pT0/is/a/1N0) and residual muscle-invasive and/or node positive disease (rMIBC, (y)pT2-4N0 and/or (y)pN1-3). Results: Of the total cohort, 175 (34.1%) patients underwent NAIC+RC, while 338 (65.9%) underwent upfront RC. NAIC+RC patients exhibited lower age and CCI-scores, along with higher cT&N-stage (all P-values < .001). The mOS was 60.5 months for NAIC+RC and 49.4 months for upfront RC (P-value = .171). In patients with rMIBC, survival was inferior after NAIC+RC compared to upfront RC. However, the clinical stage distribution between NAIC+RC and upfront RC was imbalanced, with 3% versus 49% cT2N0 patients and 47% versus 9% cT4b and/or N+ patients, respectively. Following adjustments for cT & N-stage, age, and CCI-scores in multivariable Cox proportional-hazards analysis, worse OS was associated with upfront RC (HR 1.52, [95% CI, 1.11-2.10], P-value = .009). Conclusion: The observed inferior survival in cT2-4N0-3M0 patients with rMIBC after NAIC+RC compared to those undergoing upfront RC resulted from worse preoperative characteristics, including clinical stage. The representation of clinical disease stage should not be overlooked in survival analyses.

KW - Bladder carcinoma

KW - Invasive bladder cancer

KW - Muscle invasive

KW - Radical cystectomy

KW - Systemic therapy response

UR - https://www.scopus.com/pages/publications/105000561011

U2 - 10.1016/j.clgc.2025.102319

DO - 10.1016/j.clgc.2025.102319

M3 - Article

AN - SCOPUS:105000561011

SN - 1558-7673

VL - 23

JO - Clinical Genitourinary Cancer

JF - Clinical Genitourinary Cancer

IS - 3

M1 - 102319

ER -

Reesink DJ, Voskuilen CS, van de Garde EMW, Hendricksen K, Horenblas S, van Melick HHE et al. Survival in Responders and Nonresponders of Neoadjuvant and Induction Chemotherapy in Invasive Urothelial Carcinoma of the Urinary Bladder: A Clinical and Pathological Stage-Matched Analysis. Clinical Genitourinary Cancer. 2025 Jun;23(3):102319. Epub 2025 Feb 21. doi: 10.1016/j.clgc.2025.102319

Survival in Responders and Nonresponders of Neoadjuvant and Induction Chemotherapy in Invasive Urothelial Carcinoma of the Urinary Bladder: A Clinical and Pathological Stage-Matched Analysis

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

Access to Document

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