Oncologic Outcomes for Patients with Residual Cancer at Cystectomy Following Neoadjuvant Chemotherapy

A Pathologic Stage-matched Analysis

Bimal Bhindi, Igor Frank, Ross J. Mason, Robert F. Tarrell, Prabin Thapa, John C. Cheville, Brian Costello, Lance C. Pagliaro, Robert Jeffrey Karnes, R. Houston Thompson, Matthew K. Tollefson, Stephen A. Boorjian

Research output: Contribution to journalArticle

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Abstract

While it has been demonstrated that receipt of neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) improves survival compared to RC alone, the driving factor for this benefit may be from patients with ypT0 status at surgery. Meanwhile, the implications of having residual urothelial carcinoma of the bladder (rUCB) at RC after NAC are less clear. We therefore evaluated whether survival differed between patients with rUCB at RC after NAC and stage-matched controls who underwent RC alone. Patients who underwent NAC + RC (n = 180) were matched to controls who underwent RC alone (n = 324) on the basis of pT and pN stage, margin status, and year of RC. The 5-yr recurrence-free survival (RFS; 90% vs 94%; p = 1), cancer-specific survival (CSS; 82% vs 93%; p = 0.4), and overall survival (OS; 82% vs 82%; p = 0.5) were not significantly different between the NAC and control groups for patients with ypT0N0/pT0N0 disease (n = 103). Conversely, among patients with rUCB at RC (n = 401), patients who received NAC had significantly worse 5-yr RFS (50% vs 63%; p = 0.01), CSS (40% vs 59%; p = 0.003), and OS (33% vs 48%; p = 0.02). On multivariable analysis for patients with rUCB, NAC receipt remained independently associated with worse RFS (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.28-2.66; p = 0.001), CSS (HR 1.81, 95% CI 1.30-2.52; p <. 0.001), and OS (HR 1.57, 95% CI 1.18-2.08; p = 0.002). Limitations include potential for selection bias owing to the retrospective observational design. Thus, while patients who achieve a complete response to NAC have excellent survival outcomes, those with rUCB after NAC have a worse prognosis compared to stage-matched controls undergoing RC alone. It may be worthwhile considering these patients for clinical trials evaluating the role of additional treatments after RC using newer agents while we await further research on predicting which patients achieve ypT0 status from NAC before RC. Patient summary: On surgical removal of the bladder, patients without residual bladder cancer after neoadjuvant chemotherapy have excellent survival outcomes. However, patients with residual cancer after neoadjuvant chemotherapy and surgery have worse outcomes compared to patients undergoing surgery alone. These patients should therefore be considered for additional treatments after surgery using newer agents while we await further research on predicting which patients will benefit from neoadjuvant chemotherapy before bladder removal for cancer. Patients who achieve a complete response after neoadjuvant chemotherapy have excellent survival outcomes. However, patients with residual disease at cystectomy after neoadjuvant chemotherapy have a worse prognosis compared to pathological stage-matched patients who underwent cystectomy alone.

Original languageEnglish (US)
JournalEuropean Urology
DOIs
StateAccepted/In press - 2017

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Cystectomy
Residual Neoplasm
Drug Therapy
Urinary Bladder
Survival
Carcinoma
Confidence Intervals
Urinary Bladder Neoplasms
Selection Bias

Keywords

  • Antineoplastic agents
  • Cisplatin
  • Cystectomy
  • Neoadjuvant therapy
  • Urinary bladder neoplasms

ASJC Scopus subject areas

  • Urology

Cite this

Oncologic Outcomes for Patients with Residual Cancer at Cystectomy Following Neoadjuvant Chemotherapy : A Pathologic Stage-matched Analysis. / Bhindi, Bimal; Frank, Igor; Mason, Ross J.; Tarrell, Robert F.; Thapa, Prabin; Cheville, John C.; Costello, Brian; Pagliaro, Lance C.; Karnes, Robert Jeffrey; Thompson, R. Houston; Tollefson, Matthew K.; Boorjian, Stephen A.

In: European Urology, 2017.

Research output: Contribution to journalArticle

Bhindi, Bimal ; Frank, Igor ; Mason, Ross J. ; Tarrell, Robert F. ; Thapa, Prabin ; Cheville, John C. ; Costello, Brian ; Pagliaro, Lance C. ; Karnes, Robert Jeffrey ; Thompson, R. Houston ; Tollefson, Matthew K. ; Boorjian, Stephen A. / Oncologic Outcomes for Patients with Residual Cancer at Cystectomy Following Neoadjuvant Chemotherapy : A Pathologic Stage-matched Analysis. In: European Urology. 2017.
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title = "Oncologic Outcomes for Patients with Residual Cancer at Cystectomy Following Neoadjuvant Chemotherapy: A Pathologic Stage-matched Analysis",
abstract = "While it has been demonstrated that receipt of neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) improves survival compared to RC alone, the driving factor for this benefit may be from patients with ypT0 status at surgery. Meanwhile, the implications of having residual urothelial carcinoma of the bladder (rUCB) at RC after NAC are less clear. We therefore evaluated whether survival differed between patients with rUCB at RC after NAC and stage-matched controls who underwent RC alone. Patients who underwent NAC + RC (n = 180) were matched to controls who underwent RC alone (n = 324) on the basis of pT and pN stage, margin status, and year of RC. The 5-yr recurrence-free survival (RFS; 90{\%} vs 94{\%}; p = 1), cancer-specific survival (CSS; 82{\%} vs 93{\%}; p = 0.4), and overall survival (OS; 82{\%} vs 82{\%}; p = 0.5) were not significantly different between the NAC and control groups for patients with ypT0N0/pT0N0 disease (n = 103). Conversely, among patients with rUCB at RC (n = 401), patients who received NAC had significantly worse 5-yr RFS (50{\%} vs 63{\%}; p = 0.01), CSS (40{\%} vs 59{\%}; p = 0.003), and OS (33{\%} vs 48{\%}; p = 0.02). On multivariable analysis for patients with rUCB, NAC receipt remained independently associated with worse RFS (hazard ratio [HR] 1.84, 95{\%} confidence interval [CI] 1.28-2.66; p = 0.001), CSS (HR 1.81, 95{\%} CI 1.30-2.52; p <. 0.001), and OS (HR 1.57, 95{\%} CI 1.18-2.08; p = 0.002). Limitations include potential for selection bias owing to the retrospective observational design. Thus, while patients who achieve a complete response to NAC have excellent survival outcomes, those with rUCB after NAC have a worse prognosis compared to stage-matched controls undergoing RC alone. It may be worthwhile considering these patients for clinical trials evaluating the role of additional treatments after RC using newer agents while we await further research on predicting which patients achieve ypT0 status from NAC before RC. Patient summary: On surgical removal of the bladder, patients without residual bladder cancer after neoadjuvant chemotherapy have excellent survival outcomes. However, patients with residual cancer after neoadjuvant chemotherapy and surgery have worse outcomes compared to patients undergoing surgery alone. These patients should therefore be considered for additional treatments after surgery using newer agents while we await further research on predicting which patients will benefit from neoadjuvant chemotherapy before bladder removal for cancer. Patients who achieve a complete response after neoadjuvant chemotherapy have excellent survival outcomes. However, patients with residual disease at cystectomy after neoadjuvant chemotherapy have a worse prognosis compared to pathological stage-matched patients who underwent cystectomy alone.",
keywords = "Antineoplastic agents, Cisplatin, Cystectomy, Neoadjuvant therapy, Urinary bladder neoplasms",
author = "Bimal Bhindi and Igor Frank and Mason, {Ross J.} and Tarrell, {Robert F.} and Prabin Thapa and Cheville, {John C.} and Brian Costello and Pagliaro, {Lance C.} and Karnes, {Robert Jeffrey} and Thompson, {R. Houston} and Tollefson, {Matthew K.} and Boorjian, {Stephen A.}",
year = "2017",
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language = "English (US)",
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TY - JOUR

T1 - Oncologic Outcomes for Patients with Residual Cancer at Cystectomy Following Neoadjuvant Chemotherapy

T2 - A Pathologic Stage-matched Analysis

AU - Bhindi, Bimal

AU - Frank, Igor

AU - Mason, Ross J.

AU - Tarrell, Robert F.

AU - Thapa, Prabin

AU - Cheville, John C.

AU - Costello, Brian

AU - Pagliaro, Lance C.

AU - Karnes, Robert Jeffrey

AU - Thompson, R. Houston

AU - Tollefson, Matthew K.

AU - Boorjian, Stephen A.

PY - 2017

Y1 - 2017

N2 - While it has been demonstrated that receipt of neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) improves survival compared to RC alone, the driving factor for this benefit may be from patients with ypT0 status at surgery. Meanwhile, the implications of having residual urothelial carcinoma of the bladder (rUCB) at RC after NAC are less clear. We therefore evaluated whether survival differed between patients with rUCB at RC after NAC and stage-matched controls who underwent RC alone. Patients who underwent NAC + RC (n = 180) were matched to controls who underwent RC alone (n = 324) on the basis of pT and pN stage, margin status, and year of RC. The 5-yr recurrence-free survival (RFS; 90% vs 94%; p = 1), cancer-specific survival (CSS; 82% vs 93%; p = 0.4), and overall survival (OS; 82% vs 82%; p = 0.5) were not significantly different between the NAC and control groups for patients with ypT0N0/pT0N0 disease (n = 103). Conversely, among patients with rUCB at RC (n = 401), patients who received NAC had significantly worse 5-yr RFS (50% vs 63%; p = 0.01), CSS (40% vs 59%; p = 0.003), and OS (33% vs 48%; p = 0.02). On multivariable analysis for patients with rUCB, NAC receipt remained independently associated with worse RFS (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.28-2.66; p = 0.001), CSS (HR 1.81, 95% CI 1.30-2.52; p <. 0.001), and OS (HR 1.57, 95% CI 1.18-2.08; p = 0.002). Limitations include potential for selection bias owing to the retrospective observational design. Thus, while patients who achieve a complete response to NAC have excellent survival outcomes, those with rUCB after NAC have a worse prognosis compared to stage-matched controls undergoing RC alone. It may be worthwhile considering these patients for clinical trials evaluating the role of additional treatments after RC using newer agents while we await further research on predicting which patients achieve ypT0 status from NAC before RC. Patient summary: On surgical removal of the bladder, patients without residual bladder cancer after neoadjuvant chemotherapy have excellent survival outcomes. However, patients with residual cancer after neoadjuvant chemotherapy and surgery have worse outcomes compared to patients undergoing surgery alone. These patients should therefore be considered for additional treatments after surgery using newer agents while we await further research on predicting which patients will benefit from neoadjuvant chemotherapy before bladder removal for cancer. Patients who achieve a complete response after neoadjuvant chemotherapy have excellent survival outcomes. However, patients with residual disease at cystectomy after neoadjuvant chemotherapy have a worse prognosis compared to pathological stage-matched patients who underwent cystectomy alone.

AB - While it has been demonstrated that receipt of neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) improves survival compared to RC alone, the driving factor for this benefit may be from patients with ypT0 status at surgery. Meanwhile, the implications of having residual urothelial carcinoma of the bladder (rUCB) at RC after NAC are less clear. We therefore evaluated whether survival differed between patients with rUCB at RC after NAC and stage-matched controls who underwent RC alone. Patients who underwent NAC + RC (n = 180) were matched to controls who underwent RC alone (n = 324) on the basis of pT and pN stage, margin status, and year of RC. The 5-yr recurrence-free survival (RFS; 90% vs 94%; p = 1), cancer-specific survival (CSS; 82% vs 93%; p = 0.4), and overall survival (OS; 82% vs 82%; p = 0.5) were not significantly different between the NAC and control groups for patients with ypT0N0/pT0N0 disease (n = 103). Conversely, among patients with rUCB at RC (n = 401), patients who received NAC had significantly worse 5-yr RFS (50% vs 63%; p = 0.01), CSS (40% vs 59%; p = 0.003), and OS (33% vs 48%; p = 0.02). On multivariable analysis for patients with rUCB, NAC receipt remained independently associated with worse RFS (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.28-2.66; p = 0.001), CSS (HR 1.81, 95% CI 1.30-2.52; p <. 0.001), and OS (HR 1.57, 95% CI 1.18-2.08; p = 0.002). Limitations include potential for selection bias owing to the retrospective observational design. Thus, while patients who achieve a complete response to NAC have excellent survival outcomes, those with rUCB after NAC have a worse prognosis compared to stage-matched controls undergoing RC alone. It may be worthwhile considering these patients for clinical trials evaluating the role of additional treatments after RC using newer agents while we await further research on predicting which patients achieve ypT0 status from NAC before RC. Patient summary: On surgical removal of the bladder, patients without residual bladder cancer after neoadjuvant chemotherapy have excellent survival outcomes. However, patients with residual cancer after neoadjuvant chemotherapy and surgery have worse outcomes compared to patients undergoing surgery alone. These patients should therefore be considered for additional treatments after surgery using newer agents while we await further research on predicting which patients will benefit from neoadjuvant chemotherapy before bladder removal for cancer. Patients who achieve a complete response after neoadjuvant chemotherapy have excellent survival outcomes. However, patients with residual disease at cystectomy after neoadjuvant chemotherapy have a worse prognosis compared to pathological stage-matched patients who underwent cystectomy alone.

KW - Antineoplastic agents

KW - Cisplatin

KW - Cystectomy

KW - Neoadjuvant therapy

KW - Urinary bladder neoplasms

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