Systematic Review and Individual Patient Data Meta-analysis of Randomized Trials Comparing a Single Immediate Instillation of Chemotherapy After Transurethral Resection with Transurethral Resection Alone in Patients with Stage pTa-pT1 Urothelial Carcinoma of the Bladder

Which Patients Benefit from the Instillation?

Richard J Sylvester, Willem Oosterlinck, Sten Holmang, Matthew R Sydes, Alison Birtle, Sigurdur Gudjonsson, Cosimo De Nunzio, Kikuo Okamura, Eero Kaasinen, Eduardo Solsona, Bedeir Ali-El-Dein, Can Ali Tatar, Brant A Inman, James N'Dow, Jorg R Oddens, Marek Babjuk

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

CONTEXT: The European Association of Urology non-muscle-invasive bladder cancer (NMIBC) guidelines recommend that all low- and intermediate-risk patients receive a single immediate instillation of chemotherapy after transurethral resection of the bladder (TURB), but its use remains controversial.

OBJECTIVE: To identify which NMIBC patients benefit from a single immediate instillation.

EVIDENCE ACQUISITION: A systematic review and individual patient data (IPD) meta-analysis of randomized trials comparing the efficacy of a single instillation after TURB with TURB alone in NMIBC patients was carried out.

EVIDENCE SYNTHESIS: A total of 13 eligible studies were identified. IPD were obtained for 11 studies randomizing 2278 eligible patients, 1161 to TURB and 1117 to a single instillation of epirubicin, mitomycin C, pirarubicin, or thiotepa. A total of 1128 recurrences, 108 progressions, and 460 deaths (59 due to bladder cancer [BCa]) occurred. A single instillation reduced the risk of recurrence by 35% (hazard ratio [HR]: 0.65; 95% confidence interval [CI], 0.58-0.74; p<0.001) and the 5-yr recurrence rate from 58.8% to 44.8%. The instillation did not reduce recurrences in patients with a prior recurrence rate of more than one recurrence per year or in patients with an European Organization for Research and Treatment of Cancer (EORTC) recurrence score ≥5. The instillation did not prolong either the time to progression or death from BCa, but it resulted in an increase in the overall risk of death (HR: 1.26; 95% CI, 1.05-1.51; p=0.015; 5-yr death rates 12.0% vs 11.2%), with the difference appearing in patients with an EORTC recurrence score ≥5.

CONCLUSIONS: A single immediate instillation reduced the risk of recurrence, except in patients with a prior recurrence rate of more than one recurrence per year or an EORTC recurrence score ≥5. It does not prolong either time to progression or death from BCa. The instillation may be associated with an increase in the risk of death in patients at high risk of recurrence in whom the instillation is not effective or recommended.

PATIENT SUMMARY: A single instillation of chemotherapy immediately after resection reduces the risk of recurrence in non-muscle-invasive bladder cancer; however, it should not be given to patients at high risk of recurrence due to its lack of efficacy in this subgroup.

Original languageEnglish
Pages (from-to)231-244
Number of pages14
JournalEuropean Urology
Volume69
Issue number2
Early online date16 Jun 2015
DOIs
Publication statusPublished - Feb 2016

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Meta-Analysis
Urinary Bladder
Carcinoma
Recurrence
Drug Therapy
Urinary Bladder Neoplasms
Organizations
Research
Confidence Intervals
Thiotepa
Neoplasms
Epirubicin
Mitomycin
Therapeutics
Guidelines

Keywords

  • chemotherapy
  • meta-analysis
  • non–muscle-invasive bladder cancer
  • single instillation
  • systematic review

Cite this

Systematic Review and Individual Patient Data Meta-analysis of Randomized Trials Comparing a Single Immediate Instillation of Chemotherapy After Transurethral Resection with Transurethral Resection Alone in Patients with Stage pTa-pT1 Urothelial Carcinoma of the Bladder : Which Patients Benefit from the Instillation? / Sylvester, Richard J; Oosterlinck, Willem; Holmang, Sten; Sydes, Matthew R; Birtle, Alison; Gudjonsson, Sigurdur; De Nunzio, Cosimo; Okamura, Kikuo; Kaasinen, Eero; Solsona, Eduardo; Ali-El-Dein, Bedeir; Tatar, Can Ali; Inman, Brant A; N'Dow, James; Oddens, Jorg R; Babjuk, Marek.

In: European Urology, Vol. 69, No. 2, 02.2016, p. 231-244.

Research output: Contribution to journalArticle

Sylvester, Richard J ; Oosterlinck, Willem ; Holmang, Sten ; Sydes, Matthew R ; Birtle, Alison ; Gudjonsson, Sigurdur ; De Nunzio, Cosimo ; Okamura, Kikuo ; Kaasinen, Eero ; Solsona, Eduardo ; Ali-El-Dein, Bedeir ; Tatar, Can Ali ; Inman, Brant A ; N'Dow, James ; Oddens, Jorg R ; Babjuk, Marek. / Systematic Review and Individual Patient Data Meta-analysis of Randomized Trials Comparing a Single Immediate Instillation of Chemotherapy After Transurethral Resection with Transurethral Resection Alone in Patients with Stage pTa-pT1 Urothelial Carcinoma of the Bladder : Which Patients Benefit from the Instillation?. In: European Urology. 2016 ; Vol. 69, No. 2. pp. 231-244.
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title = "Systematic Review and Individual Patient Data Meta-analysis of Randomized Trials Comparing a Single Immediate Instillation of Chemotherapy After Transurethral Resection with Transurethral Resection Alone in Patients with Stage pTa-pT1 Urothelial Carcinoma of the Bladder: Which Patients Benefit from the Instillation?",
abstract = "CONTEXT: The European Association of Urology non-muscle-invasive bladder cancer (NMIBC) guidelines recommend that all low- and intermediate-risk patients receive a single immediate instillation of chemotherapy after transurethral resection of the bladder (TURB), but its use remains controversial.OBJECTIVE: To identify which NMIBC patients benefit from a single immediate instillation.EVIDENCE ACQUISITION: A systematic review and individual patient data (IPD) meta-analysis of randomized trials comparing the efficacy of a single instillation after TURB with TURB alone in NMIBC patients was carried out.EVIDENCE SYNTHESIS: A total of 13 eligible studies were identified. IPD were obtained for 11 studies randomizing 2278 eligible patients, 1161 to TURB and 1117 to a single instillation of epirubicin, mitomycin C, pirarubicin, or thiotepa. A total of 1128 recurrences, 108 progressions, and 460 deaths (59 due to bladder cancer [BCa]) occurred. A single instillation reduced the risk of recurrence by 35{\%} (hazard ratio [HR]: 0.65; 95{\%} confidence interval [CI], 0.58-0.74; p<0.001) and the 5-yr recurrence rate from 58.8{\%} to 44.8{\%}. The instillation did not reduce recurrences in patients with a prior recurrence rate of more than one recurrence per year or in patients with an European Organization for Research and Treatment of Cancer (EORTC) recurrence score ≥5. The instillation did not prolong either the time to progression or death from BCa, but it resulted in an increase in the overall risk of death (HR: 1.26; 95{\%} CI, 1.05-1.51; p=0.015; 5-yr death rates 12.0{\%} vs 11.2{\%}), with the difference appearing in patients with an EORTC recurrence score ≥5.CONCLUSIONS: A single immediate instillation reduced the risk of recurrence, except in patients with a prior recurrence rate of more than one recurrence per year or an EORTC recurrence score ≥5. It does not prolong either time to progression or death from BCa. The instillation may be associated with an increase in the risk of death in patients at high risk of recurrence in whom the instillation is not effective or recommended.PATIENT SUMMARY: A single instillation of chemotherapy immediately after resection reduces the risk of recurrence in non-muscle-invasive bladder cancer; however, it should not be given to patients at high risk of recurrence due to its lack of efficacy in this subgroup.",
keywords = "chemotherapy, meta-analysis, non–muscle-invasive bladder cancer, single instillation, systematic review",
author = "Sylvester, {Richard J} and Willem Oosterlinck and Sten Holmang and Sydes, {Matthew R} and Alison Birtle and Sigurdur Gudjonsson and {De Nunzio}, Cosimo and Kikuo Okamura and Eero Kaasinen and Eduardo Solsona and Bedeir Ali-El-Dein and Tatar, {Can Ali} and Inman, {Brant A} and James N'Dow and Oddens, {Jorg R} and Marek Babjuk",
note = "Financial disclosures: Richard J. Sylvester certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None. Funding/Support and role of the sponsor: The European Organization for Research and Treatment of Cancer (EORTC) Charitable Trust provided core support to the EORTC that paid Richard J. Sylvester's salary. There was no dedicated funding for this academic research study.",
year = "2016",
month = "2",
doi = "10.1016/j.eururo.2015.05.050",
language = "English",
volume = "69",
pages = "231--244",
journal = "European Urology",
issn = "0302-2838",
publisher = "Elsevier",
number = "2",

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TY - JOUR

T1 - Systematic Review and Individual Patient Data Meta-analysis of Randomized Trials Comparing a Single Immediate Instillation of Chemotherapy After Transurethral Resection with Transurethral Resection Alone in Patients with Stage pTa-pT1 Urothelial Carcinoma of the Bladder

T2 - Which Patients Benefit from the Instillation?

AU - Sylvester, Richard J

AU - Oosterlinck, Willem

AU - Holmang, Sten

AU - Sydes, Matthew R

AU - Birtle, Alison

AU - Gudjonsson, Sigurdur

AU - De Nunzio, Cosimo

AU - Okamura, Kikuo

AU - Kaasinen, Eero

AU - Solsona, Eduardo

AU - Ali-El-Dein, Bedeir

AU - Tatar, Can Ali

AU - Inman, Brant A

AU - N'Dow, James

AU - Oddens, Jorg R

AU - Babjuk, Marek

N1 - Financial disclosures: Richard J. Sylvester certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None. Funding/Support and role of the sponsor: The European Organization for Research and Treatment of Cancer (EORTC) Charitable Trust provided core support to the EORTC that paid Richard J. Sylvester's salary. There was no dedicated funding for this academic research study.

PY - 2016/2

Y1 - 2016/2

N2 - CONTEXT: The European Association of Urology non-muscle-invasive bladder cancer (NMIBC) guidelines recommend that all low- and intermediate-risk patients receive a single immediate instillation of chemotherapy after transurethral resection of the bladder (TURB), but its use remains controversial.OBJECTIVE: To identify which NMIBC patients benefit from a single immediate instillation.EVIDENCE ACQUISITION: A systematic review and individual patient data (IPD) meta-analysis of randomized trials comparing the efficacy of a single instillation after TURB with TURB alone in NMIBC patients was carried out.EVIDENCE SYNTHESIS: A total of 13 eligible studies were identified. IPD were obtained for 11 studies randomizing 2278 eligible patients, 1161 to TURB and 1117 to a single instillation of epirubicin, mitomycin C, pirarubicin, or thiotepa. A total of 1128 recurrences, 108 progressions, and 460 deaths (59 due to bladder cancer [BCa]) occurred. A single instillation reduced the risk of recurrence by 35% (hazard ratio [HR]: 0.65; 95% confidence interval [CI], 0.58-0.74; p<0.001) and the 5-yr recurrence rate from 58.8% to 44.8%. The instillation did not reduce recurrences in patients with a prior recurrence rate of more than one recurrence per year or in patients with an European Organization for Research and Treatment of Cancer (EORTC) recurrence score ≥5. The instillation did not prolong either the time to progression or death from BCa, but it resulted in an increase in the overall risk of death (HR: 1.26; 95% CI, 1.05-1.51; p=0.015; 5-yr death rates 12.0% vs 11.2%), with the difference appearing in patients with an EORTC recurrence score ≥5.CONCLUSIONS: A single immediate instillation reduced the risk of recurrence, except in patients with a prior recurrence rate of more than one recurrence per year or an EORTC recurrence score ≥5. It does not prolong either time to progression or death from BCa. The instillation may be associated with an increase in the risk of death in patients at high risk of recurrence in whom the instillation is not effective or recommended.PATIENT SUMMARY: A single instillation of chemotherapy immediately after resection reduces the risk of recurrence in non-muscle-invasive bladder cancer; however, it should not be given to patients at high risk of recurrence due to its lack of efficacy in this subgroup.

AB - CONTEXT: The European Association of Urology non-muscle-invasive bladder cancer (NMIBC) guidelines recommend that all low- and intermediate-risk patients receive a single immediate instillation of chemotherapy after transurethral resection of the bladder (TURB), but its use remains controversial.OBJECTIVE: To identify which NMIBC patients benefit from a single immediate instillation.EVIDENCE ACQUISITION: A systematic review and individual patient data (IPD) meta-analysis of randomized trials comparing the efficacy of a single instillation after TURB with TURB alone in NMIBC patients was carried out.EVIDENCE SYNTHESIS: A total of 13 eligible studies were identified. IPD were obtained for 11 studies randomizing 2278 eligible patients, 1161 to TURB and 1117 to a single instillation of epirubicin, mitomycin C, pirarubicin, or thiotepa. A total of 1128 recurrences, 108 progressions, and 460 deaths (59 due to bladder cancer [BCa]) occurred. A single instillation reduced the risk of recurrence by 35% (hazard ratio [HR]: 0.65; 95% confidence interval [CI], 0.58-0.74; p<0.001) and the 5-yr recurrence rate from 58.8% to 44.8%. The instillation did not reduce recurrences in patients with a prior recurrence rate of more than one recurrence per year or in patients with an European Organization for Research and Treatment of Cancer (EORTC) recurrence score ≥5. The instillation did not prolong either the time to progression or death from BCa, but it resulted in an increase in the overall risk of death (HR: 1.26; 95% CI, 1.05-1.51; p=0.015; 5-yr death rates 12.0% vs 11.2%), with the difference appearing in patients with an EORTC recurrence score ≥5.CONCLUSIONS: A single immediate instillation reduced the risk of recurrence, except in patients with a prior recurrence rate of more than one recurrence per year or an EORTC recurrence score ≥5. It does not prolong either time to progression or death from BCa. The instillation may be associated with an increase in the risk of death in patients at high risk of recurrence in whom the instillation is not effective or recommended.PATIENT SUMMARY: A single instillation of chemotherapy immediately after resection reduces the risk of recurrence in non-muscle-invasive bladder cancer; however, it should not be given to patients at high risk of recurrence due to its lack of efficacy in this subgroup.

KW - chemotherapy

KW - meta-analysis

KW - non–muscle-invasive bladder cancer

KW - single instillation

KW - systematic review

U2 - 10.1016/j.eururo.2015.05.050

DO - 10.1016/j.eururo.2015.05.050

M3 - Article

VL - 69

SP - 231

EP - 244

JO - European Urology

JF - European Urology

SN - 0302-2838

IS - 2

ER -