eprintid: 1475096 rev_number: 29 eprint_status: archive userid: 608 dir: disk0/01/47/50/96 datestamp: 2016-02-23 11:32:45 lastmod: 2021-12-06 00:11:57 status_changed: 2016-02-23 11:32:45 type: article metadata_visibility: show creators_name: Sylvester, RJ creators_name: Oosterlinck, W creators_name: Holmang, S creators_name: Sydes, MR creators_name: Birtle, A creators_name: Gudjonsson, S creators_name: De Nunzio, C creators_name: Okamura, K creators_name: Kaasinen, E creators_name: Solsona, E creators_name: Ali-El-Dein, B creators_name: Tatar, CA creators_name: Inman, BA creators_name: N'Dow, J creators_name: Oddens, JR creators_name: Babjuk, M 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? ispublished: pub divisions: UCL divisions: B02 divisions: D65 divisions: J38 keywords: Chemotherapy, Meta-analysis, Non–muscle-invasive bladder cancer, Single instillation, Systematic review note: © 2015 European Association of Urology. Published by Elsevier B.V. This manuscript is made available under a Creative Commons Attribution Non-commercial Non-derivative 4.0 International license (CC BY-NC-ND 4.0). This license allows you to share, copy, distribute and transmit the work for personal and non-commercial use providing author and publisher attribution is clearly stated. Further details about CC BY licenses are available at http://creativecommons.org/ licenses/by/4.0. Access may be initially restricted by the publisher. 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. date: 2016-02 date_type: published official_url: http://dx.doi.org/10.1016/j.eururo.2015.05.050 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green article_type_text: Journal Article verified: verified_manual elements_id: 1041118 doi: 10.1016/j.eururo.2015.05.050 pii: S0302-2838(15)00456-X language_elements: eng lyricists_name: Sydes, Matthew lyricists_id: MRSYD21 actors_name: Sydes, Matthew actors_id: MRSYD21 actors_role: owner full_text_status: public publication: European Urology volume: 69 number: 2 pagerange: 231-244 event_location: Switzerland issn: 1873-7560 citation: Sylvester, RJ; Oosterlinck, W; Holmang, S; Sydes, MR; Birtle, A; Gudjonsson, S; De Nunzio, C; ... Babjuk, M; + view all <#> Sylvester, RJ; Oosterlinck, W; Holmang, S; Sydes, MR; Birtle, A; Gudjonsson, S; De Nunzio, C; Okamura, K; Kaasinen, E; Solsona, E; Ali-El-Dein, B; Tatar, CA; Inman, BA; N'Dow, J; Oddens, JR; Babjuk, M; - view fewer <#> (2016) 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? European Urology , 69 (2) pp. 231-244. 10.1016/j.eururo.2015.05.050 <https://doi.org/10.1016/j.eururo.2015.05.050>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1475096/1/Eur%20Urol%20Revised%20Submission%202%20Clean.pdf document_url: https://discovery.ucl.ac.uk/id/eprint/1475096/2/Sylvester_Sydes_et_al_suppl._docs.zip