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.

Duke University Medical Center Division of Urology Durham NC USA

EORTC Headquarters Department of Biostatistics Brussels Belgium

Ghent University Hospital Department of Urology Ghent Belgium

Higashi Nagoya Hospital Department of Urology Nagoya Japan

Hospital Motol and 2nd Faculty of Medicine Charles University Department of Urology Prague Czech Republic

Hyvinkaa Hospital Department of Urology Hyvinkaa Finland

Jeroen Bosch Hospital Department of Urology 's Hertogenbosch The Netherlands

Medical Research Council Clinical Trials Unit at University College London Department of Cancer and Other Non Infectious Diseases London UK

Ospedale Sant'Andrea University La Sapienza Department of Urology Rome Italy

Royal Preston Hospital Rosemere Cancer Centre Preston UK

Skane University Hospital Department of Urology Malmo Sweden

Turkiye Yuksek Ihtisas Education and Research Hospital Department of Urology Ankara Turkey

University of Aberdeen Academic Urology Unit Aberdeen UK

University of Gothenburg Department of Urology Gothenburg Sweden

Urology and Nephrology Center Mansoura University Department of Urology Mansoura Egypt

Valencia Oncology Institute Department of Urology Valencia Spain

Eur Urol. 2016 Jan;69(1):e12-3. doi: 10.1016/j.eururo.2015.07.018. PubMed

Eur Urol. 2016 Jan;69(1):e10-1. doi: 10.1016/j.eururo.2015.07.017. PubMed

Eur Urol. 2016 Feb;69(2):245-6. doi: 10.1016/j.eururo.2015.07.035. PubMed

Eur Urol. 2015 Dec;68(6):e127. doi: 10.1016/j.eururo.2015.08.019. PubMed

Eur Urol. 2015 Dec;68(6):e128. doi: 10.1016/j.eururo.2015.08.020. PubMed

J Urol. 2017 May;197(5):1219. doi: 10.1016/j.juro.2017.02.017. PubMed

References provided by Crossref.org

Recurrence mechanisms of non-muscle-invasive bladder cancer - a clinical perspective

Bladder cancer therapy using a conformationally fluid tumoricidal peptide complex

A Systematic Review of Outcome Reporting, Definition and Measurement Heterogeneity in Non-Muscle Invasive Bladder Cancer Effectiveness Trials of Adjuvant, Prophylactic Treatment After Transurethral Resection