Platinum Priority – Bladder Cancer Editorial by J. Alfred Witjes on pp. 473–474 of this issue Final Results of an EORTC-GU Cancers Group Randomized Study of Maintenance Bacillus Calmette-Gue ´ rin in Intermediate- and High- risk Ta, T1 Papillary Carcinoma of the Urinary Bladder: One-third Dose Versus Full Dose and 1 Year Versus 3 Years of Maintenance Jorg Oddens a, *, Maurizio Brausi b , Richard Sylvester c , Aldo Bono d , Cees van de Beek e , George van Andel f , Paolo Gontero g , Wolfgang Hoeltl h , Levent Turkeri i , Sandrine Marreaud c , Sandra Collette c , Willem Oosterlinck j a Department of Urology, Jeroen Bosch Ziekenhuis, ‘s-Hertogenbosch, The Netherlands; b Department of Urology, B. Ramazzini Hospital, Modena, Italy; c Headquarters, European Organization for Research and Treatment of Cancer (EORTC), Brussels, Belgium; d Department of Urology, Ospedale di Circolo, Varese, Italy; e Department of Urology, Academisch Ziekenhuis Maastricht, Maastricht, The Netherlands; f Department of Urology, OLVG, Amsterdam, The Netherlands; g Department of Urology, Ospedale Molinette, Torino, Italy; h Department of Urology, Kaiser-Franz-Josef Spital, Vienna, Austria; i Department of Urology, Marmara University School of Medicine, Istanbul, Turkey; j Department of Urology, UZ Gent, Ghent, Belgium EUROPEAN UROLOGY 63 (2013) 462–472 available at www.sciencedirect.com journal homepage: www.europeanurology.com Article info Article history: Accepted October 21, 2012 Published online ahead of print on November 2, 2012 Keywords: Non-muscle invasive bladder cancer Randomized Controlled Trial Immunotherapy Bacillus Calmette-Guerin Adjuvant treatment Urinary bladder Maintenance therapy Please visit www.eu-acme.org/ europeanurology to read and answer questions on-line. The EU-ACME credits will then be attributed automatically. Abstract Background: The optimal dose and duration of intravesical bacillus Calmette-Gue ´ rin (BCG) in the treatment of non–muscle-invasive bladder cancer (NMIBC) are controversial. Objective: To determine if a one-third dose (1/3D) is not inferior to the full dose (FD), if 1 yr of maintenance is not inferior to 3 yr of maintenance, and if 1/3D and 1 yr of maintenance are associated with less toxicity. Design, setting, and participants: After transurethral resection, intermediate- and high-risk NMIBC patients were randomized to one of four BCG groups: 1/3D-1 yr, 1/3D-3 yr, FD-1 yr, and FD-3 yr. Outcome measurements and statistical analysis: The trial was designed as a noninferiority study with the null hypothesis of a 10% decrease in the disease-free rate at 5 yr. Times to events were estimated using cumulative incidence functions and compared using the Cox proportional hazards regression model. Results and limitations: In an intention-to-treat analysis of 1355 patients with a median follow-up of 7.1 yr, there were no significant differences in toxicity between 1/3D and FD. The null hypotheses of inferiority of the disease-free interval for both 1/3D and 1 yr could not be rejected. We found that 1/3D-1 yr is suboptimal compared with FD-3 yr (hazard ratio [HR]: 0.75; 95% confidence interval [CI], 0.59–0.94; p = 0.01). Intermediate-risk patients treated with FD do not benefit from an additional 2 yr of BCG. In high-risk patients, 3 yr is associated with a reduction in recurrence (HR: 1.61; 95% CI, 1.13–2.30; p = 0.009) but only when given at FD. There were no differences in progression or survival. Conclusions: There were no differences in toxicity between 1/3D and FD. Intermediate-risk patients should be treated with FD-1 yr. In high-risk patients, FD-3 yr reduces recurrences as compared with FD-1 yr but not progressions or deaths. The benefit of the two additional years of maintenance should be weighed against its added costs and inconvenience. Trial registration: This study was registered at ClinicalTrials.gov, number NCT00002990; http://clinicaltrials.gov/ct2/show/record/NCT00002990. # 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Department of Urology, Jeroen Bosch Ziekenhuis, PO Box 90153, 5200 ME ’s-Hertogenbosch, The Netherlands. Tel. +31 73 5532407. E-mail address: j.oddens@jbz.nl (J. Oddens). 0302-2838/$ – see back matter # 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.eururo.2012.10.039