Long-Term Efficacy Results of EORTC Genito-Urinary Group Randomized Phase 3 Study 30911 Comparing Intravesical Instillations of Epirubicin, Bacillus Calmette-Guérin, and Bacillus Calmette-Guérin plus Isoniazid in Patients with Intermediate- and High-Risk Stage Ta T1 Urothelial Carcinoma of the Bladder

Abstract

Abstract© 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author: EORTC Headquarters, 83 avenue E Mounier, Bte 11, 1200 Brussels, Belgium, Tel. +322.774.1613, Fax: +322.772.3545, richard.sylvester@eortc.be. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Financial disclosures: I certify 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. Intervention-Patients received six weekly instillations of epirubicin, BCG, or BCG plus isoniazid (INH) followed by three weekly maintenance instillations at months 3, 6, 12, 18, 24, 30, and 36. NIH Public AccessAuthor Manuscript Eur Urol. Author manuscript; available in PMC 2011 May 1.Measurements-End points were time to recurrence, progression, distant metastases, overall survival, and disease-specific survival.Results and limitations-With 837 eligible patients and a median follow-up of 9.2 yr, time to first recurrence (p < 0.001), distant metastases (p = 0.046), overall survival (p = 0.023), and diseasespecific survival (p = 0.026) were significantly longer in the two BCG arms combined as compared with epirubicin; however, there was no difference for progression.

Consensus statement on best practice management regarding the use of intravesical immunotherapy with BCG for bladder cancer

“…BCG signifi cantly reduced recurrence by 15%, metastasis by 45% (P = 0.046), and both overall (P = 0.023) and cancer specific mortality (P = 0.026). 10 No other intravesi cal treatment, BCG induction only, or non3week m aintenance BCG schedule has achieved such success.…”

“…12,19 Moreover, only the 3week BCG maintenance schedule reduced disease progression and metasta sis, as well as overall and cancerspecific m ortality in RCTs. 10,12 Two other trials compared 3week maintenance BCG with alternative agents (Table 2). 10,20 EORTC 30911 compared the 3week maintenance BCG with 3week maintenance epirubicin chemotherapy.…”

“…10,12 Two other trials compared 3week maintenance BCG with alternative agents (Table 2). 10,20 EORTC 30911 compared the 3week maintenance BCG with 3week maintenance epirubicin chemotherapy. BCG signifi cantly reduced recurrence by 15%, metastasis by 45% (P = 0.046), and both overall (P = 0.023) and cancer specific mortality (P = 0.026).…”

“…5,6,8 The AUA's metaanalysis suggests 24% and 31% reduc tion in recurrence rates for BCG induction and mainten ance, respectively. 5 The EAU recommendation is based predominantly on the recent metaanalysis by Sylvester and colleagues, 10 which demonstrated a 32% relative risk reduction with the use of BCG maintenance compared with intravesical chemotherapy. The IBCG recommen dation is based on a risk assessment model.…”

Immunobiology and immunotherapy in genitourinary malignancies

“…The 5-year survival rate was 78% with induction alone compared to 83% with maintenance. Thus, only the 3-week BCG maintenance was shown to lower progression and improve overall and disease-specific mortality in randomized controlled studies (55,56). BCG remains a standard treatment after transurethral bladder tumor resection (TURBT) in patients with NMIBC (based on certain indications) and provides the backbone for immunotherapeutic combinatorial or sequential treatment strategies in this setting.…”