title: Maintenance Therapy with 3-monthly Bacillus Calmette-Guérin for 3 Years is Not Superior to Standard Induction Therapy in High-risk Non-muscle-invasive Urothelial Bladder Carcinoma: Final Results of Randomised CUETO Study 98013.
abstract: BACKGROUND
  Bacillus Calmette-Guérin (BCG) maintenance therapy for 3 yr following BCG induction can reduce the progression of urothelial bladder carcinoma versus BCG induction alone, but is associated with high toxicity.
  
  
  OBJECTIVE
  To investigate whether a modified 3-yr BCG maintenance regimen following induction therapy is more effective than standard BCG induction therapy alone and exhibits a low toxicity profile.
  
  
  METHODS
  Patients from the outpatient clinics of the participating centres with high-risk non-muscle-invasive bladder carcinoma (NMIBC) were randomised between October 1999 and April 2007.
  
  
  METHODS
  Participants received BCG induction once-weekly for 6 wk (no maintenance arm) or BCG induction followed by one BCG instillation every 3 mo for 3 yr (maintenance arm).
  
  
  METHODS
  Primary endpoints were disease-free interval (DFI) and time to progression (TTP). Secondary endpoints included survival duration and toxicity. Differences between treatment arms were tested using Student's t test and χ(2) and log-rank tests.
  
  
  CONCLUSIONS
  A total of 397 patients were randomised, 195 to the no-maintenance and 202 to the maintenance arm. A median time to recurrence was not reached in either treatment arm. DFI was similar between the arms (hazard ration [HR] 0.83; 95% CI 0.61-1.13; p=0.2) with disease relapse at 5 yr of 33.5% and 38.5%, respectively. TTP was also similar between the treatment arms (HR 0.79; 95% CI 0.50-1.26; p=0.3), with a progression rate at 5 yr of 16% and 19.5%, respectively. There were no significant differences between the treatment groups for overall survival and cancer-specific survival at 5 yr. Twenty and five patients in the maintenance and no-maintenance arms, respectively, stopped treatment because of toxicity. The most common local side effects were frequency (65% of patients), dysuria (63%), and haematuria (43%); the most frequent systemic side effects were general malaise (7.2%) and fever (34%).
  
  
  CONCLUSIONS
  In NMIBC patients treated with maintenance therapy comprising a single BCG instillation every 3 mo for 3 yr following standard induction BCG, we did not observe a decrease in recurrence and progression rates versus induction therapy alone.
  
  
  RESULTS
  Patients who undergo surgery to remove bladder cancer are usually treated with bacillus Calmette-Guérin (BCG) for 6 wk if there is a high risk of disease recurrence. Extending BCG therapy by 3 yr can further minimise disease recurrence and progression, but is associated with more side effects. We report that a modified 3-yr BCG treatment regimen showed low toxicity, but seemed to be no more effective than 6-wk treatment.
  
  
  BACKGROUND
  CUETO 98013.
authors: Department of Urology, Hospital Universitario Infanta Sofia, Madrid, Spain. Electronic address: luis.mpineiro@salud.madrid.org.
authors: Luis
authors: L
authors: Martínez-Piñeiro
authors: Department of Urology, Hospital Valdecilla, Santander, Spain.
authors: José A
authors: JA
authors: Portillo
authors: Department of Urology, Hospital Central de Asturias, Oviedo, Spain.
authors: Jesús M
authors: JM
authors: Fernández
authors: Department of Urology, Hospital de Cruces, Bilbao, Spain.
authors: José A
authors: JA
authors: Zabala
authors: Department of Urology, Hospital de Cruces, Bilbao, Spain.
authors: Iker
authors: I
authors: Cadierno
authors: Department of Urology, Hospital Virgen Macarena, Sevilla, Spain.
authors: José L
authors: JL
authors: Moyano
authors: Department of Urology, IVO, Valencia, Spain.
authors: Eduardo
authors: E
authors: Solsona
authors: Department of Urology, Hospital Civil de Basurto-Osakidetza, Bilbao, Spain.
authors: Miguel
authors: M
authors: Unda
authors: Department of Urology, Hospital del SAS de Jerez de La Frontera, Cádiz, Spain.
authors: Pastora
authors: P
authors: Beardo
authors: Department of Urology, Hospital Clínico San Carlos, Madrid, Spain.
authors: Jesús
authors: J
authors: Rodríguez-Molina
authors: Department of Urology, Complejo Hospitalario Universitario A Coruña, A Coruña, Spain.
authors: Venancio
authors: V
authors: Chantada
authors: Department of Urology, Fundación Puigvert, Barcelona, Spain.
authors: Joan
authors: J
authors: Palou
authors: Department of Urology, Hospital Alvarez Buylla, Mieres, Spain.
authors: Pedro
authors: P
authors: Muntañola
authors: Hospital Universitario La Paz, Madrid, Spain.
authors: José M
authors: JM
authors: Alonso Dorrego
authors: Department of Urology, Hospital San Agustín, Avilés, Spain.
authors: Franciso J
authors: FJ
authors: Pérez-Garcia
authors: Department of Urology, Hospital Universitario de Salamanca, Salamanca, Spain.
authors: Juan M
authors: JM
authors: Silva
authors: Department of Urology, Hospital Insular de Gran Canaria, Las Palmas, Spain.
authors: Nicolás
authors: N
authors: Chesa
authors: Department of Urology, Hospital Virgen del Camino, Pamplona, Spain.
authors: Manuel
authors: M
authors: Montesinos
authors: Department of Urology, Hospital Xeral-Cíes, Vigo, Spain.
authors: Antonio
authors: A
authors: Ojea
authors: Hospital Universitario La Paz, Madrid, Spain.
authors: Rosario
authors: R
authors: Madero
authors: Clínica La Luz, Madrid, Spain.
authors: José A
authors: JA
authors: Martínez-Piñeiro
mesh_terms: D000283:Administration, Intravesical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000553:Ambulatory Care; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001500:BCG Vaccine / Q000008:administration & dosage* / Q000009:adverse effects; D002277:Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016009:Chi-Square Distribution; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D053208:Kaplan-Meier Estimate; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012307:Risk Factors; D013030:Spain; D013997:Time Factors; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D019459:Urothelium / Q000187:drug effects* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D001500:BCG Vaccine
keywords: Bacillus Calmette-Guérin; Bladder cancer; Maintenance therapy