BACKGROUND: The optimal dose and duration of intravesical bacillus Calmette-Guérin (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.
RCT Entities:
BACKGROUND: The optimal dose and duration of intravesical bacillus Calmette-Guérin (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.
Authors: Wassim Kassouf; Samer L Traboulsi; Girish S Kulkarni; Rodney H Breau; Alexandre Zlotta; Andrew Fairey; Alan So; Louis Lacombe; Ricardo Rendon; Armen G Aprikian; D Robert Siemens; Jonathan I Izawa; Peter Black Journal: Can Urol Assoc J Date: 2015-10-13 Impact factor: 1.862
Authors: Andrew T Lenis; Nicholas M Donin; Mark S Litwin; Christopher S Saigal; Julie Lai; Jan M Hanley; Badrinath R Konety; Karim Chamie Journal: Clin Genitourin Cancer Date: 2016-06-25 Impact factor: 2.872
Authors: Ashish M Kamat; J Alfred Witjes; Maurizio Brausi; Mark Soloway; Donald Lamm; Raj Persad; Roger Buckley; Andreas Böhle; Marc Colombel; Joan Palou Journal: J Urol Date: 2014-03-25 Impact factor: 7.450
Authors: Ashish M Kamat; Daniel L Willis; Rian J Dickstein; Rooselvelt Anderson; Graciela Nogueras-González; Ruth L Katz; Xifeng Wu; H Barton Grossman; Colin P Dinney Journal: BJU Int Date: 2015-07-03 Impact factor: 5.588
Authors: Peter E Clark; Philippe E Spiess; Neeraj Agarwal; Rick Bangs; Stephen A Boorjian; Mark K Buyyounouski; Jason A Efstathiou; Thomas W Flaig; Terence Friedlander; Richard E Greenberg; Khurshid A Guru; Noah Hahn; Harry W Herr; Christopher Hoimes; Brant A Inman; A Karim Kader; Adam S Kibel; Timothy M Kuzel; Subodh M Lele; Joshua J Meeks; Jeff Michalski; Jeffrey S Montgomery; Lance C Pagliaro; Sumanta K Pal; Anthony Patterson; Daniel Petrylak; Elizabeth R Plimack; Kamal S Pohar; Michael P Porter; Wade J Sexton; Arlene O Siefker-Radtke; Guru Sonpavde; Jonathan Tward; Geoffrey Wile; Mary A Dwyer; Courtney Smith Journal: J Natl Compr Canc Netw Date: 2016-10 Impact factor: 11.908