Randomized Controlled Study of the Efficacy, Safety and Quality of Life with Low Dose bacillus Calmette-Guérin Instillation Therapy for Nonmuscle Invasive Bladder Cancer

• Published in: The Journal of urology Vol. 195; no. 1; pp. 41 - 46
• Main Authors: Yokomizo, Akira, Kanimoto, Yusuke, Okamura, Takehiko, Ozono, Seiichiro, Koga, Hirofumi, Iwamura, Masatsugu, Tanaka, Hiroshi, Takahashi, Satoru, Tsushima, Tomoyasu, Kanayama, Hiro-omi, Akaza, Hideyuki, Shinohara, Nobuo, Mugiya, Soichi, Nomata, Koichiro, Nakamura, Tsuyoshi, Naito, Seiji
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 2016
• Subjects: Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - adverse effects; administration and dosage; Administration, Intravesical; Aged; BCG Vaccine - administration & dosage; BCG Vaccine - adverse effects; Female; Humans; Male; mycobacterium bovis; Neoplasm Invasiveness; Quality of Life; Treatment Outcome; urinary bladder neoplasms; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - pathology; Urology; carcinoma in situ; TU; mitomycin C; RCT; bacillus Calmette-Guérin; NMIBC; TURBT; ITT; nonmuscle invasive bladder cancer; intent to treat; PPS; per protocol subjects; transurethral resection of bladder tumor; Club Urológico Español de Tratamiento Oncológico; urinary bladder neoplasms; 1/3D; CUETO; MMC; transurethral; AE; 1/2D; BCG; adverse event; complete response; half dose; CIS; CR; QOL; randomized controlled trial; one-third dose; one-sixth dose; administration and dosage; mycobacterium bovis; 1/6D; quality of life
• ISSN: 0022-5347; 1527-3792
• DOI: 10.1016/j.juro.2015.08.075

Purpose The optimal dose of intravesical bacillus Calmette-Guérin for the treatment of nonmuscle invasive bladder cancer is controversial. We investigated if induction therapy with low dose bacillus Calmette-Guérin could achieve a complete response rate similar to that of standard dose bacillus Calmette-Guérin, with less toxicity and higher quality of life. Materials and Methods After transurethral resection, patients with unresectable multiple nonmuscle invasive bladder cancer and/or carcinoma in situ were randomized to receive standard (80 mg) or low dose (40 mg) bacillus Calmette-Guérin instillation induction therapy (weekly, 8 times). The primary end point was noninferiority of low dose bacillus Calmette-Guérin with a null hypothesis of a 15% decrease in complete response rate. Secondary end points were recurrence-free survival, progression-free survival, overall survival, patient compliance, adverse events and quality of life using the EORTC QLQ-C30. Results In an intent to treat analysis of 166 patients the complete response rates for low dose and standard dose bacillus Calmette-Guérin were 79% (95% CI 0.70–0.88) and 85% (95% CI 0.77–0.92), respectively. Dunnett-Gent analysis revealed that the null hypothesis of inferiority of low dose bacillus Calmette-Guérin in terms of complete response could not be rejected (p = 0.119). However, there were no significant differences between the groups in terms of recurrence, progression and overall survival. Low dose bacillus Calmette-Guérin was associated with significantly less fever (p = 0.001) and micturition pain (p = 0.047), and significantly higher quality of life scores for global quality of life, role functioning and functional impairment. Conclusions The noninferiority of low dose bacillus Calmette-Guérin was not proven. However, low dose bacillus Calmette-Guérin was associated with lower toxicity and higher quality of life compared to standard dose bacillus Calmette-Guérin in patients with nonmuscle invasive bladder cancer.