Aim of our study was to evaluate safety of sequential Mitomycin and Bacillus Calmette-Guérin (BCG) treatment versus BCG monotherapy in patients with High risk Non-Muscle Invasive Bladder Cancer.
MITO-BCG is an open-label phase 4 study designed to evaluate the efficacy and safety of the sequential MMC and BCG combination treatment in patients with high-risk NMIBC. Eligibility criteria: males with a diagnosis of High risk NMIBC (T1 tumor, G3, CIS, or multiple and recurrent and large (>3 cm) Ta, G1G2 tumors or patients in the last EAU recurrence category EAU/EORTC recurrence score >/=10), age> 40 years and < 75 years, ability of consent. Patients are randomized in two groups: first with BCG induction treatment according to the standard protocol (an instillation once a week for six weeks) with 81 mg Connaught strain BCG and second receiving BCG treatment with the same protocol with a 40 mg mitomycin instillation the day before. Response will be assessed using cystoscopy and urine citology every 12 weeks for 2 years. Primary end points are recurrence rate; secondary end points are overall toxicity.
The protocol study started on March 2019. Nowadays we enrolled 36 patients with a median age of 67 (IQR 59/73). Overall, 15 (42%) patients were randomized in the group of sequential combination therapy and 21 (48%) in the group of monotherapy with BCG. After treatment, six patients experienced a post-treatment AE, three (50%) in the group of combination therapy and three (50%) in the group of BCG. Five AEs (urethral sub-stenosis, fever, asthenia, fainting, cystitis) were CTCAE grade I. None of them needed further treatment. Only one AE was a grade III, acute epididymo-orchitis with abscess requiring orchiectomy in the monotherapy BCG group (Table). No significative differences were found between the two groups (Table).
Table: Questionnaires and AEs after treatment
|Monotherapy BCG Group||Combination Therapy Group||p|
|Patients||21 (48%)||15 (42%)|
|IPSS||9 (IQR 5/11)||11 (IQR 9/13)||0,21|
|sIPSS||5 (IQR 3/7)||8 (IQR 5/10)||0,27|
|vIPSS||2 (IQR 1/5)||5 (IQR 2/6)||0,31|
|NIH-CPSI total||10 (IQR 9/11)||10 (IQR 8/21)||0,13|
|NIH-CPSI pain||3 (IQR 2/4)||3 (IQR 2/7)||0,12|
|NIH-CPSI micturition||4 (IQR 2/5)||4 (IQR 3/5)||0,74|
|NIH-CPSI Qol||4 (IQR 3/4)||4 (IQR 1/9)||0,14|
|PUF total||17 (IQR 10/22)||17 (IQR 11/23)||0,91|
|PUF SS||10 (IQR 8/11)||10 (IQR 8/11)||0,89|
|PUF BS||7 (IQR 6/8)||7 (IQR 5/8)||0,86|
Preliminary results of our experience (MITOBCG study) support that sequential combination therapy with mytomicin and BCG is a safety treatment in high risk non muscle invasive bladder cancer.