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 |
| AEs Grade I Grade II Grade III Grade IV Grade V |
3 (50%) 2 (67%) 0 1 (33%) 0 0 |
3 (50%) 3 (100%) 0 0 0 0 |
0,92 0,57 0,54 |
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.