Due to multiple reasons, not all eligible patients receive an immediate postoperative instillation of chemotherapy after transurethral resection of bladder tumors (TURBT) for non-muscle invasive bladder cancer (NMIBC). Our objective is to evaluate the efficacy of an immediate neoadjuvant instillation of chemotherapy (INAIC) in patients with NMIBC for the prevention of recurrences, here we present an interim analysis of our study.
This is an ongoing phase IV, prospective, controlled randomized clinical trial. Patients with a clinical diagnosis of NMIBC were randomized into receiving an INAIC (Mitomycin C 40mg/40ml saline) 15 minutes before TURBT or TURBT only (Control). Only patients with histologically confirmed T1-T1, G1-G3 urothelial carcinoma were included in the analysis. The primary outcome included recurrence and/or death from cancer. Secondary outcomes included complications and toxicity.
From 183 patients randomized until December 2020, 116 patients met all inclusion and exclusion criteria and were eligible for efficacy (INAIC: 52.6%, Control: 47.4%). Treatment groups were balanced in demographics, tumor characteristics, treatments, and outcomes with no statistically significant differences found (Table 1). After a median follow-up of 17 months, we found 23 recurrences (INAIC n=12 – 19.7%; Control n=11 – 20%), 7 progressions (INAIC n=2 – 3.3%; Control n=5 -9.1%), and 10 non-cancer-related deaths (5 in each group). We did not find differences in recurrence rate (log-rank test, p=0.827). Complication rates were similar among groups and no local or systemic toxicity events were noted.
| CONTROL: 55 |
INAIC: 61 |
P value | ||
| Mean age, years | 71.07 (+/-9) | 69.41 (+/-10) | 0.3 | |
| Gender % |
Male Female |
78.2 21.8 |
85.2 14.8 |
0.3 |
| Primary/recurrent % | Primary Recurrent |
58.2 41.8 |
60.7 39.3 |
0.7 |
| Largest tumor size % | 0 – 29mm ≥30mm |
89.1 10.9 |
90.2 9.8 |
0.8 |
| Clavien-Dindo complications % | 1 2 3 (a+b) |
10.9 1.8 1.8 |
11.5 3.3 – |
0.7 |
| Final result T % |
Ta T1 |
80 20 |
86.7 13.1 |
0.3 |
| Final result G % |
G1 G2 G3 |
56.4 32.7 10.9 |
62.3 19.7 18 |
0.2 |
| Final number % |
Unifocal Multifocal |
72.7 27.3 |
75.4 24.6 |
0.7 |
| CIS presence % |
No Yes |
96.4 3.6 |
90.2 9.8 |
0.2 |
| Risk group % |
Low Intermediate High |
20 56.4 23.6 |
27.9 49.2 23 |
0.5 |
| Treatment % |
Observation Local chemotherapy Chemo-hyperthermia Immunotherapy (BCG) |
40 45.5 3.6 10.9 |
50.8 29.5 – 19.7 |
0.09 |
| Primary objective % |
Continue in follow-up Recurrence Progression Death form other cause |
61.8 20 9.1 9.1 |
68.8 19.7 3.3 8,2 |
0.5 |
| Mean follow-up, months |
15.16 (+/-8.4) | 15.49 (+/-8) | 0.8 | |
The administration of an INAIC seems feasible and safe. In this interim analysis, we did not found differences in the recurrence rate. Further recruitment and longer follow-up are needed.
Supported with grants: “Rafael Molla y Rodrigo” (FIU-AEU), Immunothercan-CM(B2017/BMD3733.