The use of an immediate postoperative instillation of chemotherapy after TURBT in patients with small low grade non-muscle-invasive bladder cancer (NMIBC) reduces recurrences. Bladder perforation or logistic issues avoid its administration in an important percentage of cases. In this study we evaluate if an immediate neoadjuvant instillation of chemotherapy (INAIC) could be helpful in reducing recurrences of NMIBC.
We developed an ethical board approved, phase 4, prospective, randomized, controlled, clinical trial. Patients with a clinical diagnosis of non-muscle invasive bladder tumour were randomly assigned to receive TURBT alone or INAIC with Mitomycin C (40mg/40ml) for 15 minutes before TURBT. Additional adjuvant intravesical chemotherapy instillations were administered following the EAU guidelines.
The study started in May 2018 and 240 patients have been included. 212 have at least 12 months of follow up. 166 patients fulfilled the inclusion criteria and were analyzed. No differences were observed between groups in age, gender, smoking history, Charlson comorbidity index (CCI), BMI, history of previous low-risk NMIBC, urine cytology, number of tumors in cystoscopy.
After a median follow up of 24 months recurrence was observed in 17 patients (27.4%) in the TURBT alone group, and in 11 (16.7%) in the INAIC group (p=0.141). No difference was observed in subgroup analysis between Ta and T1 tumors (p = 0.238). However, patients not receiving adjuvant intravesical chemotherapy had a lower recurrence rate.
| TURB | MMC + TURB | TOTAL | p value | |
| Age (median) | 71.5 | 68 | 166 | 0.246 |
| Gender % Males Females |
20 (25%) 60 (75%) |
69 (80.2%) 17 (19.8%) |
129 (77.7%) 37 (22.3%) |
0.418 |
| Smoking history Never Current Ex Unknown |
29 (36.2%) |
32 (37.1%) |
61 (36.7%) |
0.861 |
| CCI 0 1-3 >3 |
0 (0%) 53 (66.2%) 27 (33.7%) |
0 (0%) 57 (66.3%) 29 (33.7%) |
0 (0%) 110 (66.3%) 56 (33.7%) |
0.73 |
| History of bladder tumour Primary Recurrent |
51 (63.7%) 29 (36.2%) |
58 (67.4%) 28 (32.6%) |
109 (65.7%) 57 34.3%) |
0.617 |
| Urine Citology Negative Positive Suspicious No citology |
59 (74.7%) 6 (7.6%) 13 (16.5%) 1 (1.3%) |
59 (68.6%) 6 (7%) 16 (18.6%) 5 (5.8%) |
118 (71.5%) 12 (7.3%) 29 (17.6%) 6 (3.6%) |
0.443 |
| Number of tumors 1 2-7 >7 |
44 (55%) 35 (43.7%) 1 (1.2%) |
49 (57%) 37 (43%) 0 (0%) |
93 (56%) 72 (43.4%) 1 (0.6%) |
0.574 |
| Adjuvant Yes No |
5 (6,25%) 75 (93,75%) |
4 (4,65%) 82 (95,35%) |
9 (5,42%) 157 (94,58%) |
0.649 |
The preliminary analysis of this trial suggests that INAIQ can reduce the risk of NMIBC recurrence in low-risk patients not receiving adjuvant therapy, and could be eventually considered as an alternative of a single postoperative instillation. A larger number of patients will be included in the trial to evaluate the real value of INAIQ in different patient subgroups.