Research Frontier Latest Discoveries! Mitomycin C The timing of bladder infusion may vary

Bladder instillation therapy is one of the
most common treatments for bladder cancer in urology.
Although mitomycin C (MMC) has been used in neoadjuvant therapy for bladder cancer through multiple dosing regimens, doses and regimens of intravesical perfusion chemotherapy to reduce the risk of recurrence in non-muscle-invasive bladder cancer (NMIBC
) are still being explored.
This phase II study conducted by the National Cancer Center of Korea evaluated the feasibility and potential efficacy
of giving patients 2 sessions of MMC treatment 1 day and 4 hours before transurethral resection of bladder tumors (TURBT).

Bladder cancer (BC) is the tenth most common cancer worldwide, with the majority (70%-75%) being non-muscle-invasive bladder cancer
.
The standard treatment for NMIBC is TURBT, but the probability of recurrence at 1 and 5 years after surgery can reach 15%-61% and 31%-78%, so domestic and foreign guidelines often recommend intravesical perfusion chemotherapy (BCG, MMC, etc.
) to reduce the risk of
cancer recurrence.
However, chemotherapy-related complications lead to low patient compliance, and the dose and regimen of intravesical chemotherapy need to be further explored
.

This is a single-center, open-label, randomized Phase II clinical trial in adult patients
suspected of NMIBC who are scheduled to receive TURBT.
The participants were randomly assigned to the intervention group and the control group 1:1, the intervention group (n=49) received one MMC (40 mg/20 mL, a total of 2 times) treatment 1 day and 4 hours before TURBT surgery, the control group (n=50) did not receive MMC treatment before surgery, and all patients received a single intravesical chemotherapy infusion (BCG/MMC)
immediately after TURBT surgery.
The primary endpoint of the study was relapse-free survival (RFS) and secondary endpoints were progression-free survival (PFS) and adverse events (AEs).

 Figure 1 Inclusion and exclusion criteria

Preliminary analysis showed that 71 patients (n=33 in the intervention group; n=38 in the control group) had similar baseline characteristics, 61 patients had no recurrence during a follow-up period of at least 10.
4 months, and after 52.
4 months of enrollment, there were 3 patients in the intervention group and 8 patients in the control group
.
The 1-year PFS rates in the intervention and control groups were 97% and 89%,
respectively.
Neoadjuvant MMC bladder instillation reduced the relative risk of recurrence by 63% (HR=0.
37).

Figure 2 Comparison of RFS between the two groups

In addition, there was no disease progression in the intervention group, but 3 patients in the control group had disease progression (P=0.
051).

Figure 3 PFS comparison between the two groups

The results of safety analysis showed that neoadjuvant MMC treatment was well tolerated, and only 15% (5/33) of patients had treatment-related AEs, all of which were local grade 1/2 events
.

Figure 4 Analysis of AEs

In patients with NMIBC, the use of neoadjuvant MMC intravesical instillation before TURBT appears to reduce the risk of tumor recurrence and progression, showing promising therapeutic efficacy and safety, and this preliminary analysis supports further studies
of neoadjuvant MMC bladder instillation.
Gemcitabine has also recently become a viable alternative to MMC, and it remains to be seen in future studies to compare the feasibility and efficacy of gemcitabine and MMC in neoadjuvant therapy for NMIBC
.

References:

Lee HW, Lee HH, Park EY, et al.
Clinical Efficacy of Neoadjuvant Intravesical Mitomycin-C Therapy Immediately Before Transurethral Resection of Bladder Tumor in Patients With Nonmuscle-invasive Bladder Cancer: Preliminary Results of a Prospective, Randomized Phase II Study.
J Urol.
2023 Jan; 209(1):131-139.