Pre-TURBT mitomycin-C improves RFS in NMIBC

In the updated 5-year analysis of a randomized phase II trial, administering two doses of intravesical mitomycin-C (MMC) immediately before transurethral resection of bladder tumour (TURBT) improves recurrence-free survival (RFS) in individuals with non-muscle invasive bladder cancer (NMIBC).

After a median follow-up of approximately 60 months, only three patients (9.1 percent) who received immediate neoadjuvant intravesical chemotherapy (INAIC) with MMC had a recurrence. With TURBT alone, 12 patients did, corresponding to a recurrence rate of 31.6 percent.

The risk of recurrence was reduced by 77 percent with pre-TURBT INAIC with MMC vs TURBT alone (hazard ratio [HR], 0.23, 95 percent confidence interval, 0.06–0.83; p=0.02), according to Dr Ho Kyung Seo from the National Cancer Center, Goyang, South Korea, who presented the results at EAU26.

The RFS probability was higher with the intervention than with the control regimen at both 3 (90.7 percent vs 78.6 percent) and 5 years (90.7 percent vs 75.3 percent). [EAU 2026, abstract LB013]

No patient in the intervention arm had disease progression; there were six in the control arm. Hence, the progression-free survival (PFS) probability was significantly better with the experimental vs the control regimen at 3 (100 percent vs 92.1 percent) and 5 years (100 percent vs 85.8 percent). A comparison between groups yielded an HR of 0.078 (p=0.014).

However, Seo noted that the PFS results should be interpreted with caution, given the limited sample size and number of events.

Study characteristics

The team conducted this single-centre trial at the National Cancer Center of South Korea between August 2016 and December 2020. Seventy-one participants were randomized to either two intravesical doses of MMC 40 mg/20 mL, administered 1 day before and 4 hrs prior to TURBT (n=33; median age 65 years, 85 percent men), or standard TURBT only (n=38; median age 70 years, 76 percent men).

According to Seo and colleagues, the intervention improved patient convenience by delivering intensive, short-term neoadjuvant therapy without postponing the planned TURBT procedure.

Overall, all but one participant in the intervention arm had complete TURBT, and approximately two-thirds had a repeat TURBT. About 85 percent had detrusor muscle inclusion. Fifty-six percent of participants were classified as high risk according to the American Urological Association risk stratification. Ninety-two percent had primary recurrence. The most commonly used adjuvant intravesical therapy was Bacillus Calmette-Guérin (56 percent).

None in either group received immediate postoperative intravesical chemotherapy (IPOIC). Fifty-six percent of participants had tumours ≥3 cm in diameter.

A pragmatic prophylactic option

Recurrence is frequent in NMIBC, and one mechanism is by peri-TURBT tumour cell reimplantation. IPOIC, though guideline-recommended, is limited by complications in large or multiple tumours, Seo noted. “Preventing early recurrence after TURBT is an unmet need in NMIBC.”

Pre-TURBT INAIC with MMC may prevent the reimplantation of free-floating cancer cells dislodged during piecemeal resection by reducing their tumorigenic potential preoperatively and increasing the concentration of MMC in the resected tumour bed, the investigators explained.

“Thus, in a setting where standard IPOIC is not feasible, such as in patients with multiple tumours or a large tumour burden, pre-TURBT MMC may serve as a pragmatic prophylactic strategy to reduce peri-TURBT tumour cell reimplantation,” Seo said.

“This updated analysis further supports INAIC with two MMC doses, yielding favourable mid- to long-term oncological outcomes across diverse NMIBC patients,” he added, calling for validation in prospective multicentre trials.