Gemcitabine for IR-NMIBC tied to more recurrence vs BCG

Treatment-naive patients with immediate-risk (IR) nonmuscle-invasive bladder cancer (NMIBC) who received gemcitabine appear to have greater recurrence risk than those given Bacillus Calmette-Guerin (BCG). Both treatments, however, are effective against disease progression.

“For patients with low-grade IR-NMIBC, adjuvant intravesical instillation of gemcitabine was associated with a lower efficacy compared with BCG in preventing recurrence after tumour resection,” the investigators said. 

A total of 151 patients with IR-NMIBC were included in this study. Of these, 78 received BCG and 73 gemcitabine. [J Urol 2025;213:730-738]

Both groups completed the 6-week induction treatment (100 percent), while 47 percent of BCG- and 53 percent of gemcitabine-treated patients received maintenance therapy (p=0.46). The median number of maintenance doses was six and eight (p=0.83), respectively. The median follow-up was 54 months in the BCG group and 36 months in the gemcitabine group.

Gemcitabine showed a significant association with a higher recurrence risk than BCG (p=0.02) after adjusting for age, International Blader Cancer Group subgroups, year of treatment, single postoperative instillation, and maintenance therapy. On the other hand, progression risk did not significantly differ between the two treatment groups (p=0.87).

In terms of safety, more patients treated with BCG experienced adverse events than those treated with gemcitabine (62 percent vs 38 percent; p=0.02).

“During the first 3 to 12 months, recurrence rates were similar between groups,” the investigators said. “However, the BCG group exhibited more durable responses over time.”

This difference is indicative of unique mechanisms of action, with some patients potentially failing to show adequate immunologic response to BCG and eventually having an early relapse. [Eur Urol 2021;80:1-3]

Gemcitabine, on the other hand, was effective at first, but it demonstrated a gradual decrease in efficacy over time. [Urol Oncol 2023;41:148.e1-148.e7]

Alternative treatment

“The result of our study contributes to the ongoing debate on adjuvant therapy for IR-NMIBC,” the investigators said. “While many urologists have shifted away from routine BCG use because of supply constraints, our findings suggest that BCG may remain the preferred option for patients with IR-NMIBC when accessible.”

Other alternatives, such as sequential gemcitabine and docetaxel, have demonstrated their effectiveness and acceptable safety profiles in recent studies. [World J Urol 2024;42:315; Urol Oncol 2023;41:485.e1-485.e7; Eur Urol Oncol 2023;6:531-534]

“Future trials should incorporate these combination regimens to better define their role in IR-NMIBC management,” according to the investigators.

Novel treatments, such as TAR-210, nadofaragene firadenovec, and cretostimogene grenadenorepvec, are currently being investigated as alternative first-line regimens for IR-NMIBC. [https://clinicaltrials.gov/study/NCT06319820; https://clinicaltrials.gov/study/NCT06510374; https://clinicaltrials.gov/study/NCT06253845]

"Although these trials hold significant promise, a key limitation is the inconsistent use of BCG as a standard-of-care comparator, complicating the interpretation and applicability of their findings,” the investigators said.

The current retrospective study included patients with low-grade IR-NMIBC, classified according to International Bladder Cancer Group criteria, without a history of induction intravesical treatment. Participants received either induction intravesical gemcitabine or BCG.

The investigators analysed survival using Kaplan-Meier estimates and identified factors associated with recurrence and progression using multivariable Cox analysis. Recurrence was defined as histologically confirmed cancer during follow-up, while disease progression involved stage or grade progression.