A recent randomized phase II trial has compared the efficacy and tolerance of intravesical gemcitabine versus mitomycin C following complete resection of non-muscle invasive bladder cancer (NMIBC). The study, presented by Dr. Brusabhanu Nayak at the 2024 International Bladder Cancer Network (IBCN) Annual Meeting, found comparable recurrence rates, time to recurrence, and adverse effects between the two treatments.
Background and Rationale
Bladder cancer is a common urological malignancy, with approximately 75% of cases initially presenting as NMIBC. Current guidelines recommend a single instillation of intravesical mitomycin C post-TURBT to prevent recurrence. However, recent NCCN guidelines suggest gemcitabine as a preferred agent for immediate perioperative intravesical therapy. This study addresses the gap in head-to-head randomized trials comparing intravesical gemcitabine with mitomycin C, the current standard of practice.
Study Design and Patient Population
The study was a two-arm randomized controlled trial. Patients were randomized to receive either 40 mg of mitomycin C (n = 48) or 2 g of gemcitabine (n = 44) within 6 hours of TURBT. Exclusion criteria included bladder perforation, hematuria, incomplete resection, prior intravesical therapy, and upper tract urothelial carcinoma. Patients were followed for one year to assess efficacy (recurrence and progression) and tolerance (adverse events).
Key Findings
After one year of follow-up, six patients (13.6%) in the gemcitabine group and nine patients (18.8%) in the mitomycin group experienced a recurrence (p = 0.96). The mean time to recurrence in the gemcitabine arm was 7 months +/- 4, compared to 5.6 months +/- 3.1 in the mitomycin arm (p = 0.068). Subgroup analysis, stratifying patients into low, intermediate, and high-risk groups, yielded similar results. Among the 15 recurrences, only one patient in the mitomycin C arm showed progression in T stage (LG Ta to LG T1), with no progression observed in tumor grade.
Cost and Adverse Events
The cost analysis revealed that gemcitabine instillation was slightly less expensive, with a mean cost of 1,946 Rupee ($24.47) for 2 gm, compared to 2,114 Rupee ($26.56) for 40 mg of mitomycin-C. There were no grade 3 or higher adverse events reported in either group. Dysuria was the most common adverse event (60.4% in the mitomycin group vs. 50% in the gemcitabine group, p = 0.40), followed by hematuria and afebrile UTI. One patient in the gemcitabine group experienced transient thrombocytopenia. Interestingly, patients in the mitomycin group exhibited more necrotic tissue/delayed healing at the operative site on routine cystoscopy.
Conclusions
The study indicates that immediate post-resection intravesical instillation of gemcitabine demonstrates comparable recurrence rates, time to recurrence, and adverse effects to mitomycin C in patients with NMIBC. While there were no recurrences in the low-risk group, recurrence rates were comparable in the intermediate and high-risk groups. Dr. Nayak noted that further follow-up and a larger patient cohort would help strengthen these results, suggesting gemcitabine as a viable alternative to mitomycin C in this setting.
