Intravesical cytosine arabinoside + Mitomycin C for bladder cancer – is it beneficial?
Reviewed by Karthik Rajan

Mitomycin C (MMC) is often used as an intravesical therapy for low / intermediate risk non-muscle invasive bladder cancer. This randomised controlled trial (RCT) was designed to assess the safety and efficacy of MMC + cytosine arabinoside (Ara-C). Ara-C was an alkalinising agent with the rationale being evidence of increased tumour exposure of MMC in alkaline pH. Randomisation was performed prior to transurethral resection of bladder tumour (TURBT) with 200 patients recruited between June 2012 and March 2017 and data for 165 patients analysed. All patients received a single instillation of MMC immediately after TURBT. Both groups had six weeks of weekly instillation of either MMC 30mg in 40ml or MMC + Ara-C 30mg+200mg in 40ml retained for one hour. Seventy-nine and eighty-six participants were treated with MMC and MMC + Ara-C therapy, respectively. Recurrence-free survival (RFS) was the primary outcome with urinary pH and toxicities being secondary outcomes. Both groups were well matched in clinicopathological parameters. Urine pH analysis showed MMC + Ara-C group (6.56±6.12) was significantly higher (P<0.001) compared to MMC group (5.78±0.64) with 96.5% patients in MMC + Ara-C group having urinary pH ≥5.5 compared to 67.1% in MMC group. Mean follow-up duration was 48.7 months vs. 43.8 months (P=0.177) in MMC + Ara-C group and MMC group, respectively. Survival analyses showed the RFS period was longer in MMC + Ara-C group vs. MMC group (P=0.018). On subgroup analysis this difference was only seen in intermediate-risk and not in high-risk disease (P=0.008 and P=0.315, respectively). Both urinary pH and MMC + Ara-C therapy were identified as independent predictors of RFS on multivariate analysis (HR 0.12, 95% CI 0.05-0.29, P<0.001: and HR 0.24, 95% CI 0.08-0.79, P=0.019, respectively). In all patients 14 and 10 adverse events occurred in MMC and MMC + Ara-C groups, respectively (P=0.113). This RCT has shown that use of MMC + Ara-C therapy in intermediate risk disease can be safely recommended with better RFS compared to MMC alone.

Intravesical mitomycin C (MMC) and MMC + cytosine arabinoside for non-muscle-invasive bladder cancer: a randomised clinical trial.
Miyata Y, Tsurusaki T, Hayashida Y, et al.
BJU INTERNATIONAL
2022;129:534–41.