Intravesical mitomycin C (MMC) and MMC + cytosine arabinoside for non‐muscle‐invasive bladder cancer: a randomised clinical trial. (24th August 2021)

• Record Type: Journal Article
• Authors: Miyata, Yasuyoshi; Tsurusaki, Toshifumi; Hayashida, Yasushi; Imasato, Yushi; Takehara, Kosuke; Aoki, Daiyu; Nishikido, Masaharu; Watanabe, Junichi; Mitsunari, Kensuke; Matsuo, Tomohiro; Ohba, Kojiro; Taniguchi, Keisuke; Sakai, Hideki
• Is Part Of: BJU international. Volume 129:Number 4(2022)
• Page Start: 534
• Page End: 541
• Publication Date: 2021-08-24
• Subjects: intravesical therapy -- mitomycin C -- cytosine arabinoside -- urinary pH -- non‐muscle‐invasive bladder cancer -- randomised trial -- #BladderCancer -- #blcsm -- #uroonc; Genitourinary organs -- Diseases -- Periodicals; Genitourinary organs -- Surgery -- Periodicals; Urology -- Periodicals; 616.6
• DOI: 10.1111/bju.15571
• Languages: English
• ISSNs: 1464-4096

Abstract

Abstract: Objectives: To compare the urinary pH, recurrence‐free survival (RFS), and safety of adjuvant intravesical therapy in patients with non‐muscle‐invasive bladder cancer (NMIBC) receiving mitomycin C (MMC) therapy and MMC + cytosine arabinoside (Ara‐C) therapy. Patients and Methods: A total of 165 patients with NMIBC from six hospitals were randomly allocated to two groups: weekly instillation of MMC + Ara‐C (30 mg/30 mL + 200 mg/10 mL) for 6 weeks and the same instillation schedule of MMC (30 mg/40 mL). The primary outcome was RFS, and secondary outcomes were urinary pH and toxicity in the two groups. Results: A total of 81 and 87 patients were randomised into the MMC and MMC + Ara‐C groups, respectively. Overall, the RFS in the MMC + Ara‐C group was significantly longer ( P = 0.018) than that in the MMC group. A similar significant difference was detected in patients with intermediate‐risk NMIBC, but not in those with high‐risk NMIBC. The mean (SD) urinary pH was significantly higher in the MMC + Ara‐C group than in the MMC group, at 6.56 (0.61) vs 5.78 (0.64) ( P < 0.001), and the frequency of a urinary pH of >7.0 in the MMC and MMC + Ara‐C groups was 6.3% and 26.7%, respectively ( P < 0.001). Multivariate analysis models including clinicopathological features and second transurethral resection demonstrated that increased urinary pH was associated with better outcomes (hazard ratio 0.18, 95% confidential interval 0.18–0.038; P < 0.001). In all, there were 14 and 10 adverse events in the MMC and MMC + Ara‐C groups, respectively, without a significant difference ( P = 0.113). Conclusions: Our randomised clinical trial suggested that intravesical therapy with MMC and Ara‐C is useful and safe for patients with intermediate‐risk NMIBC. Increase in urinary pH with Ara‐C is speculated as a mechanism for increased anti‐cancer effects.