Effect of intravesical instillation of gemcitabine vs saline immediately following resection of suspected low-grade non–muscle-invasive bladder cancer on tumor recurrence: Swog s0337 randomized clinical trial
Mené sur 383 patients avec suspicion de cancer non invasif de faible grade de la vessie (âge médian : 66 ans ; 84,7% d'hommes), cet essai multicentrique évalue, du point de vue du délai avant récidive, l'efficacité d'une instillation intravésiculaire de gemcitabine une heure après une résection transurétrale de la tumeur
Importance : Low-grade non–muscle-invasive urothelial cancer frequently recurs after excision by transurethral resection of bladder tumor (TURBT).
Objective : To determine whether immediate post-TURBT intravesical instillation of gemcitabine reduces recurrence of suspected low-grade non–muscle-invasive urothelial cancer compared with saline.
Design, Setting, and Participants : Randomized double-blind clinical trial conducted at 23 US centers. Patients with suspected low-grade non–muscle-invasive urothelial cancer based on cystoscopic appearance without any high-grade or without more than 2 low-grade urothelial cancer episodes within 18 months before index TURBT were enrolled between January 23, 2008, and August 14, 2012, and followed up every 3 months with cystoscopy and cytology for 2 years and then semiannually for 2 years. Patients were monitored for tumor recurrence, progression to muscle invasion, survival, and toxic effects. The final date of follow-up was August 14, 2016.
Interventions : Participants were randomly assigned to receive intravesical instillation of gemcitabine (2 g in 100 mL of saline) (n = 201) or saline (100 mL) (n = 205) for 1 hour immediately following TURBT.
Main Outcomes and Measures : The primary outcome was time to recurrence of cancer. Secondary end points were time to muscle invasion and death due to any cause.
Results : Among 406 randomized eligible patients (median age, 66 years; 84.7% men), 383 completed the trial. In the intention-to-treat analysis, 67 of 201 patients (4-year estimate, 35%) in the gemcitabine group and 91 of 205 patients (4-year estimate, 47%) in the saline group had cancer recurrence within 4.0 years (hazard ratio, 0.66; 95% CI, 0.48-0.90; P<.001 by 1-sided log-rank test for time to recurrence). Among the 215 patients with low-grade non–muscle-invasive urothelial cancer who underwent TURBT and drug instillation, 34 of 102 patients (4-year estimate, 34%) in the gemcitabine group and 59 of 113 patients (4-year estimate, 54%) in the saline group had cancer recurrence (hazard ratio, 0.53; 95% CI, 0.35-0.81; P = .001 by 1-sided log-rank test for time to recurrence). Fifteen patients had tumors that progressed to muscle invasion (5 in the gemcitabine group and 10 in the saline group; P = .22 by 1-sided log-rank test) and 42 died of any cause (17 in the gemcitabine group and 25 in the saline group; P = .12 by 1-sided log-rank test). There were no grade 4 or 5 adverse events and no significant differences in adverse events of grade 3 or lower.
Conclusions and Relevance : Among patients with suspected low-grade non–muscle-invasive urothelial cancer, immediate postresection intravesical instillation of gemcitabine, compared with instillation of saline, significantly reduced the risk of recurrence over a median of 4.0 years. These findings support using this therapy, but further research is needed to compare gemcitabine with other intravesical agents.
JAMA , résumé, 2017