Midterm follow-up (3 years) confirms and extends short-term results of intravesical gemcitabine as bladder-preserving treatment for non–muscle-invasive bladder cancer after BCG failure

•Salvage intravesical gemcitabine is an option for a selected unresponsive BCG population.•Salvage intravesical gemcitabine achieves a significant disease free survival at 12, 24 months and 36 months for the whole sample of 47.62%, 38.14%, and 32.69%, respectively.•These results are superior to data recently reported in a systematic review.•Overall, 19 patients presented a progression to T2-T4 or extravesical lesions. At 36 months progression free survival was 65.38%.•Intravesical gemcitabine might represent a useful treatment for patients unresponsive or intolerant to BCG, unwilling to undergo the recommended standard-of-care radical cystectomy. There is a high demand for bladder sparing therapies in patients who do not respond to bacillus Calmette-Guérin (BCG). To report the mid-term results of intravesical gemcitabine in non–muscle-invasive bladder cancer (NMIBC) patients, who failed BCG and who were unwilling to undergo radical cystectomy (RC). This is an extended confirmatory open-label, single-arm study, which enrolled consecutive patients who failed BCG or were BCG intolerant and unwilling to undergo the RC (histologically confirmed Tis (CIS), T1 high grade or multifocal Ta high grade of the urinary bladder). Intravesical gemcitabine was administered once a week for 6 consecutive weeks and once a month for 12 months. The primary outcome was disease-free survival (DFS) defined as the lack of tumor on cystoscopy and negative urine cytology. The secondary endpoint was safety, defined according a grading of side effects. overall survival, progression-free survival and DFS were described with Kaplan-Meier method at 12, 24, and 36 months. Overall 46 patients were enrolled. The mean follow-up was 40 months. The DFS was 69.05% at the end of induction phase and 32.69% at 36 months. The progression-free survival at 36 months was 65.38%. The overall survival and cancer specific survival were 66.97% (95% confidence interval 47.25%–80.70%) and 78.71% (95% confidence interval 59.16%–89.66%), respectively. There was no life-threatening event or treatment related death (grade 4 or 5). The most common mild and moderate adverse events reported were urinary symptoms (lower urinary tract symptoms) and fatigue (G1-G2). Intravesical gemcitabine seemed to represent a valid and safe alternative at 3 years follow-up for patients who failed BCG and were unwilling to undergo RC.