Introduction:

Intravesical gemcitabine and docetaxel (GEMDOCE) is a promising therapy for high-risk non-muscle invasive bladder cancer (NMIBC). However, long term data on its effectiveness remains limited. We present our institution’s experience utilizing GEMDOCE to treat Bacillus Calmette-Guerin (BCG) exposed patients with high-risk NMIBC.  

Methods:

We retrospectively reviewed our institutional bladder cancer database, identifying BCG exposed patients from January 2013 to July 2024 who received sequential intravesical GEMDOCE via the Iowa protocol for the treatment of high-risk and very high risk NMIBC. Clinicopathologic variables and outcomes were recorded. 

We evaluated GEMDOCE failure free survival (FFS) and cystectomy free survival (CFS). Failure was defined as progression of disease from Ta or carcinoma in-situ (CIS) to ≥ T1, from T1 to T2, early cystectomy, or recurrence resulting in change in treatment.  

Kaplan-Meier curves analyzed GEMDOCE FFS and CFS starting at the first induction dose with Mantel-Cox log-rank test when needed. 

Results:

We identified 143 BCG exposed patients with high risk NMIBC who received sequential intravesical GEMDOCE with median (interquartile range-IQR) follow up of 15 (10-26) months. Pre-GEMDOCE tumor pathology included 42 (29%) CIS, 22 (15%) High Grade (HG) T1, 85 (59%) with multifocal disease, and 11 (7%) with large tumor burden. Of the 137 (96%) patients who completed a six-week induction of gemcitabine/docetaxel, 105 (73%) started monthly maintenance therapy with a median (IQR) of 11 (5-13) doses. Fourteen (10%) patients discontinued GEMDOCE due to bothersome adverse events.  

At 12- and 24-months FFS was 62% and 45% and CFS was 86% and 76% respectively. (Figure 1). Patients who received GEMDOCE for more than 12 months experienced significantly better FFS at 12, 24, 36 and 48 months (p<0.001). There was no significant difference in FFS when stratified by initial pathology (p=0.095).  

Conclusion:

Intravesical GEMDOCE is a well-tolerated and effective treatment in BCG-exposed patients with high-risk NMIBC. Extended maintenance (24 vs 12 months) is associated with improved FFS rates. Although limited by its retrospective nature, FFS rates here exceed those reported in recent BCG unresponsive trials.  As the post-BCG treatment landscape increases, randomized trials including GEMDOCE are in dire need to better risk stratify patients to the available options. 

Funding: N/A