Erasmus Urology Research

IMPASSE-trial

 

Improved Patient Stratification by molecular Subtyping of high-risk non-muscle invasive bladder cancer and identification of novel treatments by Ex vivo medium-throughput drug screening.

 

The Dutch national IMPASSE study is for prospective validation of patient stratification in a real-world high-risk non–muscle invasive bladder cancer (HR-NMIBC) patient cohort. HR-NMIBC accounts for 75% of all bladder tumors and recommended treatment for patients is adjuvant intravesical instillations with Bacillus Calmette-Guérin (BCG) for 3 years. Unfortunately, there have been multiple periods of global BCG shortage since 2014, leaving surgical removal of the bladder (radical cystectomy: RC) as the only curative option besides BCG. Of the BCG treated patients, 40% will develop a recurrence at 5 years. Moreover, patients are exposed to significant toxicity, leading to early termination of therapy in 10% of cases. The current clinicopathological risk stratification is inadequate to predict progression and BCG treatment failure. Thus, there is an urgent need to improve risk stratification. We have recently identified clinically relevant molecular subtypes with a divergent response to BCG in a retrospective HR-NMIBC patient cohort (BRS: BCG Response Subtype 1/2/3). We specifically identified a group of patients with an aggressive molecular profile that was associated with a very high risk of progression (BRS3). Molecular subtyping improved guideline recommended risk stratification and we showed that a consumer-ready RNA-based pathway diagnostic test (Philips OncoSignal®) was able to accurately identify these high risk BRS3 patients (AUC 0.86). The IMPASSE study aims to prospectively validate the predictive accuracy of BRS molecular subtyping followed by identification of novel targets for alternative bladder-sparing treatments. Novel identified gene targets will be validated on patient-derived bladder cancer organoids with the ultimate aim to develop alternative bladder-sparing targeted therapies in HR-NMIBC patients who fail BCG treatment.

 

 

People working on the project

Tahlita Zuiverloon

Tahlita Zuiverloon

Assistant Professor

Tokameh Mahmoudi

Tokameh Mahmoudi

Associate Professor

Vandana Solanki

Vandana Solanki

Postdoctoral Researcher

Mitchell Olislagers

Mitchell Olislagers

PhD-candidate