Perioperative Platform for Muscle-Invasive Bladder Cancer Trials: Designs and Endpoints - Beyond the Abstract

The heterogeneity of muscle-invasive bladder cancer (MIBC) and its unresolved challenges necessitate novel well-designed clinical trial platforms to better understand the biology of each tumor in each patient at each time and its response to the ever-growing panoply of therapies. These platforms are essential for advancing personalized medicine, aiming to optimize treatment protocols and improve patient outcomes.

Trial designs within perioperative platforms must align with specific research objectives to ensure robust and meaningful outcomes. Randomized controlled trials remain the gold standard, but alternative designs such as patient-preference trials and adaptive trials are gaining traction, especially in early-phase studies. Bladder-sparing approaches, as seen in the RETAIN BLADDER and HCRN GU16-257 trials, reflect a growing interest in risk-enabled therapy following neoadjuvant chemotherapy.

Choosing appropriate endpoints is crucial for trial success. While overall survival (OS) is the historical gold standard, surrogate endpoints such as pathological complete response (pCR) and disease-free survival (DFS) are becoming more prevalent in perioperative trials. These endpoints can expedite trial results, leading to earlier approval of novel therapies. While clinical complete response (cCR) seems a promising endpoint in the neoadjuvant setting, there is a lack of standardized definition, therefore, it is not suggested as the primary endpoint in the perioperative platforms for MIBC.

As the field advances, perioperative platforms are incorporating advanced imaging techniques and liquid biopsy approaches to guide personalized treatment strategies. These tools may provide insights into tumor biology, helping to identify patients most likely to benefit from intensified or adjusted therapies.

In summary, well-designed perioperative platforms with carefully selected endpoints are pivotal in advancing MIBC treatment. With the integration of novel therapies, biomarkers, and precision medicine, these platforms are paving the way for more personalized, effective approaches that balance oncologic control with quality of life.

Written by: Ekaterina Laukhtina, MD, Medical University of Vienna, Vienna, Austria

Reference:

  1. Laukhtina E, Moschini M, Teoh JY, Shariat SF. Perioperative platform for muscle-invasive bladder cancer trials: designs and endpoints. Curr Opin Urol. 2024 Sep 12. doi: 10.1097/MOU.0000000000001228.
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