PROSIBLAD - PRecision Oncology Signature for Invasive BLADder Cancer

State of the art
Bladder cancer (BCa) ranks among the most common neoplasms in industrialized countries, and it comprises non-muscle invasive BCa (NMIBC, ~75%) and muscle-invasive BCa (MIBC, ~25%) which differ greatly in terms of prognosis and clinical management. In particular, MIBC has poor prognosis, with a 5-year overall survival of 50%, despite the use of aggressive treatments, namely cystectomy followed by adjuvant chemotherapy. In contrast, NMIBC display an overall good prognosis, although ~20-30% of the cases faces a progression to MIBC with an even worse prognosis than patients with primary MIBC.

Medical Need
Current BCa staging based on standard clinicopathological parameters is often ineffective in predicting NMIBC-to-MIBC progression, leading to disease understaging and a one-size-fits-all treatment approach. NMIBC patients often undergo costly surveillance and treatments, including intravesical instillations and perfusion chemotherapy, making NMIBC one of the most expensive cancers to manage. Therefore, there is an urgent need for accurate predictive biomarkers of recurrence and progression of the NMIBC disease

Solution
PROSIBLAD is an innovative multigene signature designed to identify NMIBC patients at high risk of progression and recurrence, providing a powerful tool for precise clinical decision-making, thanks to a prognostic model able to stratify bladder cancer patients at risk of progression from non-muscle-invasive to muscle-invasive disease. Compelling data demonstrate that PROSIBLAD effectively stratifies patients progressing to MIBC and outperforms other signatures in a retrospective analysis of over 500 NMIBC patients. PROSIBLAD also represents a signature of invasiveness in NMIBC associated with hyperactivation of a RHOA/ROCK/YAP pathway and might predict response to targeted therapies (antiROCK and –YAP drugs already available in the clinic for other diseases). In conclusion, PROSIBLAD is a unique powerful predictive tool for personalized NMIBC patients’ management, beyond currently available standard clinical parameters.

Advantages
- Game-changer in NMIBC management predicting NMIBC progression and recurrence
- Development of novel combination therapies in NMIBC based on RHOA/ROCK/YAP pathways
- Clinical tool leveraging rapid global transcriptomic profiling and in situ multiplexed imaging-based phenotyping of formalin-fixed paraffin-embedded biopsy samples from the routine to identify NMIBC tumors with intrinsic invasiveness and progression features.

IP asset
Patent application PCT/EP2025/071967; co-owned by IEO and University of Milan

References
Tucci FA et al., Nature Communications 2024