PROSIBLAD - PRecision Oncology Signature for Invasive BLADder Cancer

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.

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

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 risk model able to stratify BCa patients at risk of progression from NMIBC to MIBC. 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 (anti-ROCK 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.

Key Publications: 

Tucci FA et al. Nat Commun., 2024.
doi: 10.1038/s41467-024-54246-6 

IP rights: Patent application PCT/EP2025/071967
Owners: IEO and University of Milan