Jennifer Jones

Project Title

Evaluation of molecular markers for predicting risk of progression in high grade non-muscle invasive bladder cancer (HGNMIBC)

Funding

The Royal College of Surgeons and the Melville Trust

Supervisor

This project is surpervised by Mr Grant Stewart and Professor David Harrison.

Project Summary

High grade non-muscle invasive bladder cancer (HGNMIBC) continues to pose a management dilemma for urologists. Managed by trans-urethral resection (TUR) as per European Association of Urology guidelines, approximately 30% of HGNMIBC will progress to muscle invasive bladder cancer (MIBC) and require radical cystectomy for local disease control and 30% will ultimately die of metastatic disease. Patients progressing from HGNMIBC to MIBC are consistently found to have significantly poorer cancer-specific survival (CSS) when compared to primary MIBC outcomes. Current risk stratification indices are unable to reliably predict the poorest outcomes with established prognostic variables alone, and there is an absence of randomised phase III clinical trials of early cystectomy for HGMNIBC. This has lead to interest in the potential of novel biomarkers to identify the highest risk patients.

We hypothesize that there are morphological, protein and genetic signatures prognostic for the development of poor outcome MIBC from HGNMIBC. To examine this we will undertake a multiparametric approach utilising the following techniques: aCGH with accompanying gene expression profiling, reverse phase protein analysis, automated quantitative analysis (AQUA) and definiens morphometry for quantitative pathological analysis. The work will then be consolidated by computational biological analysis.

We propose that by combining these results with the pre-established risk indices, we can identify patients who would potentially benefit from early cystectomy over more expectant bladder conservation therapies for improved survival.