Current status of molecular markers for prognostication and outcome in invasive bladder cancer

What's known on the subject? and What does the study add? Currently, prognostication of patients with invasive BC is hampered owing to the inadequacy of standard clinicopathological risk factors to predict accurately individual treatment outcomes. This review provides a comprehensive albeit brief overview on current studies elucidating the potential role of different molecular markers to close this gap of evidence. It focuses on biostatistical considerations in the interpretation of study results which are essential to provide meaningful clinical conclusions for an individual patient.

• To improve prognostication and the management of patients with invasive bladder cancer (BC).

• Standard clinicopathological risk factors are not reliably enough to accurately predict outcomes in patients after radical treatment and guide clinicians for recommending selectively the use of adjuvant therapies. • With detailed insights into the molecular pathology of BC, biomarkers have come to the fore of researchers as a potential tool to close this gap of evidence. • However, their definitive role in the diagnostic and therapeutic management of patients with invasive BC has not clearly been addressed so far.

• Invasive BC are an extremely heterogenenous group of malignancies which are characterized by multiple genetic alterations involved in the carcinogenesis and development of metastatic spread. Thus, it is questionable whether any single marker will provide superior prognostication compared with a combination of markers. • Current studies evaluating the predictive value of a multitude of markers have used high-throughput technologies and investigated the gain in predictive accuracy within new nomograms which encompass well-established clinicopathological and novel putative molecular parameters. p53 overexpression was found to be associated with increased risk of recurrence in urothelial and non-urothelial cancer. In pT1 disease, the combination of p53, p21 and p16 as well as epigenetic alterations of myopodin expression has been shown to provide improved prognostication, and this might help to advocate more selectively the use of early radical treatment. • After the bladder-sparing approach, p53 and p21 overexpression indicate decreased probability of long-term bladder preservation. Additionally, altered retinoblastoma expression is associated with improved survival after adjuvant chemotherapy. • To provide meaningful conclusions for individual prognosis and the need of adjuvant treatment, biostatistical pitfalls in the analysis and interpretation of results have to be taken into account.

• Different molecular markers have the potential to improve prognostication of patients with invasive BC and provide improved evidence for targeted therapy in the neoadjuvant, adjuvant and metastatic setting. • However, in order to advocate their routine clinical use on a sound scientific basis prospective data are still necessary.