Combining molecular and pathologic data to prognosticate non-muscle-invasive bladder cancer

Non-muscle-invasive (NMI) bladder cancer (BC) is a chronic disease with varying oncologic outcomes requiring frequent follow-up and repeated treatments. Recurrence (in up to 80%) is the main problem for pTa NMI-BC patients, whereas progression (in up to 45%) is the main threat in pT1 and carcinoma in situ (CIS) NMI-BC. In a recent European Organization for Research and Treatment of Cancer (EORTC) analysis, multiplicity, tumor-size and prior recurrence rate are the most important variables for recurrence. Tumor grade, stage, and CIS are the most important variables for progression to muscle-invasive (MI)-BC. However, reproducibility of pathologic stage and grade is modest, which is a major concern to clinicians. Molecular markers are promising for predicting clinical outcome of NMI-BC, especially because clinicopathologic variables are not sufficient for individual prediction of prognosis. Several obstacles and opportunities have been linked to molecular markers. The role for molecular markers to predict recurrence seems limited because multifocal disease and incomplete treatment probably are more important for recurrence than the molecular features of a removed tumor. Prediction of progression with molecular markers holds considerable promise. Examples are the combination of immunohistochemical markers, gene expression signatures, and molecular grade (based on FGFR3 mutation status and Ki-67 expression). Nevertheless, the value of molecular markers over clinicopathologic indexes is still being questioned and their clinical use limited. One of the reasons may be that reproducibility of prognostic (clinical and molecular) markers in NMI-BC has been understudied.