Abstract
The majority of patients with bladder cancer are diagnosed in non-muscle invasive stage. Most of them will experience recurrence or progression to more aggressive disease during follow-up. That raises the need for improvements with regard to risk assessment. Current risk stratification, based only on clinicopathologic features, does not fully reflect biological heterogeneity of the cancer and its role in prognosis. Many studies addressed the topic of variant histology and its influence on treatment and outcomes. It has been shown that accurate identification of variant histology implicates patient prognosis and inform right treatment decisions. Most studies on histological variants of bladder cancer suggest a more aggressive clinical course, with higher risk of recurrence and progression than in conventional urothelial cancer, even when diagnosed in non-muscle invasive stage. That prompts early aggressive treatment approach whenever variant histology is detected. Emerging genomic information are expected to complement clinical and pathological data and change the paradigms in the management of bladder cancer. Several reports highlighted the clinical significance of molecular stratification of bladder cancer, but the available evidence is based on retrospective data. Molecular subtyping gives promise not only for improving risk assessment, but also in predicting response to Bacillus Calmette-Guerin (BCG) or chemotherapy. Finally, molecular alterations might become targets for novel drugs to improve the overall response of these patients. However, its implementation into clinical practice requires further validation in prospective trials, especially in the context of non-muscle invasive bladder cancer.