Overcoming tumor heterogeneity in the molecular diagnosis of urological cancers

Our understanding of tumor heterogeneity and impact on treatment response is still in its infancy, presenting significant challenges to the molecular pathologist, treating physician and ultimately for the patient. Given that tumor recurrence due to treatment resistance is the most common cause of cancer death, there remains a critical unmet need to change the current paradigm. The mechanisms which underlie tumor heterogeneity can be broadly divided into genomic instability and non-mutational processes, including stochastic variations in cellular responses, modulation by tumor microenvironment and or phenotypic/functional plasticity relating to cancer stem cells. We believe that these biological mechanisms are not mutually exclusive and emphasize the need for more suitable methodologies to exploit the spatiotemporal patterns of intratumoral heterogeneity using novel approaches such as quantitative tissue-based biomarker assessment and systemic fluid analytics. Generating a comprehensive patient-centric phenotypic disease profile should generate a 'codex' which can be employed to change the current treatment decision process.