Illustration of how a therapy may eradicate the predominant clone within a tumour (clone 1, green), accompanied by tumour shrinkage, yet in parallel a potentially more aggressive treatment-resistant clone thrives (clone 2, red). It is feasible that genome-wide or panel-based approaches to the analysis of urinary or plasma tDNA during treatment may demonstrate such phenomena and could be performed regularly, whereas one would not invasively biopsy a bladder tumour on a regular basis to identify the same phenomena. A liquid biopsy may also capture disease heterogeneity better than a solid biopsy which only samples a single part of a single tumour. Clearly, in vivo, the scenario is far more complex with multiple clones within the same tumour vying for survival, and so this illustration is a gross oversimplification.