Bladder Cancer
Urothelial cancer is divided by depth of invasion, and this division governs the entire management discussion. Molecular profiling has become relevant in advanced disease.
Disease categories
Major disease categories
- Non-muscle-invasive bladder cancer
- Muscle-invasive bladder cancer
- Metastatic urothelial carcinoma
- Upper tract urothelial carcinoma
Molecular
Molecular considerations
FGFR3 alterations, ERBB2 alterations, high tumour mutational burden and PD-L1 expression are among the features assessed in advanced disease. Nectin-4 and TROP-2 expression are relevant to antibody–drug conjugate research.
Markers commonly discussed in bladder cancer
- FGFR3
- ERBB2
- PD-L1
- TMB
- MMR / MSI
- Nectin-4
Not exhaustive, and not every marker is assessed in every patient. Which of these is relevant depends on the individual case and should be discussed with the treating team.
Testing
Genomic testing considerations
Profiling is widely discussed in advanced urothelial carcinoma.
Germline
Germline considerations
Upper tract disease raises the question of Lynch syndrome in some presentations.
Molecular monitoring
ctDNA and liquid biopsy considerations
ctDNA is under active study for molecular residual disease after cystectomy.
Single-cell & computation
Single-cell and algorithmic approaches
Single-cell sequencing in genitourinary cancer is used to characterise lineage plasticity — particularly the transition towards neuroendocrine phenotype, which is a cell-state change that bulk profiling can miss entirely. Single-cell DNA analysis addresses clonal structure across metastatic sites, which is frequently discordant. Algorithm work includes DNA damage repair pathway scoring, resistance-alteration detection from serial plasma, and models that integrate imaging and molecular trajectories.
Decisions
Treatment decision questions
Questions worth raising with a treating team when a decision is being made:
- Is invasion depth unambiguous?
- Has FGFR3 been assessed in advanced disease?
- For upper tract disease, has Lynch syndrome been considered?
Resistance
Resistance and recurrence questions
- Has the molecular profile been reassessed after progression?
Trials
Clinical trial considerations
FGFR3 status and prior therapy strongly shape eligibility.
When a precision oncology review may help
A review is most useful where the standard pathway has been exhausted or where the picture is more complicated than a protocol accounts for — rare presentations, treatment resistance, complex or apparently contradictory molecular findings, or a decision between several defensible options.
The output is a structured analysis and a set of questions for the treating team. It is not treatment, and it does not replace the treating oncologist.