Kidney Cancer
Renal cell carcinoma comprises histological subtypes with distinct biology. Clear cell disease dominates numerically, but the non-clear-cell subtypes behave differently and are discussed separately.
Disease categories
Major disease categories
- Clear cell renal cell carcinoma
- Papillary renal cell carcinoma
- Chromophobe renal cell carcinoma
- Translocation renal cell carcinoma
- Renal medullary carcinoma
Molecular
Molecular considerations
VHL alteration is characteristic of clear cell disease. MET alterations feature in papillary disease. FH and SDH alterations define hereditary syndromes with distinct tumour biology.
Markers commonly discussed in kidney cancer
- VHL
- MET
- FH
- SDH
- PBRM1
- BAP1
- TFE3 / TFEB fusions
- PD-L1
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
Subtype-directed profiling; fusion detection matters in translocation renal cell carcinoma.
Germline
Germline considerations
Germline assessment is discussed in young patients, bilateral or multifocal disease, specific histologies, and where family history suggests VHL, hereditary leiomyomatosis and renal cell cancer, or Birt–Hogg–Dubé syndrome.
Molecular monitoring
ctDNA and liquid biopsy considerations
Renal cell carcinoma is a comparatively low-shedding tumour type; ctDNA interpretation requires particular caution.
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 the histological subtype secure?
- Has germline assessment been considered given age and family history?
- For unusual histology, has fusion testing been performed?
Resistance
Resistance and recurrence questions
- Has the disease been re-characterised on progression?
Trials
Clinical trial considerations
Histological subtype strongly determines the relevant trial set.
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.