Prostate Cancer
Prostate cancer spans an unusually wide clinical range, from indolent disease appropriately managed by surveillance to aggressive metastatic disease. Molecular characterisation has become increasingly relevant in the advanced setting.
Disease categories
Major disease categories
- Localised prostate cancer
- Biochemically recurrent disease
- Metastatic hormone-sensitive prostate cancer
- Metastatic castration-resistant prostate cancer
- Neuroendocrine prostate cancer
Molecular
Molecular considerations
DNA damage repair alterations, including BRCA2, BRCA1 and ATM, are of particular interest in advanced disease. Mismatch repair deficiency occurs in a minority. AR alterations and neuroendocrine transdifferentiation are relevant to resistance.
Markers commonly discussed in prostate cancer
- BRCA1/2
- ATM
- HRR gene panel
- MMR / MSI
- AR alterations
- PSMA expression
- PSA
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
Both germline and somatic testing are widely discussed in metastatic disease.
Germline
Germline considerations
Germline testing is broadly discussed in metastatic prostate cancer, with implications for relatives including female relatives given shared DNA damage repair genes.
Molecular monitoring
ctDNA and liquid biopsy considerations
ctDNA is used in research and practice discussions in advanced disease, particularly where metastatic tissue is difficult to obtain.
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.
In practice
What a review of this disease typically surfaces
Reviews commonly find DNA damage repair testing never discussed in metastatic disease, despite its implications for the patient and for female relatives who share those genes. The disease state — hormone-sensitive or castration-resistant — is sometimes recorded ambiguously, which changes the entire evidence base being applied. Where the clinical course has outpaced the PSA trajectory, neuroendocrine transformation has usually not been considered.
Patterns observed across precision oncology case reviews. Every case differs; these are the questions worth checking, not conclusions about any individual patient.
Decisions
Treatment decision questions
Questions worth raising with a treating team when a decision is being made:
- Has germline and somatic DNA damage repair testing been discussed?
- Is the disease state clearly defined as hormone-sensitive or castration-resistant?
- Has neuroendocrine transformation been considered where the clinical course is atypical?
Resistance
Resistance and recurrence questions
- Is the rate of clinical progression consistent with the PSA trajectory?
- Has a biopsy been considered to assess for neuroendocrine transformation?
Trials
Clinical trial considerations
DNA damage repair status and disease state are frequently determinative for 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.