- Design
- Exploratory biomarker analysis of a phase 3 randomised trial
- Population
- 805 men with metastatic castration-resistant prostate cancer
- Primary outcome
- Tissue-ctDNA concordance; rPFS by ctDNA status
- Effect
- Concordance 84%; enzalutamide arm rPFS 11.0 vs 33.2 months, HR 4.03 (2.85-5.72)
An exploratory biomarker analysis of TALAPRO-2, published in Lancet Oncology on 28 October 2026, examined 805 men with metastatic castration-resistant prostate cancer randomised to talazoparib plus enzalutamide or placebo plus enzalutamide.
Homologous recombination repair status from circulating tumour DNA agreed with tissue testing in 84% of patients evaluable by both. Detectable ctDNA at baseline was strongly associated with shorter radiographic progression-free survival: in the enzalutamide-alone arm, 11.0 months against 33.2 months (HR 4.03, 95% CI 2.85 to 5.72), and in the combination arm HR 2.46. Clearance of ctDNA or falls in circulating tumour cells by week 9 were associated with better outcomes in both arms.
This supports ctDNA as a prognostic marker and as a practical alternative when tissue is inadequate for genomic testing. It is exploratory, sponsor-funded and not a test of changing treatment on the basis of ctDNA.
- Consider ctDNA testing for repair-gene alterations when tissue is unavailable or insufficient.
- Treat detectable baseline ctDNA as a marker of higher-risk disease when counselling.
- Do not switch treatment on early ctDNA changes alone outside a trial.
- Note that a negative ctDNA result can reflect low tumour shedding rather than absence of an alteration.
Why it matters
Many men lack adequate tissue for repair-gene testing; a blood test widens access to PARP inhibitor eligibility.
Don't overread it
An exploratory prognostic analysis — it does not show that acting on ctDNA changes outcomes.
The statistics, in plain English
A hazard ratio of 4.03 means about four times the rate of progression with detectable ctDNA. Prognostic markers predict outcome regardless of treatment; they do not show which treatment to choose.
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