Researchers have identified chromosomal instability in circulating tumour cells as a prognostic and predictive biomarker in metastatic castration resistant prostate cancer, using data from the phase 4 CARD trial. The findings address a major unmet need, as biomarkers to guide chemotherapy selection in this setting are currently lacking.
Biomarker Analysis From CARD Trial
The CARD trial enrolled patients with metastatic castration resistant prostate cancer whose disease progressed within 12 months of treatment with an androgen receptor pathway inhibitor, either enzalutamide or abiraterone acetate plus prednisolone or prednisone. Participants were randomised to receive cabazitaxel or the alternative androgen receptor pathway inhibitor.
As part of a preplanned biomarker analysis, circulating tumour cells were isolated from blood samples collected at baseline, at cycle 2 and at the end of treatment. Investigators assessed chromosomal instability within circulating tumour cells, building on preclinical evidence that this feature is associated with resistance to taxane chemotherapy.
Baseline circulating tumour cell counts and chromosomal instability levels were analysed for associations with imaging-based progression free survival, overall survival, time to prostate specific antigen progression, RECIST 1.1 objective response rate and prostate specific antigen 50 percent response rate.
Strong Association With Survival
High baseline chromosomal instability in circulating tumour cells was significantly associated with worse overall survival. Median overall survival was 15.3 months in patients with low chromosomal instability compared with 8.9 months in those with high levels. This corresponded to a univariate hazard ratio of 2.16 and remained statistically significant after adjustment for confounding variables, with a multivariate hazard ratio of 1.56.
Detectable chromosomal instability at baseline also appeared to predict a lack of benefit from cabazitaxel compared with an alternative androgen receptor pathway inhibitor. In this subgroup, cabazitaxel did not improve imaging-based progression free survival or overall survival, consistent with taxane resistance.
Clinical Implications
Investigators concluded that this preplanned analysis confirms chromosomal instability in circulating tumour cells as a clinically useful prognostic and predictive biomarker in metastatic castration resistant prostate cancer. The findings suggest this blood-based test could help identify patients unlikely to benefit from taxane chemotherapy.
Reference
Longoria O et al. Chromosomal instability in circulating tumor cells and cabazitaxel resistance in metastatic castration-resistant prostate cancer. JCI Insight. 2025;10(24):e196505.
