New research has found a way to predict resistance to chemotherapy in men with advanced prostate cancer.
Researchers analysed samples from over 200 men and discovered a strong link between chromosomal instability in circulating tumour cells (CTCs) and poor outcomes from cabazitaxel treatment. CTCs are cancer cells shed from the primary tumour into the bloodstream.
The study shows that measuring chromosomal instability in CTCs is feasible. It can predict clinical outcomes such as survival and tumour response. This simple marker could help doctors identify patients unlikely to benefit from cabazitaxel. Consequently, patients can avoid unnecessary toxicity and consider more effective treatments.
Genomic insights guide treatment decisions
For men with metastatic castration-resistant prostate cancer (mCRPC), treatment decisions become increasingly complex as the disease progresses. Most have already undergone hormone therapies and chemotherapy.
When these treatments fail, doctors face a difficult question: what next? Cabazitaxel is often chosen because it extends survival more than switching to another hormone-targeting agent.
The CARD trial, which included participants from 13 European countries, confirmed that cabazitaxel generally outperforms a second androgen receptor pathway inhibitor (ARPI). This established cabazitaxel as the standard of care for patients progressing after docetaxel and ARPIs.
However, some men experience harsh side effects, such as fatigue, infections, and neuropathy, without gaining extra time. Until now, clinicians had no reliable way to predict who would benefit.
Analysing blood samples for CTCs
The research team studied blood samples from CARD trial participants who had previously received docetaxel and progressed within 12 months on an ARPI.
CTCs are rare in blood, so the researchers used an innovative technique to isolate them without traditional enrichment methods. They removed red blood cells, stained the slides with fluorescent antibodies, and used semi-automated analysis to count CTCs among white blood cells.
Next, they applied a proprietary algorithm to classify cells as chromosomally unstable or normal based on cell morphology.
Chromosomal instability predicts outcomes
Patients with high chromosomal instability in CTCs had significantly worse outcomes. Median overall survival dropped from roughly 15 months in the low-instability group to under nine months in the high-instability group.
More importantly, high chromosomal instability predicted cabazitaxel resistance. In these patients, chemotherapy offered no advantage over switching to another hormone-targeting drug but did expose them to side effects.
This suggests that chromosomal instability in CTCs could serve as a biomarker. It can guide treatment decisions, helping doctors avoid ineffective chemotherapy and explore alternative strategies.
Towards precision oncology
Ossian Longoria, lead of the study and Clinical Research Fellow at the ICR, said: “Predicting an individual’s response to treatment is the holy grail in oncology. Molecular markers now offer a deeper look at what drives each patient’s cancer.”
Professor Johann de Bono, senior researcher at the ICR, added: “Our findings represent a breakthrough in liquid biopsy and CTC research. This is the first prospective confirmation that chromosomal instability predicts cabazitaxel resistance in advanced prostate cancer.”
By integrating genomic markers into clinical decisions, this research moves the field closer to precision oncology for men with advanced prostate cancer.
