DNA blood test could identify prostate cancer patients that are most likely to benefit from radium-223 radio therapy

A non-invasive circulating tumour DNA blood test can predict which patients will respond to radium-223 treatment and track their progress according to a study in Japan

A non-invasive blood test that analyses circulating tumour DNA (ctDNA) has been shown to identify which patients with metastatic castration-resistant prostate cancer (mCRPC) are most likely to benefit from radium-223 (²²³Ra) radiopharmaceutical therapy while also allowing for effective monitoring of their progress during treatment.

²²³Ra dichloride is a bone-targeted radiopharmaceutical therapy that has been shown to improve overall survival and quality of life in patients with mCRPC. However, clinical outcomes with ²²³Ra vary considerably among patients, and no reliable biomarker has yet been established to predict or monitor treatment response. An unmet need therefore remains for robust prognostic and monitoring biomarkers in patients receiving ²²³Ra.

“Circulating tumour DNA (ctDNA) testing – a simple blood test – has emerged as a promising approach to advance precision oncology,” said Dr. Masaki Shiota, associate professor in the Department of Urology in the Graduate School of Medical Sciences at Kyushu University in Fukuoka, Japan.

Researchers have suggested that incorporating this approach to DNA profiling into clinical practice has the potential to refine patient selection, to enable early detection of treatment resistance and to optimise management for prostate cancer patients.

“Compared to tumour biopsies, ctDNA can be collected less invasively and repeatedly, [and provide] a real-time genomic snapshot of the tumour and its heterogeneity that could provide valuable information in the context of 223Ra therapy,” Shiota said.

Research into ctDNA profiling in the context of ²²³Ra radiopharmaceutical therapy for mCRPC has so far been scarce, prompting Shiota and colleagues to investigate its genomic landscape and clinical utility in more depth.

The study – known as KYUCOG-1901 – enrolled 93 patients with mCRPC, who underwent targeted ctDNA testing using an 88-gene panel both before and after receiving ²²³Ra therapy. Researchers analysed associations between ctDNA profiles and clinical outcomes, including biomarker response, radiographic progression-free survival and overall survival.

Patients found to have a higher amount of tumour DNA in the blood, or specific gene alterations such as TP53, PTEN and changes to cell cycle pathways, detected through ctDNA testing before treatment began, all tended to have worse outcomes. The analysis also showed that changes in tumour DNA occurring during treatment reflected treatment response and disease trajectory more broadly.

“While 223Ra is an important treatment for prostate cancer that has spread to the bones, not all patients benefit equally,” said Shiota.

“Our findings suggest that a blood-based genomic test may help identify [those] patients who are more likely … to benefit from the therapy. This could help doctors choose treatment more carefully and monitor patients more closely, with the goal of providing more personalised care,” he added.

The authors have concluded that incorporating ctDNA fraction and genomic alteration data into clinical practice may, in time, refine patient selection for ²²³Ra therapy and support earlier, more personalised adjustments to treatment.

For further reading please visit: 10.2967/jnumed.126.272073