81 A simple blood test that analyses circulating tumour DNA (ctDNA) could help doctors identify which men with advanced prostate cancer are most likely to benefit from a bone-targeting radiopharmaceutical therapy, new research suggests. The non-invasive blood test can identify patients with metastatic castration-resistant prostate cancer (mCRPC) who are most likely to respond to ²²³Ra radiopharmaceutical therapy, and can also help monitor their progress throughout treatment. ²²³Ra dichloride is a bone-targeted radiopharmaceutical therapy shown to improve overall survival and quality of life in patients with mCRPC. However, clinical outcomes with the therapy vary among patients, and no reliable biomarker has previously been established to predict or monitor treatment response, leaving an unmet need for robust prognostic and monitoring tools. “ctDNA testing, a simple blood test, has emerged as a promising approach to advance precision oncology,” said Masaki Shiota, MD, associate professor at Kyushu University in Fukuoka, Japan. “Compared with tumour biopsies, ctDNA can be collected less invasively and repeatedly, providing a real-time genomic snapshot of the tumour and its heterogeneity that could provide valuable information in the context of ²²³Ra therapy.” Researchers from Japan conducted the KYUCOG-1901 study, a prospective, observational, multicentre investigation involving 93 patients with bone mCRPC who received ²²³Ra therapy. They performed targeted ctDNA testing using an 88-gene panel on blood samples taken before treatment and at the end of treatment. The analysis found that patients with a higher amount of tumour DNA in the blood, or certain gene changes detected through ctDNA testing before treatment, had worse outcomes. Specifically, a ctDNA fraction of at least 5%, as well as TP53 alterations, PTEN alterations, and cell-cycle pathway alterations at baseline, were significantly associated with shorter radiographic progression-free survival and overall survival. Changes in tumour DNA during treatment also reflected treatment response and disease trajectory. Dynamic changes in ctDNA fraction and PTEN alterations between baseline and the end of treatment correlated with distinct outcomes for both radiographic progression-free survival and overall survival. “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 patients who are more likely or less 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.” Prostate cancer is one of the most common cancers among men in the UK, with thousands diagnosed with advanced forms each year. Current treatments for metastatic castration-resistant disease focus on controlling symptoms and extending life, but responses can be unpredictable. Radiopharmaceuticals such as ²²³Ra target cancer cells in the bones, where the disease often spreads, delivering radiation directly while sparing much of the surrounding healthy tissue. Experts not involved in the study have welcomed the findings as a step towards more personalised approaches in oncology, noting that genomic profiling of blood samples may outperform traditional markers such as PSA and alkaline phosphatase in monitoring disease trajectory for patients receiving ²²³Ra. The study, published in the July issue of The Journal of Nuclear Medicine, adds to growing evidence supporting liquid biopsies in precision oncology. Larger trials are needed to confirm the findings in diverse populations, including UK patients, but the results point towards a future in which treatment decisions for advanced prostate cancer can be guided more precisely by individual tumour biology, potentially reducing unnecessary exposure to therapies unlikely to be effective while ensuring those most likely to benefit receive them promptly.