New ctDNA blood test improves personalized prostate cancer treatment

A non-invasive DNA blood test can identify patients with metastatic castration-resistant prostate cancer (mCRPC) who are more likely to benefit from ²²³Ra radiopharmaceutical treatment and monitoring their progress throughout treatment, according to new research published in the July issue of The Journal of Nuclear Medicine. Incorporating this new approach to DNA profiling into clinical practice has the potential to improve patient selection, enable early detection of treatment resistance, and optimize individualized management for patients with prostate cancer.

²²³Ra dichloride is a bone-targeted radiopharmaceutical that has been shown to improve overall survival and quality of life in patients with mCRPC. However, the clinical results with ²²³Ra varies between patients and has not been established as a reliable biomarker for predicting or monitoring treatment response. Therefore, there remains an unmet need for robust prognostic and follow-up biomarkers in patients receiving ²²³Ra.

Circulating tumor DNA (ctDNA) testing—a simple blood test—has emerged as a promising approach to advancing precision oncology. Compared to tumor biopsies, ctDNA can be collected less invasively and repeatedly, providing a real-time genomic snapshot of the tumor and its heterogeneity that could provide valuable information in context ²²³Ra treatment”.

Masaki Shiota, MD, PhD, Associate Professor, Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

As a survey of ctDNA profiling in ²²³Radiopharmaceutical therapy for mCRPC is rare, Shiota and colleagues sought to explore its genomic landscape and clinical utility. The study included 93 patients with mCRPC who underwent targeted ctDNA testing using an 88-gene panel before and after ²²³Ra treatment. Correlations between ctDNA profiles and clinical outcomes, including biomarker response, radiographic progression-free survival, and overall survival, were analyzed.

Patients with a higher amount of tumor DNA in the blood or certain gene changes, such as TP53, PTEN and cell cycle pathway alterations, detected through ctDNA testing before treatment, were found to have worse outcomes. The analysis also showed that changes in tumor DNA during treatment reflected treatment response and disease course.

“While ²²³Ra is an important treatment for prostate cancer that has spread to the bone, not all patients benefit equally,” Shiota said. “Our findings suggest that a blood-based genomic test may help identify patients who are more likely or less likely to benefit from treatment. This could help doctors choose treatment more carefully and monitor patients more closely, with the goal of providing more personalized care.”