A noninvasive DNA blood test can identify metastatic castration-resistant prostate cancer (mCRPC) patients who are most likely to benefit from 223Ra radiopharmaceutical therapy and monitor 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 refine patient selection, enable early detection of treatment resistance, and optimize personalized management for prostate cancer patients.
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 223Ra vary among patients, and no reliable biomarker has been established to predict or monitor treatment response. As such, there remains an unmet need for robust prognostic and monitoring biomarkers in patients receiving 223Ra.
“Circulating tumor DNA (ctDNA) testing—a simple blood test—has emerged as a promising approach to advance precision oncology,” said Masaki Shiota, MD, PhD, associate professor in the Department of Urology in the Graduate School of Medical Sciences at Kyushu University in Fukuoka, Japan. “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 the context of 223Ra therapy.”
As research on ctDNA profiling in 223Ra radiopharmaceutical therapy for mCRPC is scarce, Shiota and colleagues sought to investigate its genomic landscape and clinical utility. The study included 93 mCRPC patients who underwent targeted ctDNA testing using an 88-gene panel before and after receiving 223Ra therapy. Associations 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 trajectory.
“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 personalized care.”
Journal of Nuclear Medicine: “Circulating Tumor DNA Genomic Profiling in 223Ra-Treated Metastatic Castration-Resistant Prostate Cancer: The KYUCOG-1901 Study”. DOI: 10.2967/jnumed.126.27207