A simple blood test may soon help clinicians manage metastatic castration-resistant prostate cancer (mCRPC) more precisely, according to a study appearing in the July issue of The Journal of Nuclear Medicine. Researchers report that circulating tumor DNA (ctDNA) profiling can flag which patients are most likely to benefit from radium-223 (^223Ra) radiopharmaceutical therapy, and can track how disease responds during treatment. The work also suggests that ctDNA changes could reveal early hints of therapeutic resistance, potentially before standard imaging does.
^223Ra dichloride is designed to target bone metastases and has demonstrated improvements in overall survival and quality of life. Yet treatment outcomes vary substantially between patients, and clinicians currently lack a reliable biomarker to predict response or monitor progress. That gap limits personalization—both in selecting candidates for ^223Ra and in deciding when to adjust therapy.
To address this need, investigators led by Masaki Shiota and colleagues analyzed the genomic landscape captured in blood. The study enrolled 93 patients with mCRPC who underwent targeted ctDNA testing using an 88-gene panel before ^223Ra treatment and again after therapy began. By comparing ctDNA profiles with clinical endpoints, the team evaluated biomarker response, radiographic progression-free survival, and overall survival.
The researchers found that a higher pre-treatment tumor DNA burden in the bloodstream was linked to worse outcomes. They also observed that specific gene alterations detectable in ctDNA—such as TP53 and PTEN changes, along with alterations in cell cycle pathways—were associated with poorer prognosis. In essence, the ctDNA signal reflected both tumor aggressiveness and likely resistance biology.
Importantly, ctDNA was not just a static predictor. Changes in tumor DNA during ^223Ra therapy mirrored patient response and disease trajectory, aligning treatment dynamics with evolving genomic information. Because ctDNA can be obtained repeatedly with minimal invasiveness compared with tissue biopsies, it provides a “real-time” molecular snapshot of tumor heterogeneity.
The authors argue that incorporating ctDNA genomic profiling could refine patient selection, support earlier detection of resistance, and improve personalized management of bone-metastatic mCRPC. While further validation will be required before routine clinical adoption, the findings highlight a practical route toward more adaptive, genomics-informed radiopharmaceutical care.
Subject of Research: Circulating tumor DNA (ctDNA) as a biomarker for predicting and monitoring response to radium-223 (^223Ra) in metastatic castration-resistant prostate cancer (mCRPC)
Article Title: Circulating Tumor DNA Genomic Profiling in 223Ra-Treated Metastatic Castration-Resistant Prostate Cancer: The KYUCOG-1901 Study
News Publication Date: 1-Jul-2026
Web References: https://doi.org/10.2967/jnumed.126.272073
References: 10.2967/jnumed.126.272073
Image Credits: Image created by Masaki Shiota et al., Kyushu University, Fukuoka, Japan.
Keywords: prostate cancer; personalized medicine; ctDNA; radiopharmaceutical therapy; radium-223; metastasis; biomarker; genomic profiling; TP53; PTEN
