Circulating Tumor DNA Genomic Profiling in ²²³Ra-Treated Metastatic Castration-Resistant Prostate Cancer: The KYUCOG-1901 Study.

Abstract

Circulating tumor DNA (ctDNA) testing has emerged as a cancer precision medicine approach. We investigated the genomic landscape and clinical utility of ctDNA in patients receiving ²²³Ra dichloride for bone metastatic castration-resistant prostate cancer (mCRPC). <b>Methods:</b> This prospective, observational, multicenter study enrolled patients treated with ²²³Ra for bone mCRPC. Targeted sequencing of cell-free DNA from plasma at baseline and end of treatment (EOT), along with paired leukocyte DNA, was performed using an 88-gene panel. Associations between ctDNA profiles and clinical outcomes, including biomarker response, radiographic progression-free survival (rPFS), and overall survival (OS), were analyzed. <b>Results:</b> Of 93 patients analyzed, ctDNA was successfully profiled in 84 baseline and 74 EOT samples, with matched data available for 68 patients. A ctDNA fraction of at least 5%, as well as <i>TP53</i> alteration, <i>PTEN</i> alteration, and cell cycle pathway alterations at baseline were significantly associated with shorter rPFS and OS. Dynamic changes in ctDNA fraction and <i>PTEN</i> alteration between baseline and EOT correlated with distinct rPFS and OS. <b>Conclusion:</b> This study suggests the clinical utility of ctDNA profiling as both a prognostic and a monitoring tool in patients with bone mCRPC treated with ²²³Ra. The findings obtained in this study raise the possibility that ctDNA could contribute to future strategies for risk stratification or treatment monitoring during ²²³Ra therapy.