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Circulating Tumor DNA Genomic Profiling in 223Ra-Treated Metastatic Castration-Resistant Prostate Cancer: The
Masaki Shiota1, Maki Fujiwara2, Takayuki Sumiyoshi2
1Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; shiota.masaki.101@m.kyushu-u.ac.jp.
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). Methods: 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. Results: 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 TP53 alteration, PTEN alteration, and cell cycle pathway alterations at baseline were significantly associated with shorter rPFS and OS. Dynamic changes in ctDNA fraction and PTEN alteration between baseline and EOT correlated with distinct rPFS and OS. Conclusion: 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.
Insights
Circulating tumor DNA (ctDNA) testing shows promise for monitoring bone metastatic castration-resistant prostate cancer (mCRPC) patients treated with radium-223 (²²³Ra). Specific ctDNA profiles at baseline and during treatment correlate with survival outcomes.
Area of Science:
- Oncology
- Genomics
- Molecular Diagnostics
Background:
- Circulating tumor DNA (ctDNA) is a key tool in precision oncology.
- Radium-223 (²²³Ra) dichloride is a treatment for bone metastatic castration-resistant prostate cancer (mCRPC).
- Understanding ctDNA's role in mCRPC patients treated with ²²³Ra is crucial for treatment optimization.
Purpose of the Study:
- To investigate the genomic landscape of ctDNA in mCRPC patients receiving ²²³Ra.
- To assess the clinical utility of ctDNA for prognosis and monitoring during ²²³Ra therapy.
- To correlate ctDNA profiles with clinical outcomes such as radiographic progression-free survival (rPFS) and overall survival (OS).
Main Methods:
- Prospective, observational, multicenter study of 93 mCRPC patients treated with ²²³Ra.
- Targeted sequencing of an 88-gene panel on plasma ctDNA at baseline and end-of-treatment (EOT).
- Analysis of associations between ctDNA profiles (fraction, specific gene alterations) and clinical outcomes.
Main Results:
- ctDNA was successfully profiled in 84 baseline and 74 EOT samples.
- Elevated baseline ctDNA fraction (≥5%), TP53/PTEN alterations, and cell cycle pathway alterations were linked to shorter rPFS and OS.
- Dynamic changes in ctDNA fraction and PTEN alteration during treatment correlated with survival.
Conclusions:
- ctDNA profiling demonstrates clinical utility as a prognostic and monitoring tool in mCRPC patients undergoing ²²³Ra therapy.
- ctDNA analysis can aid in risk stratification and treatment monitoring strategies for ²²³Ra therapy.
- These findings support the integration of ctDNA testing into the management of mCRPC.
