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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.

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Summary

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.

Keywords:
223Racirculating tumor DNActDNA fractiongenomic profileliquid biopsy

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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.