Genomic profiling and clinical utility of circulating tumor DNA in metastatic prostate cancer: SCRUM-Japan MONSTAR SCREEN project

Masaki Shiota ¹, Nobuaki Matsubara ², Taigo Kato ³

¹Department of Urology, Graduate School of Medical Sciences, Kyushu University, Kyushu, Japan. shiota.masaki.101@m.kyushu-u.ac.jp.
²Department Medical Oncology, National Cancer Center Hospital East, Chiba, Japan.
³Department of Urology, Osaka University Graduate School of Medicine, Yamadaoka, Japan.
⁴Department of Urology, Graduate School of Medical Sciences, Kyushu University, Kyushu, Japan.
⁵Department of Urology, Graduate School of Medicine Hokkaido University, Hokkaido, Japan.
⁶Department of Uro-Oncology, Saitama Medical University International Medical Center, Saitama, Japan.
⁷Department of Urology, Keio University School of Medicine, Tokyo, Japan.
⁸Department Head and Neck Medical Oncology, National Cancer Center Hospital East, Chiba, Japan.
⁹Translational Research Support Office, National Cancer Center Hospital East, Chiba, Japan.
¹⁰Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan.

⁰Department of Urology, Graduate School of Medical Sciences, Kyushu University, Kyushu, Japan. shiota.masaki.101@m.kyushu-u.ac.jp.

Bjc Reports +

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November 8, 2024

View abstract on PubMed

Summary

Circulating tumor DNA (ctDNA) testing offers insights into metastatic prostate cancer. Genomic profiling revealed higher AR alterations and HRR defects in advanced stages, impacting treatment outcomes.

Area Of Science

Genomic medicine
Oncology
Molecular diagnostics

Background

Circulating tumor DNA (ctDNA) is a promising tool for precision cancer medicine.
Understanding ctDNA in metastatic prostate cancer is crucial for treatment advancements.

Purpose Of The Study

To investigate the genomic profiling of ctDNA in patients with metastatic prostate cancer.
To assess the clinical utility of ctDNA testing in this patient population.

Main Methods

Nation-wide prospective observational study including metastatic castration-sensitive (mCSPC) and castration-resistant (mCRPC) prostate cancer patients.
ctDNA analysis using FoundationOne Liquid®CDx at enrollment and post-progression.
Tissue genomic analysis using FoundationOne®CDx prior to treatment.

Main Results

Higher frequency of AR alterations and homologous recombination repair (HRR) defects observed in mCRPC compared to mCSPC.
Tumor mutational burden correlation found between tissue and ctDNA (pre-treatment) and within ctDNA (pre- and post-treatment).
HRR defects associated with shorter time to castration resistance in mCSPC; AR alterations linked to shorter treatment failure time in mCRPC.

Conclusions

Genomic profiling of ctDNA provides valuable insights for managing metastatic prostate cancer.
HRR defects may serve as predictive factors in mCSPC and warrant further validation.