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

Masaki Shiota; Nobuaki Matsubara; Taigo Kato; Masatoshi Eto; Takahiro Osawa; Takashige Abe; Nobuo Shinohara; Koshiro Nishimoto; Yota Yasumizu; Nobuyuki Tanaka; Mototsugu Oya; Takao Fujisawa; Satoshi Horasawa; Yoshiaki Nakamura; Takayuki Yoshino; Norio Nonomura

doi:10.1038/s44276-024-00049-7

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

BJC Rep. 2024 Apr 3;2(1):28. doi: 10.1038/s44276-024-00049-7.

Authors

Masaki Shiota¹, Nobuaki Matsubara², Taigo Kato³, Masatoshi Eto⁴, Takahiro Osawa⁵, Takashige Abe⁵, Nobuo Shinohara⁵, Koshiro Nishimoto⁶, Yota Yasumizu⁷, Nobuyuki Tanaka⁷, Mototsugu Oya⁷, Takao Fujisawa⁸, Satoshi Horasawa⁹, Yoshiaki Nakamura¹⁰, Takayuki Yoshino¹⁰, Norio Nonomura³

Affiliations

¹ Department of Urology, Graduate School of Medical Sciences, Kyushu University, Kyushu, Japan. [email protected].
² Department Medical Oncology, National Cancer Center Hospital East, Chiba, Japan.
³ Department of Urology, Osaka University Graduate School of Medicine, Yamadaoka, Japan.
⁴ Department of Urology, Graduate School of Medical Sciences, Kyushu University, Kyushu, Japan.
⁵ Department of Urology, Graduate School of Medicine Hokkaido University, Hokkaido, Japan.
⁶ Department of Uro-Oncology, Saitama Medical University International Medical Center, Saitama, Japan.
⁷ Department of Urology, Keio University School of Medicine, Tokyo, Japan.
⁸ Department Head and Neck Medical Oncology, National Cancer Center Hospital East, Chiba, Japan.
⁹ Translational Research Support Office, National Cancer Center Hospital East, Chiba, Japan.
¹⁰ Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan.

Abstract

Background: Circulating tumor DNA (ctDNA) testing has emerged as a novel tool for cancer precision medicine. This study investigated the genomic profiling and clinical utility of ctDNA in metastatic prostate cancer.

Methods: This is a nation-wide prospective observational study. Patients treated with systemic treatment for metastatic castration-sensitive prostate cancer (mCSPC) and metastatic castration-resistant prostate cancer (mCRPC) were included. ctDNA was analyzed using FoundationOne Liquid®CDx at enrollment. In a subset of patients, ctDNA after disease progression and tissue prior to the initiation of treatment were examined using FoundationOne Liquid®CDx and FoundationOne®CDx, respectively.

Results: The frequency of AR alterations and homologous recombination repair (HRR) defect was higher in mCRPC compared with mCSPC. Tumor mutational burden was correlated between tissue and ctDNA at pre-treatment, as well as ctDNA between at pre-treatment and at post-treatment. Patients with HRR defect were associated with shorter time to castration resistance in androgen deprivation therapy/combined androgen blockade, but not in androgen receptor pathway inhibitor, compared with patients without HRR defect in mCSPC. Time to treatment failure in patients with AR amplification or AR mutation was shorter compared with patients without AR alterations in mCRPC.

Conclusions: This study revealed valuable findings for the clinical care of metastatic prostate cancer. Especially, predictive factors such as HRR defect in mCSPC should be validated in the future.