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

Abstract

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.