Circulating tumor DNA and tissue complementarily detect genomic alterations in metastatic hormone-sensitive prostate cancer

Bin Yang; Tingting Zhao; Baijun Dong; Wei Chen; Guanjie Yang; Jun Xie; Changcheng Guo; Ruiliang Wang; Hong Wang; Longfei Huang; Bo Peng; Wei Xue; Xudong Yao

doi:10.1016/j.isci.2024.108931

Circulating tumor DNA and tissue complementarily detect genomic alterations in metastatic hormone-sensitive prostate cancer

iScience. 2024 Jan 17;27(2):108931. doi: 10.1016/j.isci.2024.108931. eCollection 2024 Feb 16.

Authors

Bin Yang^{1

2}, Tingting Zhao^{3

4}, Baijun Dong⁵, Wei Chen⁶, Guanjie Yang^{1

2}, Jun Xie⁷, Changcheng Guo^{1

2}, Ruiliang Wang^{1

2}, Hong Wang^{1

2}, Longfei Huang⁴, Bo Peng^{1

2}, Wei Xue⁵, Xudong Yao^{1

2}

Affiliations

¹ Department of Urology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
² Urologic Cancer Institute, Tongji University School of Medicine, Shanghai, China.
³ Department of Urology, the Shanghai Tenth People's Hospital, School of Medicine, School of Life Sciences and Technology, Tongji University, Shanghai, China.
⁴ Research Institute, GloriousMed Clinical Laboratory (Shanghai) Co., Ltd., Shanghai, China.
⁵ Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁶ Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
⁷ Department of Urology, Shanghai Clinical College, Anhui Medical University, Shanghai, China.

Abstract

The clinical utility of circulating tumor DNA (ctDNA) in hormone-sensitive prostate cancer (HSPC) remains inadequately elucidated. This study presents the largest real-world cohort to conduct a concordance analysis between ctDNA and tissue-based genomic profiling in HSPC patients. The findings reveal diminished ctDNA abundance in cases with low tumor burden and demonstrate an increased concordance rate between ctDNA and tissue along with the progression of disease burden. Notably, a substantial number of exclusive genomic alterations (GAs) were identified either in ctDNA or tissue in high-volume metastatic disease. Integrating tissue and ctDNA analysis identified specific gene alterations (BRCA1, BRCA2, CDK12, TP53, PTEN, or RB1) associated with a shorter time to the progression to castration-resistant prostate cancer (CRPC), with an escalated CRPC risk correlated with cumulative GAs. This multicenter, real-world investigation underscores the complementary role of ctDNA and tissue in detecting clinically pertinent GAs, highlighting their potential integration into clinical practice for advanced prostate cancer management.

Keywords: Physics; Quantum physics.