Sequencing of ctDNA is a minimally invasive approach to reveal the genomic alterations of cancer, however, its comparison with sequencing of tumor tissue has not been well documented in real-world patients with aggressive-variant prostate cancer (AVPC). Concordance of genomic alterations was assessed between progressive tumor tissue and matched ctDNA by next-generation sequencing for 63 AVPC patients. Associations of genomic alterations with progression-free survival (PFS) and overall survival (OS) were investigated using Kaplan-Meier and Cox regression analyses. A total of 161 somatic mutations (SMs) and 84 copy number variants (CNVs) were detected in tumors, of which 97 were also found in ctDNA, giving concordance of 39.6% (97/245) across all SMs and CNVs, 49.7% for SMs only and 20.2% for CNVs only. Across all AVPC patients, chemotherapy was associated with significantly longer median PFS (6 vs. 0.75 mo., P=0.001) and OS (11 vs. 8 mo., P < 0.001) than next-generation hormonal therapy (NHT). Among types of chemotherapy, additional platinum-based chemotherapy was associated with significantly longer median PFS and OS than docetaxel only in patients with TP53, RB1 or PTEN alterations, and in those with ctDNA% ≥ 13.5%. The concordance analysis first provides evidence for combining the sequencing of ctDNA and tumor tissue in real-world AVPC patients. Chemotherapy is associated with significantly better survival than NHT, and the benefit of additional platinum-based chemotherapy may depend on the presence of alterations in TP53, RB1 or PTEN and on a sufficiently high proportion of ctDNA in AVPC patients.
Cancer research communications. 2023 Oct 25 [Epub ahead of print]
Ruiliang Wang, Qiufan Xu, Hanxu Guo, Guanjie Yang, Jun Zhang, Hong Wang, Tianyuan Xu, Changcheng Guo, Jing Yuan, Yanyan He, Xiaoying Zhang, Hongliang Fu, Guang Xu, Binghui Zhao, Jun Xie, Tingting Zhao, Longfei Huang, Jiansheng Zhang, Bo Peng, Xudong Yao, Bin Yang
Shanghai Tenth People's Hospital, Shanghai, China., Shanghai Tenth People's Hospital, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China., Urologic Cancer Institute，Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China., Shanghai Fifth People's Hospital, Fudan University, Shanghai, China., Shanghai Tenth People's Hospital, School of Medicine, Tongji University, China., Shanghai Tenth People's Hospital, School of Medicine in Tongji University, China., Tongji University, shanghai, China., Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Center of Minimally Invasive Treatment for Tumor, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China., Shanghai Tenth People's Hospital Affiliated to Tongji University, China., Shanghai Clinical College, Anhui Medical University, Shanghai, China., GloriousMed Technology Co.,ltd, Shanghai, China., GloriousMed Clinical Laboratory, Shanghai, China., Shanghai Tenth People's Hospital, Nanjing Medical University, Nanjing, China.