figure posted on 2023-11-03, 14:40 authored by 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
Study design and integrative landscape of SMs, CNVs, and deleterious GMs in patients with AVPC. A, Flow diagram of patients according to treatment history. Tumor tissue and matched ctDNA from 63 patients with clinically defined AVPC. All of them underwent systemic treatment. Among them, 14 patients received local treatment, while 59 patients did not. The systemic treatment methods included NHT (enzalutamide, abiraterone, and apalutamine), Chemotherapy (additional platinum-based chemotherapy or docetaxel only), and other therapies (inhibitors of tyrosine kinases, PD-1 or PARP inhibitor). B, Landscape of alterations involving 30 selected genes in progressive tumor tissues and matched ctDNA from patients with AVPC. C, Landscape of alterations involving signaling pathways in progressive tumor tissues and matched ctDNA from patients with AVPC. Significance was determined using χ2 and Fisher exact tests. ***, P < 0.001.
Shanghai Science and Technology Development Foundation (Shanghai Science and Technology Foundation)
MOST | National Natural Science Foundation of China (NSFC)
Ministry of Health of China | Wu Jieping Medical Foundation (WJMF)
ARTICLE ABSTRACTSequencing of circulating tumor DNA (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 patients with AVPC. 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 patients with AVPC, chemotherapy was associated with significantly longer median PFS (6 vs. 0.75 months, P = 0.001) and OS (11 vs. 8 months, 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 patients with AVPC. 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 patients with AVPC.
AVPC is a highly malignant and heterogeneous disease. Sequencing of ctDNA is a minimally invasive approach to reveal genomic alterations. On the basis of the current real-world study, we found ctDNA does not fully recapitulate the landscape of genomic alterations from progressive tumor tissue in AVPC. We also revealed AVPC can benefit from chemotherapy, especially platinum-based regimens. TP53/RB1/PTEN alterations in ctDNA or tumor tissue could be biomarkers for platinum-based chemotherapy in this setting.