Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada.
Department of Medical Oncology, BC Cancer, Vancouver, BC, Canada.
Nat Commun. 2021 Jan 8;12(1):184. doi: 10.1038/s41467-020-20493-6.
Molecular stratification can improve the management of advanced cancers, but requires relevant tumor samples. Metastatic urothelial carcinoma (mUC) is poised to benefit given a recent expansion of treatment options and its high genomic heterogeneity. We profile minimally-invasive plasma circulating tumor DNA (ctDNA) samples from 104 mUC patients, and compare to same-patient tumor tissue obtained during invasive surgery. Patient ctDNA abundance is independently prognostic for overall survival in patients initiating first-line systemic therapy. Importantly, ctDNA analysis reproduces the somatic driver genome as described from tissue-based cohorts. Furthermore, mutation concordance between ctDNA and matched tumor tissue is 83.4%, enabling benchmarking of proposed clinical biomarkers. While 90% of mutations are identified across serial ctDNA samples, concordance for serial tumor tissue is significantly lower. Overall, our exploratory analysis demonstrates that genomic profiling of ctDNA in mUC is reliable and practical, and mitigates against disease undersampling inherent to studying archival primary tumor foci. We urge the incorporation of cell-free DNA profiling into molecularly-guided clinical trials for mUC.
分子分层可以改善晚期癌症的治疗效果，但需要相关的肿瘤样本。由于最近治疗选择的扩大以及其高度的基因组异质性，转移性尿路上皮癌（mUC）有望从中受益。我们对 104 名 mUC 患者的微创血浆循环肿瘤 DNA（ctDNA）样本进行了分析，并与在侵袭性手术期间获得的相同患者肿瘤组织进行了比较。在开始一线系统治疗的患者中，患者 ctDNA 丰度与总生存期独立相关。重要的是，ctDNA 分析从基于组织的队列中重现了体细胞驱动基因图谱。此外，ctDNA 与匹配的肿瘤组织之间的突变一致性为 83.4%，从而可以对拟议的临床生物标志物进行基准测试。虽然 90%的突变在连续的 ctDNA 样本中被识别，但连续肿瘤组织的一致性要低得多。总的来说，我们的探索性分析表明，mUC 中 ctDNA 的基因组分析是可靠且实用的，并且可以减轻研究存档原发性肿瘤焦点时固有的疾病采样不足的问题。我们敦促将无细胞 DNA 分析纳入 mUC 的分子指导临床试验中。
