Department of Oncology, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, Copenhagen, 5073, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
J Cancer Res Clin Oncol. 2024 Jul 8;150(7):339. doi: 10.1007/s00432-024-05850-y.
Urothelial tract cancer (UTC) ranks as the tenth most prevalent cancer and holds the seventh position in terms of mortality worldwide. Despite its prevalence and mortality ranking, there are still gaps in the knowledge of the mutational landscape in patients with advanced disease who have limited therapeutic options after multiple lines of prior treatment. This study compares the genomic and transcriptomic landscape, and targeted treatment options between metastatic UTC (mUTC) patients treated with multiple lines of therapy compared to newly diagnosed, untreated Muscle Invasive Bladder Cancer (MIBC).
We compared genomic and clinical data from two cohorts: mUTC patients who received multiple lines of therapy and were referred to the Copenhagen Prospective Personalized Oncology (CoPPO) project at Rigshospitalet, University of Copenhagen. Data for MIBC UTC patients were acquired from the Cancer Genome Atlas Bladder Cancer (TCGA BLCA) cohort. Biopsies in CoPPO were performed at the time of enrollment. 523 highly important cancer-related genes (TrueSight Oncology-500 targeted sequencing panel) were used from both cohorts for comparative analysis. Analyses included RNA count data to compare predicted molecular subtypes in each cohort separately.
Patients from the CoPPO cohort had a lower median age at first-line treatment than the TCGA BLCA cohort, with no significant gender disparity. The predominant histology was urothelial cell carcinoma in both cohorts. Genomic analysis revealed no significant difference between the top mutated genes in the two cohorts, specifically looking into DNA damage repair genes. Molecular subtyping indicated a higher frequency of neuroendocrine differentiation in the CoPPO cohort. 13% of patients in the CoPPO cohort received targeted therapy based on genomic findings, and 16% received non-targeted treatment, totaling 29% receiving CoPPO treatment (9 patients). The remaining 71% received best supportive care. Kaplan-Meier analysis showed a non-significant survival benefit for the intervention group in the CoPPO cohort.
When focusing on 523 highly relevant cancer genes, the mutational profile of mUTC patients who have undergone numerous treatment lines resembles that of newly diagnosed MIBC. These alterations can be targeted, indicating the potential advantage of early genomic testing for personalized treatment within clinical trials.
尿路上皮癌（UTC）是全球第十大常见癌症，也是第七大死亡原因。尽管其发病率和死亡率排名较高，但对于接受过多线治疗且治疗选择有限的晚期疾病患者的突变景观知识仍存在差距。本研究比较了转移性 UTC（mUTC）患者与新诊断、未经治疗的肌肉浸润性膀胱癌（MIBC）患者的基因组和转录组景观以及靶向治疗选择。
我们比较了两个队列的基因组和临床数据：在哥本哈根前瞻性个体化肿瘤学（CoPPO）项目中接受过多线治疗并转至哥本哈根大学 Rigshospitalet 的 mUTC 患者，以及来自癌症基因组图谱膀胱癌（TCGA BLCA）队列的 MIBC UTC 患者。CoPPO 中的活检是在入组时进行的。两个队列均使用 523 个高度重要的癌症相关基因（TrueSight Oncology-500 靶向测序面板）进行比较分析。分析包括 RNA 计数数据，以分别比较每个队列中预测的分子亚型。
CoPPO 队列的患者在一线治疗时的中位年龄低于 TCGA BLCA 队列，且无明显性别差异。两个队列的主要组织学均为尿路上皮细胞癌。基因组分析显示，两个队列中排名最高的突变基因之间没有显著差异，特别是在 DNA 损伤修复基因方面。分子亚型分析表明，CoPPO 队列中神经内分泌分化的频率更高。CoPPO 队列中有 13%的患者根据基因组发现接受了靶向治疗，16%接受了非靶向治疗，总共有 29%接受了 CoPPO 治疗（9 例）。其余 71%的患者接受了最佳支持治疗。CoPPO 队列中的 Kaplan-Meier 分析显示干预组的生存获益无统计学意义。
当关注 523 个高度相关的癌症基因时，接受过多线治疗的 mUTC 患者的突变谱与新诊断的 MIBC 相似。这些改变可以作为靶点，表明在临床试验中进行早期基因组检测以进行个体化治疗具有潜在优势。
