Klümper Niklas, Cox Alexander, Sjödahl Gottfrid, Roghmann Florian, Bolenz Christian, Hartmann Arndt, Grünwald Viktor, Faltas Bishoy M, Hölzel Michael, Eckstein Markus
Department of Urology and Pediatric Urology, University Hospital Bonn, Bonn, Germany.
Institute of Experimental Oncology, University Hospital Bonn, Bonn, Germany.
Nat Rev Urol. 2025 May;22(5):256-267. doi: 10.1038/s41585-024-00951-2. Epub 2024 Oct 29.
Early metastatic spread and clonal expansion of individual mutations result in a heterogeneous tumour landscape in metastatic urothelial cancer (mUC). Substantial molecular heterogeneity of common drug targets, such as membranous NECTIN4, FGFR3 mutations, PDL1 or immune phenotypes, has been documented between primary and metastatic tumours. However, translational and clinical studies frequently do not account for such heterogeneity and often investigate primary tumour samples that might not be representative in patients with mUC. We propose this as a potential factor for why many biomarkers for mUC have failed to be integrated into clinical practice. Fresh pre-treatment metastatic biopsies enable the capturing of prevailing tumour biology in real time. The characterization of metastatic tumour samples can improve response prediction to immunotherapy, the anti-NECTIN4 antibody-drug conjugate enfortumab vedotin and the FGFR inhibitor erdafitinib. Routine metastatic biopsy can thus improve the precision of identifying driver druggable alterations, thus improving treatment selection for patients with mUC.
早期转移扩散和单个突变的克隆性扩增导致转移性尿路上皮癌（mUC）出现异质性肿瘤格局。原发性肿瘤和转移性肿瘤之间已证实存在常见药物靶点的大量分子异质性，如膜性NECTIN4、FGFR3突变、PDL1或免疫表型。然而，转化研究和临床研究常常没有考虑到这种异质性，并且经常研究原发性肿瘤样本，而这些样本可能无法代表mUC患者。我们认为这是许多mUC生物标志物未能纳入临床实践的一个潜在因素。新鲜的治疗前转移性活检能够实时捕捉主要的肿瘤生物学特征。转移性肿瘤样本的特征分析可以改善对免疫治疗、抗NECTIN4抗体药物偶联物恩杂鲁胺和FGFR抑制剂厄达替尼的反应预测。因此，常规转移性活检可以提高识别驱动性可靶向改变的准确性，从而改善mUC患者的治疗选择。
