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.

早期转移扩散和个体突变的克隆扩增导致转移性尿路上皮癌 （mUC） 的异质性肿瘤景观。原发性肿瘤和转移性肿瘤之间常见药物靶标（如膜NECTIN4、FGFR3 突变、PDL1 或免疫表型）存在很大的分子异质性。然而，转化和临床研究通常没有考虑到这种异质性，并且经常调查在 mUC 患者中可能不具有代表性的原发性肿瘤样本。我们认为这是 mUC 的许多生物标志物未能整合到临床实践的潜在因素。新鲜的治疗前转移活检能够实时捕获主要的肿瘤生物学特征。转移性肿瘤样本的表征可以改善对免疫疗法、抗NECTIN4抗体-药物偶联物 enfortumab vedotin 和 FGFR 抑制剂 erdafitinib 的反应预测。因此，常规转移性活检可以提高识别驱动因素可药物改变的准确性，从而改善 mUC 患者的治疗选择。