Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Respiratory Department, Dubbo Health Service, Dubbo, NSW, Australia.
Respirology. 2020 Sep;25(9):933-943. doi: 10.1111/resp.13823. Epub 2020 Apr 25.
Molecular biomarker testing of advanced-stage NSCLC is now considered standard of care and part of the diagnostic algorithm to identify subsets of patients for molecular-targeted treatment. Tumour tissue biopsy is essential for an accurate initial diagnosis, determination of the histological subtype and for molecular testing. With the increasing use of small biopsies and cytological specimens for diagnosis and the need to identify an increasing number of predictive biomarkers, proper management of the limited amount of sampling materials available is important. Many patients with advanced NSCLC do not have enough tissue for molecular testing and/or do not have a biopsy-amenable lesion and/or do not want to go through a repeat biopsy given the potential risks. Molecular testing can be difficult or impossible if the sparse material from very small biopsy specimens has already been exhausted for routine diagnostic purposes. A limited diagnostic workup is recommended to preserve sufficient tissue for biomarker testing. In addition, tumour biopsies are limited by tumour heterogeneity, particularly in the setting of disease resistance, and thus may yield false-negative results. Hence, there have been considerable efforts to determine if liquid biopsy in which molecular alterations can be non-invasively identified in plasma cell-free ctDNA, a potential surrogate for the entire tumour genome, can overcome the issues with tissue biopsies and replace the need for the latter.
晚期 NSCLC 的分子生物标志物检测现在被认为是标准的治疗方法，也是识别分子靶向治疗患者亚组的诊断算法的一部分。肿瘤组织活检对于准确的初始诊断、确定组织学亚型和分子检测至关重要。随着小活检和细胞学标本在诊断中的使用越来越多，以及需要识别越来越多的预测性生物标志物，如何妥善管理有限数量的采样材料变得尤为重要。许多晚期 NSCLC 患者没有足够的组织进行分子检测，和/或没有可进行活检的病灶，和/或由于潜在风险不想进行重复活检。如果已经为常规诊断目的用尽了非常小的活检标本中稀少的材料，那么分子检测可能会变得困难或不可能。建议进行有限的诊断性检查，以保留足够的组织进行生物标志物检测。此外，肿瘤活检受到肿瘤异质性的限制，尤其是在耐药性的情况下，因此可能会产生假阴性结果。因此，人们一直在努力确定液体活检是否可以无创地识别血浆无细胞循环肿瘤 DNA（整个肿瘤基因组的潜在替代物）中的分子改变，从而克服组织活检的问题并取代后者的需求。
