NGS – a weapon in molecular pathology?

Molecular testing has acquired a central role in the diagnosis and clinical management of patients with cancer, and next generation sequencing (NGS) represents the key weapon of the available armamentarium. In fact, NGS is a fascinating technology that has radically modified the way molecular predictive medicine is performed, by enabling the assessment of different biomarkers in different patients simultaneously, starting from very low nucleic acid input (Cytopathology. 2021;32:588–595). The implication of NGS for targeted treatments is enormous, especially in advanced-stage cancers where we usually have only scant tissue samples for morph-molecular purposes for a not-negligible percentage of patients (J Clin Pathol. 2017;70:819–826). Beyond tissue samples, NGS can also be used for the analysis of liquid biopsy samples.

Despite the many promises of NGS, high costs still represent major barriers to its implementation into daily routine practice in laboratories. However, the KWAY study showed that a maximised NGS approach resulted in saving staff time dedicated to testing activities and reducing the overall cost of testing per patient compared to standard single gene-testing modalities (Crit Rev Oncol Hematol. 2022;169:103525). Another crucial issue when using NGS is how to report the genomic information of patients due to the high variability of gene panels that are currently available – from the smallest panels that cover only clinically relevant gene alterations to the widest that comprise all genes involved in human cancers (Br J Cancer. 2017;116:553–560). The adoption of specific tools is fundamental to interpret the different genomic alterations and to report only those that may be of interest for clinicians in the treatment of cancer patients (JCO Precis Oncol. 2017;2017:PO.17.00011; Int J Cancer. 2019;145:2996–3010; Ann Oncol. 2018;29:1895–1902). Researchers’ efforts are focussed on finding new tools and methods to address this need as highlighted by some interesting studies presented by Botticelli et al (Abstract 70MO) and Crimini et al (Abstract 71P) at the ESMO Targeted Anticancer Therapies Congress 2023 (Paris, 6–8 March). However, beyond the use of novel technologies and more sustainable approaches, it has become evident that molecular tumour boards are the true game-changer in this setting that may help to decodify the clinical relevance of NGS-identified alterations and define a path forward to manage patients most appropriately (Nat Commun. 2020;11:4965).