The diagnostic work-up for non-small cell lung cancer (NSCLC) requires biomarker testing to guide therapy choices. This article is the second of a two-part series. In Part 1, we summarised evidence-based recommendations for obtaining and processing small specimen samples (i.e. pre-analytical steps) from patients with advanced NSCLC. Here, in Part 2, we summarise evidence-based recommendations relating to analytical steps of biomarker testing (and associated reporting and quality assessment) of small specimen samples in NSCLC. As the number of biomarkers for actionable (genetic) targets and approved targeted therapies continues to increase, simultaneous testing of multiple actionable oncogenic drivers using next-generation sequencing (NGS) becomes imperative, as set forth in European Society for Medical Oncology guidelines. This is particularly relevant in advanced NSCLC, where tissue specimens are typically limited and NGS may help avoid tissue exhaustion compared with sequential biomarker testing. Despite guideline recommendations, significant discrepancies in access to NGS persist across Europe, primarily due to reimbursement constraints. The use of increasingly complex testing methods also has implications for the reporting of results. Molecular testing reports should include clinical interpretation with additional commentary on sample adequacy as appropriate. Molecular tumour boards are recommended to facilitate the interpretation of complex genetic information arising from NGS, and to collaboratively determine the optimal treatment for patients with NSCLC. Finally, whichever testing modality is employed, it is essential that adequate internal and external validation and quality control measures are implemented.

Amgen BV Breda the Netherlands

Amgen GmbH Rotkreuz Switzerland

Amsterdam University Medical Center VU Medical Center Amsterdam the Netherlands

Cell Biology and Biotherapy Unit Istituto Nazionale Tumori Fondazione Giovanni Pascale IRCCS Naples Italy

Department of Pathology Aberdeen University Medical School and Aberdeen Royal Infirmary Aberdeen UK

Department of Pathology and Molecular Pathology University Hospital Zurich and University of Zurich Zurich Switzerland

Department of Pathology Charles University Medical Faculty Hospital Hradec Králové Czech Republic

Department of Public Health Biomedical Quality Assurance Research Unit Campus Gasthuisberg University Leuven Leuven Belgium

EMQN CIC Manchester UK

GenQA Edinburgh UK

Medical Oncology Department Hospital Universitario Ramón Y Cajal University of Alcalá Madrid Spain

University Clermont Auvergne INSERM U1240 Centre Jean Perrin Clermont Ferrand France

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