Expert opinion on NSCLC small specimen biomarker testing — Part 2: Analysis, reporting, and quality assessment

Abstract

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.

Impact of Molecular Testing Using Next-Generation Sequencing in the Clinical Management of Patients with Non-Small Cell Lung Cancer in a Public Healthcare Hospital

“…Following the current recommendations, we integrated the NGS molecular profiling of advanced NSCLC into routine molecular diagnosis [ 10 , 11 , 12 , 13 ]. The accreditation of this testing strategy under the UNE-EN ISO 15189:2022 scope guarantees compliance with technical requirements, ensuring the reliability of the results and the consequent therapeutic decision making in a clinically practical turnaround time.…”

“…The significant number of actionable molecular alterations that define the molecular spectrum of NSCLC has led current clinical guidelines to strongly recommend the use of gene panels for the molecular diagnosis of NSCLC [ 10 , 11 , 12 , 13 ]. Apart from approved targeted therapies, NGS studies are recommended in clinical research centers in order to identify patients eligible for clinical trials with novel targeted agents [ 11 ].…”

Klinische Anwendungsbeispiele einer Next-Generation-Sequencing-basierten Multi-Genpanel-Analyse

“…Derzeit kommen bei Betroffenen mit NSCLC zielgerichtete Therapeutika für ALK-, BRAF-, EGFR-, MET-, NTRK-, RET-, and ROS1-Alterationen zum Einsatz [6,7]. Aktuelle Konsensus-Empfehlungen schlagen vor, dass die NGS-basierte Multi-Genpanel-Testung nicht nur genetische Biomarker der zugelassenen zielgerichteten Therapien (EGFR, ALK, ROS1, BRAF und MET), sondern auch die Onkogene HER2 und KRAS mitumfasst [5,6,8]. Die zunehmende Zahl verfügbarer und aussagekräftiger genetischer Biomarker und zielgerichteter Therapien macht eine NGS-Multi-Genpanel-Teststrategie im klinischen Bereich zunehmend erforderlich.…”

Expert opinion on NSCLC small specimen biomarker testing — Part 1: Tissue collection and management

“…Where no guidelines exist, collective recommendations are reported based on the experience of the author group. The second article [14] provides recommendations for biomarker testing, quality assessment and reporting.…”