Current European/US guidelines recommend that molecular testing in advanced non-small cell lung cancer (aNSCLC) be performed using next-generation sequencing (NGS). However, the global uptake of NGS is limited, largely owing to reimbursement constraints. We compared real-world costs of NGS and single-gene testing (SGT) in nonsquamous aNSCLC. This observational study was conducted across 10 pathology centers in 10 different countries worldwide. Biomarker data collected via structured questionnaires (1 January-31 December 2021) were used to feed micro-costing analyses for three scenarios ['Starting Point' (SP; 2021-2022), 'Current Practice' (CP; 2023-2024), and 'Future Horizons' (FH; 2025-2028)] in both a real-world model, comprising all biomarkers tested by each center, and a standardized model, comprising the same sets of biomarkers across centers. Testing costs (including retesting) encompassed personnel costs, consumables, equipment, and overheads. Overall, 4,491 patients with aNSCLC were evaluated. Mean per-patient costs decreased for NGS relative to SGT over time, with real-world model costs 18% lower for NGS than for SGT in the SP scenario, and 26% lower for NGS than for SGT in the CP scenario. Mean per-biomarker costs also decreased over time for NGS relative to SGT. In the standardized model, the tipping point for the minimum number of biomarkers required for NGS to result in cost savings (per patient) was 10 and 12 in the SP and CP scenarios, respectively. Retesting had a negligible impact on cost analyses, and results were robust to variation in cost parameters. This study provides robust real-world global evidence for cost savings with NGS-based panels over SGT to evaluate predictive biomarkers in nonsquamous aNSCLC when the number of biomarkers to be tested exceeds 10. Widespread adoption of NGS may enable more efficient use of limited healthcare resources.

• Keywords
• NSCLC, cost comparison, next‐generation sequencing, precision medicine, predictive biomarker, single‐gene testing,
• MeSH
• Cost-Benefit Analysis MeSH
• Genetic Testing * economics   methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Biomarkers, Tumor * genetics   MeSH
• Lung Neoplasms * genetics   economics   diagnosis   pathology   MeSH
• Health Care Costs * MeSH
• Carcinoma, Non-Small-Cell Lung * genetics   economics   diagnosis   pathology   MeSH
• Aged MeSH
• High-Throughput Nucleotide Sequencing * economics   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Observational Study MeSH
• Comparative Study MeSH
• Names of Substances
• Biomarkers, Tumor * MeSH

BACKGROUND: Testing for epidermal growth factor receptor (EGFR) mutations is an essential recommendation in guidelines for metastatic non-squamous non-small-cell lung cancer, and is considered mandatory in European countries. However, in practice, challenges are often faced when carrying out routine biomarker testing, including access to testing, inadequate tissue samples and long turnaround times (TATs). MATERIALS AND METHODS: To evaluate the real-world EGFR testing practices of European pathology laboratories, an online survey was set up and validated by the Pulmonary Pathology Working Group of the European Society of Pathology and distributed to 64 expert testing laboratories. The retrospective survey focussed on laboratory organisation and daily EGFR testing practice of pathologists and molecular biologists between 2018 and 2021. RESULTS: TATs varied greatly both between and within countries. These discrepancies may be partly due to reflex testing practices, as 20.8% of laboratories carried out EGFR testing only at the request of the clinician. Many laboratories across Europe still favour single-test sequencing as a primary method of EGFR mutation identification; 32.7% indicated that they only used targeted techniques and 45.1% used single-gene testing followed by next-generation sequencing (NGS), depending on the case. Reported testing rates were consistent over time with no significant decrease in the number of EGFR tests carried out in 2020, despite the increased pressure faced by testing facilities during the COVID-19 pandemic. ISO 15189 accreditation was reported by 42.0% of molecular biology laboratories for single-test sequencing, and by 42.3% for NGS. 92.5% of laboratories indicated they regularly participate in an external quality assessment scheme. CONCLUSIONS: These results highlight the strong heterogeneity of EGFR testing that still occurs within thoracic pathology and molecular biology laboratories across Europe. Even among expert testing facilities there is variability in testing capabilities, TAT, reflex testing practice and laboratory accreditation, stressing the need to harmonise reimbursement technologies and decision-making algorithms in Europe.

• Keywords
• EGFR, Europe, molecular pathology, non-small-cell lung cancer, survey,
• MeSH
• ErbB Receptors genetics   MeSH
• Laboratories MeSH
• Humans MeSH
• Mutation MeSH
• Lung Neoplasms * diagnosis   genetics   pathology   MeSH
• Carcinoma, Non-Small-Cell Lung * diagnosis   genetics   pathology   MeSH
• Pandemics MeSH
• Retrospective Studies MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Europe MeSH
• Names of Substances
• EGFR protein, human MeSH Browser
• ErbB Receptors MeSH

Biomarker testing is crucial for treatment selection in advanced non-small cell lung cancer (NSCLC). However, the quantity of available tissue often presents a key constraint for patients with advanced disease, where minimally invasive tissue biopsy typically returns small samples. In Part 1 of this two-part series, we summarise evidence-based recommendations relating to small sample processing for patients with NSCLC. Generally, tissue biopsy techniques that deliver the greatest quantity and quality of tissue with the least risk to the patient should be selected. Rapid on-site evaluation can help to ensure sufficient sample quality and quantity. Sample processing should be managed according to biomarker testing requirements, because tissue fixation methodology influences downstream nucleic acid, protein and morphological analyses. Accordingly, 10% neutral buffered formalin is recommended as an appropriate fixative, and the duration of fixation is recommended not to exceed 24-48 h. Tissue sparing techniques, including the 'one biopsy per block' approach and small sample cutting protocols, can help preserve tissue. Cytological material (formalin-fixed paraffin-embedded [FFPE] cytology blocks and non-FFPE samples such as smears and touch preparations) can be an excellent source of nucleic acid, providing either primary or supplementary patient material to complete morphological and molecular diagnoses. Considerations on biomarker testing, reporting and quality assessment are discussed in Part 2.

• Keywords
• Best practice, Biopsy, Cytological techniques, Histology, Molecular diagnostics, Non-small cell lung carcinoma,
• MeSH
• Biomarkers MeSH
• Tissue Fixation methods   MeSH
• Fixatives MeSH
• Formaldehyde MeSH
• Humans MeSH
• Lung Neoplasms * diagnosis   pathology   MeSH
• Carcinoma, Non-Small-Cell Lung * diagnosis   pathology   MeSH
• Nucleic Acids * MeSH
• Paraffin Embedding MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Biomarkers MeSH
• Fixatives MeSH
• Formaldehyde MeSH
• Nucleic Acids * MeSH