Metastatic Non–Small Cell Lung Cancer Clinical Practice Guidelines (2018)

European Society for Medical Oncology

Reviewed and summarized by Medscape editors

November 02, 2018

Pathology/Molecular Biology

Adequate tissue material for histological diagnosis and molecular testing should be obtained, to allow for individual treatment decisions.

Pathological diagnosis should be made according to the 2015 World Health Organization (WHO) classification of lung tumors.

Specific subtyping of all NSCLCs is necessary for therapeutic decision making and should be carried out wherever possible. Immunohistochemistry (IHC) stains should be used to reduce the rate of cases for which the subtype cannot be identified (ie, NSCLC not otherwise specified [NSCLC-NOS]) to less than 10%.

EGFR mutation status should be systematically analyzed in advanced NSCC. Test methodology should have adequate coverage of mutations in exons 18–21, including those associated with resistance to some therapies. At a minimum, when resources or material are limited, the most common activating mutations (exon 19 deletion, exon 21 L858R point mutation) should be determined.

The availability of tyrosine kinase inhibitors (TKIs) effective against T790M-mutant recurrent disease makes T790M testing on disease relapse mandatory.

All patients with a negative cell-free DNA blood test still require tissue biopsy.

Testing for ALK rearrangement should be systematically carried out in advanced non-squamous NSCLC.

Detection of the ALK translocation by fluorescence in situ hybridization (FISH) remains a standard, but IHC with high-performance ALK antibodies and validated assays may be used for screening and have recently been accepted as an equivalent alternative to FISH for ALK testing.

Testing for ROS1 rearrangement should be systematically carried out in advanced NSCLC. Detection of the ROS1 translocation by FISH remains a standard; IHC may be used as a screening approach.

BRAF V600 mutation status should be systematically analyzed in advanced NSCLC, to determine whether BRAF/MEK inhibitors should be used.

Molecular EGFR and ALK testing are not recommended in patients with a confident diagnosis of squamous cell carcinoma (SCC), except in unusual cases (eg, patients who never smoked or are former light smokers or long-time ex-smokers).

If available, multiplex platforms (NGS) for molecular testing are preferable.

Whatever testing modality is used, it is mandatory that adequate internal validation and quality control measures are in place and that laboratories participate in, and perform adequately in, external quality assurance schemes for each biomarker test.

Programmed death-ligand 1 (PD-L1) IHC should be systematically determined in advanced NSCLC. Testing is required for pembrolizumab therapy but may also be informative when nivolumab or atezolizumab is used.


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