Pathological reporting and molecular subtyping

In the past, all histological subgroups of NSCLC were treated uniformly. There was limited use in expanding additional efforts in pathological reporting of a biopsy sample. In recent years, we have seen a paradigm shift in lung cancer treatment to one that is individualized according to histological subtyping. For example, life-threatening toxicities such as haemoptysis are associated with the use of bevacizumab in the treatment of squamous cell carcinoma (SCC) of the lung1and pemetrexed shows benefit over gemcitabine based platinum two-drug chemotherapy in non-squamous NSCLC.2EGFR mutations and ALK gene rearrangements are almost exclusively seen in lung adenocarcinomas.3These genetic alterations have been well validated as targets for a molecularly directed systemic therapy. First line treatment should an EGFR sensitizing mutation or ALK gene rearrangement be identified would be an EGFR tyrosine kinase inhibitor (TKI)4-6, Crizotinib7or Ceritinib8respectively. Emerging local data supports ALK testing in parallel with EGFR testing. Crizotinib can also be considered in those who possess genetic alteration in the Ros1 gene.9

Recommendations on Pathological Reporting and Molecular Subtyping

There is unanimous agreement among the working group members in adopting both ESMO and NCCN guidelines.

1. Pathological diagnosis should be made according to WHO classification (category 2A). If non-squamous in histology (category 1), never or former light smokers squamous histology (level 4, A), small biopsy specimen or mixed histology, testing for EGFR activating mutations and ALK testing are recommended.

2. The workgroup supports detection of ALK translocation by fluorescence in situ hybridization (FISH) as standard, however immunohistochemistry (IHC) and RT-PCR based methods can be used if validated and qualified.

3. If possible, parallel testing for molecular aberration is preferable to avoid delay in treatment.

4. ROS1 testing can be considered and if positive treatment with crizotinib may be considered as per NCCN guidelines (category 2A).

5. The workgroup also supports NCCN endorsement of broader molecular profiling with the aims of identifying tractable mutations and informing patients on availability of clinical trials (category 2A).

6. Rebiopsy at disease progression should be considered.