OBJECTIVES: To summarise available evidence on the accuracy, and the clinical utility, as well as assessing the economic aspect of molecular tests (IHC, FISH, RT-PCR, and NGS) relevant for the detection of ROS1 (proto-oncogene tyrosine-protein kinase fusion protein) alterations in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC).

METHODS: We searched ten databases for systematic reviews and original studies from 2015 to 2020. The results were narratively summarised, as meta-analysis was not feasible. Based on the micro-cost analysis method, we estimated the costs related to testing for ROS1 alterations.

RESULTS: The evidence for the diagnostic accuracy of tests for the detection of ROS1 alterations in patients with advanced NSCLC is scarce and incomplete. None of the included studies reported on the clinical utility of the tests or how well the tests can predict the effectiveness of treatment. While the different tests had different pros and cons, single-gene testing may be unfeasible, since people with NSCLC typically are tested for more than one type of actionable gene alteration. IHC has some advantages, such as availability and low material requirement; however, positive IHC ROS1 results need confirmation with FISH or other methods, due to a tendency for false-positive staining. The cost for ROS1 testing using IHC as a pre-test with FISH confirmation is possibly less than for the other methods.

CONCLUSIONS: Future research should focus on conducting larger cohort studies with well-defined patient populations, that follows the patients from testing (or no testing) through treatment and final clinical outcomes. NGS may potentially, due to its capacity to analyse multiple genes simultaneously, reduce the cost and the risk of depletion of scarce biomaterial and the need for repeated biopsies in patients with advanced NSCLC.