OBJECTIVES: To summarise available evidence on the accuracy and the clinical utility, as well as assess the economic aspect of molecular testing (immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), reverse transcription-polymerase chain reaction (RT-PCR) and next-generation sequencing (NGS)) for the identification of NTRK neurotrophic tyrosine receptor kinase (NTRK) gene fusions in patients with locally advanced or metastatic solid tumours.

METHODS: We followed systematic review methods for the conduct of the review, seven databases were searched up to May 2021. The results were narratively summarised. Based on the micro-cost analysis method, we estimated the costs related to testing for NTRK fusions.

RESULTS: The evidence for tests’ accuracy for detecting NTRK fusions in patients with advanced solid tumours was mostly inadequate, and trial reporting was poor. None of the included studies reported tests’ clinical utility or tests’ treatment effectiveness prediction. While the different tests had different pros and cons, single-gene testing may be unfeasible, especially when the number of actionable biomarkers relevant for testing increases. IHC has some advantages, such as availability and low material requirement; however, due to a tendency for false-positive staining, positive IHC NTRK results need confirmation with other molecular methods (e.g., RT-PCR or RNA-NGS). The cost associated with NGS testing significantly decrease when parallel tests are performed for several biomarkers from multiple patients. However, at present, the capital, infrastructure, and maintenance costs are higher for NGS than the other diagnostic methods.

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