Abstract
The lack of adequate diagnostic pathways and treatment options remains an unmet clinical need for patients with cancer of unknown primary origin (CUP). The aim of this systematic review was to evaluate whether genomic profiling improves clinical outcome for CUP patients versus those who receive standard of care. The PRISMA guidelines were followed and research articles were systematically searched on: Medline, Embase, CINAHL, Trip database and Epistemonikos, yielding 232 papers. Eligible studies had to be (i) original research trials; (ii) patients diagnosed with CUP; (iii) cohort groups of more than thirty participants; and (iv) studies with available survival data. After removal of duplicates and application of in- and exclusion criteria, six studies were included. A manual citation search identified five additional studies. The modified Cochrane risk of bias tool was used to assess the quality of the included articles. An emerging theme was the predominance of single-arm non-randomised controlled trials (RCT) along with considerable heterogeneity in study design. Nine out of the 11 studies (82%) showed a trend towards improved overall & progression-free survival in the molecularly-tailored site-specific treatment groups. Survival benefit was less promising in one double-arm RCT and in a second agnostic study. Whilst this analysis shows a trend towards improved clinical outcome in molecularly-guided treatment groups, it is still uncertain whether genomic profiling contributes substantially to the management of CUP.