Metastatic malignant disease of unknown primary origin in adults: diagnosis and management

Reason for the decision

NICE received an enquiry relating to recommendation 1.2.2.7, which states "Use a panel of antibodies comprising cytokeratin 7 (CK7), CK20, thyroid transcription factor‑1 (TTF‑1), placental alkaline phosphatase (PLAP), oestrogen receptor (ER; women only) and prostate-specific antigen (PSA, men only) in all patients with adenocarcinoma of unknown origin". The enquiry indicated that clinical practice in this area may have changed since the guideline was developed.

The guideline lead clinician and a topic expert indicated that they agreed that the review question should be expanded to include additional immunohistochemistry tests, and that gene expression profiling should also be reassessed.

In response to the topic expert feedback, we undertook a focused search to identify new evidence in these areas, and included 36 studies covering immunohistochemistry, single-target RNA assays, and molecular gene expression tests. However, after reviewing the available evidence, it was considered to be insufficient to change recommendations in these areas at this time.

Evidence on biomarkers detected by immunohistochemistry did not indicate any testing strategy for diagnosing the type of adenocarcinoma likely to be more specific than the currently recommended set of tests. Gene expression profiling did not show clear benefits over immunohistochemistry. After reviewing the summary of evidence, the topic experts agreed with the decision not to update the guideline at this time.