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NICE decide not to review the CUP Guideline

April 12, 2017

NICE have decided not to review the CUP Guideline having been advised of advances in immunohistochemistry markers and molecular profiling since the guideline was developed. The decision is shown here and, more interestingly, the evidence on which the decision was made is shown here.
The recommendations from the review question are:
Immunohistochemistry 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 PSA (men only) in all patients with adenocarcinoma of unknown origin. Use additional immunohistochemistry to refine the differential diagnosis, guided by the results of the panel of antibodies in recommendation and the clinical picture.
Gene-expression-based profiling Do not use gene-expression-based profiling to identify primary tumours in patients with provisional CUP.
Our comment
It is disappointing, but not surprising, that the evidence is not (yet) sufficient to incorporate gene expression profiling in the patient work-up. The cost to the NHS would be significant but there would be potential savings (as part of the Guideline development the number of investigations per patient was found to average nineteen).
The evidence for the clinical relevance of molecular profiling is building as the evidence elicited by NICE shows.
In one place it notes: ‘A few studies directly compared gene expression testing with immunohistochemistry and appeared to be more accurate.’ Our view as a charity is that the patient benefits most (in 2017) from a combination of IHC and molecular profiling to (attempt to) determine the primary site of the cancer. There will be some patients prepared to pay for molecular profiling and this should be explained and facilitated by treating oncologists where it is appropriate.  Molecular science is fast moving and the research on ‘actionable mutations’ may be a promising avenue. What is needed is research, research and more research to validate different approaches to either eliminate the occult nature of the primary; or to target treatment effectively where the primary site is largely irrelevant.

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