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

  • Clinical guideline
  • CG104
  • Published: 
  • Last updated: 

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July 2025 exceptional surveillance of metastatic malignant disease of unknown primary origin in adults: diagnosis and management (NICE guideline CG104)

Context

The guideline on metastatic malignant disease of unknown primary origin in adults was developed in 2010. A do not use recommendation for gene-expression-based profiling during diagnosis was recommended in 2010, based on evidence from 19 studies, which were of low quality. This was due to the studies being designed to report on diagnostic development and to validate tests, so the link to patient benefit had not been established. This recommendation was removed following a surveillance review in 2023 with no further recommendation being made but a link was provided to the NHS Genomic Medicine Service. The conclusion of the surveillance review was to monitor ongoing trials, with CUPISCO being the key trial which could trigger a review of the evidence upon publication.

Trigger for the exceptional review

The CUPISCO trial is a multicenter randomised controlled trial which has been monitored since the surveillance review in 2023. It randomised patients to receive either molecular guided therapy or a standard treatment of chemotherapy. Results were published in August 2024 and may lead to a change in current recommendations.

Methods

The exceptional surveillance process consisted of:

  • Considering the new evidence from the CUPISCO trial and other studies identified during the surveillance review of 2023.

  • Considering the evidence used to develop the guideline in the 2010 update.

  • Feedback from topic experts that was gathered during the previous surveillance review.

  • Examining related NICE guidance and quality standards.

  • Examining the NICE event tracker for relevant ongoing and published events.

  • Assessing the new evidence and topic expert feedback against current recommendations to determine whether or not to update sections of the guideline, or the whole guideline.

For further details about the process and the possible update decisions that are available, see ensuring that published guidelines are current and accurate in developing NICE guidelines: the manual.

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