4 Research recommendations

The Guideline Development Group has made the following recommendations for research, based on its review of evidence, to improve NICE guidance and patient care in the future. The Guideline Development Group's full set of research recommendations is detailed in the full guideline (see section 5).

4.1 Clinical studies group for CUP

A clinical studies group should be established at National Cancer Research Network (NCRN) level for CUP, to coordinate and direct a broad portfolio of research examining basic science, clinical studies, organisational processes and patient-centred topics

Why this is important

The existence of a national organisation to guide and facilitate research has revolutionised cancer care in the UK. High-quality, rapidly accruing trials have resulted in improved outcomes for patients with all common cancers. Patients with CUP cannot benefit from similar advances because there is no national research strategy addressing their needs. Establishing an NCRN clinical studies group for CUP with a comprehensive portfolio of relevant trials would redress this inequality.

4.2 Use of PET-CT in the MUO diagnostic pathway

Further research is needed to determine whether the use of 18F-FDG PET-CT early in the CUP management pathway reduces the number of investigations that the patient is subjected to.

Why this is important

Tests early in the diagnostic pathway of patients with MUO are selected on the basis of clinical factors (suspicion about a possible primary site) and test-related factors (expected yield, ease of access, ease of use, cost). Investigation is an iterative process in which the results of one round of tests inform the selection of subsequent tests. 18F-FDG PET-CT may reveal a primary tumour that would either not be detected using standard tests, or that would have been detected only after a protracted and costly series of other tests. Using 18F-FDG PET-CT early in the diagnostic pathway may reveal useful clinical information more quickly and more cost effectively than current diagnostic strategies. Comparison of established methods of investigation with early use of 18F-FDG PET-CT is therefore warranted.

4.3 Decision aids

Decision aids should be developed and research carried out to evaluate their benefit.

Why this is important

Decision aids have been shown to help breast cancer patients when they face difficult choices. Such aids could be of even greater value to patients with CUP. Research to evaluate the benefits, ease of use and acceptability of such tools to both clinicians and patients should be conducted. Such studies could be an adjunct to larger trials of chemotherapy.

4.4 Gene-expression-based profiling

Prospective randomised trials should be undertaken in patients with confirmed CUP to evaluate whether chemotherapy guided by gene-expression-based profiling is superior to treatment guided by conventional clinical and pathological factors.

Why this is important

Selection of optimal chemotherapy for patients with cancer is largely based on knowing the organ of origin of the tumour. For patients with CUP this is not known and decisions are therefore based on the likely organ of origin, as determined by tests such as histology. The limited benefit of treatment selected on this basis highlights the ineffectiveness of current tests in guiding treatment. If the likely organ of origin were more accurately defined there may be a greater chance that treatment would be more effective. Gene-expression-based profiling reliably defines the organ of origin of tumour samples, and the information this test provides in cases of CUP may translate into superior outcomes. Comparing the outcome of chemotherapy selected using conventional factors with the outcome of chemotherapy based on a putative organ of origin defined by gene-expression-based profiling would determine whether this technique could be a beneficial addition to standard management in CUP.

4.5 Defining optimal systemic therapy

Randomised controlled clinical trials should be undertaken in patients with confirmed CUP to define optimal systemic therapy.

Why this is important

The evidence currently used to guide selection of systemic treatment for patients with CUP is very limited, and mainly based on phase II non-comparative studies. In the majority of patients it is uncertain whether systemic treatment offers any advantages over supportive care alone. Randomised controlled trials comparing different interventions should be conducted in well-defined groups of patients with CUP to define optimal treatment. Such trials should include in their design methods to assess cost-effectiveness and patient-centred factors such as quality of life.

  • National Institute for Health and Care Excellence (NICE)