Cancer of Unknown Primary (CUP) is where cancer cells are found in the body but the place the cancer began is not known. It is the 6th leading cause of cancer death in the UK and the prognosis is poor with a median survival of 6-9 months. There is a higher than average incidence of CUP in the North West (NW) of England (population of 7.4 million). Precision medicine has transformed treatment strategies in known tumour types, however in CUP there remains an urgent need to better understand CUP molecular characteristics to establish potential roles for novel therapeutic strategies. Treatment options remain limited due to difficulties in determining the primary site of the tumour and the lack of access to validated biomarkers. Access to good-quality tissue for molecular profiling remains a huge challenge in CUP. The emergence of liquid biopsies (sequence DNA in a blood test) as a source of biomarkers is also gaining rapid ground and this study aims to explore the potential utility of liquid biopsies in CUP.

Inclusion Criteria:

1. Aged 16 years or over

2. Written informed consent according to ICH/GCP and national regulations

3. ECOG Performance status 0-2

4. Confirmed diagnosis of CUP as per the ESMO guidelines. Patients must have;

   1. The local pathology reports confirming compatibility with CUP diagnosis and the associated slides used for the diagnosis
   2. Discussion at a local CUP MDT confirming diagnosis

5. Availability of archival tumour histological report

6. Willingness to provide blood samples on up to two occasions during the study

Exclusion Criteria:

1. Patient with an immunohistochemistry profile that provides a definitive clinical indication of a primary cancer with a specific treatment
2. Known HIV, Hepatitis B, C positive, due to the difficulties in handling high-risk specimens
3. Patients who are unable to provide fully informed written consent
4. Presence of any medical, psychological, familial or sociological condition that, in the investigator's opinion, will hamper compliance with the study protocol and follow-up schedule
5. Bleeding diathesis (patients' on anticoagulation are permitted to enter the trial if anticoagulation can be safely managed to enable blood sampling)
6. Conditions in which blood sampling may increase risk of complications for the patients and/or investigator

Patients diagnosed with cancer of unknown primary