Introduction

Cancer of unknown primary origin is a condition in which a patient has metastatic tumour without an identified primary source (NICE, 2010). Cancer of unknown primary is an imprecise term, and it is often applied to patients in whom limited investigations have been performed. To clarify this, NICE clinical guideline CG104 has used the terms ‘metastatic malignancy of uncertain origin’ (MUO), ‘provisional carcinoma of unknown primary’ (provisional CUP) and ‘confirmed carcinoma of unknown primary (confirmed CUP)’ as summarised in Table 9.1 (NICE, 2010).

For those patients whose primary tumour is identified, treatment should continue as for that individual tumour site. But if a primary tumour is not identified after the initial investigation, treatment has to be empirical and based on research in patients whose primary tumour is known. This chapter focuses on the investigation of patients presenting with malignancy of unidentified primary origin (MUO) and the treatment possibilities for those whose primary tumour is not identified after initial investigation.

Incidence and epidemiology

Cancer of unknown primary accounts for 3–5% of all invasive malignancies in the western world (Greco and Hainsworth, 2001; Pavlidis and Pentheroudakis, 2012) and ranks in the top 10 most common cancer diagnoses. In 2011, there were 9762 new cases of cancer of unknown primary diagnosed in the United Kingdom (http://www.cancerresearchuk.org/cancer-info/cancerstats/, accessed December 2014). The age-standardised rate in the UK is 10.2 per 100,000 population. The rate is higher in men than women. The incidence of cancer of unknown primary has halved in the last 20 years and most of this decrease is likely to be due to improved detection of the primary site using techniques such as histopathology, immunohistochemistry and cross-sectional imaging, which have resulted in patients not being registered as having cancer of unknown primary.

Hospital Episode Statistics (HES) data for England (06–07) recorded a total of 25,318 episodes of care for patients with a diagnosis of cancer of unknown primary representing 308,359 NHS bed-days. The majority of patients were first admitted as an emergency.

Deaths from CUP account for 7% of all cancer deaths (http://www.cancerresearchuk.org/cancer-info/cancerstats/, accessed December 2014). However, in the absence of a standard definition, the true rate may be underestimated.