Patients with 'cancer of unknown primary origin' have metastatic malignant disease without an identifiable primary site. For patients with this condition the type of tumour, the extent of its spread, and the outcome of treatment all vary widely. Most patients have malignancy that appears to derive from epithelial cells, that is, 'carcinoma of unknown primary origin' (CUP). Patients with tumours of non-epithelial lineage (melanoma, sarcoma, lymphoma, germ cell) are not considered in this guideline because their care is covered in existing guidelines for their specific tumour type. They form a distinct minority because their tumours can often be managed satisfactorily even without an identifiable primary site.
CUP is currently an inexact term because it is often applied to patients who have had only limited investigations. In this guideline a patient who presents with metastatic malignancy (in the form of tumour masses or effusions) identified on clinical examination or by imaging, without an obvious primary site, is regarded as having 'malignancy of undefined primary origin' (MUO). 'Provisional carcinoma of unknown primary origin' (provisional CUP) is used to refer to patients with metastatic malignancy of proven epithelial, neuro-endocrine or undifferentiated lineage, after initial, but not exhaustive investigations. Although a primary site will be found in most of these patients, or a non-epithelial malignancy diagnosed, in some patients a primary site will not be found and a diagnosis of 'provisional CUP' will change to a diagnosis of 'confirmed CUP' after the results of all tests are complete. Definitions of MUO and CUP are given in the section on terms used in this guideline.
In England and Wales, over 10,000 cases of CUP occur annually and it is the fourth most common cause of cancer death. Patients presenting with MUO and those who are ultimately diagnosed with confirmed CUP are disadvantaged in many ways. The following problems in current practice have been identified:
Lack of agreed definitions of the clinical entity.
No referral guidelines for suspected cancer relevant to patients without an obvious or strongly suspected primary.
No system to rapidly identify patients and to ensure early specialist involvement.
Lack of efficient arrangements to manage the initial diagnostic phase.
Uncertainty about appropriate diagnostic tests, including the use of new technologies.
Lack of a team structure to efficiently care for newly presenting patients.
Insufficient specialist oncology expertise.
Lack of dedicated key workers or specialist nurses.
Referral to inappropriate site-specific cancer teams.
Lack of support and information for patients.
Delays in involvement of specialist palliative care.
Lack of an overall organisational structure to ensure high-quality care.
Uncertainty about optimal treatment.
Lack of adequate epidemiology data.
No research organisation.
The aim of this guideline is to address the needs of patients with CUP, which are not covered by current NICE cancer service guidance.
There is important overlap between the developments necessary for optimal management of MUO and CUP and the acute oncology initiatives in the National Chemotherapy Advisory Group (NCAG) report on Chemotherapy Services in England: Ensuring quality and safety. This guideline complements and supports the relevant recommendations in the NCAG report.
The guideline requires the development of a CUP specialist role for oncologists, multidisciplinary team (MDT) functioning, and site-specific group organisation in line with practice for cancers with identified primary sites. It is expected that many consultant oncologists who develop a specialist interest in CUP will also be involved in organising and delivering aspects of the acute oncology service for newly presenting patients with previously undiagnosed cancer.
The guideline will assume that prescribers will use a drug's summary of product characteristics to inform decisions made with individual patients.