What are the recommended referral criteria for a patient suspected of having CUP in primary care?

Refer patients with a suspected cancer of unknown primary (CUP) if they present with symptoms or signs suggestive of malignancy that warrant urgent investigation, such as unexplained lymphadenopathy, unexplained weight loss, or systemic symptoms consistent with cancer ¹.

Patients should be referred for further assessment if initial investigations, including history, physical examination, blood tests, and imaging, do not identify a primary site but raise suspicion of metastatic malignancy ¹.

Specifically, referral is recommended when there are clinical features suggestive of metastatic epithelial or neuro-endocrine malignancy without an identifiable primary after initial tests, or if special investigations (e.g., PET-CT, immunohistochemistry) are indicated to locate the primary ¹.

In cases where initial investigations suggest a specific treatable syndrome, referral should be made accordingly, but if no primary is identified, suspicion of CUP remains, and specialist assessment is warranted ¹.