What are the current guidelines for the management and treatment options available for patients diagnosed with CUP?

Management and Treatment of Cancer of Unknown Primary (CUP):

• Organisation of Care: Every hospital with a cancer centre or unit should establish a dedicated CUP team including an oncologist, palliative care physician, and CUP specialist nurse or key worker, with a named lead clinician responsible for service management and patient care coordination. Patients must have access to this team upon diagnosis of malignancy of undefined primary origin (MUO) ¹.
• Diagnostic Approach: Diagnosis occurs in two phases. The initial phase involves core investigations such as comprehensive history and physical examination, blood tests (including full blood count, liver function, calcium, LDH), chest X-ray, CT scan of chest, abdomen and pelvis, symptom-directed endoscopy, and biopsy with histology and immunohistochemistry to distinguish carcinoma from other malignancies. Tumour markers are generally not measured except in specific presentations (e.g., AFP and hCG for germ-cell tumours) ¹.
• Further Investigations: Special investigations may be offered if clinically appropriate and if results will influence treatment decisions. Investigations should be stopped if the patient is unfit for treatment or if further tests will not alter management ¹.
• Management Decisions: Treatment decisions should consider prognostic factors such as performance status, presence of liver metastases, LDH levels, and serum albumin. These factors should be discussed with patients and carers to support informed decision-making ¹.
• Specific Presentations: Patients with potentially treatable syndromes (e.g., squamous carcinoma in neck nodes, adenocarcinoma in axillary nodes, or solitary metastases) should be referred to appropriate multidisciplinary teams (MDTs) for evaluation and consideration of radical local treatment ¹.
• Systemic Treatment: Chemotherapy may be considered for patients with confirmed CUP without specific treatable syndromes after discussing potential benefits and risks. Patients should be offered the opportunity to enter clinical trials. When chemotherapy is offered outside trials, choice of regimen should consider tumour characteristics, drug toxicity, administration ease, and response rates ¹.
• Brain Metastases: Patients presenting with brain metastases only should be referred to neuro-oncology MDT. Chemotherapy is not routinely offered except in clinical trials, and patients should be informed that no treatment has proven survival benefit, with limited symptom improvement from surgery or whole brain radiotherapy ¹.
• Supportive and Palliative Care: The CUP specialist nurse or key worker plays a major role in coordinating care, liaising with GPs and community services, providing information and support, and advocating for the patient ¹.