What initial investigations should be conducted for a patient presenting with symptoms suggestive of Cancer of Unknown Primary (CUP)?

For a patient presenting with symptoms suggestive of cancer of unknown primary (CUP), the initial investigations should include:

• Comprehensive history and physical examination, including breast, nodal areas, skin, genital, rectal, and pelvic examination.
• Blood tests: full blood count; urea, electrolytes and creatinine; liver function tests; calcium; urinalysis; lactate dehydrogenase.
• Chest X-ray to assess for thoracic malignancy.
• Myeloma screen if there are isolated or multiple lytic bone lesions.
• Symptom-directed endoscopy if clinically indicated by symptoms.
• Computed tomography (CT) scan of the chest, abdomen, and pelvis to identify possible primary sites or extent of disease.
• Tumour markers selectively: prostate-specific antigen (PSA) in men, cancer antigen 125 (CA125) in women with peritoneal malignancy or ascites, alpha-fetoprotein (AFP) and human chorionic gonadotrophin (hCG) particularly in presentations compatible with germ-cell tumours.
• Testicular ultrasound in men with presentations compatible with germ-cell tumours.
• Biopsy and standard histological examination with immunohistochemistry as necessary to distinguish carcinoma from other malignancies.

These investigations aim to identify a primary tumour site, non-epithelial malignancy, or confirm provisional CUP to guide further management.