What role do imaging studies play in the diagnosis and management of CUP, and which modalities are preferred?

Role of Imaging Studies in Diagnosis and Management of Cancer of Unknown Primary (CUP):

Imaging studies are essential in the initial diagnostic phase of cancer of unknown primary (CUP) to identify a primary tumour site, guide treatment decisions, or classify the malignancy type. They help distinguish between non-epithelial malignancies treatable regardless of primary site and metastatic epithelial or neuro-endocrine malignancies without an identifiable primary site (provisional CUP) ¹.

Preferred Imaging Modalities:

• Computed tomography (CT) scans of the chest, abdomen, and pelvis are core initial investigations offered to patients with metastatic malignant disease of unknown primary origin ¹.
• Chest X-ray is part of the initial investigations to assess for thoracic involvement ¹.
• Positron emission tomography–computed tomography (18F-FDG PET-CT) is recommended for patients with provisional CUP presenting with cervical lymphadenopathy when no primary tumour is identified on ear, nose, and throat panendoscopy, especially if radical treatment is considered ¹. It may also be considered for extra-cervical presentations after multidisciplinary team discussion ¹.
• Magnetic resonance imaging (MRI), including dynamic contrast-enhanced breast MRI, is used selectively, for example, in women with adenocarcinoma involving axillary nodes when standard breast investigations do not identify a primary tumour ¹.
• Other imaging such as testicular ultrasound is used in men with presentations compatible with germ-cell tumours ¹.

Imaging is also used to guide biopsy decisions and to avoid inappropriate investigations that may compromise radical treatment, such as percutaneous biopsy of potentially resectable liver metastases ¹.

Overall, imaging studies are integrated with clinical examination, histology, immunohistochemistry, and tumour markers to optimize diagnosis and management of CUP ¹.