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

Guideline-aligned answer with reasoning, red flags and references. Clinically reviewed by Dr Kola Tytler MBBS CertHE MBA MRCGP.

Posted: 16 August 2025Updated: 16 August 2025 Guideline-Aligned (High Confidence) Clinically Reviewed
Dr Kola Tytler MBBS CertHE MBA MRCGPClinical Lead • iatroX

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) .

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 .
  • Chest X-ray is part of the initial investigations to assess for thoracic involvement .
  • 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 . It may also be considered for extra-cervical presentations after multidisciplinary team discussion .
  • 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 .
  • Other imaging such as testicular ultrasound is used in men with presentations compatible with germ-cell tumours .

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 .

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

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