Approach to patients with distant metastases and no known primary tumor

What is the best diagnostic approach to patients presenting with distant metastases and no known primary tumor? Is the stepwise approach recommended?

Nicholas Pavlidis: It is definitely a stepwise approach. We start with a clinical examination, good history of the patient, but the major thing is to get a good biopsy. A biopsy with extensive immunohistochemistry. This is very important; it can almost tell you where the tumor probably comes from.

You also need imaging techniques, like ultrasound, computed tomography (CT) scans, magnetic resonance imaging (MRI). Sometimes you need a positron emission tomography (PET) scan; it is not sensitive and we do not have randomized studies to tell us that PET scan, PET-CT scan, is necessary in cancer of unknown primary. However, in some cases, like the head and neck cancer and the head and lung cancer, PET-CT scan is useful, as it has high sensitivity.

So, you need the clinical examination, good biopsy, imaging, and sometimes also, if you have symptoms or signs, you need endoscopy. This is the stepwise approach on how you move from the clinical [examination] to laboratory [tests].