Management of cancer from an unknown primary

Treatment of cancer is reliant on identifying the organ of origin. However, in a significant minority of cases, the primary site is never identified. This paper reviews the diagnostic work-up and therapeutic management for patients presenting with unknown primary cancer, including the role of tumour markers, conventional pathology and positron emission tomography imaging. It is important to identify atypical presentations of known tumour types, such as extragonadal germ cell tumours, lymphomas and breast cancer. The results from chemotherapy trials performed in patients with unknown primary cancer are summarised. Few trials have included > 100 patients, and most are non-randomised. There is no clear standard of care from the available data, and no trials of chemotherapy versus best supportive care have been performed. Platinum is the mainstay of treatment regimens, and from the regimens tested, a taxane seems to be among the best of the cytotoxics to combine with platinum in terms of both tolerability and efficacy. There is no data to favour a three-drug combination over a two-drug combination. To improve on existing treatment, molecular techniques may provide a means to identify the organ of origin, and/or to select appropriate targeted therapies. Further research is needed to improve knowledge on the biology of cancer from an unknown primary and to develop more effective treatment.