Abstract

About 20% of all cancer of unknown primary (CUP) cases can be classified into favorable subgroups, which are defined by either obvious analogies to certain cancers with aknown primary or amenability to local ablative treatment. In the updated European Society for Medical Oncology (ESMO) guidelines for diagnosis and treatment of CUP, the definition of favorable subgroups has been revised according to the latest scientific findings. In particular, the definition and treatment of oligometastatic CUP have undergone considerable changes in recent years. Thus, we delineate the current diagnostic and therapeutic standards for the two favorable CUP subtypes single-site/oligometastatic and head/neck CUP. The classification, diagnostic workup, and treatment of single-site and oligometastatic CUP are summarized based on the current ESMO and American Society of Clinical Oncology (ASCO) guidelines together with aliterature review. Single-site and oligometastatic CUP is defined by the presence of amaximum of five metastases that are amenable to local ablative treatment. Median overall survival is favorable and exceeds 4years after local ablation of all detectable metastases. Lymph node metastases in the head and neck region represent afrequent scenario of single-site CUP. They usually originate from human papillomavirus (HPV)-associated squamous cell carcinoma in the oropharynx. Diagnostic workup comprises computed tomography (CT), magnetic resonance imaging (MRI) if necessary, and fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), followed by panendoscopy and biopsies of suspicious mucosal sites. Neck dissection, potentially followed by adjuvant radiotherapy, and definitive radiotherapy represent equally effective oncological treatment options with respect to afavorable prognosis.

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