Advances in the Diagnosis and Treatment of Cancer of Unknown Primary

Corresponding author: Li Kesang, toney584520@126.com

DOI: 10.12201/bmr.202606.00008

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  Abstract: Cancer of unknown primary (CUP) refers to a heterogeneous group of metastatic malignancies confirmed by histopathology in which the primary tumor site remains unidentified despite standard systematic evaluation. CUP accounts for approximately 2%–4% of all malignant tumors. It is characterized by strong invasiveness, early metastasis, and poor prognosis, with a median overall survival of only 6–12 months in most patients. Owing to the occult nature of the primary lesion, the diagnosis and treatment of CUP remain highly challenging. Current diagnostic approaches mainly rely on medical history, imaging examinations, and immunohistochemistry; however, accurate identification of the tumor origin remains difficult in some cases. In recent years, the development of gene expression profiling, DNA methylation analysis, next-generation sequencing, and other emerging technologies has provided novel strategies for predicting the tissue of origin. Traditionally, empirical chemotherapy has been the mainstay of treatment for CUP. More recently, site-specific therapy based on tissue-of-origin prediction, as well as molecular targeted therapy and immunotherapy guided by molecular characteristics, have shown potential clinical value in selected studies. Nevertheless, evidence regarding their overall efficacy remains limited, and no international consensus has yet been established. This review systematically summarizes recent advances in the diagnosis and treatment of CUP and discusses the current challenges in clinical management, with the aim of providing references for future clinical practice and research.

  Key words: Cancer of unknown primary; diagnostic techniques; site-specific therapy; molecular targeted therapy; immunotherapy.

  Submit time: 3 June 2026

  Copyright: The copyright holder for this preprint is the author/funder, who has granted biomedRxiv a license to display the preprint in perpetuity.
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