Liver Metastases from Cancer of Unknown Primary (CUPL): a Retrospective Analysis of Presentation, Management and Prognosis in 49 Patients and Systematic Review of the Literature

Aim: Patients with liver metastases from cancer of unknown primary (CUPL) have a dismal prognosis. We retrospectively analysed their management and outcome and performed a systematic review of CUPL series published in the literature.

Patients And Methods: Electronic data from 49 CUPL patients referred to Hellenic Cooperative Oncology Group (HeCOG) centers were retrospectively studied for characteristics of clinical presentation, diagnostic workup, management, outcome and prognostic factors. A systematic literature review was undertaken in PubMed and EmBase databases.

Results: All our patients (males: 31, females: 18; median age: 65) underwent a computed tomography scan (CT) of the abdomen, 71% a thoracic CT, 53% gastroscopy and 47% colonoscopy. The commonest histologic subtypes encountered were adenocarcinoma (N=34) or undifferentiated carcinoma (N=12). The liver was the only metastatic site in 38% of patients, while it was accompanied with other metastatic sites in 62% (the commonest: lung, bone and lymph nodes). Forty-seven patients received first-line chemotherapy (42 platinum based) and 16 second-line. An objective response was observed in six patients (12%), median survival being 10 months (95% CI, 7-13). In univariate analysis, good performance status and normal baseline serum CEA levels were correlated with superior survival, while in multivariate analysis only age<55 (HR 0.16, p=0.02) and the absence of extrahepatic disease (HR 0.21, p=0.007) predicted for a better outcome. Published data from four relevant series (total patients=662) parallel our findings.

Conclusions: Patients with liver metastases from CUP are resistant to conventional types of treatment and carry a poor prognosis. Understanding the molecular biology of CUP is essential for the development of new, targeted effective therapies.