Epidemiology and management of neuroendocrine neoplasms of unknown primary in Switzerland

Abstract

Background Neuroendocrine neoplasms (NENs) are mainly located in the gastrointestinal tract or the lungs. In up to 14% of cases, the primary tumor remains unidentified, classified as cancer of unknown primary (CUP). Due to their rarity and heterogeneity, CUPs are poorly studied. Methods This study conducts retrospective data analyses using the data provided by the SwissNET registry from 2008 to 2022, including patients diagnosed with CUPs or metastasized NENs with known primary (mNENs). The main objective was to assess the demographics, tumor characteristics, and the diagnosis and treatment of CUPs in comparison with mNENs. The secondary objective was to evaluate the overall survival of CUPs in general and compare with mNENs using propensity score matching. Results A total of 207 CUP and 437 mNEN patients were included. Prevalence was slightly higher in men (54.6 and 57.9%, respectively). Median (IQR) age at diagnosis was higher for patients with CUPs (67.7 years (59.0, 77.2)) compared with mNENs (62.9 years (53.5, 71.5), P < 0.001). Grading in CUP patients was higher compared with mNENs, with tumors classified as G1 (20.8 vs 38.0%), G2 (30.4 vs 43.5%), and G3 (32.9 vs 9.6%; P < 0.001). Main CUP treatment involved somatostatin analogs (42%), followed by chemotherapy (32%) and PRRT (30%). Median survival time was significantly shorter for CUP patients compared with mNEN patients (23.3 months (95% CI: 15.5, 31.1) vs 151.5 months (95% CI: 122.8, 180.1; P < 0.001)). This difference persisted after propensity score matching (P = 0.007). Conclusion The overall survival time of patients with CUPs was shorter compared with mNENs, possibly due to the higher-grade tumors at diagnosis.