Endocrine Abstracts

Introduction: While most of neuroendocrine tumors (NETs) primary sites are discovered, NETs of unknown primary are not entirely uncommon in the clinical setting. The primary site is a significant factor in terms of overall prognosis. The aim is to determine whether NETs of unknown primary site location (NET-USs) have more aggressive behavior than those with a known primary location.

Matherials and Methods: We retrospectively studied 50 consecutive patients with NETs, who presented in our clinic between 2018 and 2023: 9 patients with NET-USs and 41 patients with well-differentiated, gastroenteropancreatic neuroendocrine tumors (GEP-NETs, 16 patients with pancreatic NETs).

Results: The incidence of NET-USs was 18% (n=9). The median age at diagnosis and duration of disease in the NET-USs patients were 55 ±15.9 years, respectively 4.5±3.8 years, compared to 62±11.2 years, respectively 5±5.6 years in GEP-NETs patients. At the time of diagnosis, 66.7% of NET-USs patients presented with distant metastases (mainly hepatic - 88%), versus 31.7% of patients with known primary. Majority of NET-USs patients underwent 68Ga-DOTATATE PET/CT or 99mTc-Octreotide SPECT/CT, with no origin discovered, only high uptake in hepatic metastases. Incidence of multiple organ metastases was 11.1% in NET-USs patients, respectively 31.7% in the known primary group. All patients with NET-USs received treatment with somatostatin analogues (SSAs), and one underwent hepatic metastases removal, while patients with known primary received, in addition to SSAs, more aggressive regimens, systemic therapy (chemotherapy, Everolimus, Sunitinib) and liver metastases-targeted therapies (PRRT, chemoembolization). Median progression free survival was 38 months in NET-USs patients compared to 30 months in GEP-NETs patients. At the last evaluation, 33.3% of NET-USs patients and 36.6% of patients with known primary presented progressive disease, according to RECIST criteria. No death was registered in NET-USs subgroup, while 5 deaths occurred in the GEP-NETs patients, with an overall survival of 60 months.

Conclusions: Althought the majority of studies in the literature postulated that patients with unknown primary site exhibit markedly poor prognosis, we showed similar outcomes in both subgroups. In fact, in our serie, NETs with known primary site showed a greater tendancy for multiple organ involvement, respectively more agressive regimens were needed to acquire disease control, nevertheless expressed a poorer progression free survival compared with NET-USs, most likely due to a higher tumor burden.