Patient characteristics and prognostic factors in advanced treatment lines in metastatic neuroendocrine tumors

Given the biological heterogeneity of neuroendocrine tumors (NET), several prognostic factors such as morphology, primary site, and certain blood markers have been identified. However, their prognostic significance in the context of advancing treatment lines and late-stage disease is unclear. In this retrospective monocentric study, patient characteristics including blood-based inflammation indices at initiation of different lines of therapy (LoT) were assessed, and potential prognostic factors were evaluated with regard to overall survival (OS) from LoT start. A total of 254 patients with NET G1/G2 (74%), NET G3 (8%), or typical/atypical carcinoid (18%) were included. All tumors were metastatic at treatment start, originating from the small intestine (36%), pancreas (28%), lung (17%), or other sites (19%). All patients had at least one palliative systemic therapy, the most frequent initial LoT was somatostatin analogs (SSA, n = 160, 63%), the most common second/third line peptide receptor radionuclide therapy (PRRT, n = 79 or 48% and n = 20 or 27%, respectively). Median OS from first-line start was 84.3 months (n = 250), and 48.6 months (n = 162) and 37.2 months (n = 75) from second- and third-line start, respectively. Patients reaching later LoT were more likely to have pancreatic NET with higher (≥ 10%) Ki-67 values. In univariate analysis, elevation of alkaline phosphatase (ALP) and chromogranin A (CGA) were negative prognostic factors in the first and second LoT subpopulation. Blood-based inflammation indices showed mixed prognostic value. Patients at the start of an early versus later LoT had different clinical characteristics, treatment patterns, and prognosis. These insights might help to refine prognosis estimates.