Discussion
death, tumor, CgA, DSS, unresectable primary tumors
TUMOR, RARE DISEASE, NEOPLASMS, TUMOR GROWTH, PATHOGENESIS
The CRNENs are heterogeneous neoplasms characterized by neuroendocrine secretory granules in the cytoplasm of the cells, but its pathogenesis is still unclear. As little information is available on the incidence and survival of CRNENs, it is difficult to assess its prognosis. In this study, we assessed the incidence and survival outcomes of patients with stage II-IV CRNENs from both the SEER database and external real-world cohort as well as developed relevant prognostic nomograms and convenient online tools for OS and DSS prediction.In our study of the SEER dataset, even though it is a rare disease, the incidence of CRNENs increased from 0.31 to 1.69 parts per million over the past 44 years. 20.7% of patients with CRNENs were 75 years old or older. We observed that the prognosis of OS in elderly patients was poor, while the impact of age on CRNENs’ specific death failed to show significance. In the SEER database, the grade is classified as highly differentiated (G I), moderately differentiated (G II), poorly differentiated (G III), and undifferentiated (G IV), which are determined primarily according to the level of ki-67 index and are deemed as important prognostic factors of OS and DSS (Recently, competing risk analyses have received increasing higher popularity in the clinical research of cancer-specific death (In terms of treatment, surgery can improve the prognosis of stage II-IV stage CRNENs. Although radiotherapy and chemotherapy have always been the treatment for patients with unresectable primary tumors (In recent years, some novel treatments such as somatostatin analogue (SSA) and targeted therapy are found to show efficacy in the treatment of CRNENs. SSA has been proven to inhibit tumor growth and prolong tumor progression-free survival (Some limitations remained in this study. Firstly, the SEER database lacks neuroendocrine biomarkers information like chromogranin A (CgA), synaptophysin (Syn), and CD56, which are important prognostic factors (