Tumor Differentiation is the Dominant Prognostic Factor for Patients with Colorectal Neuroendocrine Neoplasms with Distant Metastasis

Purpose Colorectal neuroendocrine neoplasms (NENs) are rare tumors. The prognosis and prognostic factors of metastatic colorectal NENs have not been fully elucidated. Methods We retrospectively enrolled 77 consecutive patients diagnosed with colorectal NENs with synchronous distant metastases between 2000 and 2021. All patients were assigned to the neuroendocrine tumor (NET) group or the neuroendocrine carcinoma (NEC) group based on histological differentiation. Propensity score matching (PSM) was performed to minimize confounding bias. The Kaplan–Meier method was used to calculate the survival rates. Univariate and multivariate logistic regression analyses were performed to identify prognostic factors. Results In total, 35 (45.5%) and 42 (54.5%) patients had well-differentiated NETs and poorly differentiated NECs, respectively. The median overall survival (OS) was 26 months for the entire cohort, and the 1-year, 3-year, and 5-year OS rates were 69.4%, 41.4%, and 27.8%, respectively. In the subgroup analysis, the median OS was 62 and 10 months for NETs and NECs, respectively. Univariate analysis demonstrated that patients with a primary tumor located in the colon, ulcerative tumors and poorly differentiated tumors were at higher risk for poorer progression-free survival (PFS) and OS. However, only histological differentiation was identified as an independent factor affecting OS (hazard ratio (HR) = 8.28, 95% confidence interval (CI): 2.98–23.01, P < 0.001) in multivariate analysis. After PSM, histological differentiation was further confirmed as the dominant factor affecting OS (HR = 6.09, 95% CI: 1.96–18.95, P=0.002)). Conclusion Histological differentiation was the most dominant prognostic factor in patients with metastatic colorectal NENs. Patients with well-differentiated NETs had a good chance of long-term survival.

[1]  H. Kashida,et al.  Characteristics of colorectal neuroendocrine tumors in patients prospectively enrolled in a Japanese multicenter study: a first report from the C-NET STUDY , 2022, Journal of Gastroenterology.

[2]  Ye Xu,et al.  Nomogram of conditional survival probability of long-term Survival for Metastatic Colorectal Cancer: A Real-World Data Retrospective Cohort Study from SEER database. , 2021, International journal of surgery.

[3]  Jia Hu,et al.  Risk and prognostic nomograms for colorectal neuroendocrine neoplasm with liver metastasis: a population-based study , 2021, International Journal of Colorectal Disease.

[4]  O. Abdel-Rahman Characterization of a Novel Entity of G3 (High-grade Well-differentiated) Colorectal Neuroendocrine Tumors (NET) in the SEER Database. , 2020, American Journal of Clinical Oncology.

[5]  H. Ueno,et al.  A nationwide, multi‐institutional collaborative retrospective study of colorectal neuroendocrine tumors in Japan , 2020, Annals of gastroenterological surgery.

[6]  Wei Wu,et al.  Endoscopic and surgical treatment of T1N0M0 colorectal neuroendocrine tumors: a population-based comparative study , 2020, Surgical Endoscopy.

[7]  Jie Chen,et al.  Genetic Characteristics of Colorectal Neuroendocrine Carcinoma: More Similar to Colorectal Adenocarcinoma. , 2020, Clinical colorectal cancer.

[8]  C. Hajdu,et al.  Characterization of a Novel Entity of G3 (High-grade Well-differentiated) Colorectal Neuroendocrine Tumors (NET) in the SEER Database , 2020, American journal of clinical oncology.

[9]  J. Hrabe Neuroendocrine Tumors of the Appendix, Colon, and Rectum. , 2020, Surgical oncology clinics of North America.

[10]  J. G. van den Berg,et al.  Change in incidence, characteristics and management of colorectal neuroendocrine tumours in the Netherlands in the last decade , 2019, United European gastroenterology journal.

[11]  D. Metz,et al.  Grade is a Dominant Risk Factor for Metastasis in Patients with Rectal Neuroendocrine Tumors , 2019, Annals of Surgical Oncology.

[12]  Ruomeng Li,et al.  Prognostic and metastasis-related factors in colorectal neuroendocrine tumors: A cross-sectional study based on the Surveillance, Epidemiology and End Results , 2019, Oncology letters.

[13]  J. Wisnivesky,et al.  Incidence Trends of Gastroenteropancreatic Neuroendocrine Tumors in the United States. , 2019, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[14]  A. Scarpa,et al.  Unmet Needs in High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms (WHO G3) , 2018, Neuroendocrinology.

[15]  Shouhao Zhou,et al.  Trends in the Incidence, Prevalence, and Survival Outcomes in Patients With Neuroendocrine Tumors in the United States , 2017, JAMA oncology.

[16]  P. Ruszniewski,et al.  Gastroenteropancreatic Well-Differentiated Grade 3 Neuroendocrine Tumors: Review and Position Statement. , 2016, The oncologist.

[17]  Eun Soo Kim,et al.  Long-Term Clinical Outcomes of Rectal Neuroendocrine Tumors According to the Pathologic Status After Initial Endoscopic Resection: A KASID Multicenter Study , 2016, The American Journal of Gastroenterology.

[18]  D. Chang,et al.  The Clinicopathologic Features and Treatment of 607 Hindgut Neuroendocrine Tumor (NET) Patients at a Single Institution , 2016, Medicine.

[19]  A. Vanoli,et al.  The Clinicopathologic Heterogeneity of Grade 3 Gastroenteropancreatic Neuroendocrine Neoplasms: Morphological Differentiation and Proliferation Identify Different Prognostic Categories , 2016, Neuroendocrinology.

[20]  P. Ruszniewski,et al.  ENETS Consensus Guidelines Update for Colorectal Neuroendocrine Neoplasms , 2016, Neuroendocrinology.

[21]  A. Rashid,et al.  High-Grade Neuroendocrine Colorectal Carcinomas: A Retrospective Study of 100 Patients. , 2015, Clinical colorectal cancer.

[22]  C. Chougnet,et al.  Characteristics and treatment of patients with G3 gastroenteropancreatic neuroendocrine neoplasms. , 2015, Endocrine-related cancer.

[23]  M. Salhab,et al.  Survival of Patients With Neuroendocrine Carcinoma of the Colon and Rectum: A Population-Based Analysis , 2015, Diseases of the colon and rectum.

[24]  K. Goodman,et al.  A Retrospective Review of 126 High-Grade Neuroendocrine Carcinomas of the Colon and Rectum , 2014, Annals of Surgical Oncology.

[25]  Seung‐Mo Hong,et al.  Clinical outcomes of rectal neuroendocrine tumors ≤ 10 mm following endoscopic resection , 2013, Endoscopy.

[26]  N. Harpaz,et al.  Clinical and Prognostic Features of Rectal Neuroendocrine Tumors , 2013, Neuroendocrinology.

[27]  A. Rashid,et al.  Neuroendocrine Tumors of the Colon and Rectum: Prognostic Relevance and Comparative Performance of Current Staging Systems , 2013, Annals of Surgical Oncology.

[28]  M. Papotti,et al.  ENETS Consensus Guidelines for the Management of Patients with Digestive Neuroendocrine Neoplasms: Colorectal Neuroendocrine Neoplasms , 2011, Neuroendocrinology.

[29]  A. Benson,et al.  The NANETS Consensus Guidelines for the Diagnosis and Management of Gastrointestinal Neuroendocrine Tumors (NETs): Well-Differentiated NETs of the Distal Colon and Rectum , 2010, Pancreas.

[30]  I. Modlin,et al.  A 5‐decade analysis of 13,715 carcinoid tumors , 2003, Cancer.