Survival in Patients with High-Grade Colorectal Neuroendocrine Carcinomas: The Role of Surgery and Chemotherapy

Abstract

Background.-Colorectal neuroendocrine tumors are a rare malignancy, yet their incidence appears to be increasing. The optimal treatment for the high-grade subset of these tumors remains unclear. We aimed to examine the relationship between different treatment modalities and outcomes for patients with high-grade neuroendocrine carcinomas (HGNECs) of the colon and rectum. Methods.-The National Cancer Database (2004-2015) was used to identify patients diagnosed with colorectal HGNECs. The primary outcome was overall survival. A Cox Proportional hazard model was used to identify risk factors for survival. Results.-Overall, 1208 patients had HGNECs; 452 (37.4%) patients had primary tumors of the rectum, and 756 (62.5%) patients had primary tumors of the colon. A total of 564 (46.7%) patients presented with stage IV disease. The median survival was 9.0 months [95% confidence interval (CI) 8.2-9.8]. In multivariable analysis, surgical resection [hazard ratio (HR) 0.54, 95% CI0.44-0.66; p < 0.001], chemotherapy (HR 0.74, 95% CI0.69-0.79; p < 0.001), and rectum as the primary site of tumor (HR 0.62, 95% CI 0.51-0.76; p < 0.001) were associated with better overall survival, while older age (HR1.01, 95% CI 1.00-1.01; p = 0.02) and the presence of metastatic disease (HR 3.34, 95% CI 2.69-4.15; p < 0.001) were associated with worse survival. Conclusions.-Patients with colorectal HGNECs selected for chemotherapy and surgical resection of the primary tumor demonstrated better overall survival than those managed without resection. Patients who were able to undergo systemic chemotherapy may benefit from potentially curative resection of the primary tumor. AUTHOR CONTRIBUTIONS All authors made substantial contributions to the design of the work, drafted the work, approved the final version submitted for publication, and agreed to be accountable for all aspects of the work. Adam C. Fields and Pamela Lu MD were co-first authors on this work. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Comprehensive analysis of mutational and clinicopathologic characteristics of poorly differentiated colorectal neuroendocrine carcinomas

“…The majority of poorly differentiated NECs had a small-cell morphology (89%) rather than a large-cell morphology (8%), and metastatic disease was noted in 64 (64%) patients at diagnosis. In another retrospective analysis of data from the National Cancer Database (2004–2015) consisting of 1208 poorly differentiated colorectal NECs, the median age at diagnosis was 65 years, and 50% of patients were male 3 . A small-cell morphology was slightly more frequent than a large-cell morphology (54% vs. 46%).…”

“…Unlike colorectal ACs, surgery alone is rarely curative for poorly differentiated NECs, and the survival benefit from surgery is controversial in prior studies 24 , 25 . According to poorly differentiated colorectal NEC data from the National Cancer Database (2004–2015), the median OS for patients who underwent surgical resection was 10.5 months compared with 6.9 months for patients who did not undergo surgery (p < 0.001) 3 . In our series, the median OS was 11.5 months; the 3-year survival was 36.4%, and the 5-year survival was 32.7%.…”

“…Poorly differentiated neuroendocrine carcinoma (NEC) in the colorectum is rare, accounting for approximately 0.6% of all colorectal carcinomas (CRCs) 1 , 2 . The majority of patients present metastatic disease at the time of diagnosis 3 . Colorectal NECs exhibit aggressive biologic behaviour with short-lived responses to therapy and inferior prognosis compared with typical CRCs 4 , 5 .…”

Analysis of 72 patients with colorectal high-grade neuroendocrine neoplasms from three Chinese hospitals

“…For patients with localized disease, surgery remains the most common choice in most cases in clinical practice. However, it is still debatable whether patients can benefit from the surgical resection of primary tumors[24,25]. In one retrospective report with 126 colorectal HGNEC patients, surgery did not offer a survival benefit for patients without metastatic disease (median survival, 27.4 mo with surgery vs 20.3 mo without surgery, P = 0.17)[15].…”

“…Many previous studies of prognosis have delineated poor clinical outcomes of colorectal HGNENs, with a median overall survival (OS) ranging from 9 mo to 20.6 mo, 3-year OS rates ranging from 8.7%-35%, and 5-year OS rates ranging from 8%-13.3%[2,15,17,25,27]. However, most of these reports only enrolled patients with NECs, and survival data for colorectal NETs G3 were scarce.…”