Published online Sep 14, 2019. doi: 10.3748/wjg.v25.i34.5197
Peer-review started: July 1, 2019
First decision: August 2, 2019
Revised: August 12, 2019
Accepted: August 19, 2019
Article in press: August 19, 2019
Published online: September 14, 2019
Colorectal high-grade neuroendocrine neoplasms (HGNENs) are aggressive malignancies with a dismal prognosis. Due to the rarity of this disease, there are still no related large multicenter prospective randomized studies. Therefore, no standard management recommendations have been established.
Most previous reports are case reports and retrospective studies with small samples from single center of Western countries, and few data from multicenter studies or China can be found. Moreover, there is a trend that colorectal HGNENs will be classified as neuroendocrine carcinomas (NECs) and neuroendocrine tumors G3 (NETs G3) based on their morphological differentiation. In prior studies, all colorectal HGNENs were considered NECs.
Based on the latest classification and grading recommendations, we aimed to improve our understanding of this rare disease through multicenter data from China.
We performed an observational study and enrolled patients with colorectal HGNENs from three Chinese hospitals. Information regarding the clinicopathologic features and clinical outcomes was collected and delineated. The prognostic factors were analyzed using the Kaplan-Meier method and the Cox proportional hazards regression model.
Colorectal HGNENs are highly aggressive, and more than half of the patients have developed distant metastasis at the date of diagnosis. It is difficult to distinguish HGNENs from adenocarcinoma through clinical presentations, and immunohistochemical evaluation is necessary. Survival analysis demonstrated that colorectal NETs G3 had a significantly better prognosis than NECs. Therefore, colorectal HGNENs were not a homogenous group of malignancies, and colorectal NETs G3 should be treated with different strategies from NECs. Moreover, increasing age and distant metastasis were statistically confirmed to be independent risk factors for poor clinical outcomes.
Colorectal HGNENs are aggressive and heterogeneous groups of malignancies. Patients with younger age, good morphological differentiation, and without metastatic disease can have a relatively favorable prognosis.
More large prospective multicenter clinical studies need to be performed so that standard management recommendations can be established. Moreover, colorectal NETs G3 is an emerging term for colorectal HGNENs with good differentiation and that present significantly different biological behavior from NECs. Distinguishing colorectal NETs G3 from NECs is not always easy. It is imperative to further explore their respective molecular mechanisms and genetic changes so that better diagnostic and treatment strategies can be achieved in the future.