High-Grade Neuroendocrine Colorectal Carcinomas: A Retrospective Study of 100 Patients

Background: Colorectal high-grade neuroendocrine carcinomas (HGNEC) are a rare but aggressive group of malignancies without standard management recommendations.

Methods: We retrospectively reviewed the records of 100 consecutive patients with histologically confirmed colorectal HGNEC diagnosed at MD Anderson Cancer Center between 1991 and 2013.

Results: In our cohort, most tumors (89%) were small cell carcinoma, and most (60%) involved the sigmoid or the anorectal regions. Sixty-four patients (64%) presented with metastatic disease at diagnosis. Striking epidemiological and clinical differences between those established in small cell lung cancer (SCLC) and our cohort were noted, including significantly lower rates of smoking and lower risk of bone, brain metastases. Over 30% of the tumors were found associated with an adenoma. Median overall survival (OS) of the cohort was 14.7 months, with 2-year and 5-year OS rates of 23% and 8%, respectively. In patients with localized disease, multimodality therapy was associated with a trend toward improved median OS (20.4 vs. 15.4 months; P = .08). Metastases at presentation (OS 20.63 vs. 8.7 months; localized vs metastatic disease at presentation; P < .001) and elevated lactate dehydrogenase levels were strongly associated with a worse outcome.

Conclusion: In comparison to SCLC, less than half of the patients with colorectal HGNEC have history of smoking; metastatic patterns are also different between the 2 cancers. Nevertheless, HGNEC also has an aggressive biology, with the rectum being the most common site of origin. For localized disease, a multimodality approach seems to be associated with better outcomes, while systemic chemotherapy is the mainstay of treatment for advanced disease.