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Originally published as JCO Early Release 10.1200/JCO.2008.19.9711 on November 17 2008 © 2008 American Society of Clinical Oncology.
Tumor Biology and Prognosis of Gastrointestinal Carcinoids
Vivantes Klinikum Am Urban, Klinik für Innere Medizin, Gastroenterologie und Gastrointestinale Onkologie, Berlin, Germany Dear Editor: Yao et al1 have published an interesting article on neuroendocrine tumors (NETs) in the United States. However, some caveats are warranted concerning the conclusions drawn by the authors. The survival data published by Yao et al1 reflects overall survival and not carcinoid-related survival. Carcinoid patients are known to have a high risk for second neoplasms. For example, patients with rectal carcinoid disease suffer from synchronous or metachronous second malignancies in up to 22% of cases.2 Important to note, the risk of lymph node metastases of rectal carcinoids is not inferior to the metastatic risk of rectal adenocarcinoma of the same size.3-4 The prognosis of patients with metastatic rectal carcinoid disease is not better than the prognosis of patients suffering from metastastic rectal adenocarcinoma.2-5 Five-year-survival of rectal carcinoid patients with distant metastases is 15% to 30%.2-6 For nodal-positive rectal carcinoid disease (without distant metastases at the time of diagnosis), 5-year-survival amounts to 54% to 73%.3,5 In contrast, nodal-negative rectal carcinoids that are smaller than 1 cm and do not show angioinvasion or infiltration of the muscularis propria have an excellent 5-year-survival of 98.9% to 100%.3-7 As Yao et al1 did not observe a statistically significant difference in survival duration among patients with local and regional NETs over time, confounding factors have to be taken into account. Obviously, the authors’ statement that "NETs generally have a better prognosis than adenocarcinomas at the same site"1 does not hold true for metastatic rectal carcinoids and metastatic rectal adenocarcinomas.3-4 As pointed out by Yao et al,1 analysis of data obtained from the Surveillance, Epidemiology, and End Results (SEER) registries likely underestimates the total number of patients with NETs. As only patients with (supposedly) malignant NETs are included in the SEER registries, many small benign-appearing NETs (ie, appendiceal tumors) likely are excluded from the SEER registries. Important to note, the distinction between benign and malignant behavior is often not possible for NETs at the time of diagnosis. The normal appearance of regional lymph nodes on radiological imaging does not exclude metastatic spread.8 Thus, a 6-mm-sized, well-differentiated carcinoid of the rectum with normal-appearing regional lymph nodes (on imaging) may be considered a benign-appearing rectal carcinoid. If lymph node dissection is performed and lymph node involvement is found histologically, the 6-mm-sized, well-differentiated rectal carcinoid (with preoperatively normal appearing lymph nodes on imaging) is postoperatively reclassified as a malignant carcinoid.8 Therefore, the quality of the data on carcinoids of the SEER registries would be much improved if all NETs were registered. The currently available SEER data on carcinoids appears to be biased. The prevalence of rectal carcinoids in adults (mean/median age, 48.8 to 54 years) undergoing screening endoscopy is known to be 0.05% to 0.07%.9-11 In 2006, 57.1% of US men and women age 50 years or older reported they had received at least one examination with flexible sigmoidoscopy or colonoscopy.12 When considering that about 55 million US citizens have been scoped and on the basis of a prevalence rate of 0.05% to 0.07%, one would expect some 27,500 to 38,500 rectal carcinoids to have been diagnosed by screening endoscopy in the United States. Coincident with the implementation of colorectal cancer screening, overall 5-year-survival of patients with rectal carcinoid disease has increased steadily in the United States.5 Therefore, we should no longer regard rectal carcinoids that are detected by screening endoscopy as incidentally identified lesions. The early detection of colorectal carcinoids is one of the aims of endoscopic screening of the colorectum. The observed shift to more localized tumor stages at the time of diagnosis of NETs argues for the effectiveness of endoscopic screening. AUTHOR's DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. NOTES published online ahead of print at www.jco.org on November 17, 2008. REFERENCES
1. Yao J, Hassan M, Phan A, et al: One hundred years after "carcinoid": Epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol 26:3063-3072, 2008 2. Tsukamoto S, Fujita S, Yamaguchi T, et al: Clinicopathological characteristics and prognosis of rectal well-differentiated neuroendocrine tumors. Int J Colorectal Dis 23:1109-1113, 2008[CrossRef][Medline] 3. Konishi T, Watanabe T, Kishimoto J, et al: Prognosis and risk factors of metastasis in colorectal carcinoids: Results of a nationwide registry over 15 years. Gut 56:863-868, 2007 4. Konishi T, Watanabe T, Kishimoto J, et al: Prognosis and metastatic potential of colorectal carcinoids compared with adenocarcinomas: Results of a nationwide registry over 15 years. J Clin Oncol 26:191s, 2008 (abstr 4054) 5. Modlin I, Drozdov I, Gustafsson B, et al: Rectal neuroendocrine: Diagnosis and treatment. In: Modlin I, Oberg K (eds): A Century of Advances in Neuroendocrine Tumor Biology and Treatment. Hannover, Germany, Felsenstein CCCP, 2007, pp. 124-133 6. Modlin I, Oberg K, Chung D, et al: Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol 9:61-72, 2008[CrossRef][Medline] 7. Soga J: Early-stage carcinoids of the gastrointestinal tract: An analysis of 1914 reported cases. Cancer 103:1587-1595, 2005[CrossRef][Medline] 8. Shinohara T, Hotta T, Oyama T: Rectal carcinoid tumor, 6 mm in diameter, with lymph node metastases. Endoscopy 40:E40-E41, 2008 (suppl 2)[CrossRef][Medline] 9. Kaminski M, Polkowski M, Regula J, et al: Prevalence and endoscopic features of rectal neuroendocrine tumors (carcinoids) among 50,148 participants of the Polish colorectal-cancer screening programme. Gut 56:A310, 2007 (suppl 3)[CrossRef] 10. Matsui K, Iwase T, Kitagawa M: Small, polypoid-appearing carcinoid tumors of the rectum: Clinicopathologic study of 16 cases and effectiveness of endoscopic treatment. Am J Gastroenterol 88:1949-1953, 1993[Medline] 11. Shim K, Yang S, Myung S, et al: Atypical endoscopic features of rectal carcinoids. Endoscopy 36:313-316, 2004[CrossRef][Medline] 12. Scherübl H: Options for gastroenteropancreatic neuroendocrine tumours. Lancet Oncology 9:203, 2008[CrossRef][Medline]
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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