Grade is a Dominant Risk Factor for Metastasis in Patients with Rectal Neuroendocrine Tumors

  • Ian W. Folkert
  • Andrew J. Sinnamon
  • Seth J. Concors
  • Bonita J. Bennett
  • Douglas L. Fraker
  • Najjia N. Mahmoud
  • David C. Metz
  • Kristen M. Stashek
  • Robert E. RosesEmail author
Endocrine Tumors



Small (< 2 cm) and diminutive (< 1 cm) rectal neuroendocrine tumors (RNETs) are often described as indolent lesions. A large single-center experience was reviewed to determine the incidence of metastasis and the risk factors for its occurrence.


Cases of RNET between 2010 and 2017 at a single institution were retrospectively reviewed. The rate of metastasis was determined, and outcomes were stratified by tumor size and grade. Uni- and multivariable predictors of metastasis were identified, and a classification and regression tree analysis was used to stratify the risk for distant metastasis.


The study identified 98 patients with RNET. The median follow-up period was 28 months. Of the 98 patients, 79 had primary tumors smaller than 1 cm, 8 had tumors 1 to 2 cm in size, and 11 had tumors 2 cm in size or larger. In terms of grade, 86 patients had grade 1 (G1) tumors, 8 patients had grade 2 (G2) tumors, and 4 patients had grade 3 (G3) tumors. Twelve patients developed metastatic disease. Both size and grade were associated with distant metastasis in the uni- and multivariable analyses, but when stratified by grade, size was predictive of metastasis only for G1 tumors (p < 0.001). Among the 12 patients with metastatic disease, 3 (25%) had diminutive primary tumors, and 9 (75%) had primary tumors 2 cm in size or larger. Diminutive tumors that metastasized were all G2.


Patients with diminutive and small RNETs are at risk for metastatic disease. Tumor grade is a dominant predictor of dissemination. More rigorous staging, closer surveillance, or more aggressive initial management may be warranted for patients with G2 tumors, irrespective of size.



There are no conflict of interest.


  1. 1.
    Mandair D, Caplin ME. Colonic and rectal NET’s. Best Pract Res Clin Gastroenterol. 2012;26:775–89. Scholar
  2. 2.
    Modlin IM, Sandor A. An analysis of 8305 cases of carcinoid tumors. Cancer. 1997;79:813–29.CrossRefGoogle Scholar
  3. 3.
    Lawrence B, Gustafsson BI, Chan A, Svejda B, Kidd M, Modlin IM. The epidemiology of gastroenteropancreatic neuroendocrine tumors. Endocrinol Metab Clin North Am. 2011;40:1–18. Scholar
  4. 4.
    Dasari A, Shen C, Halperin D, et al. Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA Oncol. 2017;3:1335–42. Scholar
  5. 5.
    Tsikitis VL, Wertheim BC, Guerrero MA. Trends of incidence and survival of gastrointestinal neuroendocrine tumors in the United States: a SEER analysis. J Cancer. 2012;3:292–302. Scholar
  6. 6.
    Scherübl H. Rectal carcinoids are on the rise: early detection by screening endoscopy. Endoscopy. 2009;41:162–5. Scholar
  7. 7.
    Yao JC, 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 Off J Am Soc Clin Oncol. 2008;26:3063–72. Scholar
  8. 8.
    Anthony LB, Strosberg JR, Klimstra DS, 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. Pancreas. 2010;39:767–74. Scholar
  9. 9.
    Caplin M, Sundin A, Nillson O, et al. ENETS Consensus Guidelines for the Management of Patients with Digestive Neuroendocrine Neoplasms: colorectal neuroendocrine neoplasms. Neuroendocrinology. 2012;95:88–97. Scholar
  10. 10.
    Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer. 2003;97:934–59. Scholar
  11. 11.
    McConnell YJ. Surgical management of rectal carcinoids: trends and outcomes from the Surveillance, Epidemiology, and End Results database (1988–2012). Am J Surg. 2016;211:877–85. Scholar
  12. 12.
    Concors SJ, Sinnamon AJ, Folkert IW, et al. Predictors of metastases in rectal neuroendocrine tumors: results of a national cohort study. Dis Colon Rectum. 2018;61:1372. Scholar
  13. 13.
    Fahy BN, Tang LH, Klimstra D, et al. Carcinoid of the rectum risk stratification (CaRRs): a strategy for preoperative outcome assessment. Ann Surg Oncol. 2007;14:1735–43. Scholar
  14. 14.
    Mani S, Modlin IM, Ballantyne G, Ahlman H, West B. Carcinoids of the rectum. J Am Coll Surg. 1994;179:231–48.Google Scholar
  15. 15.
    McDermott FD, Heeney A, Courtney D, Mohan H, Winter D. Rectal carcinoids: a systematic review. Surg Endosc. 2014;28:2020–6. Scholar
  16. 16.
    Clark OH, Benson AB, Berlin JD, et al. NCCN Clinical Practice Guidelines in Oncology: neuroendocrine tumors. J Natl Compr Cancer Netw JNCCN. 2009;7:712–47.CrossRefGoogle Scholar
  17. 17.
    Soga J. Carcinoids of the rectum: an evaluation of 1271 reported cases. Surg Today. 1997;27:112–9. Scholar
  18. 18.
    Tsuboi K, Shimura T, Suzuki H, et al. Liver metastases of a minute rectal carcinoid less than 5 mm in diameter: a case report. Hepatogastroenterology. 2004;51:1330–2.PubMedGoogle Scholar
  19. 19.
    Tomoda H, Furusawa M, Hayashi I, Okumura K. A rectal carcinoid tumor of less than 1 cm in diameter with lymph node metastasis: a case report and a review of the literature. Jpn J Surg. 1990;20:468–471.CrossRefGoogle Scholar
  20. 20.
    Shinohara T, Hotta K, Oyama T. Rectal carcinoid tumor 6 mm in diameter with lymph node metastases. Endoscopy. 2008;40(Suppl 2):E40–1. Scholar
  21. 21.
    Saito T, Ikenaga M, Yasui M, et al. [A case of 7-mm rectal carcinoid with lymph node metastasis]. Gan To Kagaku Ryoho. 2009;36:2251–3.Google Scholar
  22. 22.
    Onogawa S, Tanaka S, Kitadai Y, et al. Small rectal carcinoid with lymph node metastasis diagnosed prior to treatment. Eur J Gastroenterol Hepatol. 2003;15:195–7. Scholar
  23. 23.
    El Ali Z, Szczepanek E, Majewski P, Iwanik K, Sowinski J, Grzymislawski M. Single brain metastasis from a minute, well-differentiated, but invading beyond the tunica muscularis mucosa rectal carcinoid. Acta Gastro-Enterol Belg. 2009;72:63–6.Google Scholar
  24. 24.
    Heah S-M, Eu K-W, Ooi B-S, Ho Y-H, Seow-Choen F. Tumor size is irrelevant in predicting malignant potential of carcinoid tumors of the rectum. Tech Coloproctol. 2001;5:73–7. Scholar
  25. 25.
    Weinstock B, Ward SC, Harpaz N, Warner RRP, Itzkowitz S, Kim MK. Clinical and prognostic features of rectal neuroendocrine tumors. Neuroendocrinology. 2013;98:180–7. Scholar
  26. 26.
    Chi Y, Du F, Zhao H, Wang J-W, Cai J-Q. Characteristics and long-term prognosis of patients with rectal neuroendocrine tumors. WJG World J Gastroenterol. 2014;20:16252. Scholar
  27. 27.
    Stinner B, Kisker O, Zielke A, Rothmund M. Surgical management for carcinoid tumors of small bowel, appendix, colon, and rectum. World J Surg. 1996;20:183–8.CrossRefGoogle Scholar
  28. 28.
    Rothmund M, Kisker O. Surgical treatment of carcinoid tumors of the small bowel, appendix, colon, and rectum. Digestion. 1994;55(Suppl. 3):86–91. Scholar
  29. 29.
    PK Cullen Jr. Carcinoid tumors of the colon and rectum. Calif Med. 1973;119:89.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Berardi RSMD I. Carcinoid tumors of the colon (exclusive of the rectum): review of the literature (review). Dis Colon Rectum. 1972;15:383–91. Scholar
  31. 31.
  32. 32.
    Tumacder OC, Horn RC, Eisenstein B, Arminski TC, Wilson GS, Lucas RJ. Carcinoid tumors of the rectum: a review of 40 cases. Arch Surg. 1968;97:261–6. Scholar
  33. 33.
    Akasu T, Moriya Y, Sugihara K. Transrectal ultrasonography of a small rectal carcinoid tumor with lymph node metastasis: a case report. Jpn J Clin Oncol. 1996;26:112–5.CrossRefGoogle Scholar
  34. 34.
    Okumura Y, Maruta M, Maeda K, et al. [Minute carcinoid tumor in the rectum with liver metastasis]. Gan To Kagaku Ryoho. 1997;24(Suppl 2):307–12.PubMedGoogle Scholar
  35. 35.
    Shields CJ, Tiret E, Winter DC. Carcinoid tumors of the rectum: a multi-institutional international collaboration. Ann Surg. 2010;252:750–5. Scholar
  36. 36.
    Koura AN, Giacco GG, Curley SA, Skibber JM, Feig BW, Ellis LM. Carcinoid tumors of the rectum. Cancer. 1997;79:1294–8.;2-h.CrossRefPubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2019

Authors and Affiliations

  • Ian W. Folkert
    • 1
  • Andrew J. Sinnamon
    • 1
  • Seth J. Concors
    • 1
  • Bonita J. Bennett
    • 2
  • Douglas L. Fraker
    • 3
  • Najjia N. Mahmoud
    • 4
  • David C. Metz
    • 2
  • Kristen M. Stashek
    • 5
  • Robert E. Roses
    • 3
    Email author
  1. 1.Department of SurgeryHospital of the University of PennsylvaniaPhiladelphiaUSA
  2. 2.Division of Gastroenterology, Department of MedicineHospital of the University of PennsylvaniaPhiladelphiaUSA
  3. 3.Division of Endocrine and Oncologic Surgery, Department of SurgeryHospital of the University of PennsylvaniaPhiladelphiaUSA
  4. 4.Division of Colon and Rectal Surgery, Department of SurgeryHospital of the University of PennsylvaniaPhiladelphiaUSA
  5. 5.Department of PathologyUniversity of MarylandBaltimoreUSA

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