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Risk of metastasis and survival in patients undergoing different treatment strategies with T1 colonic neuroendocrine tumors

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Abstract

Purpose

The efficacy and safety of local excision (LE) for small (< 1‒2 cm) colonic neuroendocrine tumors (NETs) is controversial due to the higher metastasis risk when compared with rectal NETs. The study aimed to evaluate the metastasis risk of T1 colonic NETs and compare patients' long-term prognosis after LE or radical surgery (RS).

Methods

The Surveillance Epidemiology and End Results database was used to identify patients with T1 colonic NETs (2004‒2015). Multivariable logistic regression was performed to assess factors associated with metastasis risk. Propensity score matching was used to balance the variables. Cancer-specific survival (CSS) and overall survival (OS) were calculated to estimate the prognosis of patients with T1N0M0 colonic NETs who underwent LE or RS.

Results

Of the 610 patients with colonic NETs, 46 (7.54%) had metastasis at diagnosis. Tumor size (11–20 mm) (OR = 9.51; 95% confidence interval (CI): 4.32‒21.45; P < 0.001), right colon (OR = 15.79; 95% CI 7.20‒38.56; P < 0.001), submucosal infiltration (OR = 2.08; 95% CI 0.84‒5.57; P = 0.125) were independent risk factors associated with metastasis. Of the 515 patients with T1N0M0 colonic NETs, the overall long-term prognosis of LE was as good as that of RS groups (after matching, 5-year CSS: 97.9% vs. 94.6%, P = 0.450; 5-year OS: 92.7% vs. 85.6%, P = 0.009).

Conclusion

Tumor size (11‒20 mm) and site (right colon) are associated with metastasis in T1 colonic NETs. In the absence of metastasis, LE could be a viable option for 0‒10 mm T1 colonic NETs with well/moderate differentiation in the left colon in terms of long-term survival.

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Availability of data and materials

Data was from the SEER program and available to the public upon appropriate requests (http://www.seer.cancer.gov). We thank the Surveillance, Epidemiology, and End Results database for the tremendous contribution.

References

  1. Xu Z, Wang L, Dai S et al (2021) Epidemiologic trends of and factors associated with overall survival for patients with gastroenteropancreatic neuroendocrine tumors in the United States. JAMA Netw Open 4:e2124750. https://doi.org/10.1001/jamanetworkopen.2021.24750

    Article  PubMed  PubMed Central  Google Scholar 

  2. Ford MM (2017) Neuroendocrine tumors of the colon and rectum. Dis Colon Rectum 60:1018–1020. https://doi.org/10.1097/DCR.0000000000000917

    Article  PubMed  Google Scholar 

  3. Modlin IM, Lye KD, Kidd M (2003) A 5-decade analysis of 13,715 carcinoid tumors. Cancer 97:934–959. https://doi.org/10.1002/cncr.11105

    Article  PubMed  Google Scholar 

  4. Maggard MA, O’Connell JB, Ko CY (2004) Updated population-based review of carcinoid tumors. Ann Surg 240:117–122. https://doi.org/10.1097/01.sla.0000129342.67174.67

    Article  PubMed  PubMed Central  Google Scholar 

  5. Taghavi S, Jayarajan SN, Powers BD et al (2013) Examining rectal carcinoids in the era of screening colonoscopy: a surveillance, epidemiology, and end results analysis. Dis Colon Rectum 56:952–959. https://doi.org/10.1097/DCR.0b013e318291f512

    Article  PubMed  Google Scholar 

  6. Gustafsson BI, Siddique L, Chan A et al (2008) Uncommon cancers of the small intestine, appendix and colon: an analysis of SEER 1973–2004, and current diagnosis and therapy. Int J Oncol 33:1121–1131

    PubMed  Google Scholar 

  7. Ahmed M (2020) Gastrointestinal neuroendocrine tumors in 2020. World J Gastrointest Oncol 12:791–807. https://doi.org/10.4251/wjgo.v12.i8.791

    Article  PubMed  PubMed Central  Google Scholar 

  8. Dasari A, Shen C, Halperin D et al (2017) Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA Oncol 3:1335–1342. https://doi.org/10.1001/jamaoncol.2017.0589

    Article  PubMed  PubMed Central  Google Scholar 

  9. Yao JC, Hassan M, Phan A et al (2008) 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. https://doi.org/10.1200/JCO.2007.15.4377

    Article  PubMed  Google Scholar 

  10. Kooyker AI, Verbeek WH, van den Berg JG et al (2020) Change in incidence, characteristics and management of colorectal neuroendocrine tumours in the Netherlands in the last decade. United European Gastroenterol J 8:59–67. https://doi.org/10.1177/2050640619865113

    Article  PubMed  Google Scholar 

  11. Ramage JK, De Herder WW, Delle Fave G et al (2016) ENETS consensus guidelines update for colorectal neuroendocrine neoplasms. Neuroendocrinology 103:139–143. https://doi.org/10.1159/000443166

    Article  CAS  PubMed  Google Scholar 

  12. Broecker JS, Ethun CG, Postlewait LM et al (2018) Colon and rectal neuroendocrine tumors: are they really one disease? A single-institution experience over 15 years. Am Surg 84:717–726. https://doi.org/10.1177/000313481808400525

    Article  PubMed  Google Scholar 

  13. Anthony LB, Strosberg JR, Klimstra DS et al (2010) The NANETS consensus guidelines for the diagnosis and management of gastrointestinal neuroendocrine tumors (NETs): well-differentiated nets of the distal colon and rectum. Pancreas 39:767–774. https://doi.org/10.1097/MPA.0b013e3181ec1261

    Article  PubMed  Google Scholar 

  14. Yin F, Wu Z-H, Lai J-P (2022) New insights in diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms. World J Gastroenterol 28:1751–1767. https://doi.org/10.3748/wjg.v28.i17.1751

    Article  PubMed  PubMed Central  Google Scholar 

  15. (2022) NCCN Guidelines for Patients: Neuroendocrine Tumors. Neuroendocrine Tumors 96

  16. Chen Q, Chen J, Huang Z et al (2022) Comparable survival benefit of local excision versus radical resection for 10–20-mm rectal neuroendocrine tumors. Eur J Surg Oncol 48:864–872. https://doi.org/10.1016/j.ejso.2021.10.029

    Article  PubMed  Google Scholar 

  17. Ngamruengphong S, Kamal A, Akshintala V et al (2019) Prevalence of metastasis and survival of 788 patients with T1 rectal carcinoid tumors. Gastrointest Endosc 89:602–606. https://doi.org/10.1016/j.gie.2018.11.010

    Article  PubMed  Google Scholar 

  18. Sekiguchi M, Sekine S, Sakamoto T et al (2015) Excellent prognosis following endoscopic resection of patients with rectal neuroendocrine tumors despite the frequent presence of lymphovascular invasion. J Gastroenterol 50:1184–1189. https://doi.org/10.1007/s00535-015-1079-7

    Article  PubMed  ADS  Google Scholar 

  19. Ito T, Masui T, Komoto I et al (2021) JNETS clinical practice guidelines for gastroenteropancreatic neuroendocrine neoplasms: diagnosis, treatment, and follow-up: a synopsis. J Gastroenterol 56:1033–1044. https://doi.org/10.1007/s00535-021-01827-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Al Natour RH, Saund MS, Sanchez VM et al (2012) Tumor size and depth predict rate of lymph node metastasis in colon carcinoids and can be used to select patients for endoscopic resection. J Gastrointest Surg 16:595–602. https://doi.org/10.1007/s11605-011-1786-1

    Article  PubMed  Google Scholar 

  21. SEER_Overview.pdf. In: SEER. https://seer.cancer.gov/about/factsheets/SEER_Overview.pdf. Accessed 11 Dec 2022

  22. SEER*Stat databases: November 2021 submission. In: SEER. https://seer.cancer.gov/data-software/documentation/seerstat/nov2021/index.html. Accessed 13 Dec 2022

  23. American Joint Committee on Cancer. Cancer staging manual, 8th ed. In: ACS. https://www.facs.org/quality-programs/cancer-programs/american-joint-committee-on-cancer/cancer-staging-systems/cancer-staging-system-products/. Accessed 29 Dec 2022

  24. Instructions for Coding Grade for 2014+. In: SEER. https://seer.cancer.gov/tools/grade/grade-2014-coding-instructions.pdf. Accessed 29 Dec 2022

  25. SEER2003.surg.prim.site.codes.pdf. In: SEER. https://seer.cancer.gov/archive/tools/SEER2003.surg.prim.site.codes.pdf. Accessed 29 Dec 2022

  26. Cooper GS, Xu F, Barnholtz Sloan JS et al (2012) Management of malignant colonic polyps: a population-based analysis of colonoscopic polypectomy versus surgery. Cancer 118:651–659. https://doi.org/10.1002/cncr.26340

    Article  PubMed  Google Scholar 

  27. Kojima M, Ikeda K, Saito N et al (2016) Neuroendocrine tumors of the large intestine: clinicopathological features and predictive factors of lymph node metastasis. Front Oncol 6:173. https://doi.org/10.3389/fonc.2016.00173

    Article  PubMed  PubMed Central  Google Scholar 

  28. Deprez PH, Moons LMG, O’Toole D et al (2022) Endoscopic management of subepithelial lesions including neuroendocrine neoplasms: European society of gastrointestinal endoscopy (ESGE) guideline. Endoscopy 54:412–429. https://doi.org/10.1055/a-1751-5742

    Article  PubMed  Google Scholar 

  29. Cope J, Srirajaskanthan R (2022) Rectal neuroendocrine neoplasms: why is there a global variation? Curr Oncol Rep 24:257–263. https://doi.org/10.1007/s11912-021-01172-1

    Article  PubMed  PubMed Central  Google Scholar 

  30. Gleeson FC, Levy MJ, Dozois EJ et al (2014) Endoscopically identified well-differentiated rectal carcinoid tumors: impact of tumor size on the natural history and outcomes. Gastrointest Endosc 80:144–151. https://doi.org/10.1016/j.gie.2013.11.031

    Article  PubMed  Google Scholar 

  31. Konishi T, Watanabe T, Kishimoto J et al (2007) Prognosis and risk factors of metastasis in colorectal carcinoids: results of a nationwide registry over 15 years. Gut 56:863–868. https://doi.org/10.1136/gut.2006.109157

    Article  PubMed  PubMed Central  Google Scholar 

  32. Osagiede O, Habermann E, Day C et al (2020) Factors associated with worse outcomes for colorectal neuroendocrine tumors in radical versus local resections. J Gastrointest Oncol 11:836–846. https://doi.org/10.21037/jgo-20-193

    Article  PubMed  PubMed Central  Google Scholar 

  33. Lee SH, Kim BC, Chang HJ et al (2013) Rectal neuroendocrine and L-cell tumors: diagnostic dilemma and therapeutic strategy. Am J Surg Pathol 37:1044–1052. https://doi.org/10.1097/PAS.0b013e3182819f0f

    Article  PubMed  Google Scholar 

  34. Zhang Y, Shang L, Zhang P et al (2019) Clinicopathological features and prognostic validity of the European neuroendocrine tumor society (ENETS) and American Joint Committee on Cancer (AJCC) 8th staging systems in colonic neuroendocrine neoplasms. Cancer Med 8:5000–5011. https://doi.org/10.1002/cam4.2370

    Article  PubMed  PubMed Central  Google Scholar 

  35. Pavel M, Öberg K, Falconi M et al (2020) Gastroenteropancreatic neuroendocrine neoplasms: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 31:844–860. https://doi.org/10.1016/j.annonc.2020.03.304

    Article  CAS  PubMed  Google Scholar 

  36. Gallo C, Rossi RE, Cavalcoli F et al (2022) Rectal neuroendocrine tumors: Current advances in management, treatment, and surveillance. World J Gastroenterol 28:1123–1138. https://doi.org/10.3748/wjg.v28.i11.1123

    Article  PubMed  PubMed Central  Google Scholar 

  37. La Salvia A, Persano I, Siciliani A et al (2022) Prognostic significance of laterality in lung neuroendocrine tumors. Endocrine 76:733–746. https://doi.org/10.1007/s12020-022-03015-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Petrelli F, Tomasello G, Borgonovo K et al (2017) Prognostic survival associated with left-sided vs right-sided colon cancer: a systematic review and meta-analysis. JAMA Oncol 3:211–219. https://doi.org/10.1001/jamaoncol.2016.4227

    Article  PubMed  Google Scholar 

  39. Feola T, Puliani G, Sesti F et al (2022) Risk factors for gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs): a three-centric case–control study. J Endocrinol Invest 45:849–857. https://doi.org/10.1007/s40618-021-01715-0

    Article  CAS  PubMed  Google Scholar 

  40. Yu J, Refsum E, Perrin V et al (2022) Inflammatory bowel disease and risk of adenocarcinoma and neuroendocrine tumors in the small bowel. Ann Oncol 33:649–656. https://doi.org/10.1016/j.annonc.2022.02.226

    Article  CAS  PubMed  Google Scholar 

  41. West NE, Wise PE, Herline AJ et al (2007) Carcinoid tumors are 15 times more common in patients with Crohnʼs disease. Inflamm Bowel Dis 13:1129–1134. https://doi.org/10.1002/ibd.20172

    Article  CAS  PubMed  Google Scholar 

  42. Yoshikane H, Tsukamoto Y, Niwa Y et al (1993) Carcinoid tumors of the gastrointestinal tract: evaluation with endoscopic ultrasonography. Gastrointest Endosc 39:375–383. https://doi.org/10.1016/s0016-5107(93)70109-1

    Article  CAS  PubMed  Google Scholar 

  43. Scherübl H (2009) Rectal carcinoids are on the rise: early detection by screening endoscopy. Endoscopy 41:162–165. https://doi.org/10.1055/s-0028-1119456

    Article  PubMed  Google Scholar 

  44. Hawes RH (2013) Endoscopic innovations. Endoscopy 45:766–769. https://doi.org/10.1055/s-0033-1344634

    Article  PubMed  Google Scholar 

  45. Nesargikar PN, Jaunoo SS (2009) Natural orifice translumenal endoscopic surgery (N.O.T.E.S). Int J Surg 7:232–236. https://doi.org/10.1016/j.ijsu.2009.04.001

    Article  CAS  PubMed  Google Scholar 

  46. Mafficini A, Scarpa A (2019) Genetics and epigenetics of gastroenteropancreatic neuroendocrine neoplasms. Endocr Rev 40:506–536. https://doi.org/10.1210/er.2018-00160

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank the Surveillance, Epidemiology, and End Results database for the tremendous contribution. We also thank Editage for the help in language polishing.

Funding

This study was supported by National Natural Science Foundation of China (82270570 and 82070551). This study is also supported by the Taishan Scholars Program of Shandong Province and the Clinical Research Center of Shandong University (2015BAI13B07).

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Author notes

  1. Xiaoqi Wu and Cheng Peng contributed equally to this work.

Authors and Affiliations

  1. Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China

    X. Wu, C. Peng, M. Lin, Z. Li, X. Yang, J. Liu, X. Yang & X. Zuo

  2. Laboratory of Translational Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China

    Z. Li, X. Yang, X. Yang & X. Zuo

  3. Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan, Shandong, China

    X. Yang

  4. Robot engineering laboratory for precise diagnosis and therapy of GI tumor, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China

    X. Zuo

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Contributions

XW and CP: conceptualization, methodology, software, formal analysis, data curation, writing—original draft, writing—review & editing. ML and ZL: conceptualization, writing—review & editing. XY: formal analysis, writing—review & editing. JL: writing—review & editing. XY: conceptualization, writing—review & editing, supervision, project administration. XZ: conceptualization, methodology, writing—review & editing, supervision, project administration, funding acquisition.

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Correspondence to X. Zuo.

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Data used in this study were acquired from a publicly available database. Thus, the approval of the Ethics Committee of Qilu Hospital of Shandong University (China) was not required for this study.

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Wu, X., Peng, C., Lin, M. et al. Risk of metastasis and survival in patients undergoing different treatment strategies with T1 colonic neuroendocrine tumors. J Endocrinol Invest 47, 671–681 (2024). https://doi.org/10.1007/s40618-023-02185-2

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