Skip to main content
SpringerLink
Log in

Risk and prognostic nomograms for colorectal neuroendocrine neoplasm with liver metastasis: a population-based study

  • Original Article
  • Published:
International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

Liver metastasis (LM) significantly shortens the survival time of colorectal neuroendocrine neoplasms (NENs) patients. This research aimed to explore risk and prognostic factors in colorectal NENs patients with LM and develop nomograms for predicting the risk of LM and survival probability quantitatively.

Methods

A total of 9926 colorectal NENs patients registered in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2017 were included. Risk factors for LM in colorectal NENs patients were identified by multivariate logistic regression analysis. Potential prognostic factors for colorectal NENs patients with LM were identified by multivariable Cox regression analysis. Nomograms were constructed for quantifying the probability of LM occurrence and survival.

Results

At diagnosis, 8.7% of colorectal NENs patients suffered LM, with 1-, 3-, and 5-year cancer-specific survival (CSS) rates of 44.3%, 26.5%, and 18.0%, respectively. Factors associated with LM occurrence included gender, age at diagnosis, primary tumor location, carcinoembryonic antigen (CEA), histological differentiation, T stage, and N stage. Age at diagnosis, race, histological differentiation, N stage, tumor size, primary tumor location, primary site surgery, and extraliver metastasis were prognostic factors of cancer-specific mortality. The area under the receiver operating characteristics (ROC) curve of the nomogram for predicting LM was 0.888 (95% CI: 0.877–0.898), and the C-index of the nomogram for estimating CSS probability was 0.705 (95% CI: 0.682–0.729).

Conclusions

This research identified the risk and prognostic factors in colorectal NENs patients with LM. The nomograms constructed by this study can be convenient tools for facilitating clinical decision-making.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Availability of data and material

The data we used can be downloaded from the SEER*Stat software (version 8.3.8; https://seer.cancer.gov/seerstat/)

Code availability

Not applicable.

References

  1. Bernick PE, Klimstra DS, Shia J, Minsky B, Saltz L, Shi W, Thaler H, Guillem J, Paty P, Cohen AM, Wong WD (2004) Neuroendocrine carcinomas of the colon and rectum. Dis Colon Rectum 47(2):163–169. https://doi.org/10.1007/s10350-003-0038-1

    Article  CAS  PubMed  Google Scholar 

  2. Starzyńska T, Londzin-Olesik M, Bałdys-Waligórska A, Bednarczuk T, Blicharz-Dorniak J, Bolanowski M, Boratyn-Nowicka A, Borowska M, Cichocki A, Ćwikła JB, Deptała A, Falconi M, Foltyn W, Handkiewicz-Junak D, Hubalewska-Dydejczyk A, Jarząb B, Junik R, Kajdaniuk D, Kamiński G, Kolasińska-Ćwikła A, Kowalska A, Król R, Królicki L, Kunikowska J, Kuśnierz K, Lampe P, Lange D, Lewczuk-Myślicka A, Lewiński A, Lipiński M, Marek B, Nasierowska-Guttmejer A, Nowakowska-Duława E, Pilch-Kowalczyk J, Remiszewski P, Rosiek V, Ruchała M, Siemińska L, Sowa-Staszczak A, Steinhof-Radwańska K, Strzelczyk J, Sworczak K, Syrenicz A, Szawłowski A, Szczepkowski M, Wachuła E, Zajęcki W, Zemczak A, Zgliczyński W, Kos-Kudła B (2017) Colorectal neuroendocrine neoplasms - management guidelines (recommended by the Polish Network of Neuroendocrine Tumours). Endokrynologia Polska 68(2):250–260. https://doi.org/10.5603/ep.2017.0019

    Article  CAS  PubMed  Google Scholar 

  3. Ramage JK, De Herder WW, Delle Fave G, Ferolla P, Ferone D, Ito T, Ruszniewski P, Sundin A, Weber W, Zheng-Pei Z, Taal B, Pascher A (2016) ENETS consensus guidelines update for colorectal neuroendocrine neoplasms. Neuroendocrinology 103(2):139–143. https://doi.org/10.1159/000443166

    Article  CAS  PubMed  Google Scholar 

  4. Wang ZJ, An K, Li R, Shen W, Bao MD, Tao JH, Chen JN, Mei SW, Shen HY, Ma YB, Zhao FQ, Wei FZ, Liu Q (2019) Analysis of 72 patients with colorectal high-grade neuroendocrine neoplasms from three Chinese hospitals. World J Gastroenterol: WJG 25(34):5197–5209. https://doi.org/10.3748/wjg.v25.i34.5197

    Article  PubMed  PubMed Central  Google Scholar 

  5. Zou J, Chen S, Lian G, Li R, Li Y, Huang K, Chen Y (2019) Prognostic and metastasis-related factors in colorectal neuroendocrine tumors: a cross-sectional study based on the Surveillance, Epidemiology and End Results. Oncol Lett 18(5):5129–5138. https://doi.org/10.3892/ol.2019.10876

    Article  PubMed  PubMed Central  Google Scholar 

  6. Wu Z, Wang Z, Zheng Z, Bi J, Wang X, Feng Q (2020) Risk factors for lymph node metastasis and survival outcomes in colorectal neuroendocrine tumors. Cancer Manag Res 12:7151–7164. https://doi.org/10.2147/cmar.s256723

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Nishikawa Y, Chino A, Ide D, Saito S, Igarashi M, Takamatsu M, Fujisaki J, Igarashi Y (2019) Clinicopathological characteristics and frequency of multiple rectal neuroendocrine tumors: a single-center retrospective study. Int J Color Dis 34(11):1887–1894. https://doi.org/10.1007/s00384-019-03405-z

    Article  Google Scholar 

  8. Zheng Z, Chen C, Jiang L, Zhou X, Dai X, Song Y, Li Y (2019) Incidence and risk factors of gastrointestinal neuroendocrine neoplasm metastasis in liver, lung, bone, and brain: a population-based study. Cancer Med 8(17):7288–7298. https://doi.org/10.1002/cam4.2567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Huang L, Jansen L, Balavarca Y, Molina-Montes E, Babaei M, van der Geest L, Lemmens V, Van Eycken L, De Schutter H, Johannesen TB, Fristrup CW, Mortensen MB, Primic-Žakelj M, Zadnik V, Becker N, Hackert T, Mägi M, Cassetti T, Sassatelli R, Grützmann R, Merkel S, Gonçalves AF, Bento MJ, Hegyi P, Lakatos G, Szentesi A, Moreau M, van de Velde T, Broeks A, Sant M, Minicozzi P, Mazzaferro V, Real FX, Carrato A, Molero X, Besselink MG, Malats N, Büchler MW, Schrotz-King P, Brenner H (2019) Resection of pancreatic cancer in Europe and USA: an international large-scale study highlighting large variations. Gut 68(1):130–139. https://doi.org/10.1136/gutjnl-2017-314828

    Article  PubMed  Google Scholar 

  10. Blum KA, Keller FG, Castellino S, Phan A, Flowers CR (2018) Incidence and outcomes of lymphoid malignancies in adolescent and young adult patients in the United States. Br J Haematol 183(3):385–399. https://doi.org/10.1111/bjh.15532

    Article  PubMed  PubMed Central  Google Scholar 

  11. Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, Abdalla EK, Fleming JB, Vauthey JN, Rashid A, Evans DB (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 : official journal of the American Society of Clinical Oncology 26(18):3063–3072. https://doi.org/10.1200/jco.2007.15.4377

    Article  Google Scholar 

  12. Ge Y, Lei S, Cai B, Gao X, Wang G, Wang L, Wang Z (2020) Incidence and prognosis of pulmonary metastasis in colorectal cancer: a population-based study. Int J Color Dis 35(2):223–232. https://doi.org/10.1007/s00384-019-03434-8

    Article  Google Scholar 

  13. Dasari A, Shen C, Halperin D, Zhao B, Zhou S, Xu Y, Shih T, Yao JC (2017) Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA Oncol 3(10):1335–1342. https://doi.org/10.1001/jamaoncol.2017.0589

    Article  PubMed  PubMed Central  Google Scholar 

  14. Kooyker AI, Verbeek WH, van den Berg JG, Tesselaar ME, van Leerdam ME (2020) Change in incidence, characteristics and management of colorectal neuroendocrine tumours in the Netherlands in the last decade. United Eur Gastroenterol J 8(1):59–67. https://doi.org/10.1177/2050640619865113

    Article  Google Scholar 

  15. Yoon SN, Yu CS, Shin US, Kim CW, Lim SB, Kim JC (2010) Clinicopathological characteristics of rectal carcinoids. Int J Color Dis 25(9):1087–1092. https://doi.org/10.1007/s00384-010-0949-y

    Article  Google Scholar 

  16. Duffy MJ (2001) Carcinoembryonic antigen as a marker for colorectal cancer: is it clinically useful? Clin Chem 47(4):624–630

    Article  CAS  PubMed  Google Scholar 

  17. Jelski W, Mroczko B (2020) Biochemical markers of colorectal cancer - present and future. Cancer Manag Res 12:4789–4797. https://doi.org/10.2147/cmar.s253369

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Li J, Liu F, Yu H, Zhao C, Li Z, Wang H (2019) Different distant metastasis patterns based on tumor size could be found in extensive-stage small cell lung cancer patients: a large, population-based SEER study. PeerJ 7:e8163. https://doi.org/10.7717/peerj.8163

    Article  PubMed  PubMed Central  Google Scholar 

  19. Wang R, Zhu Y, Liu X, Liao X, He J, Niu L (2019) The Clinicopathological features and survival outcomes of patients with different metastatic sites in stage IV breast cancer. BMC Cancer 19(1):1091. https://doi.org/10.1186/s12885-019-6311-z

    Article  PubMed  PubMed Central  Google Scholar 

  20. Purushotham A, Shamil E, Cariati M, Agbaje O, Muhidin A, Gillett C, Mera A, Sivanadiyan K, Harries M, Sullivan R, Pinder SE, Garmo H, Holmberg L (2014) Age at diagnosis and distant metastasis in breast cancer--a surprising inverse relationship. Eur J Cancer 50(10):1697–1705. https://doi.org/10.1016/j.ejca.2014.04.002

    Article  CAS  PubMed  Google Scholar 

  21. Tang M, Wang H, Cao Y, Zeng Z, Shan X, Wang L (2020) Nomogram for predicting occurrence and prognosis of liver metastasis in colorectal cancer: a population-based study. Int J Color Dis 36:271–282. https://doi.org/10.1007/s00384-020-03722-8

    Article  Google Scholar 

  22. DeNardo DG, Barreto JB, Andreu P, Vasquez L, Tawfik D, Kolhatkar N, Coussens LM (2009) CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell 16(2):91–102. https://doi.org/10.1016/j.ccr.2009.06.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Pili R, Guo Y, Chang J, Nakanishi H, Martin GR, Passaniti A (1994) Altered angiogenesis underlying age-dependent changes in tumor growth. J Natl Cancer Inst 86(17):1303–1314. https://doi.org/10.1093/jnci/86.17.1303

    Article  CAS  PubMed  Google Scholar 

  24. Yamamoto Y, Okamura Y, Uemura S, Sugiura T, Ito T, Ashida R, Kato Y, Ohgi K, Yamada M, Sasaki K, Aramaki T, Uesaka K (2017) Vascularity and tumor size are significant predictors for recurrence after resection of a pancreatic neuroendocrine tumor. Ann Surg Oncol 24(8):2363–2370. https://doi.org/10.1245/s10434-017-5823-5

    Article  PubMed  Google Scholar 

  25. Panzuto F, Campana D, Massironi S, Faggiano A, Rinzivillo M, Lamberti G, Sciola V, Lahner E, Manuzzi L, Colao A, Annibale B (2019) Tumour type and size are prognostic factors in gastric neuroendocrine neoplasia: a multicentre retrospective study. Dig Liver Dis : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 51(10):1456–1460. https://doi.org/10.1016/j.dld.2019.04.016

    Article  Google Scholar 

  26. Lei S, Ge Y, Tian S, Cai B, Gao X, Wang N, Wang G, Wang L, Wang Z (2020) Colorectal cancer metastases to brain or bone and the relationship to primary tumor location: a population-based study. J Gastrointest Surg : official journal of the Society for Surgery of the Alimentary Tract 24(8):1833–1842. https://doi.org/10.1007/s11605-019-04308-8

    Article  Google Scholar 

  27. Rumpold H, Kirchweger P, Niedersüß-Beke D, Falch D, Wundsam H, Metz-Gercek S, Piringer G, Thaler J (2020) Prognostic value of metastatic pattern in colorectal cancer: a multicenter retrospective analysis in a real-life cohort. Acta Oncol (Stockholm, Sweden) 60(2):180–186. 1-7. https://doi.org/10.1080/0284186x.2020.1837945

    Article  Google Scholar 

  28. Caplin M, Sundin A, Nillson O, Baum RP, Klose KJ, Kelestimur F, Plöckinger U, Papotti M, Salazar R, Pascher A (2012) ENETS consensus guidelines for the management of patients with digestive neuroendocrine neoplasms: colorectal neuroendocrine neoplasms. Neuroendocrinology 95(2):88–97. https://doi.org/10.1159/000335594

    Article  CAS  PubMed  Google Scholar 

  29. Smith JD, Reidy DL, Goodman KA, Shia J, Nash GM (2014) A retrospective review of 126 high-grade neuroendocrine carcinomas of the colon and rectum. Ann Surg Oncol 21(9):2956–2962. https://doi.org/10.1245/s10434-014-3725-3

    Article  PubMed  PubMed Central  Google Scholar 

  30. Aytac E, Ozdemir Y, Ozuner G (2014) Long term outcomes of neuroendocrine carcinomas (high-grade neuroendocrine tumors) of the colon, rectum, and anal canal. J Visceral Surg 151(1):3–7. https://doi.org/10.1016/j.jviscsurg.2013.12.007

    Article  CAS  Google Scholar 

  31. Zheng M, Li Y, Li T, Zhang L, Zhou L (2019) Resection of the primary tumor improves survival in patients with gastro-entero-pancreatic neuroendocrine neoplasms with liver metastases: a SEER-based analysis. Cancer Med 8(11):5128–5136. https://doi.org/10.1002/cam4.2431

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Riihimäki M, Hemminki A, Sundquist J, Hemminki K (2016) Patterns of metastasis in colon and rectal cancer. Sci Rep 6:29765. https://doi.org/10.1038/srep29765

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Chernyavskiy P, Kennerley VM, Jemal A, Little MP, Rosenberg PS (2019) Heterogeneity of colon and rectum cancer incidence across 612 SEER counties, 2000-2014. Int J Cancer: Journal international du cancer 144(8):1786–1795. https://doi.org/10.1002/ijc.31776

    Article  CAS  PubMed  Google Scholar 

  34. Missiaglia E, Jacobs B, D'Ario G, Di Narzo AF, Soneson C, Budinska E, Popovici V, Vecchione L, Gerster S, Yan P, Roth AD, Klingbiel D, Bosman FT, Delorenzi M, Tejpar S (2014) Distal and proximal colon cancers differ in terms of molecular, pathological, and clinical features. Ann Oncol : official journal of the European Society for Medical Oncology / ESMO 25(10):1995–2001. https://doi.org/10.1093/annonc/mdu275

    Article  CAS  Google Scholar 

  35. Shen H, Yang J, Huang Q, Jiang MJ, Tan YN, Fu JF, Zhu LZ, Fang XF, Yuan Y (2015) Different treatment strategies and molecular features between right-sided and left-sided colon cancers. World J Gastroenterol: WJG 21(21):6470–6478. https://doi.org/10.3748/wjg.v21.i21.6470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Engstrand J, Nilsson H, Strömberg C, Jonas E, Freedman J (2018) Colorectal cancer liver metastases - a population-based study on incidence, management and survival. BMC Cancer 18(1):78. https://doi.org/10.1186/s12885-017-3925-x

    Article  PubMed  PubMed Central  Google Scholar 

  37. Xu GH, Zou HW, Grossman AB (2019) Difference in survival between right- versus left-sided colorectal neuroendocrine neoplasms. J Zhejiang Univ Sci B 20(11):933–939. https://doi.org/10.1631/jzus.B1900210

    Article  PubMed  PubMed Central  Google Scholar 

  38. Kattan MW (2002) Nomograms. Introduction. Semin Urol Oncol 20(2):79–81

    PubMed  Google Scholar 

Download references

Acknowledgements

We thank the Surveillance, Epidemiology, and End Results (SEER) Program for providing the clinical data kindly.

Funding

This work was supported by the Natural Science Foundation Program of China Programs (81472740, 31701202, 81572866, and 81773104), the Frontier Exploration Program of Huazhong University of Science and Technology (2015TS153), the Integrated Innovative Team for Major Human Diseases Program of Tongji Medical College of HUST, and the Academic Medical Doctor Supporting Program of Tongji Medical College of HUST.

Author information

Author notes

  1. Xueliang Ding and Shaobo Tian contributed equally to this work.

Authors and Affiliations

  1. Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Xueliang Ding, Shaobo Tian, Jia Hu, Xiangnan Yu, Daan Fu, Ye Yuan, Lin Wang & Zheng Wang

  2. Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Xueliang Ding & Lin Wang

  3. Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Shaobo Tian, Guobin Wang, Xiangnan Yu, Daan Fu, Ye Yuan & Zheng Wang

Authors
  1. Xueliang Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shaobo Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jia Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Guobin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiangnan Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Daan Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ye Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Lin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Zheng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Xueliang Ding and Shaobo Tian: research design, conducting, data collection, interpretation and analysis, artworks drafting and manuscript, and paper writing. Jia Hu and Guobin Wang: work design and manuscript’s critical revision. Xiangnan Yu, Daan Fu, and Ye Yuan: technique assistance and data curation. Zheng Wang and Lin Wang: research design, results interpretation, paper writing, and critical revision of the manuscript. All the authors approved the final version and agreed to be accountable for all aspects of the work.

Corresponding authors

Correspondence to Lin Wang or Zheng Wang.

Ethics declarations

Ethics approval

All the data used in this study were extracted from publicly available database, so this study was exempted by the Ethics Committee of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ding, X., Tian, S., Hu, J. et al. Risk and prognostic nomograms for colorectal neuroendocrine neoplasm with liver metastasis: a population-based study. Int J Colorectal Dis 36, 1915–1927 (2021). https://doi.org/10.1007/s00384-021-03920-y

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00384-021-03920-y

Keywords

Search

Navigation