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Lymphovascular Space Invasion as a Risk Factor in Early Endometrial Cancer

  • Gynecologic Cancers (NS Reed, Section Editor)
  • Published:
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Abstract

Management of early endometrial cancer is contentious these days with little agreement between oncologists as well as across MDTs or tumour boards and indeed across countries. This is because of the state of knowledge with regards to risk factors in early endometrial cancer; although we recognise risk factors affect outcome, we haven’t yet been able to demonstrate that our treatments make a significant difference. We have reviewed available literature on LVSI and are able to demonstrate that it is an independent risk factor for nodal metastasis as well as distant recurrence. We need a randomised trial integrating grade and LVSI and testing therapeutic options of radiotherapy and chemotherapy. However, it is unlikely to see the light of day. Therefore, we are left with this knowledge of prognostic factors and it is our duty to integrate this into our decision-making during our multidisciplinary team meetings and make decisions tailored to individual patient circumstances.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Nout RA, van de Poll-Franse LV, Lybeert MLM, Wárlám-Rodenhuis CC, Jobsen JJ, Mens JWM, et al. Long-term outcome and quality of life of patients with endometrial carcinoma treated with or without pelvic radiotherapy in the post operative radiation therapy in endometrial carcinoma 1 (PORTEC-1) Trial. J Clin Oncol. 2011;29:1692–700.

    Article  PubMed  Google Scholar 

  2. Keys HM, Roberts JA, Brunetto VL, Zaino RJ, Spirtos NM, Bloss JD, et al. A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2004;92:744–51.

    Article  PubMed  Google Scholar 

  3. Nout RA, Smit VTHBM, Putter H, Jürgenliemk-Schulz IM, Jobsen JJ, Lutgens LCHW, et al. Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial. Lancet. 2010;375:816–23.

    Article  CAS  PubMed  Google Scholar 

  4. Lee CM, Szabo A, Shrieve DC, Macdonald OK, Gaffney DK. Frequency and effect of adjuvant radiation therapy among women with stage I endometrial adenocarcinoma. JAMA. 2006;295:389–97.

    Article  CAS  PubMed  Google Scholar 

  5. Hogberg T, Signorelli M, de Oliveira CF, Fossati R, Lissoni AA, Sorbe B, et al. Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer—results from two randomised studies. Eur J Cancer. 2010;46(13):2422–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Cohn DE, Horowitz NS, Mutch DG, Kim S-M, Manolitsas T, Fowler JM. Should the presence of lymphvascular space involvement be used to assign patients to adjuvant therapy following hysterectomy for unstaged endometrial cancer? Gynecol Oncol. 2002;87:243–6.

    Article  PubMed  Google Scholar 

  7. Briet JM, Hollema H, Reesink N, Aalders JG, Mourits MJE, ten Hoor KA, et al. Lymphvascular space involvement: an independent prognostic factor in endometrial cancer. Gynecol Oncol. 2005;96:799–804.

    Article  PubMed  Google Scholar 

  8. Koskas M, Bassot K, Graesslin O, Aristizabal P, Barranger E, Clavel-Chapelon F, et al. Impact of lymphovascular space invasion on a nomogram for predicting lymph node metastasis in endometrial cancer. Gynecol Oncol. 2013;129:292–7. Presence of LVSI was associated with higher grade tumours, more than 50% myometrial invasion, cervical involvement and nodal spread.

  9. Narayan K, Khaw P, Bernshaw D, Mileshkin L, Kondalsamy-Chennakesavan S. Prognostic significance of lymphovascular space invasion and nodal involvement in intermediate- and high-risk endometrial cancer patients treated with curative intent using surgery and adjuvant radiotherapy. Int J Gynecol Cancer. 2012;22:260–6.

    Article  PubMed  Google Scholar 

  10. Guntupalli SR, Zighelboim I, Kizer NT, Zhang Q, Powell MA, Thaker PH, et al. Lymphovascular space invasion is an independent risk factor for nodal disease and poor outcomes in endometrioid endometrial cancer. Gynecol Oncol. 2012;124:31–5. LVSI (OR 6.34) and deep myometrial invasion (OR 4.9) were strong predictors for node positivity.

  11. Cheewakriangkrai C, Panggid K, Siriaungkul S, Khunamornpong S, Suprasert P, Srisomboon J. Lymphovascular space invasion as a prognostic determinant in uterine cancer. Asian Pac J Cancer Prev. 2007;8:363–6.

    PubMed  Google Scholar 

  12. Bosse T, Peters EEM, Creutzberg CL, Jürgenliemk-Schulz IM, Jobsen JJ, Mens JWM, et al. Substantial lymph-vascular space invasion (LVSI) is a significant risk factor for recurrence in endometrial cancer – a pooled analysis of PORTEC 1 and 2 trials. Eur J Cancer. 2015;51:1742–50. In a multivariate analysis, (including: age, depth of myometrial invasion, grade, treatment) substantial LVSI remained the strongest independent prognostic factor for pelvic regional recurrence (HR 6.2 CI 2.4–16).

  13. Zhang GY, Wu LY, Li B, Huang MN, Zhang R, Li XG. Retrospective analysis of prognostic variables and clinical outcomes in surgically staged intermediate risk endometrial carcinoma. Eur J Obstet Gynecol Reprod Biol. 2013;169(2):309–16.

    Article  CAS  PubMed  Google Scholar 

  14. Zhang C, Wang C, Feng W. Clinicopathological risk factors for pelvic lymph node metastasis in clinical early-stage endometrioid endometrial adenocarcinoma. Int J Gynecol Cancer. 2012;22:1373–7.

    Article  PubMed  Google Scholar 

  15. Ho-Suap HAHN, In-Ho LEE, Tae-Jin KIM, Ki-Heon LEE, Jae-Uk SHIM, Jae-Wook KIM, et al. Lymphovascular space invasion is highly associated with lymph node metastasis and recurrence in endometrial cancer. Aust N Z J Obstet Gynaecol. 2013;53:293–7.

    Article  Google Scholar 

  16. Boren T, Lea J, Kehoe S, Miller DS, Richardson D. Lymph node metastasis in endometrioid adenocarcinomas of the uterine corpus with occult cervical involvement. Gynecol Oncol. 2012;127(1):43–6.

    Article  PubMed  Google Scholar 

  17. Akbayir O, Corbacioglu A, Goksedef BP, Numanoglu C, Akca A, Guraslan H, et al. The novel criteria for predicting pelvic lymph node metastasis in endometrioid adenocarcinoma of endometrium. Gynecol Oncol. 2012;125(2):400–3.

    Article  PubMed  Google Scholar 

  18. Chang SJ, Kong TW, Kim WY, Yoo SC, Yoon JH, Chang KH, et al. Lymph-vascular space invasion as a significant risk factor for isolated para-aortic lymph node metastasis in endometrial cancer: a study of 203 consecutive patients. Ann Surg Oncol. 2011;18(1):58–64.

    Article  PubMed  Google Scholar 

  19. Hachisuga T, Kaku T, Fukuda K, Eguchi F, Emoto M, Kamura T, et al. The grading of lymphovascular space invasion in endometrial carcinoma. Cancer. 1999;86(10):2090–7.

    Article  CAS  PubMed  Google Scholar 

  20. Vaizoglu F, Yuce K, Salman MC, Basaran D, Calis P, Ozgul N, et al. Lymphovascular space involvement is the sole independent predictor of lymph node metastasis in clinical early stage endometrial cancer. Arch Gynecol Obstet. 2013;288(6):1391–7.

    Article  PubMed  Google Scholar 

  21. Watari H, Todo Y, Takeda M, Ebina Y, Yamamoto R, Sakuragi N. Lymph-vascular space invasion and number of positive para-aortic node groups predict survival in node-positive patients with endometrial cancer. Gynecol Oncol. 2005;96:651–7.

    Article  PubMed  Google Scholar 

  22. Nofech-Mozes S, Ackerman I, Ghorab Z, Thomas NIG, Covens A, Khalifa MA. Lymphovascular invasion is a significant predictor for distant recurrence in patients with early-stage endometrial endometrioid adenocarcinoma. Am J Clin Pathol. 2008;129:912–7.

    Article  PubMed  Google Scholar 

  23. Gadducci A, Cavazzana A, Cosio S, di Cristofano C, Tana R, Fanucchi A, et al. Lymph-vascular space involvement and outer one-third myometrial invasion are strong predictors of distant haematogeneous failures in patients with stage I-II endometrioid-type endometrial cancer. Anticancer Res. 2009;29:1715–20.

    PubMed  Google Scholar 

  24. O’Brien DJ, Flannelly G, Mooney EE, Foleya M. Lymphovascular space involvement in early stage well-differentiated endometrial cancer is associated with increased mortality. BJOG. 2009;116:991–4.

    Article  PubMed  Google Scholar 

  25. Puljiz M, Puljiz Ž, Danolić D, Alvir I, Tomica D, Mamić I, et al. Prognostic value of lymphovascular space invasion in endometrial cancer. Med Glas. 2013;10(2):288–92.

    Google Scholar 

  26. Alexander-Sefre F, Singh N, Ayhan A, Thomas JM, Jacobs IJ. Clinical value of immunohistochemically detected lymphovascular invasion in endometrioid endometrial cancer. Gynecol Oncol. 2004;92:653–9.

    Article  CAS  PubMed  Google Scholar 

  27. Lim S, Lee K-B, Park C-Y. The prognostic significance of lymphovascular space involvement in patients with uterine confined endometrioid endometrial cancer. Korean J Obstet Gynecol. 2012;55(2):76–82.

    Article  Google Scholar 

  28. Song T, Lee JW, Choi CH, Kim TJ, Bae DS, Sung CO, et al. Ploidy and S-phase fraction are correlated with lymphovascular space invasion that is predictive of outcomes in endometrial cancer. Int J Clin Oncol. 2012;17(6):590–7.

    Article  PubMed  Google Scholar 

  29. Mariani A, Dowdy SC, Keeney GL, Haddock MG, Lesnick TG, Podratz KC. Predictors of vaginal relapse in stage I endometrial cancer. Gynecol Oncol. 2005;97:820–7.

    Article  PubMed  Google Scholar 

  30. Simpkins F, Papadia A, Kunos C, Michener C, Frasure H, AbuShahin F, et al. Patterns of recurrence in stage i endometrioid endometrial adenocarcinoma with lymphovascular space invasion. Int J Gynecol Cancer. 2013;23:98–104.

    Article  PubMed  Google Scholar 

  31. Gadducci A, Cosio S, Fabrini MG, Fanucchi A, Barsotti C, Cristofani R, et al. Patterns of failures in endometrial cancer: clinicopathological variables predictive of the risk of local, distant and retroperitoneal failure. Anticancer Res. 2011;31(10):3483–8.

    PubMed  Google Scholar 

  32. Panggid K, Cheewakriangkrai C, Khunamornpong S, Siriaunkgul S. Factors related to recurrence in non-obese women with endometrial endometrioid adenocarcinoma. J Obstet Gynaecol Res. 2010;36(5):1044–8.

    Article  PubMed  Google Scholar 

  33. Vandenput I, Vanhove T, Calster BV, Gorp TV, Moerman P, Verbist G, et al. The use of lymph vessel markers to predict endometrial cancer outcome. Int J Gynecol Cancer. 2010;20(3):363–7.

    Article  PubMed  Google Scholar 

  34. Gemer O, Ben Arie A, Levy T, Gdalevich M, Lorian M, Barak F, et al. Lymphvascular space involvement compromises the survival of patients with stage I endometrial cancer: results of a multicenter study. Eur J Surg Oncol. 2007;33:644–7.

    Article  CAS  PubMed  Google Scholar 

  35. Loizzi V, Cormio G, Lorusso M, Latorre D, Falagario M, Demitri P, et al. The impact of lymphvascular space invasion on recurrence and survival in patients with early stage endometrial cancer. Eur J Cancer Care. 2014;23(3):380–4.

    Article  CAS  Google Scholar 

  36. Aristizabal P, Graesslin O, Barranger E, Clavel-Chapelon F, Haddad B, Luton D, et al. A suggested modification to FIGO stage I endometrial cancer. Gynecol Oncol. 2014;133(2):192–6.

    Article  PubMed  Google Scholar 

  37. Weinberg LE, Kunos CA, Zanotti KM. Lymphovascular space invasion (LVSI) is an isolated poor prognostic factor for recurrence and survival among women with intermediate- to high-risk early-stage endometrioid endometrial cancer. Int J Gynecol Cancer. 2013;23(8):1438–45.

    Article  PubMed  Google Scholar 

  38. Kong A, Johnson N, Kitchener HC, Lawrie TA. Adjuvant radiotherapy for stage I endometrial cancer: an updated Cochrane systematic review and meta-analysis. J Natl Cancer Inst. 2012;104(21):1625–34.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Beatson West of Scotland Cancer Centre, Gartnavel General Hospital, Glasgow, G12 0YN, UK

    Azmat H. Sadozye, Rosie L. Harrand & Nick S. Reed

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  1. Azmat H. Sadozye
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  2. Rosie L. Harrand
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  3. Nick S. Reed
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Correspondence to Azmat H. Sadozye.

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Azmat H. Sadozye, Rosie L. Harrand, and Nick S. Reed declare that they have no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Gynecologic Cancers

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Sadozye, A.H., Harrand, R.L. & Reed, N.S. Lymphovascular Space Invasion as a Risk Factor in Early Endometrial Cancer. Curr Oncol Rep 18, 24 (2016). https://doi.org/10.1007/s11912-016-0505-1

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  • DOI: https://doi.org/10.1007/s11912-016-0505-1

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