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Lymphadenectomy in Ovarian Cancer: Is It Still Justified?

Abstract

Purpose of Review

The aim of this review is to determine, in the light of recent evidences, the role of lymphadenectomy in ovarian cancer.

Recent Findings

The lymphadenectomy in ovarian neoplasms (LION) trial reports no better outcomes and higher complication and mortality rates associated with lymphadenectomy. Even if performed by expert hands, lymphadenectomy has a cost in terms of longer operative time, blood loss, higher rates of transfusions, and intensive unit care.

Summary

If on the one hand retroperitoneal staging is not correlated to survival benefits both in early and advanced ovarian cancer, on the other hand it is associated with an increased surgery-related morbidity. Surgical treatment of isolated nodal recurrences seems to be feasible and associated with survival benefits.

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References

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

  1. 1.

    J. Ferlay, H.R. Shin, F. Bray, D. Forman, C. Mathers, D.M. Parkin, GLOBOCAN 2008 (Version 1.2), Cancer incidence and mortality worldwide, Lyon, France, International Agency for Research on Cancer, 2010 Available from

  2. 2.

    Musella A, Vertechy L, Romito A, Marchetti C, Giannini A, Sciuga V, et al. Bevacizumab in ovarian cancer: state of the art and unanswered questions. Chemotherapy. 2017;62(2):111–20. https://doi.org/10.1159/000448942 Epub 2016 Oct 29. Review.PMID: 27794568.

  3. 3.

    Cancer Statistics Center, American Cancer Society, cancerstatisticscenter.otg.

  4. 4.

    Jemal A, Murray T, Ward E, et al. Cancer statistics, 2005. CA Cancer J Clin. 2005;55(1):10–30.

  5. 5.

    Ries LAG, Eisner MP, Kosary CL, et al, eds. SEER cancer statistics review, 1975–2001. Bethesda (MD): National Cancer Institute.

  6. 6.

    American Cancer Society: ovarian cancer, Available at: www.cancer.org Last accessed: December 11, 2016.

  7. 7.

    Desteli D, Gultekin M, Usubutin A, et al. Lymph node metastasis in grossly apparent clinical stage Ia epithelial ovarian cancer: hacettepe experience and review of literature. World J Surg Oncol. 2010;30(8):106.

  8. 8.

    Benedetti-Panici P, Greggi S, Maneschi F, et al. Anatomical and pathological study of retroperitoneal nodes in epithelial ovarian cancer. Gynecol Oncol. 1993;51:150–4.

  9. 9.

    Morice P, Joulie F, Camatte S, et al. Lymph node involvement in epithelial ovarian cancer: analysis of 276 pelvic and paraaortic lymphadenectomies and surgical implications. J Am Coll Surg. 2003;197:198–205.

  10. 10.

    Pereira A, Pérez-Medina T, Magrina JF, et al. Correlation between the extent of intraperitoneal disease and nodal metastasis in node-positive ovarian cancer patients. Eur J Surg Oncol. 2014;40(8):917–24.

  11. 11.

    Legge F, Petrillo M, Adamo V, et al. Epithelial ovarian cancer relapsing as isolated lymph node disease: natural history and clinical outcome. BMC Cancer. 2008;8:367.

  12. 12.

    Signorelli M, Guerra L, Pirovano C, et al. Detection of nodal metastases by 18F-FDG PET/CT in apparent early stage ovarian cancer: a prospective study. Gynecol Oncol. 2013;131(2):395–9.

  13. 13.

    Kitajima K, Murakami K, Yamasaki E, Kaji Y, Fukasawa I, Inaba N, et al. Diagnostic accuracy of integrated FDG-PET/contrast-enhanced CT in staging ovarian cancer: comparison with enhanced CT. Eur J Nucl Med Mol Imaging. 2008;35(10):1912–20. https://doi.org/10.1007/s00259-008-0890-2.

  14. 14.

    De Iaco P, Musto A, Orazi L, Zamagni C, Rosati M, Allegri V, et al. FDG-PET/CT in advanced ovarian cancer staging: value and pitfalls in detecting lesions in different abdominal and pelvic quadrants compared with laparoscopy. Eur J Radiol. 2011;80(2):e98–103. https://doi.org/10.1016/j.ejrad.2010.07.013 Epub 2010 Aug 4.

  15. 15.

    Kleppe M, Wang T, Van Gorp T, Slangen BF, Kruse AJ, Kruitwagen RF. Lymph node metastasis in stages I and II ovarian cancer: a review. Gynecol Oncol. 2011;123(3):610–4. https://doi.org/10.1016/j.ygyno.2011.09.013 Epub 2011 Oct 6. Review.

  16. 16.

    Bogani G, Tagliabue E, Ditto A, Signorelli M, Martinelli F, Casarin J, et al. Assessing the risk of pelvic and para-aortic nodal involvement in apparent early-stage ovarian cancer: a predictors- and nomogram-based analyses. Gynecol Oncol. 2017;147(1):61–5. https://doi.org/10.1016/j.ygyno.2017.07.139 Epub 2017 Aug 2.

  17. 17.

    Lago V, Minig L, Fotopoulou C. Incidence of lymph node metastases in apparent early-stage low-grade epithelial ovarian cancer: a comprehensive review. Int J Gynecol Cancer. 2016;26(8):1407–14. https://doi.org/10.1097/IGC.0000000000000787 Review.

  18. 18.

    Powless CA, Aletti GD, Bakkum-Gamez JN, Cliby WA. Risk factors for lymph node metastasis in apparent early-stage epithelial ovarian cancer: implications for surgical staging. Gynecol Oncol. 2011;122(3):536–40. https://doi.org/10.1016/j.ygyno.2011.05.001 Epub 2011 Jun 1.

  19. 19.

    • Maggioni A, Benedetti Panici P, Dell-Anna T, et al. Randomised study of systematic lymphadenectomy in patients with epithelial ovarian cancer macroscopically confined to the pelvis. Br J Cancer. 2006;95(6):699–704 (A multicentric randomized trial evaluating the value of systematic lymphadenectomy in early EOC demonstrates no statistically significant difference in 5-year overall survival among the lymphadenectomy group and the control group.).

  20. 20.

    Dizon DS, Restivo A, Lomme M, Charbonneau N, Brard L, Hughes T, et al. For women receiving chemotherapy for clinically apparent early ovarian cancer, is there a benefit to surgical staging? Am J Clin Oncol. 2008;31(1):39–42. https://doi.org/10.1097/COC.0b013e318134ee6f.

  21. 21.

    Colombo N, Pecorelli S. What have we learned from ICON1 and ACTION? Int J Gynecol Cancer. 2003;13(Suppl 2):140–3.

  22. 22.

    • Panici PB, Maggioni A, Hacker N, et al. Systematic aortic and pelvic lymphadenectomy versus resection of bulky nodes only in optimally debulked advanced ovarian cancer: a randomized clinical trial. J Natl Cancer Inst. 2005;97:560–6 (One of the most important randomized study shows that retroperitoneal staging is correlated with a higher incidence of surgery-related morbidity, post-operative stay, and costs.).

  23. 23.

    Uccella S, Nero C, Vizza E, Vargiu V, Corrado G, Bizzarri N, et al. Sentinel-node biopsy in early-stage ovarian cancer: preliminary results of a prospective multicentre study (SELLY). Am J Obstet Gynecol. 2019;221(4):324.e1–324.e10. https://doi.org/10.1016/j.ajog.2019.05.005 Epub 2019 May 10.

  24. 24.

    Ledermann JA, Raja FA, Fotopoulou C, et al. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(Suppl 6):24–32.

  25. 25.

    NCCN Clinical practice guidelines in oncology (NCCN Guidelines Version 2.2019 Panel Members Ovarian Cancer). http://www.nccn.org/professionals/physician_ gls/f_guidelines.asp.

  26. 26.

    Zhou J, Zhang W, Zhang QG, He ZY, Sun JY, Chen QH, et al. The effect of lymphadenectomy in advanced ovarian cancer according to residual tumor status: a population-based study. Int J Surg. 2018;52:11–5.

  27. 27.

    Harter P, Gnauert K, Hils R, Lehmann TG, Fisseler-Eckhoff A, Traut A, et al. Pattern and clinical predictors of lymph node metastases in epithelial ovarian cancer. Int J Gynecol Cancer. 2007;17:1238–44.

  28. 28.

    Eisenkop SM, Spirtos NM. The clinical significance of occult macroscopically positive retroperitoneal nodes in patients with epithelial ovarian cancer. Gynecol Oncol. 2001;82:143–9.

  29. 29.

    Ferrero A, Ditto A, Giorda G, et al. Secondary cytoreductive surgery for isolated lymph node recurrence of epithelial ovarian cancer: a multicenter study. Eur J Surg Oncol. 2014;40(7):891–8.

  30. 30.

    Du Bois A, Reuss A, Harter P, et al. Potential role of lymphadenectomy in advanced ovarian cancer: a combined exploratory analysis of three prospectively randomized phase III multicenter trials. J Clin Oncol. 2010;28:1733–9.

  31. 31.

    •• Harter P, Sehouli J, Lorusso D, Reuss A, Vergote I, Marth C, et al. A randomized trial of lymphadenectomy in patients with advanced ovarian neoplasms. N Engl J Med. 2019;380(9):822–32. https://doi.org/10.1056/NEJMoa1808424 (The last randomized trial shows that level one evidence has no survival benefit correlated to lymphadenectomy in complete debulky ovarian cancer.).

  32. 32.

    • Di Donato V, Kontopantelis E, Aletti G, Casorelli A, Piacenti I, Bogani G, et al. Trends in mortality after primary cytoreductive surgery for ovarian cancer: a systematic review and metaregression of randomized clinical trials and observational studies. Ann Surg Oncol. 2017;24(6):1688–97. https://doi.org/10.1245/s10434-016-5680-7 (This study analyzes all study present in literature and shows incidence and predictor of peri-operative mortality in the surgery treatment for advanced EOC.).

  33. 33.

    Benedetti Panici P, Di Donato V, Fischetti M, Casorelli A, Perniola G, Musella A, et al. Predictors of postoperative morbidity after cytoreduction for advanced ovarian cancer: analysis and management of complications in upper abdominal surgery. Gynecol Oncol. 2015;137(3):406–11. https://doi.org/10.1016/j.ygyno.2015.03.043 Epub 2015 Mar 28.

  34. 34.

    Gasparri ML, Attar R, Palaia I, Perniola G, Marchetti C, Di Donato V, et al. Tumor infiltrating lymphocytes in ovarian cancer. Asian Pac J Cancer Prev. 2015;16(9):3635–8 Review.

  35. 35.

    Benedetti Panici P, Perniola G, Angioli R, Zullo MA, Manci N et al. Basile S Bulky lymph node resection in patients with recurrent epithelial ovarian cancer: impact of surgery. Int J Gynecol Cancer 2007;17(6):1245–1251. Epub 2007 Apr 8.

  36. 36.

    Fotiou S, Aliki T, Petros Z, et al. Secondary cytoreductive surgery in patients presenting with isolated nodal recurrence of epithelial ovarian cancer. Gynecol Oncol. 2009;114:178–82.

  37. 37.

    Uzan C, Morice P, Rey A, et al. Outcomes after combined therapy including surgical resection in patients with epithelial ovarian cancer recurrence(s) exclusively in lymph nodes. Ann Surg Oncol. 2004;11:658–64.

  38. 38.

    Santillan A, Karam AK, Li AJ, et al. Secondary cytoreductive surgery for isolated nodal recurrence in patients with epithelial ovarian cancer. Gynecol Oncol. 2007;104:686–90.

  39. 39.

    Du Bois A, Vergote I, Ferron G, Reuss A, Meier W, Greggi S, et al. Randomized controlled phase III study evaluating the impact of secondary cytoreductive surgery in recurrent ovarian cancer: AGO DESKTOP III/ENGOT ov20. J Clin Oncol. 2017;35(15_suppl):5501.

  40. 40.

    Coleman RL, Enserro D, Spirtos N, Herzog TJ, Sabbatini P, Armstrong DK, et al. A phase III randomized controlled trial of secondary surgical cytoreduction (SSC) followed by platinum-based combination chemotherapy (PBC), with or without bevacizumab (B) in platinum-sensitive, recurrent ovarian cancer (PSOC): a NRG Oncology/Gynecologic Oncology Group (GOG) study. J Clin Oncol. 2018;36(15_suppl):5501. https://doi.org/10.1200/JCO.2018.36.15_suppl.5501.

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Correspondence to Pierluigi Benedetti Panici.

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Benedetti Panici, P., Giannini, A., Fischetti, M. et al. Lymphadenectomy in Ovarian Cancer: Is It Still Justified?. Curr Oncol Rep 22, 22 (2020). https://doi.org/10.1007/s11912-020-0883-2

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Keywords

  • Lymphadenectomy
  • Ovarian cancer
  • Nodal recurrences
  • Surgical-related morbidity
  • Prognostic factor
  • Nodal metastasis