When Should Surgery Be Performed for the First-Line Treatment of Advanced Ovarian Cancer?

  • Ganendra Raj K. A. Mohan
  • Jane Hook
  • Jonathan A. Ledermann
  • Michael A. Quinn


Seventy-five percent of patients diagnosed with ovarian cancer still present with advanced stage disease (FIGO stages III and IV). The standard management for these patients has always been up-front surgery, with the aim of achieving complete macroscopic removal of tumor followed by chemotherapy. In 2010, the results from a large phase III randomized study performed by the EORTC suggested no difference in survival whether the chemotherapy was given following the surgery or as neoadjuvant treatment prior to surgery. This review will tease out the pros and cons of either management strategy based on the current evidence available and make recommendations for future research in the area.


Primary Surgery Advanced Ovarian Cancer Primary Chemotherapy Stage IIIC Debulking Surgery 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Vergote I, Trope CG, Amant F, Kristensen GB, Ehlen T, Johnson N, et al. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 2010;363(10):943–53.PubMedCrossRefGoogle Scholar
  2. 2.
    Griffiths CT. Surgical resection of tumour bulk in the primary treatment of ovarian carcinoma. Natl Cancer Inst Monogr. 1975;42:101–4.PubMedGoogle Scholar
  3. 3.
    Fader AN, Rose PG. Role of surgery in ovarian carcinoma. J Clin Oncol. 2007;25(20):2873–83.PubMedCrossRefGoogle Scholar
  4. 4.
    Skipper HE, Schabel Jr FM, Mellett LB, Montgomery JA, Wilkoff LJ, Lloyd HH, et al. Implications of biochemical, cytokinetic, pharmacologic, and toxicologic relationships in the design of optimal therapeutic schedules. Cancer Chemother Rep. 1970;54(6):431–50.PubMedGoogle Scholar
  5. 5.
    Covens AL. A critique of surgical cytoreduction in advanced ovarian cancer. Gynecol Oncol. 2000;78(3 Pt 1):269–74.PubMedCrossRefGoogle Scholar
  6. 6.
    Bristow RE, Tomacruz RS, Armstrong DK, Trimble EL, Montz FJ. Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. J Clin Oncol. 2002;20(5):1248–59.PubMedCrossRefGoogle Scholar
  7. 7.
    Du Bois A, Reuss A, Pujade-Lauraine E, Harter P, Ray-Coquard I, Pfisterer J. Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials. Cancer. 2009;115(6):1234–44.PubMedCrossRefGoogle Scholar
  8. 8.
    Winter III WE, Maxwell GL, Tian C, Carlson JW, Ozols RF, Rose PG, et al. Prognostic factors for stage III epithelial ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2007;25(24):3621–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Winter WE, Maxwell GL, Tian C, Sundborg MJ, Rose GS, Rose PG, et al. Tumor residual after surgical cytoreduction in prediction of clinical outcome in stage IV epithelial ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2008;26(1):83–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Polterauer S, Vergote I, Concin N, Braicu I, Chekerov R, Mahner S, et al. Prognostic value of residual tumor size in patients with epithelial ovarian cancer FIGO stages IIA-IV: analysis of the OVCAD data. Int J Gynecol Cancer. 2012;22(3):380–5.PubMedCrossRefGoogle Scholar
  11. 11.
    Stuart GC, Kitchener H, Bacon M, duBois A, Friedlander M, Ledermann J, et al. 2010 Gynecologic Cancer InterGroup (GCIG) consensus statement on clinical trials in ovarian cancer: report from the Fourth Ovarian Cancer Consensus Conference. Int J Gynecol Cancer. 2011;21(4):750–5.PubMedCrossRefGoogle Scholar
  12. 12.
    Bookman MA, Brady MF, McGuire WP, Harper PG, Alberts DS, Friedlander M, et al. Evaluation of new platinum-based treatment regimens in advanced-stage ovarian cancer: a phase III trial of the Gynecologic Cancer InterGroup. J Clin Oncol. 2009;27(9):1419–25.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Crawford SC, Vasey PA, Paul J, Hay A, Davis JA, Kaye SB. Does aggressive surgery only benefit patients with less advanced ovarian cancer? Results from an international comparison within the SCOTROC-1 Trial. J Clin Oncol. 2005;23(34):8802–11.PubMedCrossRefGoogle Scholar
  14. 14.
    Hoskins WJ, Bundy BN, Thigpen JT, Omura GA. The influence of cytoreductive surgery on recurrence-free interval and survival in small-volume stage III epithelial ovarian cancer: a Gynecologic Oncology Group study. Gynecol Oncol. 1992;47(2):159–66.PubMedCrossRefGoogle Scholar
  15. 15.
    van der Burg ME, van Lent M, Buyse M, Kobierska A, Colombo N, Favalli G, et al. The effect of debulking surgery after induction chemotherapy on the prognosis in advanced epithelial ovarian cancer. Gynecological Cancer Cooperative Group of the European Organization for Research and Treatment of Cancer. N Engl J Med. 1995;332(10):629–34.PubMedCrossRefGoogle Scholar
  16. 16.
    du Bois A, Rochon J, Pfisterer J, Hoskins WJ. Variations in institutional infrastructure, physician specialization and experience, and outcome in ovarian cancer: a systematic review. Gynecol Oncol. 2009;112(2):422–36.PubMedCrossRefGoogle Scholar
  17. 17.
    Junor EJ, Hole DJ, McNulty L, Mason M, Young J. Specialist gynaecologists and survival outcome in ovarian cancer: a Scottish national study of 1866 patients. Br J Obstet Gynaecol. 1999;106(11):1130–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Trope C, Kaern J. Primary surgery for ovarian cancer. Eur J Surg Oncol. 2006;32(8):844–52.PubMedCrossRefGoogle Scholar
  19. 19.
    Aletti GD, Dowdy SC, Gostout BS, Jones MB, Stanhope CR, Wilson TO, et al. Aggressive surgical effort and improved survival in advanced-stage ovarian cancer. Obstet Gynecol. 2006;107(1):77–85.PubMedCrossRefGoogle Scholar
  20. 20.
    Chi DS, Eisenhauer EL, Zivanovic O, Sonoda Y, Abu-Rustum NR, Levine DA, et al. Improved progression-free and overall survival in advanced ovarian cancer as a result of a change in surgical paradigm. Gynecol Oncol. 2009;114(1):26–31.PubMedCrossRefGoogle Scholar
  21. 21.
    Ang C, Chan KK, Bryant A, Naik R, Dickinson HO. Ultra-radical (extensive) surgery versus standard surgery for the primary cytoreduction of advanced epithelial ovarian cancer. Cochrane Database Syst Rev. 2011;4, CD007697.PubMedGoogle Scholar
  22. 22.
    Du Bois A, Marth C, Pfisterer J, Harter P, Hilpert F, Zeimet AG, et al. Neoadjuvant chemotherapy cannot be regarded as adequate routine therapy strategy of advanced ovarian cancer. Int J Gynecol Cancer. 2012;22(2):182–5.PubMedCrossRefGoogle Scholar
  23. 23.
    Thrall MM, Gray HJ, Symons RG, Weiss NS, Flum DR, Goff BA. Trends in treatment of advanced epithelial ovarian cancer in the Medicare population. Gynecol Oncol. 2011;122(1):100–6.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Verleye L, Vergote I, van der Zee AG. Patterns of care in surgery for ovarian cancer in Europe. Eur J Surg Oncol. 2010;36 Suppl 1:S108–14.PubMedCrossRefGoogle Scholar
  25. 25.
    du Bois A, Harter P, editors. Understanding and optimizing the potential role of surgical debulking in advanced epithelial ovarian cancer. In: American Society of Clinical Oncology annual meeting, Chicago, 4–8 Jun 2010.Google Scholar
  26. 26.
    Bristow RE, Chi DS. Platinum-based neoadjuvant chemotherapy and interval surgical cytoreduction for advanced ovarian cancer: a meta-analysis. Gynecol Oncol. 2006;103(3):1070–6.PubMedCrossRefGoogle Scholar
  27. 27.
    Kang S, Nam BH. Does neoadjuvant chemotherapy increase optimal cytoreduction rate in advanced ovarian cancer? Meta-analysis of 21 studies. Ann Surg Oncol. 2009;16(8):2315–20.PubMedCrossRefGoogle Scholar
  28. 28.
    Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011;365(26):2484–96.PubMedCrossRefGoogle Scholar
  29. 29.
    Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R, Lele S, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006;354(1):34–43.PubMedCrossRefGoogle Scholar
  30. 30.
    Katsumata N, Yasuda M, Takahashi F, Isonishi S, Jobo T, Aoki D, et al. Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial. Lancet. 2009;374(9698):1331–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Kehoe S, Hook J, Nankivell M, Jayson GC, Kitchener HC, Lopes T, et al. Chemotherapy or upfront surgery for newly diagnosed advanced ovarian cancer: Results from the MRC CHORUS trial. J Clin Oncol (Meeting Abstracts). 2013;31(15_suppl):5500.Google Scholar
  32. 32.
    Fagö-Olsen CL, Ottesen B, Kehlet H, Markauskas A, Mosgaard BJ, Ottosen C, et al. Neoadjuvant chemotherapy as ovarian cancer treatment: ever more used with major regional differences. Dan Med J [Serial on the Internet]. 2012;59(8):A4477.Google Scholar
  33. 33.
    Vergote I, du Bois A, Amant F, Heitz F, Leunen K, Harter P. Neoadjuvant chemotherapy in advanced ovarian cancer: on what do we agree and disagree? Gynecol Oncol. 2012;24:1–6.CrossRefGoogle Scholar
  34. 34.
    Chi DS, Bristow RE, Armstrong DK, Karlan BY. Is the easier way ever the better way? J Clin Oncol. 2011;29(31):4073–5.PubMedCrossRefGoogle Scholar
  35. 35.
    Vergote I, Trope CG, Amant F, Ehlen T, Reed NS, Casado A. Neoadjuvant chemotherapy is the better treatment option in some patients with stage IIIc to IV ovarian cancer. J Clin Oncol. 2011;29(31):4076–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Vergote I, du Bois A, Amant F, Heitz F, Leunen K, Harter P. Neoadjuvant chemotherapy in advanced ovarian cancer: on what do we agree and disagree? Gynecol Oncol. 2013;128(1):6–11.PubMedCrossRefGoogle Scholar
  37. 37.
    Aletti GD, Eisenhauer EL, Santillan A, Axtell A, Aletti G, Holschneider C, et al. Identification of patient groups at highest risk from traditional approach to ovarian cancer treatment. Gynecol Oncol. 2011;120(1):23–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Thrall MM, Goff BA, Symons RG, Flum DR, Gray HJ. Thirty-day mortality after primary cytoreductive surgery for advanced ovarian cancer in the elderly. Obstet Gynecol. 2011;118(3):537–47.PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Wright JD, Lewin SN, Deutsch I, Burke WM, Sun X, Neugut AI, et al. Defining the limits of radical cytoreductive surgery for ovarian cancer. Gynecol Oncol. 2011;123(3):467–73.PubMedCrossRefGoogle Scholar
  40. 40.
    Rauh-Hain JA, Rodriguez N, Growdon WB, Goodman AK, Boruta DM, Horowitz NS, et al. Primary debulking surgery versus neoadjuvant chemotherapy in stage IV ovarian cancer. Ann Surg Oncol. 2012;19(3):959–65.PubMedCrossRefGoogle Scholar
  41. 41.
    Thrall MM, Gray HJ, Symons RG, Weiss NS, Flum DR, Goff BA. Neoadjuvant chemotherapy in the Medicare cohort with advanced ovarian cancer. Gynecol Oncol. 2011;123(3):461–6.PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Ibeanu OA, Bristow RE. Predicting the outcome of cytoreductive surgery for advanced ovarian cancer: a review. Int J Gynecol Cancer. 2010;20 Suppl 1:S1–11.PubMedCrossRefGoogle Scholar
  43. 43.
    Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365(26):2473–83.PubMedCrossRefGoogle Scholar
  44. 44.
    Bear HD, Tang G, Rastogi P, Geyer Jr CE, Robidoux A, Atkins JN, et al. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med. 2012;366(4):310–20.PubMedCentralPubMedCrossRefGoogle Scholar
  45. 45.
    von Minckwitz G, Eidtmann H, Rezai M, Fasching PA, Tesch H, Eggemann H, et al. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med. 2012;366(4):299–309.CrossRefGoogle Scholar
  46. 46.
    Van Cutsem E, Rivera F, Berry S, Kretzschmar A, Michael M, DiBartolomeo M, et al. Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol. 2009;20(11):1842–7.PubMedCrossRefGoogle Scholar
  47. 47.
    Kozloff M, Yood MU, Berlin J, Flynn PJ, Kabbinavar FF, Purdie DM, et al. Clinical outcomes associated with bevacizumab-containing treatment of metastatic colorectal cancer: the BRiTE observational cohort study. Oncologist. 2009;14(9):862–70.PubMedCrossRefGoogle Scholar
  48. 48.
    Okines AF, Langley RE, Thompson LC, Stenning SP, Stevenson L, Falk S, et al. Bevacizumab with peri-operative epirubicin, cisplatin and capecitabine (ECX) in localised gastro-oesophageal adenocarcinoma: a safety report. Ann Oncol. 2013;24(3):702–9.PubMedCrossRefGoogle Scholar
  49. 49.
    Ledermann JA. Primary chemotherapy: the future for the management of advanced ovarian cancer? Int J Gynecol Cancer. 2010;20(11 Suppl 2):S17–9.PubMedCrossRefGoogle Scholar
  50. 50.
    Glimelius B, Lahn M. Window-of-opportunity trials to evaluate clinical activity of new molecular entities in oncology. Ann Oncol. 2011;22:1717–25.PubMedCrossRefGoogle Scholar
  51. 51.
    Barnholtz-Sloan JS, Schwartz AG, Qureshi F, Jacques S, Malone J, Munkarah AR. Ovarian cancer: changes in patterns at diagnosis and relative survival over the last three decades. Am J Obstet Gynecol. 2003;189(4):1120–7.PubMedCrossRefGoogle Scholar
  52. 52.
    Cannistra SA. Cancer of the ovary. N Engl J Med. 2004;351(24):2519–29.PubMedCrossRefGoogle Scholar
  53. 53.
    Elattar A, Bryant A, Winter-Roach BA, Hatem M, Naik R. Optimal primary surgical treatment for advanced epithelial ovarian cancer. Cochrane Database Syst Rev. 2011;8, CD007565.PubMedGoogle Scholar
  54. 54.
    Rose PG, Nerenstone S, Brady MF, Clarke-Pearson D, Olt G, Rubin SC, et al. Secondary surgical cytoreduction for advanced ovarian carcinoma. N Engl J Med. 2004;351(24):2489–97.PubMedCrossRefGoogle Scholar
  55. 55.
    Chi DS, Musa F, Dao F, Zivanovic O, Sonoda Y, Leitao MM, et al. An analysis of patients with bulky advanced stage ovarian, tubal, and peritoneal carcinoma treated with primary debulking surgery (PDS) during an identical time period as the randomized EORTC-NCIC trial of PDS vs neoadjuvant chemotherapy (NACT). Gynecol Oncol. 2012;124(1):10–4.PubMedCrossRefGoogle Scholar
  56. 56.
    Axtell AE, Lee MH, Bristow RE, Dowdy SC, Cliby WA, Raman S, et al. Multi-institutional reciprocal validation study of computed tomography predictors of suboptimal primary cytoreduction in patients with advanced ovarian cancer. J Clin Oncol. 2007;25(4):384–9.PubMedCrossRefGoogle Scholar
  57. 57.
    Salani R, Axtell A, Gerardi M, Holschneider C, Bristow RE. Limited utility of conventional criteria for predicting unresectable disease in patients with advanced stage epithelial ovarian cancer. Gynecol Oncol. 2008;108(2):271–5.PubMedCrossRefGoogle Scholar
  58. 58.
    Qayyum A, Coakley FV, Westphalen AC, Hricak H, Okuno WT, Powell B. Role of CT and MR imaging in predicting optimal cytoreduction of newly diagnosed primary epithelial ovarian cancer. Gynecol Oncol. 2005;96(2):301–6.PubMedCrossRefGoogle Scholar
  59. 59.
    Angioli R, Palaia I, Zullo MA, Muzii L, Manci N, Calcagno M, et al. Diagnostic open laparoscopy in the management of advanced ovarian cancer. Gynecol Oncol. 2006;100(3):455–61.PubMedCrossRefGoogle Scholar
  60. 60.
    Fagotti A, Fanfani F, Ludovisi M, Lo Voi R, Bifulco G, Testa AC, et al. Role of laparoscopy to assess the chance of optimal cytoreductive surgery in advanced ovarian cancer: a pilot study. Gynecol Oncol. 2005;96(3):729–35.PubMedCrossRefGoogle Scholar
  61. 61.
    Fagotti A, Ferrandina G, Fanfani F, Garganese G, Vizzielli G, Carone V, et al. Prospective validation of a laparoscopic predictive model for optimal cytoreduction in advanced ovarian carcinoma. Am J Obstet Gynecol. 2008;199(6):642.e1–6.Google Scholar
  62. 62.
    Rutten MJ, Gaarenstroom KN, Van Gorp T, van Meurs HS, Arts HJ, Bossuyt PM, et al. Laparoscopy to predict the result of primary cytoreductive surgery in advanced ovarian cancer patients (LapOvCa-trial): a multicentre randomized controlled study. BMC Cancer. 2012;12:31.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2014

Authors and Affiliations

  • Ganendra Raj K. A. Mohan
    • 1
  • Jane Hook
    • 2
  • Jonathan A. Ledermann
    • 3
  • Michael A. Quinn
    • 4
  1. 1.Gynaecology OncologyKing Edward Memorial HospitalPerthAustralia
  2. 2.MRC Clinical Trials UnitAviation HouseLondonUK
  3. 3.UCL Cancer Institute, University College London, Cancer Research UK and UCL Cancer Trials CentreLondonUK
  4. 4.The University of Melbourne, Royal Women’s HospitalMelbourneAustralia

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