Clinical Management of Epithelial Ovarian Cancer

  • Yusuke KobayashiEmail author
  • Hiroyuki Nomura
  • Fumio Kataoka
  • Eiichiro Tominaga
  • Kouji Banno
  • Daisuke Aoki


Ovarian cancer has high morbidity and mortality worldwide, and its mortality is the highest among female genital cancers. Improvement in clinical outcome is an urgent issue for ovarian cancer, and clinical management including treatment has been repeatedly studied. Tumor markers such as CA125, CA19–9, and HE4 and image diagnosis using MRI, CT, PET, etc. are indispensable diagnostic aid tools. In the initial treatment, primary debulking surgery (PDS) is basically effective, but fertility preservation can be considered depending on the case. For advanced cancers, interval debulking surgery (IDS) is considered after several cycles of neoadjuvant chemotherapy (NAC). Although the combination of paclitaxel and carboplatin (TC) regimen was originally established as the standard chemotherapy for ovarian cancer regardless of tissue type, new treatments in clinical trials, including molecular-targeted therapeutic agents, are being investigated. The main treatment for recurrent cancer is chemotherapy, and sensitivity to chemotherapy based on the disease-free interval has been considered in the choice of treatment. Furthermore, in recent years, risk-reducing bilateral salpingo-oophorectomy has been undertaken to prevent the onset of hereditary breast and ovarian cancer. It is also being studied how to manage the follow-up after treatment and hormone replacement.


Tumor marker Diagnostic imaging Staging laparotomy Primary debulking surgery Interval debulking surgery Risk-reducing salpingo-oophorectomy Adjuvant chemotherapy Neoadjuvant chemotherapy Molecular-targeted drugs Follow-up after treatment Hormone replacement therapy 


  1. 1.
    Menon U, Gentry-Maharaj A, Hallett R, et al. Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Lancet Oncol. 2009;10:327–40.PubMedCrossRefGoogle Scholar
  2. 2.
    Cramer DW, Bast RC Jr, Berg CD, et al. Ovarian cancer biomarker performance in prostate, lung, colorectal, and ovarian cancer screening trial specimens. Cancer Prev Res (Philadelphia, PA). 2011;4:365–74.CrossRefGoogle Scholar
  3. 3.
    Skates SJ. Ovarian cancer screening: development of the risk of ovarian cancer algorithm (ROCA) and ROCA screening trials. Int J Gynecol Cancer. 2012;22:S24–6.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Drescher CW, Shah C, Thorpe J, et al. Longitudinal screening algorithm that incorporates change over time in CA125 levels identifies ovarian cancer earlier than a single-threshold rule. J Clin Oncol Off J Am Soc Clin Oncol. 2013;31:387–92.CrossRefGoogle Scholar
  5. 5.
    Bast RC Jr, Feeney M, Lazarus H, Nadler LM, Colvin RB, Knapp RC. Reactivity of a monoclonal antibody with human ovarian carcinoma. J Clin Invest. 1981;68:1331–7.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Yin BW, Lloyd KO. Molecular cloning of the CA125 ovarian cancer antigen: identification as a new mucin, MUC16. J Biol Chem. 2001;276:27371–5.PubMedCrossRefGoogle Scholar
  7. 7.
    Gubbels JA, Belisle J, Onda M, et al. Mesothelin-MUC16 binding is a high affinity. N-glycan dependent interaction that facilitates peritoneal metastasis of ovarian tumors. Mol Cancer. 2006;5:50.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Gubbels JA, Felder M, Horibata S, et al. MUC16 provides immune protection by inhibiting synapse formation between NK and ovarian tumor cells. Mol Cancer. 2010;9:11.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Gupta D, Lis CG. Role of CA125 in predicting ovarian cancer survival – a review of the epidemiological literature. J Ovarian Res. 2009;2:13.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Morales-Vasquez F, Pedernera E, Reynaga-Obregon J, et al. High levels of pretreatment CA125 are associated to improved survival in high grade serous ovarian carcinoma. J Ovarian Res. 2016;9:41.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Hogdall EV, Christensen L, Kjaer SK, et al. CA125 expression pattern, prognosis and correlation with serum CA125 in ovarian tumor patients. From The Danish “MALOVA” Ovarian Cancer Study. Gynecol Oncol. 2007;104:508–15.PubMedCrossRefGoogle Scholar
  12. 12.
    Riedinger JM, Wafflart J, Ricolleau G, et al. CA 125 half-life and CA 125 nadir during induction chemotherapy are independent predictors of epithelial ovarian cancer outcome: results of a French multicentric study. Ann Oncol. 2006;17:1234–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Lee CK, Friedlander M, Brown C, et al. Early decline in cancer antigen 125 as a surrogate for progression-free survival in recurrent ovarian cancer. J Natl Cancer Inst. 2011;103:1338–42.PubMedCrossRefGoogle Scholar
  14. 14.
    Krivak TC, Tian C, Rose GS, Armstrong DK, Maxwell GL. A Gynecologic Oncology Group Study of serum CA-125 levels in patients with stage III optimally debulked ovarian cancer treated with intraperitoneal compared to intravenous chemotherapy: an analysis of patients enrolled in GOG 172. Gynecol Oncol. 2009;115:81–5.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    van Altena AM, Kolwijck E, Spanjer MJ, Hendriks JC, Massuger LF, de Hullu JA. CA125 nadir concentration is an independent predictor of tumor recurrence in patients with ovarian cancer: a population-based study. Gynecol Oncol. 2010;119:265–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Geurts SM, de Vegt F, van Altena AM, et al. Considering early detection of relapsed ovarian cancer: a review of the literature. Int J Gynecol Cancer. 2011;21:837–45.PubMedCrossRefGoogle Scholar
  17. 17.
    Gadducci A, Cosio S, Zola P, Landoni F, Maggino T, Sartori E. Surveillance procedures for patients treated for epithelial ovarian cancer: a review of the literature. Int J Gynecol Cancer. 2007;17:21–31.PubMedCrossRefGoogle Scholar
  18. 18.
    Rustin GJ, van der Burg ME, Griffin CL, et al. Early versus delayed treatment of relapsed ovarian cancer (MRC OV05/EORTC 55955): a randomised trial. Lancet (London). 2010;376:1155–63.CrossRefGoogle Scholar
  19. 19.
    Koprowski H, Steplewski Z, Mitchell K, Herlyn M, Herlyn D, Fuhrer P. Colorectal carcinoma antigens detected by hybridoma antibodies. Somatic Cell Genet. 1979;5:957–71.PubMedCrossRefGoogle Scholar
  20. 20.
    Cho HY, Kyung MS. Serum CA19-9 as a predictor of malignancy in primary ovarian mucinous tumors: a matched case-control study. Med Sci Monitor. 2014;20:1334–9.CrossRefGoogle Scholar
  21. 21.
    Clauss A, Lilja H, Lundwall A. A locus on human chromosome 20 contains several genes expressing protease inhibitor domains with homology to whey acidic protein. Biochem J. 2002;368:233–42.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Drapkin R, von Horsten HH, Lin Y, et al. Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas. Cancer Res. 2005;65:2162–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Galgano MT, Hampton GM, Frierson HF Jr. Comprehensive analysis of HE4 expression in normal and malignant human tissues. Modern Pathol. 2006;19:847–53.CrossRefGoogle Scholar
  24. 24.
    Ferraro S, Braga F, Lanzoni M, Boracchi P, Biganzoli EM, Panteghini M. Serum human epididymis protein 4 vs carbohydrate antigen 125 for ovarian cancer diagnosis: a systematic review. J Clin Pathol. 2013;66:273–81.PubMedCrossRefGoogle Scholar
  25. 25.
    Jia MM, Deng J, Cheng XL, et al. Diagnostic accuracy of urine HE4 in patients with ovarian cancer: a meta-analysis. Oncotarget. 2017;8:9660–71.PubMedGoogle Scholar
  26. 26.
    Kinkel K, Hricak H, Lu Y, Tsuda K, Filly RA. US characterization of ovarian masses: a meta-analysis. Radiology. 2000;217:803–11.PubMedCrossRefGoogle Scholar
  27. 27.
    Bazot M, Darai E, Nassar-Slaba J, Lafont C, Thomassin-Naggara I. Value of magnetic resonance imaging for the diagnosis of ovarian tumors: a review. J Comput Assist Tomogr. 2008;32:712–23.PubMedCrossRefGoogle Scholar
  28. 28.
    Hricak H, Chen M, Coakley FV, et al. Complex adnexal masses: detection and characterization with MR imaging--multivariate analysis. Radiology. 2000;214:39–46.PubMedCrossRefGoogle Scholar
  29. 29.
    Bazot M, Nassar-Slaba J, Thomassin-Naggara I, Cortez A, Uzan S, Darai E. MR imaging compared with intraoperative frozen-section examination for the diagnosis of adnexal tumors; correlation with final histology. Eur Radiol. 2006;16:2687–99.PubMedCrossRefGoogle Scholar
  30. 30.
    Moyle P, Addley HC, Sala E. Radiological staging of ovarian carcinoma. Semin Ultrasound CT MR. 2010;31:388–98.PubMedCrossRefGoogle Scholar
  31. 31.
    Iyer VR, Lee SI. MRI, CT, and PET/CT for ovarian cancer detection and adnexal lesion characterization. AJR Am J Roentgenol. 2010;194:311–21.PubMedCrossRefGoogle Scholar
  32. 32.
    Thomassin-Naggara I, Balvay D, Aubert E, et al. Quantitative dynamic contrast-enhanced MR imaging analysis of complex adnexal masses: a preliminary study. Eur Radiol. 2012;22:738–45.PubMedCrossRefGoogle Scholar
  33. 33.
    Koh DM, Collins DJ. Diffusion-weighted MRI in the body: applications and challenges in oncology. AJR Am J Roentgenol. 2007;188:1622–35.PubMedCrossRefGoogle Scholar
  34. 34.
    Thomassin-Naggara I, Darai E, Cuenod CA, et al. Contribution of diffusion-weighted MR imaging for predicting benignity of complex adnexal masses. Eur Radiol. 2009;19:1544–52.PubMedCrossRefGoogle Scholar
  35. 35.
    Takeuchi M, Matsuzaki K, Nishitani H. Diffusion-weighted magnetic resonance imaging of ovarian tumors: differentiation of benign and malignant solid components of ovarian masses. J Comput Assist Tomogr. 2010;34:173–6.PubMedCrossRefGoogle Scholar
  36. 36.
    Komiyama S, Katabuchi H, Mikami M, et al. Japan Society of Gynecologic Oncology guidelines 2015 for the treatment of ovarian cancer including primary peritoneal cancer and fallopian tube cancer. Int J Clin Oncol. 2016;21:435–46.PubMedCrossRefGoogle Scholar
  37. 37.
    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 Off J Am Soc Clin Oncol. 2002;20:1248–59.CrossRefGoogle Scholar
  38. 38.
    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.PubMedCrossRefGoogle Scholar
  39. 39.
    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 Off J Am Soc Clin Oncol. 2005;23:8802–11.CrossRefGoogle Scholar
  40. 40.
    Chi DS, Eisenhauer EL, Zivanovic O, et al. Improved progression-free and overall survival in advanced ovarian cancer as a result of a change in surgical paradigm. Gynecol Oncol. 2009;114:26–31.PubMedCrossRefGoogle Scholar
  41. 41.
    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: by the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and the Groupe d'Investigateurs Nationaux Pour les Etudes des Cancers de l'Ovaire (GINECO). Cancer. 2009;115:1234–44.PubMedCrossRefGoogle Scholar
  42. 42.
    Chi DS, Eisenhauer EL, Lang J, et al. What is the optimal goal of primary cytoreductive surgery for bulky stage IIIC epithelial ovarian carcinoma (EOC)? Gynecol Oncol. 2006;103:559–64.PubMedCrossRefGoogle Scholar
  43. 43.
    Eisenhauer EL, Abu-Rustum NR, Sonoda Y, et al. The addition of extensive upper abdominal surgery to achieve optimal cytoreduction improves survival in patients with stages IIIC-IV epithelial ovarian cancer. Gynecol Oncol. 2006;103:1083–90.PubMedCrossRefGoogle Scholar
  44. 44.
    Bristow RE, Peiretti M, Zanagnolo V, Salani R, Giuntoli RL II, Maggioni A. Transverse colectomy in ovarian cancer surgical cytoreduction: operative technique and clinical outcome. Gynecol Oncol. 2008;109:364–9.PubMedCrossRefGoogle Scholar
  45. 45.
    Juretzka MM, Barakat RR. Pelvic cytoreduction with rectosigmoid resection. Gynecol Oncol. 2007;104:40–4.PubMedCrossRefGoogle Scholar
  46. 46.
    Ayhan A, Gultekin M, Taskiran C, et al. Routine appendectomy in epithelial ovarian carcinoma: is it necessary? Obstet Gynecol. 2005;105:719–24.PubMedCrossRefGoogle Scholar
  47. 47.
    Dietrich CS III, Desimone CP, Modesitt SC, et al. Primary appendiceal cancer: gynecologic manifestations and treatment options. Gynecol Oncol. 2007;104:602–6.PubMedCrossRefGoogle Scholar
  48. 48.
    Dowdy SC, Loewen RT, Aletti G, Feitoza SS, Cliby W. Assessment of outcomes and morbidity following diaphragmatic peritonectomy for women with ovarian carcinoma. Gynecol Oncol. 2008;109:303–7.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Fanfani F, Fagotti A, Gallotta V, et al. Upper abdominal surgery in advanced and recurrent ovarian cancer: role of diaphragmatic surgery. Gynecol Oncol. 2010;116:497–501.PubMedCrossRefGoogle Scholar
  50. 50.
    Eisenkop SM, Spirtos NM, Lin WC. Splenectomy in the context of primary cytoreductive operations for advanced epithelial ovarian cancer. Gynecol Oncol. 2006;100:344–8.PubMedCrossRefGoogle Scholar
  51. 51.
    Marpeau O, Schilder J, Zafrani Y, et al. Prognosis of patients who relapse after fertility-sparing surgery in epithelial ovarian cancer. Ann Surg Oncol. 2008;15:478–83.PubMedCrossRefGoogle Scholar
  52. 52.
    Cho YH, Kim DY, Kim JH, et al. Is complete surgical staging necessary in patients with stage I mucinous epithelial ovarian tumors? Gynecol Oncol. 2006;103:878–82.PubMedCrossRefGoogle Scholar
  53. 53.
    Satoh T, Tsuda H, Kanato K, et al. A non-randomized confirmatory study regarding selection of fertility-sparing surgery for patients with epithelial ovarian cancer: Japan Clinical Oncology Group Study (JCOG1203). Jpn J Clin Oncol. 2015;45:595–9.PubMedCrossRefGoogle Scholar
  54. 54.
    Satoh T, Hatae M, Watanabe Y, et al. Outcomes of fertility-sparing surgery for stage I epithelial ovarian cancer: a proposal for patient selection. J Clin Oncol Off J Am Soc Clin Oncol. 2010;28:1727–32.CrossRefGoogle Scholar
  55. 55.
    Langstraat C, Aletti GD, Cliby WA. Morbidity, mortality and overall survival in elderly women undergoing primary surgical debulking for ovarian cancer: a delicate balance requiring individualization. Gynecol Oncol. 2011;123:187–91.PubMedCrossRefGoogle Scholar
  56. 56.
    Gerestein CG, Damhuis RA, de Vries M, Reedijk A, Burger CW, Kooi GS. Causes of postoperative mortality after surgery for ovarian cancer. Eur J Cancer (Oxford, England: 1990). 2009;45:2799–803.CrossRefGoogle Scholar
  57. 57.
    Lim MC, Kang S, Song YJ, Park SH, Park SY. Feasibility and safety of extensive upper abdominal surgery in elderly patients with advanced epithelial ovarian cancer. J Korean Med Sci. 2010;25:1034–40.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst. 2009;101:80–7.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Domchek SM, Friebel TM, Singer CF, et al. Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA. 2010;304:967–75.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Onda T, Kobayashi H, Nakanishi T, et al. Feasibility study of neoadjuvant chemotherapy followed by interval debulking surgery for stage III/IV ovarian, tubal, and peritoneal cancers: Japan Clinical Oncology Group Study JCOG0206. Gynecol Oncol. 2009;113:57–62.PubMedCrossRefGoogle Scholar
  61. 61.
    Kehoe S, Hook J, Nankivell M, et al. Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial. Lancet (London). 2015;386:249–57.CrossRefGoogle Scholar
  62. 62.
    Vergote I, Trope CG, Amant F, et al. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 2010;363:943–53.PubMedCrossRefGoogle Scholar
  63. 63.
    Onda T, Satoh T, Saito T, et al. Comparison of treatment invasiveness between upfront debulking surgery versus interval debulking surgery following neoadjuvant chemotherapy for stage III/IV ovarian, tubal, and peritoneal cancers in a phase III randomised trial: Japan Clinical Oncology Group Study JCOG0602. Eur J Cancer (Oxford, England: 1990). 2016;64:22–31.CrossRefGoogle Scholar
  64. 64.
    Kuhn W, Rutke S, Spathe K, et al. Neoadjuvant chemotherapy followed by tumor debulking prolongs survival for patients with poor prognosis in International Federation of Gynecology and Obstetrics Stage IIIC ovarian carcinoma. Cancer. 2001;92:2585–91.PubMedCrossRefGoogle Scholar
  65. 65.
    Lee SJ, Kim BG, Lee JW, Park CS, Lee JH, Bae DS. Preliminary results of neoadjuvant chemotherapy with paclitaxel and cisplatin in patients with advanced epithelial ovarian cancer who are inadequate for optimum primary surgery. J Obstet Gynaecol Res. 2006;32:99–106.PubMedCrossRefGoogle Scholar
  66. 66.
    Hegazy MA, Hegazi RA, Elshafei MA, et al. Neoadjuvant chemotherapy versus primary surgery in advanced ovarian carcinoma. World J Surg Oncol. 2005;3:57.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Giannopoulos T, Butler-Manuel S, Taylor A, Ngeh N, Thomas H. Clinical outcomes of neoadjuvant chemotherapy and primary debulking surgery in advanced ovarian carcinoma. Eur J Gynaecol Oncol. 2006;27:25–8.PubMedGoogle Scholar
  68. 68.
    Chan YM, Ng TY, Ngan HY, Wong LC. Quality of life in women treated with neoadjuvant chemotherapy for advanced ovarian cancer: a prospective longitudinal study. Gynecol Oncol. 2003;88:9–16.PubMedCrossRefGoogle Scholar
  69. 69.
    Ozols RF, Bundy BN, Greer BE, et al. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol Off J Am Soc Clin Oncol. 2003;21:3194–200.CrossRefGoogle Scholar
  70. 70.
    du Bois A, Luck HJ, Meier W, et al. A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J Natl Cancer Inst. 2003;95:1320–9.PubMedCrossRefGoogle Scholar
  71. 71.
    Bookman MA, Brady MF, McGuire WP, 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 Off J Am Soc Clin Oncol. 2009;27:1419–25.CrossRefGoogle Scholar
  72. 72.
    Katsumata N, Yasuda M, Takahashi F, 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 (London). 2009;374:1331–8.CrossRefGoogle Scholar
  73. 73.
    Markman M, Bundy BN, Alberts DS, et al. Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group. J Clin Oncol Off J Am Soc Clin Oncol. 2001;19:1001–7.CrossRefGoogle Scholar
  74. 74.
    Armstrong DK, Bundy B, Wenzel L, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006;354:34–43.PubMedCrossRefGoogle Scholar
  75. 75.
    Jaaback K, Johnson N, Lawrie TA. Intraperitoneal chemotherapy for the initial management of primary epithelial ovarian cancer. Cochrane Database Syst Rev. 2016;2016:Cd005340.Google Scholar
  76. 76.
    Fujiwara K, Markman M, Morgan M, Coleman RL. Intraperitoneal carboplatin-based chemotherapy for epithelial ovarian cancer. Gynecol Oncol. 2005;97:10–5.PubMedCrossRefGoogle Scholar
  77. 77.
    Fujiwara K, Sakuragi N, Suzuki S, et al. First-line intraperitoneal carboplatin-based chemotherapy for 165 patients with epithelial ovarian carcinoma: results of long-term follow-up. Gynecol Oncol. 2003;90:637–43.PubMedCrossRefGoogle Scholar
  78. 78.
    Fujiwara K, Nagao S, Kigawa J, et al. Phase II study of intraperitoneal carboplatin with intravenous paclitaxel in patients with suboptimal residual epithelial ovarian or primary peritoneal cancer: a Sankai Gynecology Cancer Study Group Study. Int J Gynecol Cancer. 2009;19:834–7.PubMedCrossRefGoogle Scholar
  79. 79.
    Vasey PA, Jayson GC, Gordon A, et al. Phase III randomized trial of docetaxel-carboplatin versus paclitaxel-carboplatin as first-line chemotherapy for ovarian carcinoma. J Natl Cancer Inst. 2004;96:1682–91.PubMedCrossRefGoogle Scholar
  80. 80.
    Pignata S, Scambia G, Ferrandina G, et al. Carboplatin plus paclitaxel versus carboplatin plus pegylated liposomal doxorubicin as first-line treatment for patients with ovarian cancer: the MITO-2 randomized phase III trial. J Clin Oncol Off J Am Soc Clin Oncol. 2011;29:3628–35.CrossRefGoogle Scholar
  81. 81.
    Heintz AP, Odicino F, Maisonneuve P, et al. Carcinoma of the ovary. FIGO 26th annual report on the results of treatment in gynecological cancer. Int J Gynaecol Obstetr. 2006;95:S161–92.CrossRefGoogle Scholar
  82. 82.
    Ho CM, Huang YJ, Chen TC, et al. Pure-type clear cell carcinoma of the ovary as a distinct histological type and improved survival in patients treated with paclitaxel-platinum-based chemotherapy in pure-type advanced disease. Gynecol Oncol. 2004;94:197–203.PubMedCrossRefGoogle Scholar
  83. 83.
    Takano M, Kikuchi Y, Yaegashi N, et al. Clear cell carcinoma of the ovary: a retrospective multicentre experience of 254 patients with complete surgical staging. Br J Cancer. 2006;94:1369–74.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Utsunomiya H, Akahira J, Tanno S, et al. Paclitaxel-platinum combination chemotherapy for advanced or recurrent ovarian clear cell adenocarcinoma: a multicenter trial. Int J Gynecol Cancer. 2006;16:52–6.PubMedCrossRefGoogle Scholar
  85. 85.
    Takano M, Kikuchi Y, Yaegashi N, et al. Adjuvant chemotherapy with irinotecan hydrochloride and cisplatin for clear cell carcinoma of the ovary. Oncol Rep. 2006;16:1301–6.PubMedGoogle Scholar
  86. 86.
    Takano M, Sugiyama T, Yaegashi N, et al. Progression-free survival and overall survival of patients with clear cell carcinoma of the ovary treated with paclitaxel-carboplatin or irinotecan-cisplatin: retrospective analysis. Int J Clin Oncol. 2007;12:256–60.PubMedCrossRefGoogle Scholar
  87. 87.
    Sugiyama T, Yakushiji M, Kamura T, et al. Irinotecan (CPT-11) and cisplatin as first-line chemotherapy for advanced ovarian cancer. Oncology. 2002;63:16–22.PubMedCrossRefGoogle Scholar
  88. 88.
    Sugiyama T, Okamoto A, Enomoto T, et al. Randomized phase III trial of irinotecan plus cisplatin compared with paclitaxel plus carboplatin as first-line chemotherapy for ovarian clear cell carcinoma: JGOG3017/GCIG Trial. J Clin Oncol Off J Am Soc Clin Oncol. 2016;34:2881–7.CrossRefGoogle Scholar
  89. 89.
    Seidman JD, Kurman RJ, Ronnett BM. Primary and metastatic mucinous adenocarcinomas in the ovaries: incidence in routine practice with a new approach to improve intraoperative diagnosis. Am J Surg Pathol. 2003;27:985–93.PubMedCrossRefGoogle Scholar
  90. 90.
    Shimada M, Kigawa J, Ohishi Y, et al. Clinicopathological characteristics of mucinous adenocarcinoma of the ovary. Gynecol Oncol. 2009;113:331–4.PubMedCrossRefGoogle Scholar
  91. 91.
    Hess V, A'Hern R, Nasiri N, et al. Mucinous epithelial ovarian cancer: a separate entity requiring specific treatment. J Clin Oncol Off J Am Soc Clin Oncol. 2004;22:1040–4.CrossRefGoogle Scholar
  92. 92.
    Burger RA, Brady MF, Bookman MA, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365:2473–83.PubMedCrossRefGoogle Scholar
  93. 93.
    Perren TJ, Swart AM, Pfisterer J, et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011;365:2484–96.PubMedCrossRefGoogle Scholar
  94. 94.
    Eisenhauer EL, Tew WP, Levine DA, et al. Response and outcomes in elderly patients with stages IIIC-IV ovarian cancer receiving platinum-taxane chemotherapy. Gynecol Oncol. 2007;106:381–7.PubMedCrossRefGoogle Scholar
  95. 95.
    Hilpert F, du Bois A, Greimel ER, et al. Feasibility, toxicity and quality of life of first-line chemotherapy with platinum/paclitaxel in elderly patients aged >or =70 years with advanced ovarian cancer—a study by the AGO OVAR Germany. Ann Oncol. 2007;18:282–7.PubMedCrossRefGoogle Scholar
  96. 96.
    Ozols RF. Systemic therapy for ovarian cancer: current status and new treatments. Semin Oncol. 2006;33:S3–11.PubMedCrossRefGoogle Scholar
  97. 97.
    Colombo N, Gore M. Treatment of recurrent ovarian cancer relapsing 6–12 months post platinum-based chemotherapy. Crit Rev Oncol Hematol. 2007;64:129–38.PubMedCrossRefGoogle Scholar
  98. 98.
    Markman M, Markman J, Webster K, et al. Duration of response to second-line, platinum-based chemotherapy for ovarian cancer: implications for patient management and clinical trial design. J Clin Oncol Off J Am Soc Clin Oncol. 2004;22:3120–5.CrossRefGoogle Scholar
  99. 99.
    Parmar MK, Ledermann JA, Colombo N, et al. Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet (London). 2003;361:2099–106.CrossRefGoogle Scholar
  100. 100.
    Pfisterer J, Vergote I, Du Bois A, Eisenhauer E. Combination therapy with gemcitabine and carboplatin in recurrent ovarian cancer. Int J Gynecol Cancer. 2005;15:36–41.PubMedCrossRefGoogle Scholar
  101. 101.
    Harries M, Gore M. Part II: chemotherapy for epithelial ovarian cancer-treatment of recurrent disease. Lancet Oncol. 2002;3:537–45.PubMedCrossRefGoogle Scholar
  102. 102.
    Gronlund B, Hogdall C, Hansen HH, Engelholm SA. Results of reinduction therapy with paclitaxel and carboplatin in recurrent epithelial ovarian cancer. Gynecol Oncol. 2001;83:128–34.PubMedCrossRefGoogle Scholar
  103. 103.
    Buda A, Floriani I, Rossi R, et al. Randomised controlled trial comparing single agent paclitaxel vs epidoxorubicin plus paclitaxel in patients with advanced ovarian cancer in early progression after platinum-based chemotherapy: an Italian Collaborative Study from the Mario Negri Institute, Milan, G.O.N.O. (Gruppo Oncologico Nord Ovest) group and I.O.R. (Istituto Oncologico Romagnolo) group. Br J Cancer. 2004;90:2112–7.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Sehouli J, Stengel D, Oskay-Oezcelik G, et al. Nonplatinum topotecan combinations versus topotecan alone for recurrent ovarian cancer: results of a phase III study of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group. J Clin Oncol Off J Am Soc Clin Oncol. 2008;26:3176–82.CrossRefGoogle Scholar
  105. 105.
    Gonzalez-Martin AJ, Calvo E, Bover I, et al. Randomized phase II trial of carboplatin versus paclitaxel and carboplatin in platinum-sensitive recurrent advanced ovarian carcinoma: a GEICO (Grupo Espanol de Investigacion en Cancer de Ovario) study. Ann Oncol. 2005;16:749–55.PubMedCrossRefGoogle Scholar
  106. 106.
    Aghajanian C, Blank SV, Goff BA, et al. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2012;30:2039–45.CrossRefGoogle Scholar
  107. 107.
    Pujade-Lauraine E, Hilpert F, Weber B, et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: the AURELIA open-label randomized phase III trial. J Clin Oncol Off J Am Soc Clin Oncol. 2014;32:1302–8.CrossRefGoogle Scholar
  108. 108.
    Bristow RE, Puri I, Chi DS. Cytoreductive surgery for recurrent ovarian cancer: a meta-analysis. Gynecol Oncol. 2009;112:265–74.PubMedCrossRefGoogle Scholar
  109. 109.
    Tinger A, Waldron T, Peluso N, et al. Effective palliative radiation therapy in advanced and recurrent ovarian carcinoma. Int J Radiat Oncol Biol Phys. 2001;51:1256–63.PubMedCrossRefGoogle Scholar
  110. 110.
    E C QM, Gallant V, Samant R. Effective palliative radiotherapy for symptomatic recurrent or residual ovarian cancer. Gynecol Oncol. 2006;102:204–9.PubMedCrossRefGoogle Scholar
  111. 111.
    Ledermann JA, Raja FA, Fotopoulou C, Gonzalez-Martin A, Colombo N, Sessa C. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24:vi24–32.PubMedCrossRefGoogle Scholar
  112. 112.
    Rubin SC, Wong GY, Curtin JP, Barakat RR, Hakes TB, Hoskins WJ. Platinum-based chemotherapy of high-risk stage I epithelial ovarian cancer following comprehensive surgical staging. Obstet Gynecol. 1993;82:143–7.PubMedGoogle Scholar
  113. 113.
    Gadducci A, Sartori E, Maggino T, et al. Analysis of failures after negative second-look in patients with advanced ovarian cancer: an Italian multicenter study. Gynecol Oncol. 1998;68:150–5.PubMedCrossRefGoogle Scholar
  114. 114.
    Dembo AJ. Controversy over combination chemotherapy in advanced ovarian cancer: what we learn from reports of matured data. J Clin Oncol Off J Am Soc Clin Oncol. 1986;4:1573–6.CrossRefGoogle Scholar
  115. 115.
    Aebi S, Castiglione M. Epithelial ovarian carcinoma: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol. 2008;19:ii14–6.PubMedCrossRefGoogle Scholar
  116. 116.
    Harmandayan GZ, Gao F, Mutch DG, Virgo KS, Gibb RK, Johnson FE. Ovarian cancer patient surveillance after curative-intent initial treatment. Gynecol Oncol. 2011;120:205–8.PubMedCrossRefGoogle Scholar
  117. 117.
    Gadducci A, Fuso L, Cosio S, et al. Are surveillance procedures of clinical benefit for patients treated for ovarian cancer?: A retrospective Italian multicentric study. Int J Gynecol Cancer. 2009;19:367–74.PubMedCrossRefGoogle Scholar
  118. 118.
    Tanner EJ, Chi DS, Eisenhauer EL, Diaz-Montes TP, Santillan A, Bristow RE. Surveillance for the detection of recurrent ovarian cancer: survival impact or lead-time bias? Gynecol Oncol. 2010;117:336–40.PubMedCrossRefGoogle Scholar
  119. 119.
    Rocca WA, Grossardt BR, de Andrade M, Malkasian GD, Melton LJ 3rd. Survival patterns after oophorectomy in premenopausal women: a population-based cohort study. Lancet Oncol. 2006;7:821–8.PubMedCrossRefGoogle Scholar
  120. 120.
    Mascarenhas C, Lambe M, Bellocco R, et al. Use of hormone replacement therapy before and after ovarian cancer diagnosis and ovarian cancer survival. Int J Cancer. 2006;119:2907–15.PubMedCrossRefGoogle Scholar
  121. 121.
    Guidozzi F, Daponte A. Estrogen replacement therapy for ovarian carcinoma survivors: a randomized controlled trial. Cancer. 1999;86:1013–8.PubMedCrossRefGoogle Scholar
  122. 122.
    Eeles RA, Tan S, Wiltshaw E, et al. Hormone replacement therapy and survival after surgery for ovarian cancer. BMJ (Clin Res ed). 1991;302:259–62.CrossRefGoogle Scholar
  123. 123.
    Ursic-Vrscaj M, Bebar S, Zakelj MP. Hormone replacement therapy after invasive ovarian serous cystadenocarcinoma treatment: the effect on survival. Menopause (New York, NY). 2001;8:70–5.CrossRefGoogle Scholar
  124. 124.
    Li L, Pan Z, Gao K, et al. Impact of post-operative hormone replacement therapy on life quality and prognosis in patients with ovarian malignancy. Oncol Lett. 2012;3:244–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd 2018

Authors and Affiliations

  • Yusuke Kobayashi
    • 1
    Email author
  • Hiroyuki Nomura
    • 1
  • Fumio Kataoka
    • 1
  • Eiichiro Tominaga
    • 1
  • Kouji Banno
    • 1
  • Daisuke Aoki
    • 1
  1. 1.Department of Obstetrics and GynecologyKeio University School of MedicineTokyoJapan

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