Review of the Outcomes of Ovarian Cancer Treated with Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy

  • Carrie LangstraatEmail author
Part of the following topical collections:
  1. Controversies to Consensus : Recent advances


Ovarian, fallopian tube and primary peritoneal carcinomas (OVCA) most commonly present in advanced stages and despite aggressive surgical resection and chemotherapy will likely recur. Although OVCA can recur in the liver, chest or brain, it most commonly recurs within the peritoneal cavity. Peritoneal spread is problematic and often results in bowel obstruction and the inability to maintain nutritional goals. Given the lethality of peritoneal disease as well as the difficulty in treating this recurrence pattern, novel tactics to treat peritoneal dissemination have been a focus of research in OVCA. Heated intraperitoneal chemotherapy (HIPEC) has been well studied and is utilized to treat appendiceal malignancies, which similarly involve the peritoneum. HIPEC has been shown to improve survival and decrease the risk of peritoneal recurrence in patients with appendiceal malignancies. This technique has also been shown to improve outcomes in patients with peritoneal metastases due to colorectal cancers and gastric cancers. Over the past three decades, HIPEC has been used to treat OVCA with mixed results. The aim of this paper is to review the use of HIPEC in the treatment of OVCA in the upfront and recurrent setting.


HIPEC Heated intraperitoneal chemotherapy Ovarian cancer 




Compliance with Ethical Standards

Conflict of interest

The author declares that there is no conflict of interest.


  1. 1.
    Coalition WOC. The world ovarian cancer coalition atlas. Accessed 22 July 2019.
  2. 2.
    Torre LA, Trabert B, DeSantis CE, et al. Ovarian cancer statistics, 2018. CA A Cancer J Clin. 2018;68(4):284–96. Scholar
  3. 3.
    Webb PM, Jordan SJ. Epidemiology of epithelial ovarian cancer. Best Pract Res Clin Obstet Gynaecol. 2017;41:3–14. Scholar
  4. 4.
    Armstrong DK, Bundy B, Wenzel L, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006;354(1):34–43. Scholar
  5. 5.
    Wright AA, Cronin A, Milne DE, et al. Use and effectiveness of intraperitoneal chemotherapy for treatment of ovarian cancer. J Clin Oncol. 2015;33(26):2841–7. Scholar
  6. 6.
    Giovanella BC, Stehlin JS Jr, Morgan AC. Selective lethal effect of supranormal temperatures on human neoplastic cells. Cancer Res. 1976;36(11 Pt 1):3944–50.PubMedGoogle Scholar
  7. 7.
    Los G, Sminia P, Wondergem J, et al. Optimisation of intraperitoneal cisplatin therapy with regional hyperthermia in rats. Eur J Cancer (Oxford, England: 1990). 1991;27(4):472–7. Scholar
  8. 8.
    Los G, van Vugt MJ, den Engelse L, et al. Effects of temperature on the interaction of cisplatin and carboplatin with cellular DNA. Biochem Pharmacol. 1993;46(7):1229–37. Scholar
  9. 9.
    Los G, van Vugt MJ, Pinedo HM. Response of peritoneal solid tumours after intraperitoneal chemohyperthermia treatment with cisplatin or carboplatin. Br J Cancer. 1994;69(2):235–41. Scholar
  10. 10.
    Cashin PH, Mahteme H, Spang N, et al. Cytoreductive surgery and intraperitoneal chemotherapy versus systemic chemotherapy for colorectal peritoneal metastases: a randomised trial. Eur J Cancer (Oxford, England: 1990). 2016;53:155–62. Scholar
  11. 11.
    Chua TC, Moran BJ, Sugarbaker PH, et al. Early- and long-term outcome data of patients with pseudomyxoma peritonei from appendiceal origin treated by a strategy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. J Clin Oncol. 2012;30(20):2449–56. Scholar
  12. 12.
    Faris JE, Ryan DP. Controversy and consensus on the management of patients with pseudomyxoma peritonei. Curr Treat Opt Oncol. 2013;14(3):365–73. Scholar
  13. 13.
    Mohamed F, Cecil T, Moran B, et al. A new standard of care for the management of peritoneal surface malignancy. Curr Oncol (Toronto). 2011;18(2):e84–96. Scholar
  14. 14.
    Shaib WL, Martin LK, Choi M, et al. Hyperthermic intraperitoneal chemotherapy following cytoreductive surgery improves outcome in patients with primary appendiceal mucinous adenocarcinoma: a pooled analysis from three tertiary care centers. Oncologist. 2015;20(8):907–14. Scholar
  15. 15.
    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(9990):249–57. Scholar
  16. 16.
    Vergote I, Coens C, Nankivell M, et al. Neoadjuvant chemotherapy versus debulking surgery in advanced tubo-ovarian cancers: pooled analysis of individual patient data from the EORTC 55971 and CHORUS trials. Lancet Oncol. 2018;19(12):1680–7. Scholar
  17. 17.
    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(10):943–53. Scholar
  18. 18.
    Chang SJ, Hodeib M, Chang J, et al. Survival impact of complete cytoreduction to no gross residual disease for advanced-stage ovarian cancer: a meta-analysis. Gynecol Oncol. 2013;130(3):493–8. Scholar
  19. 19.
    Narasimhulu DM, Khoury-Collado F, Chi DS. Radical surgery in ovarian cancer. Curr Oncol Rep. 2015;17(4):16. Scholar
  20. 20.
    Ahmed S, Stewart JH, Shen P, et al. Outcomes with cytoreductive surgery and HIPEC for peritoneal metastasis. J Surg Oncol. 2014;110(5):575–84. Scholar
  21. 21.
    Amblard I, Mercier F, Bartlett DL, et al. Cytoreductive surgery and HIPEC improve survival compared to palliative chemotherapy for biliary carcinoma with peritoneal metastasis: a multi-institutional cohort from PSOGI and BIG RENAPE groups. Eur J Surg Oncol. 2018;44(9):1378–83. Scholar
  22. 22.
    Ji ZH, Peng KW, Yu Y, et al. Current status and future prospects of clinical trials on CRS + HIPEC for gastric cancer peritoneal metastases. Int J Hyperth. 2017;33(5):562–70. Scholar
  23. 23.
    D’Hondt V, Goffin F, Roca L, et al. Interval cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in first-line treatment for advanced ovarian carcinoma: a feasibility study. Int J Gynecol Cancer. 2016;26(5):912–7. Scholar
  24. 24.
    Di Giorgio A, De Iaco P, De Simone M, et al. Cytoreduction (peritonectomy procedures) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in advanced ovarian cancer: retrospective Italian multicenter observational study of 511 cases. Ann Surg Oncol. 2017;24(4):914–22. Scholar
  25. 25.
    Gouy S, Ferron G, Glehen O, et al. Results of a multicenter phase I dose-finding trial of hyperthermic intraperitoneal cisplatin after neoadjuvant chemotherapy and complete cytoreductive surgery and followed by maintenance bevacizumab in initially unresectable ovarian cancer. Gynecol Oncol. 2016;142(2):237–42. Scholar
  26. 26.
    Lee YJ, Lee JY, Cho MS, et al. Incorporation of paclitaxel-based hyperthermic intraperitoneal chemotherapy in patients with advanced-stage ovarian cancer treated with neoadjuvant chemotherapy followed by interval debulking surgery: a protocol-based pilot study. J Gynecol Oncol. 2019;30(1):e3. Scholar
  27. 27.
    Lentz SS, Miller BE, Kucera GL, et al. Intraperitoneal hyperthermic chemotherapy using carboplatin: a phase I analysis in ovarian carcinoma. Gynecol Oncol. 2007;106(1):207–10. Scholar
  28. 28.
    Lim MC, Kang S, Choi J, et al. Hyperthermic intraperitoneal chemotherapy after extensive cytoreductive surgery in patients with primary advanced epithelial ovarian cancer: interim analysis of a phase II study. Ann Surg Oncol. 2009;16(4):993–1000. Scholar
  29. 29.
    Paris I, Cianci S, Vizzielli G, et al. Upfront HIPEC and bevacizumab-containing adjuvant chemotherapy in advanced epithelial ovarian cancer. Int J Hyperth. 2018;35(1):370–4. Scholar
  30. 30.
    Pomel C, Ferron G, Lorimier G, et al. Hyperthermic intra-peritoneal chemotherapy using oxaliplatin as consolidation therapy for advanced epithelial ovarian carcinoma. Results of a phase II prospective multicentre trial. CHIPOVAC study. J Surg Oncol. 2010;36(6):589–93. Scholar
  31. 31.
    van Driel WJ, Koole SN, Sikorska K, et al. Hyperthermic intraperitoneal chemotherapy in ovarian cancer. N Engl J Med. 2018;378(3):230–40. Scholar
  32. 32.
    Zivanovic O, Abramian A, Kullmann M, et al. HIPEC ROC I: a phase I study of cisplatin administered as hyperthermic intraoperative intraperitoneal chemoperfusion followed by postoperative intravenous platinum-based chemotherapy in patients with platinum-sensitive recurrent epithelial ovarian cancer. Int J Cancer. 2015;136(3):699–708. Scholar
  33. 33.
    Bakrin N, Bereder JM, Decullier E, et al. Peritoneal carcinomatosis treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced ovarian carcinoma: a French multicentre retrospective cohort study of 566 patients. Eur J Surg Oncol. 2013;39(12):1435–43. Scholar
  34. 34.
    Bakrin N, Cotte E, Golfier F, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for persistent and recurrent advanced ovarian carcinoma: a multicenter, prospective study of 246 patients. Ann Surg Oncol. 2012;19(13):4052–8. Scholar
  35. 35.
    Cascales-Campos PA, Gil J, Feliciangeli E, et al. The role of hyperthermic intraperitoneal chemotherapy using paclitaxel in platinum-sensitive recurrent epithelial ovarian cancer patients with microscopic residual disease after cytoreduction. Ann Surg Oncol. 2015;22(3):987–93. Scholar
  36. 36.
    Ceelen WP, Van Nieuwenhove Y, Van Belle S, et al. Cytoreduction and hyperthermic intraperitoneal chemoperfusion in women with heavily pretreated recurrent ovarian cancer. Ann Surg Oncol. 2012;19(7):2352–9. Scholar
  37. 37.
    Classe JM, Glehen O, Decullier E, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for first relapse of ovarian cancer. Anticancer Res. 2015;35(9):4997–5005.PubMedGoogle Scholar
  38. 38.
    Fagotti A, Costantini B, Petrillo M, et al. Cytoreductive surgery plus HIPEC in platinum-sensitive recurrent ovarian cancer patients: a case–control study on survival in patients with two year follow-up. Gynecol Oncol. 2012;127(3):502–5. Scholar
  39. 39.
    Fagotti A, Costantini B, Vizzielli G, et al. HIPEC in recurrent ovarian cancer patients: morbidity-related treatment and long-term analysis of clinical outcome. Gynecol Oncol. 2011;122(2):221–5. Scholar
  40. 40.
    Fagotti A, Paris I, Grimolizzi F, et al. Secondary cytoreduction plus oxaliplatin-based HIPEC in platinum-sensitive recurrent ovarian cancer patients: a pilot study. Gynecol Oncol. 2009;113(3):335–40. Scholar
  41. 41.
    Spiliotis J, Halkia E, Lianos E, et al. Cytoreductive surgery and HIPEC in recurrent epithelial ovarian cancer: a prospective randomized phase III study. Ann Surg Oncol. 2015;22(5):1570–5. Scholar
  42. 42.
    van der Vange N, van Goethem AR, Zoetmulder FA, et al. Extensive cytoreductive surgery combined with intra-operative intraperitoneal perfusion with cisplatin under hyperthermic conditions (OVHIPEC) in patients with recurrent ovarian cancer: a feasibility pilot. Eur J Surg Oncol. 2000;26(7):663–8. Scholar
  43. 43.
    Petrillo M, De Iaco P, Cianci S, et al. Long-term survival for platinum-sensitive recurrent ovarian cancer patients treated with secondary cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC). Ann Surg Oncol. 2016;23(5):1660–5. Scholar
  44. 44.
    Lim SL, Havrilesky LJ, Habib AS, et al. Cost-effectiveness of hyperthermic intraperitoneal chemotherapy (HIPEC) at interval debulking of epithelial ovarian cancer following neoadjuvant chemotherapy. Gynecol Oncol. 2019;153(2):376–80. Scholar
  45. 45.
    Koole SN, van Lieshout C, van Driel WJ, et al. Cost effectiveness of interval cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in stage III ovarian cancer on the basis of a randomized phase III trial. J Clin Oncol. 2019;37(23):2041–50. Scholar
  46. 46.
    Wu J, Sun H, Yang L, et al. Improved survival in ovarian cancer, with widening survival gaps of races and socioeconomic status: a period analysis, 1983–2012. J Cancer. 2018;9(19):3548–56. Scholar
  47. 47.
    Lemoine L, Sugarbaker P, Van der Speeten K. Drugs, doses, and durations of intraperitoneal chemotherapy: standardising HIPEC and EPIC for colorectal, appendiceal, gastric, ovarian peritoneal surface malignancies and peritoneal mesothelioma. Int J Hyperth. 2017;33(5):582–92. Scholar

Copyright information

© Association of Gynecologic Oncologists of India 2019

Authors and Affiliations

  1. 1.Department of Obstetrics and GynecologyMayo ClinicRochesterUSA

Personalised recommendations