Updates in Surgery

, Volume 66, Issue 2, pp 109–113 | Cite as

The role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of ovarian cancer relapse

  • E. Saladino
  • F. Fleres
  • S. Irato
  • C. Famulari
  • A. Macrì
Review Article


Nowadays the standard clinical management for advanced epithelial ovarian cancer is constituted by primary cytoreductive surgery associated to adjuvant systemic chemotherapy. Even if this first-line chemotherapy shows a high rate of complete responses, the disease recurrences occur especially in stage-III patients. Actually an option for this subset of patients is represented by secondary cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy that represents a promising therapy, having shown positive results in terms of median overall survival, progression free survival and overall survival. However, a much more research is still required especially by prospective randomised trials to improve outcomes in recurrent ovarian cancer.


CRS HIPEC Epithelial ovarian cancer Recurrence 


Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Yancik R (1993) EOC: age contrast in incidence, histology, disease stage at diagnosis, and mortality. Cancer 71(2 Suppl):517–523PubMedGoogle Scholar
  2. 2.
    McGuire WP, Hoskin WJ, Brady MF et al (1996) Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and IV EOC. N Engl J Med 334:1–6PubMedCrossRefGoogle Scholar
  3. 3.
    Ozolos RF, Bundy BN, Greer BE et al (2003) 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 21:194–200CrossRefGoogle Scholar
  4. 4.
    Ozolos RF, Young RC (1988) Epithelial ovarian cancer. Curr Probl Cancer 11:57–122Google Scholar
  5. 5.
    Leitao MM Jr, Chi DS (2009) Surgical management of recurrent ovarian cancer. Semin Oncol 36:106–111PubMedCrossRefGoogle Scholar
  6. 6.
    Armstrong DK, Bundy B, Wenzel L et al (2006) Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med 354:34–43PubMedCrossRefGoogle Scholar
  7. 7.
    Helm CW, Bristow RE, Kusamura S, Baratti D, Deraco M (2008) Hyperthermic intraperitoneal chemotherapy with and without cytoreductive surgery for epithelial ovarian cancer. J Surg Oncol 98:283–290PubMedCrossRefGoogle Scholar
  8. 8.
    Deraco M, Virzì S, Raspagliesi F et al (2012) Secondary cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent epithelial ovarian cancer: a multi-institutional study. BJOG 119:800–809PubMedCrossRefGoogle Scholar
  9. 9.
    Hennessy BT, Coleman RL, Markman M (2009) Ovarian cancer. Lancet 374:1371–1382PubMedCrossRefGoogle Scholar
  10. 10.
    Chi DS, McCaughty K, Diaz JP et al (2006) Guidelines and selection criteria for secondary cytoreductive surgery in patients with recurrent, platinum-sensitive epithelial ovarian carcinoma. Cancer 106:1933–1939PubMedCrossRefGoogle Scholar
  11. 11.
    Bae J, Lim MC, Choi JH et al (2009) Prognostic factors of secondary cytoreductive surgery for patients with recurrent epithelial ovarian cancer. J Gynecol Oncol 20:101–106PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Harter P, du Bois A, Hahmann M et al (2006) The Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) DESKTOP OVAR trial. Ann Surg Oncol 13:1702–1710PubMedCrossRefGoogle Scholar
  13. 13.
    Harter P, Hahmann M, Lueck HJ et al (2009) Surgery for recurrent ovarian cancer: role of peritoneal carcinomatosis: exploratory analysis of the DESKTOP I trial about risk factors, surgical implications, and prognostic value of peritoneal carcinomatosis. Ann Surg Oncol 16:1324–1330PubMedCrossRefGoogle Scholar
  14. 14.
    Baratti D, Scivales A, Balestra MR et al (2010) Cost analysis of the combined procedure of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). Eur J Surg Oncol 36:463–469PubMedCrossRefGoogle Scholar
  15. 15.
    Helm CW (2009) The role of hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer. Oncologist 14:683–694PubMedCrossRefGoogle Scholar
  16. 16.
    Bristow RE, Tomacruz RS, Arstrong DK, Trimble EL, Montz FJ (2002) Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. J Clin Oncol 20:1248–1259PubMedCrossRefGoogle Scholar
  17. 17.
    Chi DS, Eisenhauer EL, Zivanovic O et al (2009) Improved progression-free and overall survival in advanced ovarian cancer as a result of a change in surgical paradigm. Gynecol Oncol 114:26–31PubMedCrossRefGoogle Scholar
  18. 18.
    Alberts DS, Liu PY, Hannigan EV et al (1996) Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med 335:1950–1955PubMedCrossRefGoogle Scholar
  19. 19.
    Markman M, Bundy BN, Alberts DS et al (2001) 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 gynaecologic oncology group, southwestern oncology group, and eastern cooperative oncology group. J Clin Oncol 19:1001–1007PubMedGoogle Scholar
  20. 20.
    Dedrick RI, Myers CE, Bungay PM et al (1978) Pharmacokinetic rationale for peritoneal drug administration in the treatment of ovarian cancer. Cancer Treat Rep 62:1–11PubMedGoogle Scholar
  21. 21.
    Jaaback K, Jhonson N (2006) Intraperitoneal chemotherapy for the initial management of primary epithelial ovarian cancer. Cochrane Database Syst Rev 1:CD005340PubMedGoogle Scholar
  22. 22.
    Rowan K (2009) Intraperitoneal therapy for ovarian cancer: why has it not become standard? J Natl Cancer Inst 101:775–777PubMedCrossRefGoogle Scholar
  23. 23.
    Deraco M, Baratti D, Laterza B et al (2011) Advanced cytoreduction as surgical standard of care and hyperthermic intraperitoneal chemotherapy as promising treatment in epithelial ovarian cancer: review of literature data. Eur J Surg Oncol 37:4–9PubMedCrossRefGoogle Scholar
  24. 24.
    Markman M (2001) Intraperitoneal chemotherapy in the management of malignant disease. Expert Rev Anticancer Ther 1:142–148PubMedCrossRefGoogle Scholar
  25. 25.
    Macrì A, Fortugno A, Saladino E (2011) Rationale and techniques of cytoreductive surgery and peritoneal chemohyperthermia. World J Gastrointest Oncol 3:169–174PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Yan TD, Black D, Savady R, Sugarbaker PH (2007) A systematic review on the efficacy of cytoreductive surgery and perioperative intraperitoneal chemotherapy for pseudomixoma peritonei. Ann Surg Oncol 14:484–492PubMedCrossRefGoogle Scholar
  27. 27.
    Yan TD, Black D, Savady R, Sugarbaker PH (2006) Systematic review on the efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal carcinoma. J Clin Oncol 24:4011–4019PubMedCrossRefGoogle Scholar
  28. 28.
    Yan TD, Deraco M, Baratti D et al (2009) Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: multi-institutional experience. J Clin Oncol 27:6237–6242PubMedCrossRefGoogle Scholar
  29. 29.
    Fujimoto S, Takahashi M, Mutou T et al (1997) Improved mortality rate of gastric carcinoma patients with peritoneal carcinomatosis treated with intraperitoneal hyperthermic chemoperfusion combined with surgery. Cancer 79:884–891PubMedCrossRefGoogle Scholar
  30. 30.
    Helm CW, Toler CR, Martin RS III et al (2007) Surgical cytoreduction and intraperitoneal heated chemotherapy (IPHC) for endometrial carcinoma recurrent within the peritoneal cavity. Int J Gynecol Cancer 17:204–209PubMedCrossRefGoogle Scholar
  31. 31.
    Griffiths CT (1975) Surgical resection of tumor bulk in the primary treatment of ovarian carcinoma. Natl Cancer Inst Monogr 42:101–104PubMedGoogle Scholar
  32. 32.
    Winter WE 3rd, Maxwell GL, Tian C et al (2008) Tumor residual after surgical cytoreduction in prediction of clinical outcome in stage IV epithelial ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol 26:83–89PubMedCrossRefGoogle Scholar
  33. 33.
    Eisenkop SM, Spirtos NM (2001) What are the current surgical objectives, strategies, and technical capabilities of gynaecologic oncologist treating advanced epithelial ovarian cancer? Gynecol Oncol 82:489–497PubMedCrossRefGoogle Scholar
  34. 34.
    Munkarah AR, Coleman RL (2004) Critical evaluation of secondary cytoreduction in recurrent ovarian cancer. Gynecol Oncol 95:273–280PubMedCrossRefGoogle Scholar
  35. 35.
    Salom E, Almeida Z, Mirhashemi R (2002) Management of recurrent ovarian cancer: evidence-based decision. Curr Opin Oncol 14:519–527PubMedCrossRefGoogle Scholar
  36. 36.
    Di Giorgio A, Naticchioni E, Biacchi D et al (2008) Cytoreductive surgery (peritonectomy procedures) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of diffuse peritoneal carcinomatosis from ovarian cancer. Cancer 113:315–325PubMedCrossRefGoogle Scholar
  37. 37.
    de Bree E, Romanos J, Michalakis J et al (2003) Intraoperative hyperthermic intraperitoneal chemotherapy with docetaxel as second-line treatment for peritoneal carcinomatosis of gynaecological origin. Anticancer Res 23:3019–3027PubMedGoogle Scholar
  38. 38.
    Chatzigeorgiou K, Economou S, ChrysaWs G et al (2003) Treatment of recurrent epithelial ovarian cancer with secondary cytoreduction and continuous intraoperative intraperitoneal hyperthermic chemoperfusion (CIIPHCP). Z Gynäkol 125:424–429CrossRefGoogle Scholar
  39. 39.
    Rufian S, Munoz-Casares FC, Briceno J et al (2006) Radical surgery—peritonectomy and intraoperative intraperitoneal chemotherapy for the treatment of peritoneal carcinomatosis in recurrent or primary ovarian cancer. J Surg Oncol 94:316–324PubMedCrossRefGoogle Scholar
  40. 40.
    Cotte E, Glehen O, Mohamed F et al (2007) Cytoreductive surgery and intraperitoneal chemo-hyperthermia for chemo-resistant and recurrent advanced epithelial ovarian cancer: prospective study of 81 patients. World J Surg 31:1813–1820PubMedCrossRefGoogle Scholar
  41. 41.
    Helm CW, Randall-Whitis L, Martin RS III et al (2007) Hyperthermic intraperitoneal chemotherapy in conjunction with surgery for the treatment of recurrent ovarian carcinoma. Gynecol Oncol 105:90–96PubMedCrossRefGoogle Scholar
  42. 42.
    Pavlov MJ, Kovacevic PA, Ceranic MS, Stamenkovic AB, Ivanovic AM, Kecmanovic DM (2009) Cytoreductive surgery and modified heated intraoperative intraperitoneal chemotherapy (HIPEC) for advanced and recurrent ovarian cancer—12-year single center experience. Eur J Surg Oncol 35:1186–1191PubMedCrossRefGoogle Scholar
  43. 43.
    Bakrin N, Cotte E, Golfier F, et al (2012) Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for persistent and recurrent advanced ovarian carcinoma: a multicenter prospective study of 246 patients. Ann Surg Oncol 19:4052–4058PubMedCrossRefGoogle Scholar
  44. 44.
    Fagotti A, Paris I, Grimolizzi F et al (2009) Secondary cytoreduction plus oxaliplatin-based HIPEC in platinum sensitive recurrent ovarian cancer patients: a pilot study. Gynecol Oncol 113:335–340PubMedCrossRefGoogle Scholar
  45. 45.
    Frenel JS, Leux C, Pouplin L et al (2011) Oxaliplatin-based hyperthermic intraperitoneal chemotherapy in primary or recurrent epithelial ovarian cancer: a pilot study of 31 patients. J Surg Oncol 103:10–16PubMedCrossRefGoogle Scholar
  46. 46.
    Spiliotis J, Vaxevanidou A, Sergouniotis F, Lambropoulou E, Datsis A, Christopoulou A (2011) The role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of recurrent advanced ovarian cancer: a prospective study. J BUON 16:74–79PubMedGoogle Scholar
  47. 47.
    Deraco M, Rossi CR, Pennacchioli E et al (2001) Cytoreductive surgery followed by intraperitoneal hyperthermic perfusion in the treatment of recurrent epithelial ovarian cancer: a phase II clinical study. Tumori 87:120–126PubMedGoogle Scholar
  48. 48.
    Zanon C, Clara R, Chiappino I et al (2004) Cytoreductive surgery and intraperitoneal chemohyperthermia for recurrent peritoneal carcinomatosis from ovarian cancer. World J Surg 28:1040–1045PubMedCrossRefGoogle Scholar
  49. 49.
    Panteix G, Beaujard A, Garbit F et al (2002) Population pharmacokinetics of cisplatin in patients with advanced ovarian cancer during intraperitoneal hyperthermia chemotherapy. Anticancer Res 22:1329–1336PubMedGoogle Scholar
  50. 50.
    Riechman TW, Cracchiolo B, Sama J et al (2005) Cytoreductive surgery and intraoperative hyperthermic chemoperfusion for advanced ovarian carcinoma. J Surg Oncol 90:51–56CrossRefGoogle Scholar
  51. 51.
    Raspagliesi F, Kusamura S, Campos Torres JC et al (2006) Cytoreduction combined with intraperitoneal hyperthermic perfusion chemotherapy in advance/recurrent ovarian cancer patients: The experience of National Cancer Institute of Milan. Eur J Surg Oncol 32:671–675PubMedCrossRefGoogle Scholar
  52. 52.
    Chan DL, Morris DL, Rao A, Chua TC (2012) Intraperitoneal chemotherapy in ovarian cancer: a review of tolerance and efficacy. Cancer Manag Res 4:413–422PubMedCentralPubMedGoogle Scholar
  53. 53.
    Stuart OA, Stephens AD, Welch L et al (2002) Safety monitoring of the coliseum technique for heated intraoperative intraperitoneal chemotherapy with mytomicin C. Ann Surg Oncol 9:186–191PubMedCrossRefGoogle Scholar
  54. 54.
    Gonzalez-Bayon L, Gonzalez-Moreno S, Ortega-Perez G (2006) Safety consideration for operating room personnel during hyperthermic intraoperative intraperitoneal chemotherapy perfusion. Eur J Surg Oncol 32:619–624PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2013

Authors and Affiliations

  • E. Saladino
    • 1
  • F. Fleres
    • 1
  • S. Irato
    • 2
  • C. Famulari
    • 1
  • A. Macrì
    • 1
  1. 1.General Surgery Unit, Department of Human PathologyUniversity of MessinaMessinaItaly
  2. 2.Gynecological and Obstetrical Unit, Department of Sciences and Reproductive MedicineUniversity of MessinaMessinaItaly

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