International Journal of Colorectal Disease

, Volume 33, Issue 11, pp 1559–1567 | Cite as

Benefit of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy in patients with isolated peritoneal metastases from colorectal cancer

  • Pompiliu PisoEmail author
  • Kathrin Stierstorfer
  • Michael Gerken
  • Monika Klinkhammer-Schalke
Original Article



Ever since Sugarbaker has established the cytoreductive surgery (CRS) in combination with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC), there is a chance of cure for selected patients with peritoneal metastases from colorectal cancer. Objective of this study was to investigate the benefit of CRS and HIPEC compared to other therapy options in patients with isolated synchronous and metachronous peritoneal metastases of colorectal origin in terms of long-term overall survival.


A retrospective population-based cohort study, including 370 patients diagnosed with isolated synchronous and metachronous peritoneal metastases of colorectal origin, was carried out. Therefore, data were acquired from the cancer registry at the Regensburg Tumor Center in Bavaria, Germany. Patients’ overall survival (OAS) according to their therapy received was analyzed by means of Kaplan-Meier method and multivariable Cox regression.


Overall median survival was 41.6 months for patients treated with CRS and HIPEC, compared with surgery and chemotherapy (24.0 months, log-rank p = 0.015), chemotherapy only (14.1 months, p < 0.001), surgery only (11.4 months, p < 0.001), and best supportive care (7.9 months, p < 0.001). This benefit persisted after adjustment for further risk factors in multivariable analysis.


The effect of CRS and HIPEC stands out significantly in comparison to all other therapies. The multimodality approach should be a regular option for patients with isolated peritoneal metastases.


Cytoreductive surgery Hyperthermic intraperitoneal chemotherapy Colorectal cancer Peritoneal metastases Survival analysis Population-based analysis 


  1. 1.
    Sadeghi B, Arvieux C, Glehen O, Beaujard AC, Rivoire M, Baulieux J, Fontaumard E, Brachet A, Caillot JL, Faure JL, Porcheron J, Peix JL, François Y, Vignal J, Gilly FN (2000) Peritoneal carcinomatosis from non-gynecologic malignancies: results of the EVOCAPE 1 multicentric prospective study. Cancer 88(2):358–363CrossRefGoogle Scholar
  2. 2.
    Piso P, Glockzin G, von Breitenbuch P, Sulaiman T, Popp F, Dahlke M, Esquivel J, Schlitt HJ (2009) Patient selection for a curative approach to carcinomatosis. Cancer J 15(3):236–242CrossRefGoogle Scholar
  3. 3.
    Piso P, Arnold D (2011) Multimodal treatment approaches for peritoneal carcinosis in colorectal cancer. Dtsch Arztebl Int 108(47):802–808PubMedPubMedCentralGoogle Scholar
  4. 4.
    Franko J, Ibrahim Z, Gusani NJ, Holtzman MP, Bartlett DL, Zeh HJ III (2010) Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion versus systemic chemotherapy alone for colorectal peritoneal carcinomatosis. Cancer 116(16):3756–3762CrossRefGoogle Scholar
  5. 5.
    Klaver CEL, Musters GD, Bemelman WA, Punt CJA, Verwaal VJ, Dijkgraaf MGW, Aalbers AGJ, van der Bilt JDW, Boerma D, Bremers AJA, Burger JWA, Buskens CJ, Evers P, van Ginkel RJ, van Grevenstein WMU, Hemmer PHJ, de Hingh IHJT, Lammers LA, van Leeuwen BL, Meijerink WJHJ, Nienhuijs SW, Pon J, Radema SA, van Ramshorst B, Snaebjornsson P, Tuynman JB, te Velde EA, Wiezer MJ, de Wilt JHW, Tanis PJ (2015) Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colon cancer at high risk of peritoneal carcinomatosis; the COLOPEC randomized multicentre trial. BMC Cancer 15:428CrossRefGoogle Scholar
  6. 6.
    Franko J, Shi Q, Meyers JP, Maughan TS, Adams RA, Seymour MT, Saltz L, Punt CJA, Koopman M, Tournigand C, Tebbutt NC, Diaz-Rubio E, Souglakos J, Falcone A, Chibaudel B, Heinemann V, Moen J, De Gramont A, Sargent DJ, Grothey A, Analysis and Research in Cancers of the Digestive System (ARCAD) Group (2016) Prognosis of patients with peritoneal metastatic colorectal cancer given systemic therapy: an analysis of individual patient data from prospective randomised trials from the Analysis and Research in Cancers of the Digestive System (ARCAD) database. Lancet Oncol 17(12):1709–1719CrossRefGoogle Scholar
  7. 7.
    Verwaal VJ, Bruin S, Boot H, van Slooten G, van Tinteren H (2008) 8-year follow-up of randomized trial: cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy in patients with peritoneal carcinomatosis of colorectal cancer. Ann Surg Oncol 15(9):2426–2432CrossRefGoogle Scholar
  8. 8.
    Chua TC, Yan TD, Saxena A, Morris DL (2009) Should the treatment of peritoneal carcinomatosis by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy still be regarded as a highly morbid procedure?: a systematic review of morbidity and mortality. Ann Surg 249(6):900–907CrossRefGoogle Scholar
  9. 9.
    Beckert S, Struller F, Horvath P, Falcke A, Königsrainer A, Königsrainer I (2015) Overall morbidity but not mortality is increased in elderly patients following cytoreductive surgery and HIPEC. Langenbeck’s Arch Surg 400(6):693–698CrossRefGoogle Scholar
  10. 10.
    Simkens GA, van Oudheusden TR, Braam HJ, Wiezer MJ, Nienhuijs SW, Rutten HJ, van Ramshorst B, de Hingh IH (2016) Cytoreductive surgery and HIPEC offers similar outcomes in patients with rectal peritoneal metastases compared to colon cancer patients: a matched case control study. J Surg Oncol 113(5):548–553CrossRefGoogle Scholar
  11. 11.
    Razenberg L, van Gestel Y, Creemers G-J et al (2015) Trends in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for the treatment of synchronous peritoneal carcinomatosis of colorectal origin in the Netherlands. Eur J Surg Oncol 41(4):466–471CrossRefGoogle Scholar
  12. 12.
    Hackl C, Neumann P, Gerken M, Loss M, Klinkhammer-Schalke M, Schlitt HJ (2014) Treatment of colorectal liver metastases in Germany: a ten-year population-based analysis of 5772 cases of primary colorectal adenocarcinoma. BMC Cancer 14:810CrossRefGoogle Scholar
  13. 13.
    Word Medical Association Declaration of Helsinki. Ethical Principles for Medical Research Involving Human Subjects. Accessed 25 May 2016
  14. 14.
    Landtag des Freistaates Bayern. Gesetz über das bevölkerungsbezogene Krebsregister Bayern (BayKRG). Accessed 27 May 2016
  15. 15.
    DIMDI: Deutsches Institut für Medizinische Dokumentation und Information. ICD-10-WHO. Updated May 10, 2016. Accessed 26 May 2016
  16. 16.
    Glehen O, Kwiatkowski F, Sugarbaker PH, Elias D, Levine EA, de Simone M, Barone R, Yonemura Y, Cavaliere F, Quenet F, Gutman M, Tentes AAK, Lorimier G, Bernard JL, Bereder JM, Porcheron J, Gomez-Portilla A, Shen P, Deraco M, Rat P (2004) Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study. J Clin Oncol 22(16):3284–3292CrossRefGoogle Scholar
  17. 17.
    Sugarbaker PH (1995) Peritonectomy procedures. Ann Surg 221(1):29–42CrossRefGoogle Scholar
  18. 18.
    Glockzin G, Rochon J, Arnold D, Lang SA, Klebl F, Zeman F, Koller M, Schlitt HJ, Piso P (2013) A prospective multicenter phase II study evaluating multimodality treatment of patients with peritoneal carcinomatosis arising from appendiceal and colorectal cancer: the COMBATAC trial. BMC Cancer 13:67CrossRefGoogle Scholar
  19. 19.
    Segelman J, Granath F, Holm T, Machado M, Mahteme H, Martling A (2012) Incidence, prevalence and risk factors for peritoneal carcinomatosis from colorectal cancer. Br J Surg 99(5):699–705CrossRefGoogle Scholar
  20. 20.
    Pox C, Aretz S, Bischoff SC, Graeven U, Hass M, Heußner P, Hohenberger W, Holstege A, Hübner J, Kolligs F, Kreis M, Lux P, Ockenga J, Porschen R, Post S, Rahner N, Reinacher-Schick A, Riemann JF, Sauer R, Sieg A, Scheppach W, Schmitt W, Schmoll HJ, Schulmann K, Tannapfel A, Schmiegel W, Leitlinienprogramm Onkologie der AWMF, Deutschen Krebsgesellschaft e. V, Deutschen Krebshilfe e. V (2013) S3-guideline colorectal cancer version 1.0. Z Gastroenterol 51(8):753–854CrossRefGoogle Scholar
  21. 21.
    Razenberg, Lieke GEM, Lemmens et al (2016) Challenging the dogma of colorectal peritoneal metastases as an untreatable condition: results of a population-based study. Eur J Cancer 65:113–120CrossRefGoogle Scholar
  22. 22.
    Van Oudheusden TR, Braam HJ, Bienhuijs SW et al (2015) Poor outcome after cytoreductive surgery and HIPEC for colorectal peritoneal carcinomatosis with signet ring cell histology. J Surg Oncol 111:237–242CrossRefGoogle Scholar
  23. 23.
    Jacquet P, Sugarbaker PH (1996) Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. In: Sugarbaker PH (ed) Peritoneal carcinomatosis: principles of management; Cancer treatment and research vol. 82. Springer US, Boston, pp 359–374CrossRefGoogle Scholar
  24. 24.
    Piso P, Leebmann H, Marz L et al (2015) Cytoreductive surgery for malignant peritoneal tumors. Chirurg 86(1):38–46CrossRefGoogle Scholar
  25. 25.
    Ceelen WP, Bracke ME (2009) Peritoneal minimal residual disease in colorectal cancer. Mechanisms, prevention, and treatment. Lancet Oncol 10(1):72–79CrossRefGoogle Scholar
  26. 26.
    Tabrizian P, Jayakrishnan TT, Zacharias A, Aycart S, Johnston FM, Sarpel U, Labow DM, Turaga KK (2015) Incorporation of diagnostic laparoscopy in the management algorithm for patients with peritoneal metastases: a multi-institutional analysis. J Surg Oncol 111:1035–1040CrossRefGoogle Scholar
  27. 27.
    Franko J, Shi Q, Goldman CD, Pockaj BA, Nelson GD, Goldberg RM, Pitot HC, Grothey A, Alberts SR, Sargent DJ (2012) Treatment of colorectal peritoneal carcinomatosis with systemic chemotherapy: a pooled analysis of north central cancer treatment group phase III trials N9741 and N9841. J Clin Oncol 30(3):263–267CrossRefGoogle Scholar
  28. 28.
    Goere D, Malka D, Tzanis D et al (2013) Is there a possibility of a cure in patients with colorectal peritoneal carcinomatosis amenable to complete cytoreductive surgery and intraperitoneal chemotherapy? Ann Surg 257(6):1065–1071CrossRefGoogle Scholar
  29. 29.
    Elias D, Lefevre JH, Chevalier J, Brouquet A, Marchal F, Classe JM, Ferron G, Guilloit JM, Meeus P, Goéré D, Bonastre J (2009) Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J Clin Oncol 27(5):681–685CrossRefGoogle Scholar
  30. 30.
    Quenet F, Elias D, Roca L et al (2018) A UNICANCER phase III trial of hyperthermic intra-peritoneal chemotherapy (HIPEC) for colorectal peritoneal carcinomatosis (PC): PRODIGE 7. J Clin Oncol 36 (suppl; abstr LBA3503)CrossRefGoogle Scholar
  31. 31.
    Elias D, Mariani A, Cloutier A-S, Blot F, Goéré D, Dumont F, Honoré C, Billard V, Dartigues P, Ducreux M (2014) Modified selection criteria for complete cytoreductive surgery plus HIPEC based on peritoneal cancer index and small bowel involvement for peritoneal carcinomatosis of colorectal origin. Eur J Surg Oncol 40(11):1467–1473CrossRefGoogle Scholar
  32. 32.
    Elias D, Honore C, Dumont F et al (2011) Results of systematic second-look surgery plus HIPEC in asymptomatic patients presenting a high risk of developing colorectal peritoneal carcinomatosis. Ann Surg 254(2):289–293CrossRefGoogle Scholar
  33. 33.
    Braam HJ, van Oudheusden TR, de Hingh et al (2014) Patterns of recurrence following complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal carcinomatosis of colorectal cancer. J Surg Oncol 109(8):841–847CrossRefGoogle Scholar
  34. 34.
    Desolneux G, Maziere C, Vara J et al (2015) Cytoreductive surgery of colorectal peritoneal metastases: outcomes after complete cytoreductive surgery and systemic chemotherapy only. PLoS One 10(3):e0122816CrossRefGoogle Scholar
  35. 35.
    Elias D, Faron M, Iuga BS, Honoré C, Dumont F, Bourgain JL, Dartigues P, Ducreux M, Goéré D (2015) Prognostic similarities and differences in optimally resected liver metastases and peritoneal metastases from colorectal cancers. Ann Surg 261(1):157–163CrossRefGoogle Scholar
  36. 36.
    Pelz JOW, Chua TC, Esquivel J, Stojadinovic A, Doerfer J, Morris DL, Maeder U, Germer CT, Kerscher AG (2010) Evaluation of best supportive care and systemic chemotherapy as treatment stratified according to the retrospective peritoneal surface disease severity score (PSDSS) for peritoneal carcinomatosis of colorectal origin. BMC Cancer 10:689CrossRefGoogle Scholar
  37. 37.
    Braam HJ, Boerma D, Wiezer MJ, van Ramshorst B (2015) Cytoreductive surgery and HIPEC in treatment of colorectal peritoneal carcinomatosis: experiment or standard care? A survey among oncologic surgeons and medical oncologists. Int J Clin Oncol 20(5):928–934CrossRefGoogle Scholar
  38. 38.
    Piso P, Arnold D, Glockzin G (2015) Challenges in the multidisciplinary management of stage IV colon and rectal cancer. Expert Rev Gastroenterol Hepatol 9(3):317–326CrossRefGoogle Scholar
  39. 39.
    Goere D, Souadka A, Faron M et al (2015) Extent of colorectal peritoneal carcinomatosis: attempt to define a threshold above which HIPEC does not offer survival benefit: a comparative study. Ann Surg Oncol 22(9):2958–2964CrossRefGoogle Scholar
  40. 40.
    Koppe MJ, Boerman OC, Oyen WJ, Bleichrodt RP (2006) Peritoneal carcinomatosis of colorectal origin: incidence and current treatment strategies. Ann Surg 243(2):212–222CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of General and Visceral SurgeryBarmherzige Brueder Hospital RegensburgRegensburgGermany
  2. 2.Klinik für Allgemein- und ViszeralchirurgieKrankenhaus Barmherzige Brueder RegensburgRegensburgGermany
  3. 3.Tumor Center – University Institute of Quality Assurance and Health Services ResearchRegensburgGermany

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