Annals of Surgical Oncology

, Volume 23, Issue 9, pp 2841–2848 | Cite as

Increased Survival of Patients with Synchronous Colorectal Peritoneal Metastases Receiving Preoperative Chemotherapy Before Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

  • R. A. Devilee
  • G. A. Simkens
  • T. R. van Oudheusden
  • H. J. Rutten
  • G. J. Creemers
  • A. J. ten Tije
  • I. H. de Hingh
Colorectal Cancer



Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) can result in long-term survival for selected patients with colorectal peritoneal metastases (PM). Most patients are additionally treated with systemic chemotherapy, but timing (adjuvant vs. preoperative) varies between treatment centers. This study aimed to compare short- and long-term outcomes for patients with synchronous colorectal PM undergoing CRS + HIPEC who received preoperative or adjuvant chemotherapy.


This study enrolled patients with synchronous colorectal PM who underwent macroscopically complete or near complete CRS + HIPEC. Data were collected from a prospective database containing all patients between 2007 and 2014. Perioperative outcome and survival were compared between patients who underwent adjuvant chemotherapy (adjuvant strategy [AS]) and those who had preoperative chemotherapy followed by adjuvant systemic chemotherapy if possible (preoperative strategy [PS]).


The study enrolled 91 patients, 25 (28 %) of whom received preoperative chemotherapy. The peritoneal cancer index (PCI) score was lower and the operation length shorter for the patients receiving preoperative chemotherapy (both p = 0.02). The complication rates were comparable between the two groups. The median survival after diagnosis was 38.6 months in the AS group, whereas median survival was not reached in the PS group (p < 0.01). The 3-year overall survival rates were 50 and 89 %, respectively. After correction for other significant prognostic factors, preoperative chemotherapy was independently associated with improved survival (HR 0.23; 95 % confidence interval, 0.07–0.75; p = 0.01).


Treatment with preoperative chemotherapy was associated with improved long-term survival after CRS + HIPEC compared with adjuvant chemotherapy. Ideally, a randomized controlled trial should be performed to investigate the optimal timing of systemic chemotherapy for colorectal PM patients.


Bevacizumab Systemic Chemotherapy Preoperative Chemotherapy Peritoneal Metastasis Peritoneal Cancer Index 
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.



There are no conflicts of interest.


  1. 1.
    Kerscher AG, Chua TC, Gasser M, et al. Impact of peritoneal carcinomatosis in the disease history of colorectal cancer management: a longitudinal experience of 2406 patients over two decades. Br J Cancer. 2013;108:1432–9.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Chua TC, Morris DL, Saxena A, et al. Influence of modern systemic therapies as adjunct to cytoreduction and perioperative intraperitoneal chemotherapy for patients with colorectal peritoneal carcinomatosis: a multicenter study. Ann Surg Oncol. 2011;18:1560–7.CrossRefPubMedGoogle Scholar
  3. 3.
    Klaver YL, Lemmens VE, Creemers GJ, Rutten HJ, Nienhuijs SW, de Hingh IH. Population-based survival of patients with peritoneal carcinomatosis from colorectal origin in the era of increasing use of palliative chemotherapy. Ann Oncol. 2011;22:2250–6.CrossRefPubMedGoogle Scholar
  4. 4.
    Cao C, Yan TD, Black D, Morris DL. A systematic review and meta-analysis of cytoreductive surgery with perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis of colorectal origin. Ann Surg Oncol. 2009;16:2152–65.CrossRefPubMedGoogle Scholar
  5. 5.
    Verwaal VJ, van Ruth S, de Bree E, et al. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol. 2003;21:3737–43.CrossRefPubMedGoogle Scholar
  6. 6.
    Glehen O, Kwiatkowski F, Sugarbaker PH, et al. Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study. J Clin Oncol. 2004;22:3284–92.CrossRefPubMedGoogle Scholar
  7. 7.
    Franko J, Ibrahim Z, Gusani NJ, Holtzman MP, Bartlett DL, Zeh HJ III. Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion versus systemic chemotherapy alone for colorectal peritoneal carcinomatosis. Cancer. 2010;116:3756–62.CrossRefPubMedGoogle Scholar
  8. 8.
    Elias D, Gilly F, Boutitie F, et al. Peritoneal colorectal carcinomatosis treated with surgery and perioperative intraperitoneal chemotherapy: retrospective analysis of 523 patients from a multicentric French study. J Clin Oncol. 2010;28:63–8.CrossRefPubMedGoogle Scholar
  9. 9.
    Elias D, Lefevre JH, Chevalier J, et al. Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J Clin Oncol. 2009;27:681–5.CrossRefPubMedGoogle Scholar
  10. 10.
    Glockzin G, Rochon J, Arnold D, et al. 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. 2013;13:67.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Maillet M, Glehen O, Lambert J, et al. Early postoperative chemotherapy after complete cytoreduction and hyperthermic intraperitoneal chemotherapy for isolated peritoneal carcinomatosis of colon cancer: a multicenter study. Ann Surg Oncol. 2016;23:863–9.CrossRefPubMedGoogle Scholar
  12. 12.
    Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11–20.CrossRefGoogle Scholar
  13. 13.
    van Hagen P, Hulshof MC, van Lanschot JJ, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366:2074–84.CrossRefPubMedGoogle Scholar
  14. 14.
    Sauer R, Liersch T, Merkel S, et al. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012;30:1926–33.CrossRefPubMedGoogle Scholar
  15. 15.
    Nordlinger B, Vauthey JN, Poston G, Benoist S, Rougier P, Van Cutsem E. The timing of chemotherapy and surgery for the treatment of colorectal liver metastases. Clin Colorect Cancer. 2010;9:212–8.CrossRefGoogle Scholar
  16. 16.
    van Oudheusden TR, Braam HJ, Nienhuijs SW, et al. Cytoreduction and hyperthermic intraperitoneal chemotherapy: a feasible and effective option for colorectal cancer patients after emergency surgery in the presence of peritoneal carcinomatosis. Ann Surg Oncol. 2014;21:2621–6.PubMedGoogle Scholar
  17. 17.
    Jacquet P, Sugarbaker PH. Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. Cancer Treat Res. 1996;82:359–74.CrossRefPubMedGoogle Scholar
  18. 18.
    Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240:205–13.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Yan TD, Sim J, Morris DL. Selection of patients with colorectal peritoneal carcinomatosis for cytoreductive surgery and perioperative intraperitoneal chemotherapy. Ann Surg Oncol. 2007;14:1807–17.CrossRefPubMedGoogle Scholar
  20. 20.
    Bijelic L, Kumar AS, Stuart OA, Sugarbaker PH. Systemic chemotherapy prior to cytoreductive surgery and HIPEC for carcinomatosis from appendix cancer: impact on perioperative outcomes and short-term survival. Gastroenterol Res Pract. 2012;2012:163284.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351:1731–40.CrossRefPubMedGoogle Scholar
  22. 22.
    Chua TC, Yan TD, Saxena A, Morris DL. 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. 2009;249:900–7.CrossRefPubMedGoogle Scholar
  23. 23.
    Scaife CL, Hartz A, Pappas L, et al. Association between postoperative complications and clinical cancer outcomes. Ann Surg Oncol. 2013;20:4063–6.CrossRefPubMedGoogle Scholar
  24. 24.
    Simkens GA, van Oudheusden TR, Luyer MD, et al. Serious postoperative complications affect early recurrence after cytoreductive surgery and HIPEC for colorectal peritoneal carcinomatosis. Ann Surg Oncol. 2015;22:2656–62.CrossRefPubMedGoogle Scholar
  25. 25.
    Kuijpers AM, Mehta AM, Boot H, et al. Perioperative systemic chemotherapy in peritoneal carcinomatosis of lymph node positive colorectal cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Ann Oncol. 2014;25:864–9.CrossRefPubMedGoogle Scholar
  26. 26.
    Passot G, Vaudoyer D, Cotte E, et al. Progression following neoadjuvant systemic chemotherapy may not be a contraindication to a curative approach for colorectal carcinomatosis. Ann Surg. 2012;256:125–9.CrossRefPubMedGoogle Scholar
  27. 27.
    Ceelen W, Van Nieuwenhove Y, Putte DV, Pattyn P. Neoadjuvant chemotherapy with bevacizumab may improve outcome after cytoreduction and hyperthermic intraperitoneal chemoperfusion (HIPEC) for colorectal carcinomatosis. Ann Surg Oncol. 2014;21:3023–8.CrossRefPubMedGoogle Scholar
  28. 28.
    Eveno C, Passot G, Goere D, et al. Bevacizumab doubles the early postoperative complication rate after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis of colorectal origin. Ann Surg Oncol. 2014;21:1792–800.CrossRefPubMedGoogle Scholar
  29. 29.
    Passot G, Bakrin N, Garnier L, et al. Intraperitoneal vascular endothelial growth factor burden in peritoneal surface malignancies treated with curative intent: the first step before intraperitoneal antivascular endothelial growth factor treatment? Eur J Cancer. 2014;50:722–30.CrossRefPubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2016

Authors and Affiliations

  • R. A. Devilee
    • 1
  • G. A. Simkens
    • 1
  • T. R. van Oudheusden
    • 1
  • H. J. Rutten
    • 1
  • G. J. Creemers
    • 2
  • A. J. ten Tije
    • 3
  • I. H. de Hingh
    • 1
  1. 1.Department of Surgical OncologyCatharina HospitalEindhovenThe Netherlands
  2. 2.Department of Medical OncologyCatharina HospitalEindhovenThe Netherlands
  3. 3.Department of Medical OncologyAmphia HospitalBredaThe Netherlands

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