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The Landmark Series: Surgical Treatment of Colorectal Cancer Peritoneal Metastases

Abstract

Background

Peritoneal metastases (PM) are a form of metastatic spread affecting approximately 5-15% of colon cancer patients. The attitude towards management of peritoneal metastases has evolved from therapeutic nihilism towards a more comprehensive and multidisciplinary approach, in large part due to the development of cytoreductive surgery (CRS), usually coupled with heated intraperitoneal chemotherapy (HIPEC), along with the constant improvement of systemic chemotherapy of colorectal cancer. Several landmark studies, including 5 randomized controlled trials have marked the development and refinement of surgical approaches to treating colorectal cancer peritoneal metastases.

Methods

This review article focuses on these landmark studies and their influence in 4 key areas: the evidence supporting surgical resection of peritoneal metastases, the identification and standardization of important prognostic variables influencing patient selection, the role of surgery and intraperitoneal chemotherapy in prevention of colorectal PM and the role of intraperitoneal chemotherapy as an adjuvant to surgical resection.

Results

These landmark studies indicate that surgical resection of colorectal PM should be considered as a therapeutic option in appropriately selected patients and when adequate surgical expertise is available. Standardized prognostic variables including the Peritoneal Cancer Index and the Completeness of Cytoreduction Score should be used for evaluating both indications and outcomes.

Conclusions

Current evidence does not support the use of second look surgery with oxaliplatin HIPEC or prophylactic oxaliplatin HIPEC in patients with high risk colon cancer nor the use of oxaliplatin HIPEC with CRS of colorectal PM.

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References

  1. 1.

    Klaver CEL, Groenen H, Morton DG, et al. Recommendations and consensus on the treatment of peritoneal metastases of colorectal origin: a systematic review of national and international guidelines. Colorectal Dis. 2017;19(3):224–36.

    CAS  PubMed  Google Scholar 

  2. 2.

    Van Cutsem E, Cervantes A, Nordlinger B and Arnold D on behalf of the EG, Group. Metastatic colorectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014; 25.

  3. 3.

    NCCN Clinical Practice Guidelines in Oncology; Colon Cancer; Version 2.2021-Jan 21, 2021. www.nccn.org

  4. 4.

    Li Y, Zhou YF, Liang H, et al. Chinese expert consensus on cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal malignancies. World J Gastroenterol. 2016;22(30):6906–16.

    PubMed  PubMed Central  Google Scholar 

  5. 5.

    GBD 2017 Colorectal Cancer Collaborators. The global, regional, and national burden of colorectal cancer and its attributable risk factors in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol. 2019: 4: 913–33.

  6. 6.

    Sugarbaker PH. Intraperitoneal chemotherapy and cytoreductive surgery for the prevention and treatment of peritoneal carcinomatosis and sarcomatosis. Semin Surg Oncol. 1998;14:254–61.

    CAS  PubMed  Google Scholar 

  7. 7.

    Fujimura T, Yonemura Y, Fujita H, et al. Chemohyperthermic peritoneal perfusion for peritoneal dissemination in various intra-abdominal malignancies. Int Surg. 1999;84:60–6.

    CAS  PubMed  Google Scholar 

  8. 8.

    Sugarbaker PH. Peritonectomy procedures. Ann Surg. 1995;221:29–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Gilly FN, Carry PY, Sayag AC. Regional chemotherapy (with mitomycin C) and intra-operative hyperthermia for digestive cancers with peritoneal carcinomatosis. Hepatogastroenterology. 1994;41(2):124–9.

    CAS  PubMed  Google Scholar 

  10. 10.

    Sugarbaker PH, Schellinx M, Chang D, et al. Peritoneal carcinomatosis from adenocarcinoma of the colon. World J Surg. 1996;20:585–92.

    CAS  PubMed  Google Scholar 

  11. 11.

    Elias D, Blot F, El Otmany A, et al. Curative treatment of peritoneal carcinomatosis arising from colorectal cancer by complete resection and intraperitoneal chemotherapy. Cancer. 2001;92:71–6.

    CAS  PubMed  Google Scholar 

  12. 12.

    Shen P, Levine EA, Hall J, et al. Factors predicting survival after intraperitoneal hyperthermic chemotherapy with mitomycin C after cytoreductive surgery patients with peritoneal carcinomatosis. Arch Surg. 2003;138:26–33.

    CAS  PubMed  Google Scholar 

  13. 13.

    Verwaal V, 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.

    PubMed  Google Scholar 

  14. 14.

    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.

    CAS  PubMed  Google Scholar 

  15. 15.

    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.

    PubMed  Google Scholar 

  16. 16.

    Franko J, Ibrahim Z, Gusani N, et al. Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion versus systemic chemotherapy alone for colorectal peritoneal carcinomatosis. Cancer. 2010;116:3756–62.

    PubMed  Google Scholar 

  17. 17.

    Cashin PH, Mahteme H, Spång N, et al. Cytoreductive surgery and intraperitoneal chemotherapy versus systemic chemotherapy for colorectal peritoneal metastases: A randomised trial. Eur J Cancer. 2016;53:155–62.

    CAS  PubMed  Google Scholar 

  18. 18.

    Franko J, Shi Q, Meyers JP, et al. 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. 2016;17(12):1709–19.

    PubMed  Google Scholar 

  19. 19.

    Sugarbaker PH. Epithelial appendiceal neoplasms. Cancer J. 2009;15:225–35.

    PubMed  Google Scholar 

  20. 20.

    GomezPortilla A, Kusamura S, Baratti D, Deraco M. The intraoperative staging systems in the management of peritoneal surface malignancy. J Surg Oncol. 2008;98:228–31.

    Google Scholar 

  21. 21.

    Jacquet P, Sugarbaker PH. Clinical research methodologies in diagnosis and staging of patients with peritoneal carcinomatosis. Cancer Treat Res. 1996;82:359–74.

    CAS  PubMed  Google Scholar 

  22. 22.

    da Silva RG, Sugarbaker PH. Analysis of prognostic factors in seventy patients having a complete cytoreduction plus perioperative intraperitoneal chemotherapy for carcinomatosis from colorectal cancer. J Am Coll Surg. 2006;203(6):878–86.

    PubMed  Google Scholar 

  23. 23.

    Yan TD, Chu F, Links M, et al. Cytoreductive surgery and perioperative intraperitoneal chemotherapy for colorectal peritoneal carcinomatosis—non-mucinous tumor associated with an improved survival. Eur J Surg Oncol. 2006;32:1119–24.

    CAS  PubMed  Google Scholar 

  24. 24.

    Kecmanovic DM, Pavlov MJ, Ceranic MS, et al. Treatment of peritoneal carcinomatosis from colorectal cancer by cytoreductive surgery and hyperthermic perioperative intraperitoneal chemotherapy. Eur J Surg Oncol. 2005;31:147–52.

    CAS  PubMed  Google Scholar 

  25. 25.

    Goéré D, Souadka A, Faron M, Cloutier AS, Viana B, Honoré C, Dumont F, Elias D. Extent of colorectal peritoneal carcinomatosis: attempt to define a threshold above which HIPEC does not offer survival benefit: a comparative study. Ann Surg Oncol. 2015;22(9):2958–64.

    PubMed  Google Scholar 

  26. 26.

    Bakrin N, Bereder JM, Decullier E, FROGHI (French Oncologic and Gynecologic HIPEC) Group. 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.

    CAS  PubMed  Google Scholar 

  27. 27.

    Chua TC, Moran BJ, Sugarbaker PH. 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.

    PubMed  Google Scholar 

  28. 28.

    Glehen O, Gilly FN, Boutitie F, Bereder JM, Quenet F, Sideris L, et al. Toward curative treatment of peritoneal carcinomatosis from nonovarian origin by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy: a multi-institutional study of 1,290 patients. Cancer. 2010;116(24):5608–18.

    PubMed  Google Scholar 

  29. 29.

    Tentes AAK, Tripsiani G, Markakidis SK. Peritoneal cancer index: a prognostic indicator of survival in advanced ovarian cancer. Eur J Surg Oncol. 2003;29:69–73.

    PubMed  Google Scholar 

  30. 30.

    Yonemura Y, Elnemr A, Endou Y, Hirano M, Mizumoto A, Takao N, et al. Multidisciplinary therapy for treatment of patients with peritoneal carcinomatosis from gastric cancer. World J Gastrointest Oncol. 2010;2(2):85–97.

    PubMed  PubMed Central  Google Scholar 

  31. 31.

    Hallam S, Tyler R, Price M, Beggs A, Youssef H. Meta-analysis of prognostic factors for patients with colorectal peritoneal metastasis undergoing cytoreductive surgery and heated intraperitoneal chemotherapy. BJS Open. 2019;3(5):585–94.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Narasimhan V, Tan S, Kong J, Pham T, Michael M, Ramsay R, et al. Prognostic factors influencing survival in patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for isolated colorectal peritoneal metastases: a systematic review and meta-analysis. Colorectal Dis. 2020;22(11):1482–95.

    CAS  PubMed  Google Scholar 

  33. 33.

    Winer J, Zenati M, Ramalingam L, et al. Impact of aggressive histology and location of primary tumor on the efficacy of surgical therapy for peritoneal carcinomatosis of colorectal origin. Ann Surg Oncol. 2014;21:1456–62.

    PubMed  Google Scholar 

  34. 34.

    Elias D, Gilly F. 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.

    PubMed  Google Scholar 

  35. 35.

    Pelz JO, Stojadinovic A, Nissan A, Hohenberger W, Esquivel J. Evaluation of a peritoneal surface disease severity score in patients with colon cancer with peritoneal carcinomatosis. J Surg Oncol. 2009;99:9–15.

    PubMed  Google Scholar 

  36. 36.

    Van Oudheusden TR, Braam HJ, Nienhuijs SW, et al. Poor outcome after cytoreductive surgery and HIPEC for colorectal peritoneal carcinomatosis with signet ring cell histology. J Surg Oncol. 2015;111(2):237–42.

    PubMed  Google Scholar 

  37. 37.

    Sugarbaker PH, Ryan DP. Cytoreductive surgery plus hyperthermic perioperative chemotherapy to treat peritoneal metastases from colorectal cancer: standard of care or an experimental approach? Lancet Oncol. 2012;13(8):e362–9.

    PubMed  Google Scholar 

  38. 38.

    Honoré C, Goere D, Souadka A, Dumont F, Elias D. Definition of patients presenting a high risk of developing peritoneal carcinomatosis after curative surgery for colorectal cancer: a systematic review. Ann Surg Oncol. 2013;20(1):183–92.

    PubMed  Google Scholar 

  39. 39.

    Segelman J, Akre O, Gustafsson UO, Bottai M, Martling A. Individualized prediction of risk of metachronous peritoneal carcinomatosis from colorectal cancer. Colorectal Dis. 2014;16(5):359–67.

    CAS  PubMed  Google Scholar 

  40. 40.

    Sugarbaker PH. Update on the prevention of local recurrence and peritoneal metastases in patients with colorectal cancer. World J Gastroenterol. 2014;20(28):9286–91.

    PubMed  PubMed Central  Google Scholar 

  41. 41.

    Klaver CE, Wisselink DD, Punt C, et al. Adjuvant hyperthermic intraperitoneal chemotherapy in patients with locally advanced colon cancer (COLOPEC): a multicentre, open-label, randomised trial. Lancet Gastroenterol Hepatol. 2019;4(10):761–70.

    PubMed  Google Scholar 

  42. 42.

    Elias D, Goere D, Di Pietrantonio D, et al. Results of systematic second-look surgery in patients at high risk of developing colorectal peritoneal carcinomatosis. Ann Surg. 2008;247(3):445–50.

    PubMed  Google Scholar 

  43. 43.

    Elias D, Honore C, Dumont F, et al. Results of systematic second-look surgery plus HIPEC in asymptomatic patients presenting a high risk of developing colorectal peritoneal carcinomatosis. Ann Surg. 2011;254(2):289–93.

    CAS  PubMed  Google Scholar 

  44. 44.

    Goéré Diane, Glehen Olivier, Quenet François, et al. Second-look surgery plus hyperthermic intraperitoneal chemotherapy versus surveillance in patients at high risk of developing colorectal peritoneal metastases (PROPHYLOCHIP–PRODIGE 15): a randomised, phase 3 study. Lancet Oncol. 2020;21(9):1147–54.

    PubMed  Google Scholar 

  45. 45.

    Koga S, Hamazoe R, Marta M, et al. Treatment of implanted peritoneal cancer in rats by continuous hyperthermic peritoneal perfusion in combination with an anticancer drug. Cancer Res. 1984;44:1840–6.

    CAS  PubMed  Google Scholar 

  46. 46.

    Van der Speeten K, Stuart OA, Sugarbaker PH. Pharmacology of perioperative intraperi-toneal and intravenous chemotherapy in patients with peritoneal surface malignancy. Surg Oncol Clin N Am. 2012;21(4):577–97.

    PubMed  Google Scholar 

  47. 47.

    Fujimoto S, Shrestha RD, Kokubun M, et al. Intraperitoneal hyperthermic perfusion combined with surgery effective for gastric cancer patients with peritoneal seeding. Ann Surg. 1988;208:36–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Demuytere J, Ceelen W, Van Dorpe J, Hoorens A. The role of the peritoneal microenvironment in the pathogenesis of colorectal peritoneal carcinomatosis. Exp Mol Pathol. 2020;115:104442.

    CAS  PubMed  Google Scholar 

  49. 49.

    Quenet F, Elias D, Roca L, et al. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multi centre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021. https://doi.org/10.1016/S1470-2045(20)30599-4.

    Article  PubMed  Google Scholar 

  50. 50.

    Elias D, Bonnay M, Puizillou JM, Antoun S, Demirdjian S, El OA, et al. Heated intra-operative intraperitoneal oxaliplatin after complete resection of peritoneal carcinomatosis: pharmacokinetics and tissue distribution. Ann Oncol. 2002;13(2):267–72.

    CAS  PubMed  Google Scholar 

  51. 51.

    Abboud K, André T, Brunel M, et al. Management of colorectal peritoneal metastases: expert opinion. J Visc Surg. 2019;156:377–9.

    CAS  PubMed  Google Scholar 

  52. 52.

    Chicago Consensus Working Group. The Chicago consensus on peritoneal surface malignancies: management of colorectal metastases. Ann Surg Oncol. 2020;27(6):1761–7.

    Google Scholar 

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Acknowledgements

The authors thank Dr. Sergio Mompart for creating the drawings used in Fig. 2.

Disclosures

L.B.: consulting fees Merce Electromedicina; D.G. and I.R.: nothing to disclose.

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Correspondence to Lana Bijelic MD.

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Bijelic, L., Ramos, I. & Goeré, D. The Landmark Series: Surgical Treatment of Colorectal Cancer Peritoneal Metastases. Ann Surg Oncol 28, 4140–4150 (2021). https://doi.org/10.1245/s10434-021-10049-3

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