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Synchronous liver metastases and peritoneal carcinomatosis from colorectal cancer: different strategies for curative treatment?

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Abstract

Background

Management of patients with resectable hepatic metastases (HMs) and colorectal peritoneal carcinomatosis (CRPC) is not currently standardised.

Objective

The aims of this study were to evaluate the safety of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) and hepatic surgery for patients with CRPC with synchronous hepatic metastases (HM), and its impact on survival rates.

Methods

A retrospective analysis was performed, including patients undergoing CRS/HIPEC for CRPC from 2007 to September 2016 in two groups, with (HM+) and without (HM−) synchronous hepatic metastases. Patients with extra-abdominal metastases were excluded. The hepatic strategy was described. Morbimortality and survival were compared between the two groups.

Results

One hundred nine patients underwent CRS/HIPEC for CRPC with or without hepatic surgery with curative intent: 33 patients with (HM+) and 76 patients without (HM−) synchronous HM. The median follow-up was 30 months. All patients with HM (HM+) received neoadjuvant chemotherapy vs. 88.1% in the HM− group (p = 0.04) associated with monoclonal antibody in 66.6% of cases in the HM+ group vs. 57% in the HM− group (p = 0.01). In the HM+ group, two steps were implemented to treat peritoneal and hepatic metastases in 15 patients (45%). In this group, planned hepatic resection in two procedures was performed for eight patients, all presenting bilobar HM. Postoperative morbidity did not differ between the two groups. No deaths occurred. Median overall survival (OS) and recurrence-free survival (RFS) were 31 and 65 months (p = 0.188), versus 21 and 24 months (p = 0.119), respectively, in the HM+ versus HM− groups. In multivariate analysis, the peritoneal cancer index (PCI) was the only significant prognostic factor whereas synchronous HM was not a significant prognostic factor.

Conclusion

Curative surgical treatment for CRPC with synchronous HM seems to be feasible and safe, and could facilitate long survival rates, compared to patients without HM. The hepatic strategy is not standardised. However, a “two-step” surgical strategy could be proposed in order to reduce postoperative morbidity rates.

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References

  1. Koppe MJ, Boerman OC, Oyen WJ, Bleichrodt RP (2006) Peritoneal carcinomatosis of colorectal origin: incidence and current treatment strategies. Ann Surg 243:212–222

    Article  PubMed  PubMed Central  Google Scholar 

  2. Klaver YL, Lemmens VE, Nienhuijs SW, Luyer MD, de Hingh IH (2012) Peritoneal carcinomatosis of colorectal origin: incidence, prognosis and treatment options. World J Gastroenterol 18:5489–5494

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. 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 muticenter trial. BMC Cancer 15:428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Glehen O, Osinsky D, Beaujard AC, Gilly FN (2003) Natural history of peritoneal carcinomatosis from non gynecological malignancies. Surg Oncol Clin N Am 12:729–739

    Article  PubMed  Google Scholar 

  5. März L, Piso P (2015) Treatment of peritoneal metastases from colorectal cancer. Gastroenterology 3:298–302

    Google Scholar 

  6. 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 30:263–267

    Article  Google Scholar 

  7. Fong Y, Fortner J, Sun RL, Brennan MF, Blumgart LH (1999) Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer. Analysis of 1001 consecutive cases. Ann Surg 130:309–321

    Article  Google Scholar 

  8. Köhne CH, Cunningham D, Di Costanzo F, Glimelius B, Blijham G, Aranda E, Scheithauer W, Rougier P, Palmer M, Wils J, Baron B, Pignatti F, Schöffski P, Micheel S, Hecker H (2002) Clinical determinants of survival in patients with 5-fluorouracil-based treatment for metastatic colorectal cancer: results of a multivariate analysis of 3825 patients. Ann Oncol 13:308–317

    Article  PubMed  Google Scholar 

  9. 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 17:1709–1719

    Article  Google Scholar 

  10. Verwaal VJ, van Ruth S, de Bree E, van Sloothen GW, van Tinteren H, Boot H, Zoetmulder FA (2003) 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 21:3737–3743

    Article  Google Scholar 

  11. 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 27:681–685

    Article  PubMed  Google Scholar 

  12. Elias D, Gilly F, Boutitie F, Quenet F, Bereder JM, Mansvelt B, Lorimier G, Dubè P, Glehen O (2010) Peritoneal colorectal carcinomatosis treated with surgery and perioperative intraperitoneal chemotherapy: retrospective analysis of 523 patients from a multicentric French study. J Clin Oncol 28:63–68

    Article  Google Scholar 

  13. Sugarbaker PH, Ryan DP (2012) Cytoreductive surgery plus hyperthermic perioperative chemotherapy to treat peritoneal metastases from colorectal cancer: standard of care or an experimental approach ? Lancet Oncol 13:362–369

    Article  Google Scholar 

  14. Chua TC, Yan TD, Zhao J, Morris DL (2009) Peritoneal carcinomatosis and liver metastases from colorectal cancer treated with cytoreductive surgery perioperative intraperitoneal chemotherapy and liver resection. Eur J Surg Oncol 35:1299–1305

    Article  CAS  PubMed  Google Scholar 

  15. Quenet F, Goéré D, Mehta SS, Roca L, Dumont F, Hessissen M, Saint-Aubert B, Elias D (2011) Results of two bi-institutional prospective studies using intraperitoneal oxaliplatin with or without irinotecan during HIPEC after cytoreductive surgery for colorectal carcinomatosis. Ann Surg 254:294–301

    Article  Google Scholar 

  16. Desantis M, Bernard JL, Casanova V, Cegarra-Escolano M, Benizri E, Rahili AM, Benchimol D, Bereder JM (2015) Morbidity, mortality, and oncological outcomes of 401 consecutive cytoreductive procedures with hyperthermic intraperitoneal chemotherapy (HIPEC). Langenbeck's Arch Surg 400:37–488

    Article  Google Scholar 

  17. Carmignani CP, Ortega-Perez G, Sugarbaker PH (2004) The management of synchronous peritoneal carcinomatosis and hematogenous metastasis from colorectal cancer. Eur J Surg Oncol 30:391–398

    Article  CAS  PubMed  Google Scholar 

  18. Thomassen I, van Gestel YR, Lemmens VE, de Hingh IH (2013) Incidence, prognosis, and treatment options for patients with synchronous peritoneal carcinomatosis and liver metastases from colorectal origins. Dis Colon Rectum 56:1373–1380

    Article  PubMed  Google Scholar 

  19. Hughes KS, Simon R, Songhorabodi S, Adson MA, Ilstrup DM, Fortner JG, Maclean BJ, Foster JH, Daly JM, Fitzherbert D et al (1986) Resection of the liver for colorectal carcinoma metastases: a multi-institutional study of indications for resection. Surgery 103:278–288

    Google Scholar 

  20. Elias D, Quenet F, Goéré D (2012) Current status and future directions in the treatment of peritoneal dissemination from colorectal carcinoma. Surg Oncol Clin N Am 27:611–623

    Article  Google Scholar 

  21. Esquivel J, Sticca R, Sugarbaker P, Levine E, Yan TD, Alexander R, Baratti D, Bartlett D, Barone R, Barrios P, Bieligk S, Bretcha-Boix P, Chang CK, Chu F, Chu Q, Daniel S, de Bree E, Deraco M, Dominguez-Parra L, Elias D, Flynn R, Foster J, Garofalo A, Gilly FN, Glehen O, Gomez-Portilla A, Gonzalez-Bayon L, Gonzalez-Moreno S, Goodman M, Gushchin V, Hanna N, Hartmann J, Harrison L, Hoefer R, Kane J, Kecmanovic D, Kelley S, Kuhn J, LaMont J, Lange J, Li B, Loggie B, Mahteme H, Mann G, Martin R, Misih RA, Moran B, Morris D, Onate-Ocana L, Petrelli N, Philippe G, Pingpank J, Pitroff A, Piso P, Quinones M, Riley L, Rutstein L, Saha S, Alrawi S, Sardi A, Schneebaum S, Shen P, Shibata D, Spellman J, Stojadinovic A, Stewart J, Torres-Melero J, Tuttle T, Verwaal V, Villar J, Wilkinson N, Younan R, Zeh H, Zoetmulder F, Sebbag G (2007) Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin: a consensus statement. Society of Surgical Oncology. Ann Surg Oncol 14:128–133

    Article  CAS  Google Scholar 

  22. Elias D, Benizri E, Pocard M, Ducreux M, Boige V, Lasser P (2006) Treatment of synchronous peritoneal carcinomatosis and liver metastases from colorectal cancer. Eur J Surg Oncol 32:632–636

    Article  CAS  PubMed  Google Scholar 

  23. Kianmanesh R, Scaringi S, Sabate JM, Castel B, Pons-Kerjean N, Coffin B, Hay JM, Flamant Y, Msika S (2007) Iterative cytoreductive surgery associated with hyperthermic intraperitoneal chemotherapy for treatment of peritoneal carcinomatosis of colorectal origin with or without liver metastases. Ann Surg 245:597–603

    Article  PubMed  PubMed Central  Google Scholar 

  24. Varban O, Levine EA, Stewart JH, McCoy TP, Shen P (2009) Outcomes associated with cytoreductive surgery and intraperitoneal hyperthermic chemotherapy in colorectal cancer patients with peritoneal surface disease and hepatic metastases. Cancer 115:3427–3436

    Article  PubMed  Google Scholar 

  25. Duraj FF, Cashin PH (2013) Cytoreductive surgery and intraperitoneal chemotherapy for colorectal peritoneal and hepatic metastases: a case-control study. J Gastrointest Oncol 4:388–339

    PubMed  PubMed Central  Google Scholar 

  26. Lo Dico R, Passot G, Elias D, et al (2013) Multimodality treatment combining chemotherapy, liver surgery, peritoneal resection and hyperthermic intraperitoneal chemotherapy for metastatic colorectal cancer patients with synchronous liver metastases and peritoneal carcinomatosis: a multicenter study of the French Association of Surgery. J Clin Oncol 31 (suppl; abst 14534)

  27. Maggiori L, Goéré D, Viana B, Tzanis D, Dumont F, Honoré C, Eveno C, Elias D (2013) Should patients with peritoneal carcinomatosis of colorectal origin with synchronous liver metastases be treated with a curative intent? A case-control study. Ann Surg 258:116–121

    Article  PubMed  Google Scholar 

  28. De Cuba EM, Kwakman R, Knol DL et al (2013) Cytoreductive surgery and HIPEC for peritoneal metastases combined with curative treatment of colorectal liver metastases: systematic review of all literature and metaanalysis of observational studies. Cancer Treat Rev 39:321–327

    Article  PubMed  Google Scholar 

  29. Lorimier G, Linot B, Paillocher N, Dupoiron D, Verriele V, Wernert R, Hamy A, Capitain O (2007) Curative cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy in patients with peritoneal carcinomatosis and synchronous resectable liver metastases arising from colorectal cancer. EJSO 43:150–158

    Article  Google Scholar 

  30. Morales Soriano R, Morón Canis JM, Molina Romero X, Pérez Celada J, Tejada Gavela S, Segura Sampedro JJ, Jiménez Morillas P, Díaz Jover P, García Pérez JM, Sena Ruiz F, González Argente X (2017) Influence of simultaneous liver and peritoneal resection on postoperative morbi-mortality and survival in patients with colon cancer treated with surgical cytoreduction and intraperitoneal hyperthermic chemotherapy. Cir Esp 95:214–221

    Article  PubMed  Google Scholar 

  31. Jacquet P, Sugarbaker PH (1996) Current methodologies for clinical assessment of patients with peritoneal carcinomatosis. J Exp Clin Cancer Res 15:49–58

    Google Scholar 

  32. Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240:205–213

    Article  PubMed  PubMed Central  Google Scholar 

  33. Charrier T, Passot G, Peron J, Maurice C, Gocevska S, Quenet F, Eveno C, Pocard M, Goere D, Elias D, Ortega-Deballon P, Vaudoyer D, Cotte E, Glehen O (2016) Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy with oxaliplatin increases the risk of postoperative hemorrhagic complications: analysis of predictive factors. Ann Surg Oncol 23:2315–2322

    Article  PubMed  Google Scholar 

  34. Ceelen W (2018) HIPEC with oxaliplatin for colorectal peritoneal metastasis: the end of the road? Eur J Surg Oncol

  35. Luo LX, Yu ZY, Huang JW, Wu H (2014) Selecting patients for a second hepatectomy for colorectal metastases: an systemic review and meta-analysis. Eur J Surg Oncol 40:1036–1034

    Article  CAS  PubMed  Google Scholar 

  36. Schnitzbauer AA, Lang SA, Goessmann H, Nadalin S, Baumgart J, Farkas SA, Fichtner-Feigl S, Lorf T, Goralcyk A, Hörbelt R, Kroemer A, Loss M, Rümmele P, Scherer MN, Padberg W, Königsrainer A, Lang H, Obed A, Schlitt HJ (2012) Right portal vein ligation combined with in situ splitting induces rapid left lateral liver lobe hypertrophy enabling 2-staged extended right hepatic resection in small-for-size settings. Ann Surg 255:405–414

    Article  Google Scholar 

  37. Abreu de Carvalho LF, Scuderi V, Maes H, Cupo P, Geerts B, Van Bockstal M, Gremonprez F, Willaert W, Pattyn P, Troisi R, Ceelen W (2015) Simultaneous parenchyma-preserving liver resection, cytoreductive surgery and intraperitoneal chemotherapy for stage IV colorectal cancer. Acta Chir Belg 115:261–267

    Article  CAS  PubMed  Google Scholar 

  38. Berger Y, Aycart S, Tabrizian P, Agmon Y, Mandeli J, Heskel M, Hiotis S, Sarpel U, Labow DM (2016) Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with liver involvement. J Surg Oncol 113:432–437

    Article  PubMed  Google Scholar 

  39. Delhorme JB, Dupont-Kazma L, Addeo P, Lefebvre F, Triki E, Romain B, Meyer N, Bachellier P, Rohr S, Brigand C (2016) Peritoneal carcinomatosis with synchronous liver metastases from colorectal cancer: who will benefit from complete cytoreductive surgery? Int J Surg 25:98–105

    Article  PubMed  Google Scholar 

  40. Navez J, Remue C, Leonard D, Bachmann R, Kartheuser A, Hubert C, Coubeau L, Komuta M, Van den Eynde M, Zech F, Jabbour N (2016) Surgical treatment of colorectal cancer with peritoneal and liver metastases using combined liver and cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: report from a single-centre experience. Ann Surg Oncol 23:S666–S673

    Article  Google Scholar 

  41. Elias D, Faron M, Goéré D, Dumont F, Honoré C, Boige V, Malka D, Ducreux M (2014) A simple tumor load-based nomogram for surgery in patients with colorectal liver and peritoneal metastases. Ann Surg Oncol 21:2052–2058

    Article  PubMed  Google Scholar 

  42. Elias D, Liberale G, Vernerey D, Pocard M, Ducreux M, Boige V, Malka D, Pignon JP, Lasser P (2005) Hepatic and extrahepatic colorectal metastases: when resectable, their localization does not matter, but their total number has a prognostic effect. Ann Surg Oncol 12:900–909

    Article  PubMed  Google Scholar 

  43. Rovers KP, Simkens GA, Punt CJ, van Dieren S, Tanis PJ, de Hingh IH (2017) Perioperative systemic therapy for resectable colorectal peritoneal metastases: sufficient evidence for its widespread use? A critical systematic review. Crit Rev Oncol Hematol 114:53–62

    Article  PubMed  Google Scholar 

  44. Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, Bechstein WO, Primrose JN, Walpole ET, Finch-Jones M, Jaeck D, Mirza D, Parks RW, Mauer M, Tanis E, Van Cutsem E, Scheithauer W, Gruenberger T, EORTC Gastro-Intestinal Tract Cancer Group; Cancer Research UK; Arbeitsgruppe Lebermetastasen und–tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO); Australasian Gastro-Intestinal Trials Group (AGITG); Fédération Francophone de Cancérologie Digestive (FFCD) (2013) Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. Lancet Oncol 14(12):1208–1215

    Article  CAS  PubMed  Google Scholar 

  45. Heinemann V, von Weikersthal LF, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran SE, Heintges T, Lerchenmüller C, Kahl C, Seipelt G, Kullmann F, Stauch M, Scheithauer W, Hielscher J, Scholz M, Müller S, Link H, Niederle N, Rost A, Höffkes HG, Moehler M, Lindig RU, Modest DP, Rossius L, Kirchner T, Jung A, Stintzing S (2014) FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol 15(10):1065–1075

    Article  CAS  Google Scholar 

  46. Wang JX, Wu HL, Zhu M, Zhou R (2018) Role of anti-epidermal growth factor receptor therapy compared with anti-vascular endothelial growth factor therapy for metastatic colorectal cancer: an update meta-analysis of randomized clinical trials. Pathol Oncol Res. https://doi.org/10.1007/s12253-017-0365-5

  47. Matsuhashi N, Takahashi T, Matsui S, Tanahashi T, Imai H, Tanaka Y, Yamaguchi K, Yoshida K (2018) A novel therapeutic strategy of personalized medicine based on anti-epidermal growth factor receptor monoclonal antibodies in patients with metastatic colorectal cancer. Int J Oncol 52:1391–1400

    CAS  PubMed Central  Google Scholar 

  48. Gallois C, Pernot S, Zaanan A, Taieb J (2018) Colorectal cancer: why does side matter? Drugs 78(8):789–798

    Article  CAS  PubMed  Google Scholar 

  49. da Silva RG, Sugarbaker PH (2006) Analysis of prognostic factors in seventy patients having a complete cytoreduction plus perioperative intraperitoneal chemotherapy for carcinomatosis from colorectal cancer. J Am Coll Surg 203:878–886

    Article  Google Scholar 

  50. Faron M, Macovei R, Goéré D, Honoré C, Benhaim L, Elias D (2016) Linear relationship of peritoneal cancer index and survival in patients with peritoneal metastases from colorectal cancer. Ann Surg Oncol 23:114–119

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of General and Digestive Surgery, Purpan Hospital, CHU de Toulouse (University Hospital Centre), Paul Sabatier Toulouse III University, Place du Dr Baylac, 31059, Toulouse, France

    Amandine Pinto, Antoine Philis, Sylvain Kirzin, Nicolas Carrère & Laurent Ghouti

  2. Unité Inserm, Paris 7, CAP Paris Tech U1275, hôpital Lariboisière, Paris Diderot University, Sorbonne Paris Cité, 2, rue Ambroise-Paré, 75010, Paris, France

    Amandine Pinto & Christian Hobeika

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  1. Amandine Pinto
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  2. Christian Hobeika
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  3. Antoine Philis
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  4. Sylvain Kirzin
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Correspondence to Laurent Ghouti.

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Pinto, A., Hobeika, C., Philis, A. et al. Synchronous liver metastases and peritoneal carcinomatosis from colorectal cancer: different strategies for curative treatment?. Langenbecks Arch Surg 404, 477–488 (2019). https://doi.org/10.1007/s00423-019-01787-w

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