Prognostic Impact of R0 Resection and Targeted Therapy for Colorectal Cancer with Synchronous Peritoneal Metastasis

  • Dai Shida
  • Takefumi Yoshida
  • Taro Tanabe
  • Shunsuke Tsukamoto
  • Hiroki Ochiai
  • Yukihide Kanemitsu
Gastrointestinal Oncology
  • 140 Downloads

Abstract

Background

The National Comprehensive Cancer Network guidelines recommend R0 resection and targeted therapy, a combination of cytotoxic and molecular targeted agents, such as bevacizumab, cetuximab, and panitumumab, for colorectal cancer with synchronous peritoneal metastasis (M1c). While these therapeutic strategies are drawing attention, their efficacy has not been fully examined.

Methods

The study population comprised 248 consecutive M1c patients who were treated at the National Cancer Center Hospital from 1997 to 2013. Multivariate analyses were performed to evaluate relationships between overall survival and R0 resection and targeted therapy using Cox proportional hazards regression models.

Results

The 3-year overall survival (3 yOS) was 19.5%, and median survival time (MST) was 16.2 months in 248 M1c patients. R0 resection was performed in 34 patients (14%), yielding a 3-year overall survival (OS) of 48.3% and median survival time (MST) of 29.9 months. Targeted therapy was performed in 54 patients (22%) at least once during the course of treatment, yielding a 3-yr OS of 38.2% and MST of 23.9 months. After adjusting for other key clinical factors, such as the number of organs involved with metastases, performance status, primary tumor site, and extent of peritoneal metastasis, both R0 resection and targeted therapy were independent factors associated with longer OS. Targeted therapy was associated with a significantly longer OS compared with multiple cytotoxic agent therapy [hazard ratio 0.65; 95% confidence interval (0.44–0.94); p = 0.02].

Conclusions

If achievable, R0 resection is a desirable therapeutic strategy for patients with M1c colorectal cancer. Moreover, targeted therapy might be the optimal chemotherapy in this patient population.

Notes

Disclosure

None to report.

Supplementary material

10434_2018_6436_MOESM1_ESM.docx (15 kb)
Supplementary material 1 (DOCX 16 kb)

References

  1. 1.
    UICC. TNM classification of malignant tumours eighth edition. New York: John Wiley & Sons, Ltd; 2017.Google Scholar
  2. 2.
    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.CrossRefPubMedGoogle Scholar
  3. 3.
    Benson AB, 3rd, Venook AP, Cederquist L, et al. Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2017;15(3):370–98.CrossRefPubMedGoogle Scholar
  4. 4.
    Mulsow J, Merkel S, Agaimy A, Hohenberger W. Outcomes following surgery for colorectal cancer with synchronous peritoneal metastases. Br J Surg. 2011;98(12):1785–91.CrossRefPubMedGoogle Scholar
  5. 5.
    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.CrossRefPubMedGoogle Scholar
  6. 6.
    Shida D, Tsukamoto S, Ochiai H, Kanemitsu Y. Long-term outcomes after R0 resection of synchronous peritoneal metastasis from colorectal cancer without cytoreductive surgery or hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol. 2018;25(1):173–8.CrossRefPubMedGoogle Scholar
  7. 7.
    Fakih MG. Metastatic colorectal cancer: current state and future directions. J Clin Oncol. 2015;33(16):1809–24.CrossRefPubMedGoogle Scholar
  8. 8.
    Razenberg LG, van Gestel YR, Lemmens VE, de Hingh IH, Creemers GJ. Bevacizumab in addition to palliative chemotherapy for patients with peritoneal carcinomatosis of colorectal origin: a nationwide population-based study. Clin Colorectal Cancer. 2016;15(2):e41–6.CrossRefPubMedGoogle Scholar
  9. 9.
    Stillwell AP, Ho YH, Veitch C. Systematic review of prognostic factors related to overall survival in patients with stage IV colorectal cancer and unresectable metastases. World J Surg. 2011;35(3):684–92.CrossRefPubMedGoogle Scholar
  10. 10.
    Arnold D, Lueza B, Douillard JY, et al. Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials. Ann Oncol. 2017;28(8):1713–29.CrossRefPubMedGoogle Scholar
  11. 11.
    Vallicelli C, Cavaliere D, Catena F, et al. Management of peritoneal carcinomatosis from colorectal cancer: review of the literature. Int J Colorectal Dis. 2014;29(8):895–8.CrossRefPubMedGoogle Scholar
  12. 12.
    Japanese Society for Cancer of the Colon and Rectum. Japanese classification of colorectal carcinoma (8th edn). Tokyo: Kanehara & Co., Ltd; 2013.Google Scholar
  13. 13.
    Kobayashi H, Kotake K, Sugihara K, Study Group for Peritoneal Metastasis from Colorectal Cancer by the Japanese Society for Cancer of the C, Rectum. Enhancing the objectivity of the Japanese classification of peritoneal metastases from colorectal cancer. Jpn J Clin Oncol. 2014;44(10):898–902.CrossRefPubMedGoogle Scholar
  14. 14.
    Shida D, Tsukamoto S, Ochiai H, Kanemitsu Y. Long-term outcomes after R0 resection of synchronous peritoneal metastasis from colorectal cancer without cytoreductive surgery or hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol. 2017;25(1):173–178.Google Scholar
  15. 15.
    Watanabe T, Muro K, Ajioka Y, et al. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer. Int J Clin Oncol. 2017;23(1):1–34.Google Scholar
  16. 16.
    Sato H, Maeda K, Kotake K, Sugihara K, Takahashi H. Factors affecting recurrence and prognosis after R0 resection for colorectal cancer with peritoneal metastasis. J Gastroenterol. 2016;51(5):465–72.CrossRefPubMedGoogle Scholar
  17. 17.
    Noura S, Ohue M, Ito Y, et al. New staging system for colorectal cancer patients with synchronous peritoneal metastasis in accordance with the Japanese classification of colorectal carcinoma: a multi-institutional study. Dig Surg. 2016;33(1):66–73.CrossRefPubMedGoogle Scholar
  18. 18.
    Kobayashi H, Kotake K, Sugihara K. Outcomes of surgery without HIPEC for synchronous peritoneal metastasis from colorectal cancer: data from a multi-center registry. Int J Clin Oncol. 2014;19(1):98–105.CrossRefPubMedGoogle Scholar
  19. 19.
    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(1):63–8.CrossRefPubMedGoogle Scholar
  20. 20.
    Ihemelandu C, Sugarbaker PH. Management for peritoneal metastasis of colonic origin: role of cytoreductive surgery and perioperative intraperitoneal chemotherapy: a single institution’s experience during two decades. Ann Surg Oncol. 2017;24(4):898–905.CrossRefPubMedGoogle Scholar
  21. 21.
    Elias D, Glehen O, Pocard M, et al. A comparative study of complete cytoreductive surgery plus intraperitoneal chemotherapy to treat peritoneal dissemination from colon, rectum, small bowel, and nonpseudomyxoma appendix. Ann Surg. 2010;251(5):896–901.CrossRefPubMedGoogle Scholar
  22. 22.
    Shida D, Hamaguchi T, Ochiai H, et al. Prognostic impact of palliative primary tumor resection for unresectable stage 4 colorectal cancer: using a propensity score analysis. Ann Surg Oncol. 2016;23(11):3602–8.CrossRefPubMedGoogle Scholar
  23. 23.
    Tarantino I, Warschkow R, Worni M, et al. Prognostic relevance of palliative primary tumor removal in 37,793 metastatic colorectal cancer patients: a population-based, propensity score-adjusted trend analysis. Ann Surg. 2015;262(1):112–20.CrossRefPubMedGoogle Scholar
  24. 24.
    Allegra CJ, Yothers G, O’Connell MJ, et al. Phase III trial assessing bevacizumab in stages II and III carcinoma of the colon: results of NSABP protocol C-08. J Clin Oncol. 2011;29(1):11–6.CrossRefPubMedGoogle Scholar
  25. 25.
    Alberts SR, Sargent DJ, Nair S, et al. Effect of oxaliplatin, fluorouracil, and leucovorin with or without cetuximab on survival among patients with resected stage III colon cancer: a randomized trial. JAMA. 2012;307(13):1383–93.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Taieb J, Tabernero J, Mini E, et al. Oxaliplatin, fluorouracil, and leucovorin with or without cetuximab in patients with resected stage III colon cancer (PETACC-8): an open-label, randomised phase 3 trial. Lancet Oncol. 2014;15(8):862–73.CrossRefPubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2018

Authors and Affiliations

  • Dai Shida
    • 1
  • Takefumi Yoshida
    • 1
  • Taro Tanabe
    • 1
  • Shunsuke Tsukamoto
    • 1
  • Hiroki Ochiai
    • 1
  • Yukihide Kanemitsu
    • 1
  1. 1.Colorectal Surgery DivisionNational Cancer Center HospitalTokyoJapan

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