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Primary Tumor Resection for Stage IV Colorectal Cancer in the Era of Targeted Chemotherapy

  • Original Article
  • Published:
Journal of Gastrointestinal Surgery

Abstract

Background

In the current era of targeted therapies, the benefits of resection of primary tumors in patients with unresectable stage IV colorectal cancer, specifically with regard to overall survival, are unknown.

Methods

Our study population comprised 208 consecutive patients with unresectable stage IV colorectal cancer who received chemotherapy containing at least one molecular target agent, bevacizumab, cetuximab, and panitumumab, at the National Cancer Center Hospital from 2006 to 2013. To lessen the effects of confounding factors between two treatment groups (resection versus non-resection) such as performance status, presence of severe symptoms, M subcategories (M1a versus M1b, M1c) according to the TNM classification, primary tumor site, and CEA value, we conducted three different propensity score analyses (regression adjustment, stratification, and matching).

Results

Of the 208 patients, 108 (52%) underwent resection of the primary tumor, while 100 (48%) did not. Regression adjustment revealed that resection was not associated with longer overall survival (hazard ratio of 0.70 (95% CI [0.49–1.00]; p = 0.051)). Stratification analysis of five strata revealed inconsistent results (hazard ratios ranged from 0.50 to 1.58); specifically, resection was associated with longer overall survival in four strata, but with shorter survival in one stratum. The propensity score-matched cohort (64 matched pairs) yielded a hazard ratio of 0.76 (95% CI [0.51–1.15]; p = 0.197).

Conclusions

All three analyses revealed that, in the current era of chemotherapy with target agents, primary tumor resection was only marginally influential and did not significantly improve overall survival over chemotherapy alone.

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Abbreviations

CEA:

Carcinoembryonic antigen

CI:

Confidence interval

CRC:

Colorectal cancer

HR:

Hazard ratio

OS:

Overall survival

PS:

Performance status

References

  1. Watanabe T, Muro K, Ajioka Y, Hashiguchi Y, Ito Y, Saito 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 2018;23(1):1–34. https://doi.org/10.1007/s10147-017-1101-6.

    Article  PubMed  Google Scholar 

  2. Shida D, Hamaguchi T, Ochiai H, Tsukamoto S, Takashima A, Boku N 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. https://doi.org/10.1245/s10434-016-5299-8.

    Article  PubMed  Google Scholar 

  3. Tarantino I, Warschkow R, Worni M, Cerny T, Ulrich A, Schmied BM 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. https://doi.org/10.1097/SLA.0000000000000860.

    Article  PubMed  Google Scholar 

  4. Ishihara S, Hayama T, Yamada H, Nozawa K, Matsuda K, Miyata H et al. Prognostic impact of primary tumor resection and lymph node dissection in stage IV colorectal cancer with unresectable metastasis: a propensity score analysis in a multicenter retrospective study. Ann Surg Oncol. 2014;21(9):2949–55. https://doi.org/10.1245/s10434-014-3719-1.

    Article  PubMed  Google Scholar 

  5. Gresham G, Renouf DJ, Chan M, Kennecke HF, Lim HJ, Brown C et al. Association between palliative resection of the primary tumor and overall survival in a population-based cohort of metastatic colorectal cancer patients. Ann Surg Oncol. 2014;21(12):3917–23. https://doi.org/10.1245/s10434-014-3797-0.

    Article  PubMed  Google Scholar 

  6. Fakih MG. Metastatic colorectal cancer: current state and future directions. J Clin Oncol. 2015;33(16):1809–24. https://doi.org/10.1200/JCO.2014.59.7633.

    Article  CAS  PubMed  Google Scholar 

  7. D’Agostino RB Jr Propensity scores in cardiovascular research. Circulation. 2007;115(17):2340–3. https://doi.org/10.1161/CIRCULATIONAHA.105.594952.

    Article  PubMed  Google Scholar 

  8. Zhu J, Sharma DB, Gray SW, Chen AB, Weeks JC, Schrag D. Carboplatin and paclitaxel with vs without bevacizumab in older patients with advanced non-small cell lung cancer. JAMA. 2012;307(15):1593–601. https://doi.org/10.1001/jama.2012.454.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. 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. https://doi.org/10.1245/s10434-017-6133-7.

    Article  PubMed  Google Scholar 

  10. UICC. TNM classification of malignant tumors 8th edition. New York: John Wiley & Sons, Ltd; 2017.

    Google Scholar 

  11. Arnold D, Lueza B, Douillard JY, Peeters M, Lenz HJ, Venook A 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. https://doi.org/10.1093/annonc/mdx175.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Tejpar S, Stintzing S, Ciardiello F, Tabernero J, Van Cutsem E, Beier F et al. Prognostic and Predictive Relevance of Primary Tumor Location in Patients With RAS Wild-Type Metastatic Colorectal Cancer: Retrospective Analyses of the CRYSTAL and FIRE-3 Trials. JAMA Oncol. 2016. https://doi.org/10.1001/jamaoncol.2016.3797.

    Article  Google Scholar 

  13. Loupakis F, Yang D, Yau L, Feng S, Cremolini C, Zhang W et al. Primary tumor location as a prognostic factor in metastatic colorectal cancer. J Natl Cancer Inst. 2015;107(3). https://doi.org/10.1093/jnci/dju427.

  14. Shida D, Yoshida T, Tanabe T, Tsukamoto S, Ochiai H, Kanemitsu Y. Prognostic Impact of R0 Resection and Targeted Therapy for Colorectal Cancer with Synchronous Peritoneal Metastasis. Ann Surg Oncol. 2018;25(6):1646–53. https://doi.org/10.1245/s10434-018-6436-3.

    Article  PubMed  Google Scholar 

  15. Franko J, Shi Q, Meyers JP, Maughan TS, Adams RA, Seymour MT 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. https://doi.org/10.1016/S1470-2045(16)30500-9.

    Article  PubMed  Google Scholar 

  16. Ferrand F, Malka D, Bourredjem A, Allonier C, Bouche O, Louafi S et al. Impact of primary tumour resection on survival of patients with colorectal cancer and synchronous metastases treated by chemotherapy: results from the multicenter, randomised trial Federation Francophone de Cancerologie Digestive 9601. Eur J Cancer. 2013;49(1):90–7. https://doi.org/10.1016/j.ejca.2012.07.006.

    Article  CAS  PubMed  Google Scholar 

  17. Hu CY, Bailey CE, You YN, Skibber JM, Rodriguez-Bigas MA, Feig BW et al. Time trend analysis of primary tumor resection for stage IV colorectal cancer: less surgery, improved survival. JAMA Surg. 2015;150(3):245–51. https://doi.org/10.1001/jamasurg.2014.2253.

    Article  PubMed  Google Scholar 

  18. Stillwell AP, Buettner PG, Ho YH. Meta-analysis of survival of patients with stage IV colorectal cancer managed with surgical resection versus chemotherapy alone. World J Surg. 2010;34(4):797–807. https://doi.org/10.1007/s00268-009-0366-y.

    Article  CAS  PubMed  Google Scholar 

  19. Anwar S, Peter MB, Dent J, Scott NA. Palliative excisional surgery for primary colorectal cancer in patients with incurable metastatic disease. Is there a survival benefit? A systematic review. Colorectal Dis. 2012;14(8):920–30. https://doi.org/10.1111/j.1463-1318.2011.02817.x.

    Article  CAS  PubMed  Google Scholar 

  20. Eisenberger A, Whelan RL, Neugut AI. Survival and symptomatic benefit from palliative primary tumor resection in patients with metastatic colorectal cancer: a review. Int J Colorectal Dis. 2008;23(6):559–68. https://doi.org/10.1007/s00384-008-0456-6.

    Article  PubMed  Google Scholar 

  21. Tebbutt NC, Norman AR, Cunningham D, Hill ME, Tait D, Oates J et al. Intestinal complications after chemotherapy for patients with unresected primary colorectal cancer and synchronous metastases. Gut. 2003;52(4):568–73.

    Article  CAS  Google Scholar 

  22. t Lam-Boer J, Mol L, Verhoef C, de Haan AF, Yilmaz M, Punt CJ et al. The CAIRO4 study: the role of surgery of the primary tumour with few or absent symptoms in patients with synchronous unresectable metastases of colorectal cancer--a randomized phase III study of the Dutch Colorectal Cancer Group (DCCG). BMC Cancer. 2014;14:741. https://doi.org/10.1186/1471-2407-14-741.

    Article  Google Scholar 

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Acknowledgements

The authors thank Moriya M., Shimada Y., Akasu T., Fujita S., Yamamoto S., Hamaguchi T., and Ochiai H., who were former staff members of our divisions and nurses who took care of the patients.

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Authors and Affiliations

  1. Colorectal Surgery Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 1040045, Japan

    Dai Shida, Taro Tanabe, Takefumi Yoshida, Shunsuke Tsukamoto & Yukihide Kanemitsu

  2. Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 1040045, Japan

    Narikazu Boku & Atsuo Takashima

Authors
  1. Dai Shida
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  2. Narikazu Boku
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  3. Taro Tanabe
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  4. Takefumi Yoshida
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  5. Shunsuke Tsukamoto
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  6. Atsuo Takashima
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  7. Yukihide Kanemitsu
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Contributions

NB and YK designed the study. NB, TT, TY, ST, and AT collected the data, performed the treatments, and wrote the paper. DS convinced of the study, and participated in its design and coordination. DS was responsible for writing the paper and for its supervision. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Dai Shida.

Ethics declarations

This retrospective study was approved by the Institutional Review Board (IRB) of the National Cancer Center Hospital (IRB code, 2015-320).

Conflict of Interest

The authors declare that they have no conflicts of interest.

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Shida, D., Boku, N., Tanabe, T. et al. Primary Tumor Resection for Stage IV Colorectal Cancer in the Era of Targeted Chemotherapy. J Gastrointest Surg 23, 2144–2150 (2019). https://doi.org/10.1007/s11605-018-4044-y

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  • DOI: https://doi.org/10.1007/s11605-018-4044-y

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