Annals of Surgical Oncology

, Volume 23, Issue 3, pp 928–935 | Cite as

Benefit of Adjuvant Chemotherapy After Curative Resection of Lung Metastasis in Colorectal Cancer

  • Hyung Soon Park
  • Minkyu JungEmail author
  • Sang Joon Shin
  • Su Jin Heo
  • Chang Gon Kim
  • Min Goo Lee
  • Seung Hoon Beom
  • Chang Young Lee
  • Jin Gu Lee
  • Dae Joon Kim
  • Joong Bae Ahn
Thoracic Oncology



The survival benefit of adjuvant chemotherapy after colorectal cancer (CRC) lung metastasectomy is uncertain.


We enrolled 221 CRC patients who underwent pulmonary metastasectomy between October 2002 and July 2013, including those with previous liver metastasis that had been curatively resected. Disease-free survival (DFS) and overall survival (OS) were calculated from the day of lung metastasectomy.


Among all patients, 176 (79.6 %) received adjuvant chemotherapy after lung metastasectomy. Median follow-up was 34.7 months from the time of lung metastasectomy [95 % confidence interval (95 % CI), 7.4–90.9 months]. Patients treated with adjuvant chemotherapy had longer DFS compared with surgery alone (median 32.7 vs 11.2 months respectively, P = 0.076). Multivariate analysis revealed previous liver metastasis, preoperative carcinoembryonic antigen ≥5 ng/mL, disease-free interval <24 months, and surgery without adjuvant chemotherapy as independent risk factors for recurrence. Low-risk patients who had 0–1 risk factors received a significant survival benefit from adjuvant chemotherapy [hazard ratio (HR) 0.54; 95 % CI 0.32–0.91, P = 0.020]; however, high-risk patients with ≥2 risk factors did not (HR 1.02; 95 % CI 0.48–2.14, P = 0.964). Patients treated with adjuvant chemotherapy showed no OS benefit compared with patients who received surgery alone (median 89.6 vs 86.8 months respectively, P = 0.833).


CRC patients received lung metastasectomy could have a DFS benefit from adjuvant chemotherapy, especially in low-risk patients. Larger, prospective studies are needed to evaluate the role of adjuvant chemotherapy after CRC lung metastasectomy.


Overall Survival Liver Metastasis Adjuvant Chemotherapy Lung Metastasis National Comprehensive Cancer Network 
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.



We thank Han Na Park (Yonsei Cancer Center, Yonsei University College of Medicine) for her help with data collection.

Conflict of Interest

The authors declare no conflicts of interest.


  1. 1.
    Villeneuve PJ, Sundaresan RS. Surgical management of colorectal lung metastasis. Clin Colon Rectal Surg. 2009;22:233–41.PubMedCentralCrossRefPubMedGoogle Scholar
  2. 2.
    Van Cutsem E, Nordlinger B, Cervantes A. Advanced colorectal cancer: ESMO clinical practice guidelines for treatment. Ann Oncol. 2010;21 Suppl 5:v93–7.CrossRefPubMedGoogle Scholar
  3. 3.
    Nordlinger B, Sorbye H, Glimelius B, et al. Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet. 2008;371:1007–16.PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    August DA, Ottow RT, Sugarbaker PH. Clinical perspective of human colorectal cancer metastasis. Cancer Metastasis Rev. 1984;3:303–24.CrossRefPubMedGoogle Scholar
  5. 5.
    Johnston FM, Kneuertz PJ, Pawlik TM. Resection of non-hepatic colorectal cancer metastasis. J Gastrointest Oncol. 2012;3:59–68.PubMedCentralPubMedGoogle Scholar
  6. 6.
    McCormack PM, Burt ME, Bains MS, Martini N, Rusch VW, Ginsberg RJ. Lung resection for colorectal metastases. 10-year results. Arch Surg. 1992;127:1403–6.CrossRefPubMedGoogle Scholar
  7. 7.
    Treasure T. Pulmonary metastasectomy for colorectal cancer: weak evidence and no randomised trials. Eur J Cardiothorac Surg. 2008;33:300–2.CrossRefPubMedGoogle Scholar
  8. 8.
    Landes U, Robert J, Perneger T, Mentha G, Ott V, Morel P, Gervaz P. Predicting survival after pulmonary metastasectomy for colorectal cancer: previous liver metastases matter. BMC Surg. 2010;10:17.PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    Salah S, Watanabe K, Welter S, et al. Colorectal cancer pulmonary oligometastases: pooled analysis and construction of a clinical lung metastasectomy prognostic model. Ann Oncol. 2012;23:2649–55.CrossRefPubMedGoogle Scholar
  10. 10.
    Rama N, Monteiro A, Bernardo JE, Eugenio L, Antunes MJ. Lung metastases from colorectal cancer: surgical resection and prognostic factors. Eur J Cardiothorac Surg. 2009;35:444–9.CrossRefPubMedGoogle Scholar
  11. 11.
    Takakura Y, Miyata Y, Okajima M, Okada M, Ohdan H. Short disease-free interval is a significant risk factor for intrapulmonary recurrence after resection of pulmonary metastases in colorectal cancer. Colorectal Dis. 2010;12:e68–75.PubMedGoogle Scholar
  12. 12.
    Lin BR, Chang TC, Lee YC, Lee PH, Chang KJ, Liang JT. Pulmonary resection for colorectal cancer metastases: duration between cancer onset and lung metastasis as an important prognostic factor. Ann Surg Oncol. 2009;16:1026–32.CrossRefPubMedGoogle Scholar
  13. 13.
    Watanabe K, Nagai K, Kobayashi A, Sugito M, Saito N. Factors influencing survival after complete resection of pulmonary metastases from colorectal cancer. Br J Surg. 2009;96:1058–65.CrossRefPubMedGoogle Scholar
  14. 14.
    Borasio P, Gisabella M, Bille A, Righi L, Longo M, Tampellini M, Ardissone F. Role of surgical resection in colorectal lung metastases: analysis of 137 patients. Int J Colorectal Dis. 2011;26:183–90.CrossRefPubMedGoogle Scholar
  15. 15.
    Kim HK, Cho JH, Lee HY, Lee J, Kim J. Pulmonary metastasectomy for colorectal cancer: how many nodules, how many times? World J Gastroenterol. 2014;20:6133–45.PubMedCentralCrossRefPubMedGoogle Scholar
  16. 16.
    Lee WS, Yun SH, Chun HK, et al. Pulmonary resection for metastases from colorectal cancer: prognostic factors and survival. Int J Colorectal Dis. 2007;22:699–704.CrossRefPubMedGoogle Scholar
  17. 17.
    Onaitis MW, Petersen RP, Haney JC, et al. Prognostic factors for recurrence after pulmonary resection of colorectal cancer metastases. Ann Thorac Surg. 2009;87:1684–8.CrossRefPubMedGoogle Scholar
  18. 18.
    Saito Y, Omiya H, Kohno K, et al. Pulmonary metastasectomy for 165 patients with colorectal carcinoma: A prognostic assessment. J Thorac Cardiovasc Surg. 2002;124:1007–13.CrossRefPubMedGoogle Scholar
  19. 19.
    Hawkes EA, Ladas G, Cunningham D, et al. Peri-operative chemotherapy in the management of resectable colorectal cancer pulmonary metastases. BMC Cancer. 2012;12:326.PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Kemeny MM, Adak S, Gray B, et al. Combined-modality treatment for resectable metastatic colorectal carcinoma to the liver: surgical resection of hepatic metastases in combination with continuous infusion of chemotherapy–an intergroup study. J Clin Oncol. 2002;20:1499–505.CrossRefPubMedGoogle Scholar
  21. 21.
    Portier G, Elias D, Bouche O, et al. Multicenter randomized trial of adjuvant fluorouracil and folinic acid compared with surgery alone after resection of colorectal liver metastases: FFCD ACHBTH AURC 9002 trial. J Clin Oncol. 2006;24:4976–82.CrossRefPubMedGoogle Scholar
  22. 22.
    Kaira K, Okumura T, Ohde Y, et al. Prognostic significance of thymidylate synthase expression in the adjuvant chemotherapy after resection for pulmonary metastases from colorectal cancer. Anticancer Res. 2011;31:2763–71.PubMedGoogle Scholar
  23. 23.
    de Jong MC, Pulitano C, Ribero D, et al. Rates and patterns of recurrence following curative intent surgery for colorectal liver metastasis: an international multi-institutional analysis of 1669 patients. Ann Surg. 2009;250:440–8.PubMedGoogle Scholar
  24. 24.
    Zabaleta J, Aguinagalde B, Fuentes MG, et al. Survival after lung metastasectomy for colorectal cancer: importance of previous liver metastasis as a prognostic factor. Eur J Surg Oncol. 2011;37:786–90.CrossRefPubMedGoogle Scholar
  25. 25.
    Welter S, Jacobs J, Krbek T, Poettgen C, Stamatis G. Prognostic impact of lymph node involvement in pulmonary metastases from colorectal cancer. Eur J Cardiothorac Surg. 2007;31:167–72.CrossRefPubMedGoogle Scholar
  26. 26.
    Youden WJ. Index for rating diagnostic tests. Cancer. 1950;3:32–5.CrossRefPubMedGoogle Scholar
  27. 27.
    Pfannschmidt J, Dienemann H, Hoffmann H. Surgical resection of pulmonary metastases from colorectal cancer: a systematic review of published series. Ann Thorac Surg. 2007;84:324–38.CrossRefPubMedGoogle Scholar
  28. 28.
    Yoon HH, Tougeron D, Shi Q, et al. KRAS codon 12 and 13 mutations in relation to disease-free survival in BRAF-wild-type stage III colon cancers from an adjuvant chemotherapy trial (N0147 alliance). Clin Cancer Res. 2014;20:3033–43.PubMedCentralCrossRefPubMedGoogle Scholar
  29. 29.
    Tie J, Lipton L, Desai J, et al. KRAS mutation is associated with lung metastasis in patients with curatively resected colorectal cancer. Clin Cancer Res. 2011;17:1122–30.CrossRefPubMedGoogle Scholar
  30. 30.
    Blons H, Emile JF, Le Malicot K, et al. Prognostic value of KRAS mutations in stage III colon cancer: post hoc analysis of the PETACC8 phase III trial dataset. Ann Oncol. 2014;25:2378–85.CrossRefPubMedGoogle Scholar
  31. 31.
    Pereira AA, Rego JF, Morris V, et al. Association between KRAS mutation and lung metastasis in advanced colorectal cancer. Br J Cancer. 2015;112:424–8.PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2015

Authors and Affiliations

  • Hyung Soon Park
    • 1
  • Minkyu Jung
    • 2
    Email author
  • Sang Joon Shin
    • 2
  • Su Jin Heo
    • 2
  • Chang Gon Kim
    • 2
  • Min Goo Lee
    • 1
  • Seung Hoon Beom
    • 2
  • Chang Young Lee
    • 3
  • Jin Gu Lee
    • 3
  • Dae Joon Kim
    • 3
  • Joong Bae Ahn
    • 2
  1. 1.Department of Pharmacology and Brain Korea 21 Plus Project for Medical SciencesYonsei University College of MedicineSeoulSouth Korea
  2. 2.Division of Medical Oncology, Department of Internal MedicineYonsei University College of MedicineSeoulSouth Korea
  3. 3.Department of Thoracic and Cardiovascular SurgeryYonsei University College of MedicineSeoulSouth Korea

Personalised recommendations