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The Role of Surgery in Management of Locally Advanced Non-Small Cell Lung Cancer

  • Darren S. Bryan
  • Jessica S. DoningtonEmail author
Lung Cancer (HA Wakelee, Section Editor)
  • 50 Downloads
Part of the following topical collections:
  1. Topical Collection on Lung Cancer

Opinion statement

Patients with locally advanced non-small cell lung cancer (NSCLC) are treated for cure, but treatment decisions are not straightforward. Chemotherapy is essential due to the high risk of systemic relapse, but local therapy is also required for cure. In the small subset of stage III patients with N0 or N1 disease, surgery is typically the initial therapy and extended resections are frequent. The majority of IIIA patients present with N2 disease and treatment paradigms for these patients are controversial, particularly concerning the role of resection. Surgery has a limited role in bulky IIIA, IIIB, and IIIC disease, which is typically treated with combined systemic therapy and radiation. The authors believe that in resectable IIIA disease, the addition of surgery to multimodality treatment appears to improve local control and overall survival. Induction therapy is essential, and the use of chemotherapy alone or chemoradiotherapy remains an area of debate. Pneumonectomy should be used with caution in IIIA disease, as numerous prospective trials have noted excessive perioperative mortality. The introduction of immunotherapies in this stage may quickly transform treatment decisions.

Keywords

Non-small cell lung cancer Surgery Stage III Induction therapy Multimodality therapy 

Notes

Compliance with Ethical Standards

Conflict of Interest

Darren S. Bryan declares that he has no conflict of interest.

Jessica S. Donington has received honoraria and reimbursement for travel expenses from AstraZeneca.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7–30.CrossRefGoogle Scholar
  2. 2.
    Howlader N, Noone A, Krapcho M, Miller D, Bishop K, Altekruse S, et al. SEER Cancer statistics review, 1975–2013. Bethesda, MD: National Cancer Institute; 2016.Google Scholar
  3. 3.
    Detterbeck F. What to do with “surprise” N2?: intraoperative Management of Patients with non-small cell lung Cancer. J Thorac Oncol. 2008;3(3):289–302.CrossRefGoogle Scholar
  4. 4.
    Ramnath N, Dilling TJ, Harris LJ, Kim AW, Michaud GC, Balekian AA, et al. Treatment of stage III non-small cell lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2013;143(5, Supplement):e314S–e40S.CrossRefGoogle Scholar
  5. 5.
    Gospodarowicz MK, Brierley JD, Wittekind C. TNM classification of malignant tumours. Hoboken: Wiley; 2017.Google Scholar
  6. 6.
    Riquet M, Bagan P, Le Pimpec BF, Banu E, Scotte F, Foucault C, et al. Completely resected non-small cell lung cancer: reconsidering prognostic value and significance of N2 metastases. Ann Thorac Surg. 2007;84(6):1818–24.CrossRefGoogle Scholar
  7. 7.
    Veeramachaneni NK, Feins RH, Stephenson BJK, Edwards LJ, Fernandez FG. Management of stage IIIA non-small cell lung cancer by thoracic surgeons in North America. Ann Thorac Surg. 2012;94(3):922–8.CrossRefGoogle Scholar
  8. 8.
    Tanner NT, Gomez M, Rainwater C, Nietert PJ, Simon GR, Green MR, et al. Physician preferences for management of patients with stage IIIA NSCLC: impact of bulk of nodal disease on therapy selection. J Thorac Oncol. 2012;7(2):365–9.CrossRefGoogle Scholar
  9. 9.
    Albain KS, Swann RS, Rusch VW, Turrisi AT III, Shepherd FA, Smith C, et al. Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial. Lancet. 2009;374(9687):379–86.CrossRefGoogle Scholar
  10. 10.
    Kang CH, Ra YJ, Kim YT, Jheon SH, Sung SW, Kim JH. The impact of multiple metastatic nodal stations on survival in patients with resectable N1 and N2 nonsmall-cell lung cancer. Ann Thorac Surg. 2008;86(4):1092–7.CrossRefGoogle Scholar
  11. 11.
    Andre F, Grunenwald D, Pignon JP, Dujon A, Pujol JL, Brichon PY, et al. Survival of patients with resected N2 non-small-cell lung cancer: evidence for a subclassification and implications. J Clin Oncol Off J Am Soc Clin Oncol. 2000;18(16):2981–9.CrossRefGoogle Scholar
  12. 12.
    Casali C, Stefani A, Natali P, Rossi G, Morandi U. Prognostic factors in surgically resected N2 non-small cell lung cancer: the importance of patterns of mediastinal lymph nodes metastases. Eur J Cardiothorac Surg. 2005;28(1):33–8.Google Scholar
  13. 13.
    Pataer A, Kalhor N, Correa AM, Raso MG, Erasmus JJ, Kim ES, et al. Histopathologic response criteria predict survival of patients with resected lung cancer after neoadjuvant chemotherapy. J Thorac Oncol. 2012;7(5):825–32.CrossRefGoogle Scholar
  14. 14.
    Suntharalingam M, Paulus R, Edelman MJ, Krasna M, Burrows W, Gore E, et al. Radiation therapy oncology group protocol 02-29: a phase II trial of neoadjuvant therapy with concurrent chemotherapy and full-dose radiation therapy followed by surgical resection and consolidative therapy for locally advanced non-small cell carcinoma of the lung. Int J Radiat Oncol Biol Phys. 2012;84(2):456–63.CrossRefGoogle Scholar
  15. 15.
    Chiou VL, Burotto M. Pseudoprogression and immune-related response in solid tumors. J Clin Oncol. 2015;33(31):3541–3.CrossRefGoogle Scholar
  16. 16.
    Depierre A, Milleron B, Moro-Sibilot D, Chevret S, Quoix E, Lebeau B, et al. Preoperative chemotherapy followed by surgery compared with primary surgery in resectable stage I (except T1N0), II, and IIIa non–small-cell lung cancer. J Clin Oncol. 2002;20(1):247–53.PubMedGoogle Scholar
  17. 17.
    Cerfolio RJ, Maniscalco L, Bryant AS. The treatment of patients with stage IIIA non-small cell lung cancer from N2 disease: who returns to the surgical arena and who survives. Ann Thorac Surg. 2008;86(3):912–20.CrossRefGoogle Scholar
  18. 18.
    van Meerbeeck JP, On behalf of the European Organisation for R, Treatment of Cancer-Lung Cancer G, Kramer GWPM, On behalf of the European Organisation for R, Treatment of Cancer-Lung Cancer G, et al. Randomized controlled trial of resection versus radiotherapy after induction chemotherapy in stage IIIA-N2 non–small-cell lung cancer. J Natl cancer Inst. 2007;99(6):442–50.Google Scholar
  19. 19.
    Kim AW, Boffa DJ, Wang Z, Detterbeck FC. An analysis, systematic review, and meta-analysis of the perioperative mortality after neoadjuvant therapy and pneumonectomy for non-small cell lung cancer. J Thorac Cardiovasc Surg. 2012;143(1):55–63.CrossRefGoogle Scholar
  20. 20.
    •• Pless M, Stupp R, Ris H-B, Stahel RA, Weder W, Thierstein S, et al. Induction chemoradiation in stage IIIA/N2 non-small-cell lung cancer: a phase 3 randomised trial. Lancet. 2015;386(9998):1049–56 Randomized controlled trial evaluating outcomes following sequential neoadjuvant chemotherapy and radiation or che-motherapy alone in patients with IIIA N2 NSCLC. There was no observed difference in median overall survival between groups.Google Scholar
  21. 21.
    Cheung MC, Hamilton K, Sherman R, Byrne MM, Nguyen DM, Franceschi D, et al. Impact of teaching facility status and high-volume centers on outcomes for lung cancer resection: an examination of 13,469 surgical patients. Ann Surg Oncol. 2009;16(1):3–13.CrossRefGoogle Scholar
  22. 22.
    Group NM-aC. Preoperative chemotherapy for non-small-cell lung cancer: a systematic review and meta-analysis of individual participant data. Lancet (London, England). 2014;383(9928):1561–71.CrossRefGoogle Scholar
  23. 23.
    Eberhardt WE, Pottgen C, Gauler TC, Friedel G, Veit S, Heinrich V, et al. Phase III study of surgery versus definitive concurrent chemoradiotherapy boost in patients with resectable stage IIIA(N2) and selected IIIB non-small-cell lung cancer after induction chemotherapy and concurrent chemoradiotherapy (ESPATUE). J Clin Oncol Off J Am Soc Clin Oncol. 2015;33(35):4194–201.CrossRefGoogle Scholar
  24. 24.
    Donington J, Paulus R, Edelman M, M K, Q L, M S, et al., editors. Safety and feasibility of lobectomy following concurrent chemotherapy and high dose radiation for IIIA NSCLC: pooled surgical results of NRG oncology RTOG 0229 and 039. American Association for Thoracic Surgery annual meeting; 2017; Boston, MA.Google Scholar
  25. 25.
    Katakami N, Tada H, Mitsudomi T, Kudoh S, Senba H, Matsui K, et al. A phase 3 study of induction treatment with concurrent chemoradiotherapy versus chemotherapy before surgery in patients with pathologically confirmed N2 stage IIIA nonsmall cell lung cancer (WJTOG9903). Cancer. 2012;118(24):6126–35.CrossRefGoogle Scholar
  26. 26.
    Girard N, Mornex F, Douillard J-Y, Bossard N, Quoix E, Beckendorf V, et al. Is neoadjuvant chemoradiotherapy a feasible strategy for stage IIIA-N2 non-small cell lung cancer? Mature results of the randomized IFCT-0101 phase II trial. Lung Cancer (Amsterdam, Netherlands). 2010;69(1):86–93.CrossRefGoogle Scholar
  27. 27.
    Chen Y, Peng X, Zhou Y, Xia K, Zhuang W. Comparing the benefits of chemoradiotherapy and chemotherapy for resectable stage III A/N2 non-small cell lung cancer: a meta-analysis. World J Surg Oncol. 2018;16(1):8.CrossRefGoogle Scholar
  28. 28.
    Yang CF, Gulack BC, Gu L, Speicher PJ, Wang X, Harpole DH, et al. Adding radiation to induction chemotherapy does not improve survival of patients with operable clinical N2 non-small cell lung cancer. J Thorac Cardiovasc Surg. 2015;150(6):1484–92 discussion 92-3.Google Scholar
  29. 29.
    Toyooka S, Kiura K, Shien K, Katsui K, Hotta K, Kanazawa S, et al. Induction chemoradiotherapy is superior to induction chemotherapy for the survival of non-small-cell lung cancer patients with pathological mediastinal lymph node metastasis. Interact Cardiovasc Thorac Surg. 2012;15(6):954–60.CrossRefGoogle Scholar
  30. 30.
    Higgins K, Chino JP, Marks LB, Ready N, D'Amico TA, Clough RW, et al. Preoperative chemotherapy versus preoperative chemoradiotherapy for stage III (N2) non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2009;75(5):1462–7.CrossRefGoogle Scholar
  31. 31.
    Thomas M, Rube C, Hoffknecht P, Macha HN, Freitag L, Linder A, et al. Effect of preoperative chemoradiation in addition to preoperative chemotherapy: a randomised trial in stage III non-small-cell lung cancer. Lancet Oncol. 2008;9(7):636–48.CrossRefGoogle Scholar
  32. 32.
    Pezzetta E, Stupp R, Zouhair A, Guillou L, Taffe P, von Briel C, et al. Comparison of neoadjuvant cisplatin-based chemotherapy versus radiochemotherapy followed by resection for stage III (N2) NSCLC. Eur J Cardiothorac Surg. 2005;27(6):1092–8.Google Scholar
  33. 33.
    Yang CF, Adil SM, Anderson KL, Meyerhoff RR, Turley RS, Hartwig MG, et al. Impact of patient selection and treatment strategies on outcomes after lobectomy for biopsy-proven stage IIIA pN2 non-small cell lung cancer. Eur J Cardiothorac Surg. 2016;49(6):1607–13.Google Scholar
  34. 34.
    Moya-Horno I, Viteri S, Karachaliou N, Rosell R. Combination of immunotherapy with targeted therapies in advanced non-small cell lung cancer (NSCLC). Ther Adv Med Oncol. 2018;10:1758834017745012.Google Scholar
  35. 35.
    Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. Durvalumab after chemoradiotherapy in stage III non–small-cell lung cancer. N Engl J Med. 2017;377(20):1919–29.CrossRefGoogle Scholar
  36. 36.
    Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. New England Journal of Medicine. 2018.Google Scholar
  37. 37.
    •• Forde PM, Chaft JE, Smith KN, Anagnostou V, Cottrell TR, Hellmann MD, et al. Neoadjuvant PD-1 Blockade in Resectable Lung Cancer. N Engl J Med. 2018;378(21):1976–86. Initial prospective evaluation of neoadjuvant immunotherapy in resectable NSCLC., demonstrated safety and efficacy of this approach.Google Scholar
  38. 38.
    • Broderick SR, Bott M, Park B, Isbell J, Adusumilli P. Operative Experience with Pulmonary Resection following Neoadjuvant Nivolumab in Patients with Resectable Non-small Cell Lung Cancer. American Association for Thoracic Surgery Annual Meeting; San Diego, CA 2018. Initial operative experience in patients with resectable stage I, II, or IIIA NSCLC who underwent neoadjuvant PD-1 blockade with nivolumab. There was no observed increase in perioperative morbidity or mortality.Google Scholar
  39. 39.
    • Rusch VW, Chaft JE, Johnson B, Wistuba II, Kris MG, Lee JM, et al. Neoadjuvant atezolizumab in resectable non-small cell lung cancer (NSCLC): Initial results from a multicenter study (LCMC3). J Clin Oncol. 2018;36(15_suppl):8541. Initial results from a large multicenter trial evaluating out-comes following neoadjuvant PD-L1 blockade with atezoli-zumab in patients with resectable stage IB to IIIB NSCLC. The authors found no delay in time to surgery, an acceptable side effect profile, and poor correlation between radiographic and pathologic response.Google Scholar
  40. 40.
    Cascone T, William WN, Weissferdt A, Leung CH, Federico L, Haymaker C, et al. Neoadjuvant nivolumab (N) or nivolumab plus ipilimumab (NI) for resectable non-small cell lung cancer (NSCLC). Munich: European Society for Medical Oncology; 2018.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of SurgeryThe University of Chicago Medicine and Biological SciencesChicagoUSA
  2. 2.Section of Thoracic Surgery, Department of SurgeryThe University of Chicago Medicine and Biological SciencesChicagoUSA

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