Management of stage I and stage II non-small cell lung cancer
- Howard J West, MD
Howard J West, MD
- Medical Director
- Thoracic Oncology Program
- Swedish Cancer Institute (Seattle)
- Eric Vallières, MD, FRCSC
Eric Vallières, MD, FRCSC
- Surgical Director of the Lung Cancer Program
- Swedish Cancer Institute
- Steven E Schild, MD
Steven E Schild, MD
- Section Editor — Radiation Therapy
- Professor of Radiation Oncology
- Mayo Clinic College of Medicine
- Section Editors
- James R Jett, MD
James R Jett, MD
- Section Editor — Lung Cancer
- Professor of Medicine Emeritus
- National Jewish Health
- Joseph S Friedberg, MD
Joseph S Friedberg, MD
- Section Editor — Thoracic Surgery
- Charles Reid Edwards Professor of Surgery
- University of Maryland
- Rogerio C Lilenbaum, MD, FACP
Rogerio C Lilenbaum, MD, FACP
- Section Editor — Lung Cancer
- Yale Cancer Center
The treatment for lung cancer depends upon tumor histology (small cell versus non-small cell), extent (stage) and patient specific factors (eg, age, pulmonary function, comorbidity). The major subtypes of non-small cell lung cancer (NSCLC) include adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, in decreasing order of frequency of occurrence. (See "Pathology of lung malignancies".)
Patients with NSCLC who have disease limited to one lung and not involving the mediastinum or more distant sites have localized, stage I or stage II disease (table 1). Stage I plus stage II disease accounts for approximately 30 percent of patients with NSCLC . In this setting, surgical resection is the primary approach to treatment if there are no contraindications.
The approach to treatment of patients with stage I and stage II disease will be reviewed here. Overviews of other aspects of lung cancer are presented separately. (See "Overview of the risk factors, pathology, and clinical manifestations of lung cancer" and "Overview of the initial evaluation, treatment and prognosis of lung cancer".)
The tumor node metastasis (TNM) staging system is used for treatment planning and prognostic purposes in patients with non-small cell lung cancer (NSCLC) (table 1) . The current (seventh) edition of the TNM system was validated in a large clinical database and correlates better with survival than earlier versions of the TNM staging system (figure 1) . (See "Overview of the initial evaluation, diagnosis, and staging of patients with suspected lung cancer" and "Tumor node metastasis (TNM) staging system for non-small cell lung cancer".)
Clinical staging is often unreliable, and patients thought to have stage I or II disease are restaged pathologically following surgery. Pathologic staging of the mediastinal lymph nodes is performed either prior to or at the time of resection. The issue of when to pathologically stage patients with stage I or II disease is discussed separately. (See "Management of stage III non-small cell lung cancer", section on 'Mediastinal evaluation'.)
- Groome PA, Bolejack V, Crowley JJ, et al. The IASLC Lung Cancer Staging Project: validation of the proposals for revision of the T, N, and M descriptors and consequent stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours. J Thorac Oncol 2007; 2:694.
- Goldstraw P, Crowley J, Chansky K, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol 2007; 2:706.
- López-Encuentra A, García-Luján R, Rivas JJ, et al. Comparison between clinical and pathologic staging in 2,994 cases of lung cancer. Ann Thorac Surg 2005; 79:974.
- National Comprehensive Cancer Network guidelines http://www.nccn.org/professionals/physician_gls/f_guidelines.asp (Accessed on March 19, 2014).
- Birkmeyer JD. Improving outcomes with lung cancer surgery: selective referral or quality improvement? Ann Surg Oncol 2009; 16:1.
- Lüchtenborg M, Riaz SP, Coupland VH, et al. High procedure volume is strongly associated with improved survival after lung cancer surgery. J Clin Oncol 2013; 31:3141.
- Ginsberg RJ, Rubinstein LV. Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group. Ann Thorac Surg 1995; 60:615.
- Yan TD, Black D, Bannon PG, McCaughan BC. Systematic review and meta-analysis of randomized and nonrandomized trials on safety and efficacy of video-assisted thoracic surgery lobectomy for early-stage non-small-cell lung cancer. J Clin Oncol 2009; 27:2553.
- Ferguson MK, Lehman AG. Sleeve lobectomy or pneumonectomy: optimal management strategy using decision analysis techniques. Ann Thorac Surg 2003; 76:1782.
- Dai C, Shen J, Ren Y, et al. Choice of Surgical Procedure for Patients With Non-Small-Cell Lung Cancer ≤ 1 cm or > 1 to 2 cm Among Lobectomy, Segmentectomy, and Wedge Resection: A Population-Based Study. J Clin Oncol 2016; 34:3175.
- Mery CM, Pappas AN, Bueno R, et al. Similar long-term survival of elderly patients with non-small cell lung cancer treated with lobectomy or wedge resection within the surveillance, epidemiology, and end results database. Chest 2005; 128:237.
- Okami J, Ito Y, Higashiyama M, et al. Sublobar resection provides an equivalent survival after lobectomy in elderly patients with early lung cancer. Ann Thorac Surg 2010; 90:1651.
- Billmeier SE, Ayanian JZ, Zaslavsky AM, et al. Predictors and outcomes of limited resection for early-stage non-small cell lung cancer. J Natl Cancer Inst 2011; 103:1621.
- Landreneau RJ, Normolle DP, Christie NA, et al. Recurrence and survival outcomes after anatomic segmentectomy versus lobectomy for clinical stage I non-small-cell lung cancer: a propensity-matched analysis. J Clin Oncol 2014; 32:2449.
- Khullar OV, Liu Y, Gillespie T, et al. Survival After Sublobar Resection versus Lobectomy for Clinical Stage IA Lung Cancer: An Analysis from the National Cancer Data Base. J Thorac Oncol 2015; 10:1625.
- El-Sherif A, Gooding WE, Santos R, et al. Outcomes of sublobar resection versus lobectomy for stage I non-small cell lung cancer: a 13-year analysis. Ann Thorac Surg 2006; 82:408.
- Kodama K, Doi O, Higashiyama M, Yokouchi H. Intentional limited resection for selected patients with T1 N0 M0 non-small-cell lung cancer: a single-institution study. J Thorac Cardiovasc Surg 1997; 114:347.
- Lee W, Daly BD, DiPetrillo TA, et al. Limited resection for non-small cell lung cancer: observed local control with implantation of I-125 brachytherapy seeds. Ann Thorac Surg 2003; 75:237.
- Kodama K, Higashiyama M, Okami J, et al. Oncologic Outcomes of Segmentectomy Versus Lobectomy for Clinical T1a N0 M0 Non-Small Cell Lung Cancer. Ann Thorac Surg 2016; 101:504.
- Nakata M, Sawada S, Saeki H, et al. Prospective study of thoracoscopic limited resection for ground-glass opacity selected by computed tomography. Ann Thorac Surg 2003; 75:1601.
- Yamato Y, Tsuchida M, Watanabe T, et al. Early results of a prospective study of limited resection for bronchioloalveolar adenocarcinoma of the lung. Ann Thorac Surg 2001; 71:971.
- Asamura H. Role of limited sublobar resection for early-stage lung cancer: steady progress. J Clin Oncol 2014; 32:2403.
- Veluswamy RR, Ezer N, Mhango G, et al. Limited Resection Versus Lobectomy for Older Patients With Early-Stage Lung Cancer: Impact of Histology. J Clin Oncol 2015; 33:3447.
- Bao F, Ye P, Yang Y, et al. Segmentectomy or lobectomy for early stage lung cancer: a meta-analysis. Eur J Cardiothorac Surg 2014; 46:1.
- Fernando HC, Landreneau RJ, Mandrekar SJ, et al. Impact of brachytherapy on local recurrence rates after sublobar resection: results from ACOSOG Z4032 (Alliance), a phase III randomized trial for high-risk operable non-small-cell lung cancer. J Clin Oncol 2014; 32:2456.
- Mentzer SJ, DeCamp MM, Harpole DH Jr, Sugarbaker DJ. Thoracoscopy and video-assisted thoracic surgery in the treatment of lung cancer. Chest 1995; 107:298S.
- Petersen RP, Pham D, Burfeind WR, et al. Thoracoscopic lobectomy facilitates the delivery of chemotherapy after resection for lung cancer. Ann Thorac Surg 2007; 83:1245.
- Yang CF, Sun Z, Speicher PJ, et al. Use and Outcomes of Minimally Invasive Lobectomy for Stage I Non-Small Cell Lung Cancer in the National Cancer Data Base. Ann Thorac Surg 2016; 101:1037.
- McKenna RJ Jr, Houck W, Fuller CB. Video-assisted thoracic surgery lobectomy: experience with 1,100 cases. Ann Thorac Surg 2006; 81:421.
- Swanson SJ, Herndon JE 2nd, D'Amico TA, et al. Video-assisted thoracic surgery lobectomy: report of CALGB 39802--a prospective, multi-institution feasibility study. J Clin Oncol 2007; 25:4993.
- Flores RM, Park BJ, Dycoco J, et al. Lobectomy by video-assisted thoracic surgery (VATS) versus thoracotomy for lung cancer. J Thorac Cardiovasc Surg 2009; 138:11.
- Paul S, Isaacs AJ, Treasure T, et al. Long term survival with thoracoscopic versus open lobectomy: propensity matched comparative analysis using SEER-Medicare database. BMJ 2014; 349:g5575.
- http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf (Accessed on March 23, 2015).
- Manser R, Wright G, Hart D, et al. Surgery for early stage non-small cell lung cancer. Cochrane Database Syst Rev 2005; :CD004699.
- Gajra A, Newman N, Gamble GP, et al. Effect of number of lymph nodes sampled on outcome in patients with stage I non-small-cell lung cancer. J Clin Oncol 2003; 21:1029.
- Lardinois D, De Leyn P, Van Schil P, et al. ESTS guidelines for intraoperative lymph node staging in non-small cell lung cancer. Eur J Cardiothorac Surg 2006; 30:787.
- Lim E, Baldwin D, Beckles M, et al. Guidelines on the radical management of patients with lung cancer. Thorax 2010; 65 Suppl 3:iii1.
- Darling GE, Allen MS, Decker PA, et al. Randomized trial of mediastinal lymph node sampling versus complete lymphadenectomy during pulmonary resection in the patient with N0 or N1 (less than hilar) non-small cell carcinoma: results of the American College of Surgery Oncology Group Z0030 Trial. J Thorac Cardiovasc Surg 2011; 141:662.
- Robinson BM, Kennedy C, McLean J, McCaughan BC. Node-negative non-small cell lung cancer: pathological staging and survival in 1765 consecutive cases. J Thorac Oncol 2011; 6:1691.
- Vallières E, Van Houtte P, Travis WD, et al. Carcinoma in situ at the bronchial resection margin: a review. J Thorac Oncol 2011; 6:1617.
- Kawaguchi T, Watanabe S, Kawachi R, et al. The impact of residual tumor morphology on prognosis, recurrence, and fistula formation after lung cancer resection. J Thorac Oncol 2008; 3:599.
- Massard G, Doddoli C, Gasser B, et al. Prognostic implications of a positive bronchial resection margin. Eur J Cardiothorac Surg 2000; 17:557.
- Snijder RJ, Brutel de la Rivière A, Elbers HJ, van den Bosch JM. Survival in resected stage I lung cancer with residual tumor at the bronchial resection margin. Ann Thorac Surg 1998; 65:212.
- Wang EH, Corso CD, Rutter CE, et al. Postoperative Radiation Therapy Is Associated With Improved Overall Survival in Incompletely Resected Stage II and III Non-Small-Cell Lung Cancer. J Clin Oncol 2015; 33:2727.
- Doddoli C, D'Journo B, Le Pimpec-Barthes F, et al. Lung cancer invading the chest wall: a plea for en-bloc resection but the need for new treatment strategies. Ann Thorac Surg 2005; 80:2032.
- Kelsey CR, Marks LB, Hollis D, et al. Local recurrence after surgery for early stage lung cancer: an 11-year experience with 975 patients. Cancer 2009; 115:5218.
- Cai XW, Xu LY, Wang L, et al. Comparative survival in patients with postresection recurrent versus newly diagnosed non-small-cell lung cancer treated with radiotherapy. Int J Radiat Oncol Biol Phys 2010; 76:1100.
- British Thoracic Society, Society of Cardiothoracic Surgeons of Great Britain and Ireland Working Party. BTS guidelines: guidelines on the selection of patients with lung cancer for surgery. Thorax 2001; 56:89.
- Chang JY, Li QQ, Xu QY, et al. Stereotactic ablative radiation therapy for centrally located early stage or isolated parenchymal recurrences of non-small cell lung cancer: how to fly in a "no fly zone". Int J Radiat Oncol Biol Phys 2014; 88:1120.
- Timmerman R, Paulus R, Galvin J, et al. Stereotactic body radiation therapy for inoperable early stage lung cancer. JAMA 2010; 303:1070.
- Baumann P, Nyman J, Hoyer M, et al. Outcome in a prospective phase II trial of medically inoperable stage I non-small-cell lung cancer patients treated with stereotactic body radiotherapy. J Clin Oncol 2009; 27:3290.
- Senthi S, Lagerwaard FJ, Haasbeek CJ, et al. Patterns of disease recurrence after stereotactic ablative radiotherapy for early stage non-small-cell lung cancer: a retrospective analysis. Lancet Oncol 2012; 13:802.
- Chang JY, Senan S, Paul MA, et al. Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Oncol 2015; 16:630.
- Palma D, Lagerwaard F, Rodrigues G, et al. Curative treatment of Stage I non-small-cell lung cancer in patients with severe COPD: stereotactic radiotherapy outcomes and systematic review. Int J Radiat Oncol Biol Phys 2012; 82:1149.
- Haasbeek CJ, Lagerwaard FJ, Antonisse ME, et al. Stage I nonsmall cell lung cancer in patients aged > or =75 years: outcomes after stereotactic radiotherapy. Cancer 2010; 116:406.
- Palma D, Visser O, Lagerwaard FJ, et al. Impact of introducing stereotactic lung radiotherapy for elderly patients with stage I non-small-cell lung cancer: a population-based time-trend analysis. J Clin Oncol 2010; 28:5153.
- Rowell NP, Williams CJ. Radical radiotherapy for stage I/II non-small cell lung cancer in patients not sufficiently fit for or declining surgery (medically inoperable). Cochrane Database Syst Rev 2001; :CD002935.
- Pennell NA, Neal JW, Chaft JE, et al SELECT: A multicenter phase II trial of adjuvant erlotinib in resected early-stage EGFR mutation-positive NSCLC. J Clin Oncol 32:5s, 2014 (suppl; abstr 7514).
- Shepherd FA, Altorki NK, Eberhardt WE, et al. Adjuvant erlotinib (E) versus placebo (P) in non-small cell lung cancer (NSCLC) patients (pts) with tumors carrying EGFR-sensitizing mutations from the RADIANT trial. J Clin Oncol 32:5s, 2014 (suppl; abstr 7513).
- Bezjak A, Temin S, Franklin G, et al. Definitive and Adjuvant Radiotherapy in Locally Advanced Non-Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Endorsement of the American Society for Radiation Oncology Evidence-Based Clinical Practice Guideline. J Clin Oncol 2015; 33:2100.
- Effects of postoperative mediastinal radiation on completely resected stage II and stage III epidermoid cancer of the lung. The Lung Cancer Study Group. N Engl J Med 1986; 315:1377.
- Feng QF, Wang M, Wang LJ, et al. A study of postoperative radiotherapy in patients with non-small-cell lung cancer: a randomized trial. Int J Radiat Oncol Biol Phys 2000; 47:925.
- Stephens RJ, Girling DJ, Bleehen NM, et al. The role of post-operative radiotherapy in non-small-cell lung cancer: a multicentre randomised trial in patients with pathologically staged T1-2, N1-2, M0 disease. Medical Research Council Lung Cancer Working Party. Br J Cancer 1996; 74:632.
- Dautzenberg B, Arriagada R, Chammard AB, et al. A controlled study of postoperative radiotherapy for patients with completely resected nonsmall cell lung carcinoma. Groupe d'Etude et de Traitement des Cancers Bronchiques. Cancer 1999; 86:265.
- Trodella L, Granone P, Valente S, et al. Adjuvant radiotherapy in non-small cell lung cancer with pathological stage I: definitive results of a phase III randomized trial. Radiother Oncol 2002; 62:11.
- Burdett S, Rydzewska L, Tierney J, et al. Postoperative radiotherapy for non-small cell lung cancer. Cochrane Database Syst Rev 2016; 9:CD002142.
- Postoperative radiotherapy in non-small-cell lung cancer: systematic review and meta-analysis of individual patient data from nine randomised controlled trials. PORT Meta-analysis Trialists Group. Lancet 1998; 352:257.
- Lally BE, Zelterman D, Colasanto JM, et al. Postoperative radiotherapy for stage II or III non-small-cell lung cancer using the surveillance, epidemiology, and end results database. J Clin Oncol 2006; 24:2998.
- Lung. In: American Joint Committee on Cancer Staging Manual, 7th, Edge SB, Byrd DR, Compton CC, et al (Eds), Springer, New York 2010. p.253.
- Rusch VW, Hawes D, Decker PA, et al. Occult metastases in lymph nodes predict survival in resectable non-small-cell lung cancer: report of the ACOSOG Z0040 trial. J Clin Oncol 2011; 29:4313.
- Sun Z, Aubry MC, Deschamps C, et al. Histologic grade is an independent prognostic factor for survival in non-small cell lung cancer: an analysis of 5018 hospital- and 712 population-based cases. J Thorac Cardiovasc Surg 2006; 131:1014.
- https://www.iaslc.org/sites/default/files/wysiwyg-assets/cap_iaslc_amp_summary_of_recommendations.pdf (Accessed on September 25, 2013).
- Battafarano RJ, Piccirillo JF, Meyers BF, et al. Impact of comorbidity on survival after surgical resection in patients with stage I non-small cell lung cancer. J Thorac Cardiovasc Surg 2002; 123:280.
- Bach PB, Cramer LD, Schrag D, et al. The influence of hospital volume on survival after resection for lung cancer. N Engl J Med 2001; 345:181.
- http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf (Accessed on April 13, 2015).
- Calman L, Beaver K, Hind D, et al. Survival benefits from follow-up of patients with lung cancer: a systematic review and meta-analysis. J Thorac Oncol 2011; 6:1993.
- Walsh GL, O'Connor M, Willis KM, et al. Is follow-up of lung cancer patients after resection medically indicated and cost-effective? Ann Thorac Surg 1995; 60:1563.
- Younes RN, Gross JL, Deheinzelin D. Follow-up in lung cancer: how often and for what purpose? Chest 1999; 115:1494.
- Westeel V, Choma D, Clément F, et al. Relevance of an intensive postoperative follow-up after surgery for non-small cell lung cancer. Ann Thorac Surg 2000; 70:1185.
- Harpole DH Jr, Herndon JE 2nd, Young WG Jr, et al. Stage I nonsmall cell lung cancer. A multivariate analysis of treatment methods and patterns of recurrence. Cancer 1995; 76:787.
- National Comprehensive Cancer Network (NCCN). NCCN Clinical practice guidelines in oncology. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp (Accessed on February 27, 2016).
- McAvoy S, Ciura K, Wei C, et al. Definitive reirradiation for locoregionally recurrent non-small cell lung cancer with proton beam therapy or intensity modulated radiation therapy: predictors of high-grade toxicity and survival outcomes. Int J Radiat Oncol Biol Phys 2014; 90:819.
- Hearn JW, Videtic GM, Djemil T, Stephans KL. Salvage stereotactic body radiation therapy (SBRT) for local failure after primary lung SBRT. Int J Radiat Oncol Biol Phys 2014; 90:402.
- GENERAL APPROACH TO TREATMENT
- SURGICAL CANDIDATES
- Preoperative evaluation
- Limited (sublobar) resection
- - Intraoperative brachytherapy
- Video-assisted thoracoscopic surgery
- Mediastinal lymph node dissection
- Positive resection margins
- Chest wall involvement
- Local recurrence after surgery
- NONSURGICAL CANDIDATES
- Stereotactic body radiation therapy
- Conventionally fractionated radiation therapy
- Other ablative techniques
- ADJUVANT THERAPY
- Molecularly targeted therapy
- Postoperative RT
- Tumor grade
- Molecular markers
- Hospital case volume
- POST-THERAPY SURVEILLANCE
- Efficacy of surveillance
- Management of isolated thoracic recurrence
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS
- Mediastinal staging
- Surgical candidates
- Nonsurgical candidates
- Adjuvant therapy