, Volume 197, Issue 6, pp 741–751 | Cite as

Postoperative Radiotherapy for Resected Stage IIIA-N2 Non-small-cell Lung Cancer: A Population-Based Time-Trend Study

  • Wan-Qin Zeng
  • Wen Feng
  • Li Xie
  • Chen-Chen Zhang
  • Wen Yu
  • Xu-Wei Cai
  • Xiao-Long FuEmail author



The value of postoperative radiotherapy (PORT) for resected stage IIIA-N2 non-small-cell lung cancer (NSCLC) is controversial with few studies focusing on whether PORT always plays a part in clinical practice and generates benefits to patients across different time periods. We investigated this issue using the Surveillance, Epidemiology, and End Results Database (SEER) and assessed the temporal trends spanning 27 years.


Within SEER, we selected stage IIIA-N2 NSCLC patients who underwent a lobectomy or pneumonectomy and coded as receiving PORT or never receiving radiotherapy over three time periods: 1988 to 1996, 1997 to 2005, 2006 to 2014. For each period, survival analyses were performed and propensity score matching (PSM) was used in the potentially beneficial subgroup.


45.4% of 5568 eligible patients received PORT. The yearly PORT use rates varied largely from 27.8% to 74.4%. Overall survival (OS) was distinctly improved over the period. The application of PORT had a significant impact on survival only in period 1 and 3. In subgroup analysis, the OS benefit of PORT was significant in each period in patients with 50% or more lymph node ratio (LNR) both before (hazard ratios, and P values of 0.647, P = .002; 0.804, P = .008; 0.721, P < .001 for period 1, 2, 3, respectively) and after PSM (0.642, P = .006; 0.785, P = .004; 0.748, P = .003 for period 1, 2, 3, respectively).


The benefits of PORT are lasting and stable throughout the years in patients with LNR of 50% or more. This might provide a clue on proper patient selection for PORT application.


Non-small-cell lung cancer Stage IIIA-N2 Survival Postoperative radiotherapy Trend 



This study is supported by National Key Research and Development Program of China (Grant Number 2016YFC0905502), The Project of Multi-center Clinical Research, Shanghai Jiao Tong University School of Medicine (Grant Number DLY201619) and Shanghai Chest Hospital Project of Collaborative Innovation (Grant Number YJXT20190101). We sincerely appreciate the great work of the Surveillance, Epidemiology, and End Results (SEER) Program.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Informed Consent

Informed consent was not required as this is a retrospective study using an open population-based dataset.

Research Involving Human Participants or Animals

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

Supplementary material

408_2019_284_MOESM1_ESM.jpg (5.2 mb)
Electronic supplementary material 1 (JPG 5340 kb)
408_2019_284_MOESM2_ESM.jpg (5.2 mb)
Electronic supplementary material 2 (JPG 5332 kb)
408_2019_284_MOESM3_ESM.docx (36 kb)
Electronic supplementary material 3 (DOCX 36 kb)
408_2019_284_MOESM4_ESM.docx (40 kb)
Electronic supplementary material 4 (DOCX 40 kb)


  1. 1.
    Bray F, Ferlay J, Soerjomataram I et al (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424CrossRefGoogle Scholar
  2. 2.
    Siegel RL, Miller KD, Jemal A (2019) Cancer statistics, 2019. CA Cancer J Clin 69:7–34CrossRefGoogle Scholar
  3. 3.
    Le Pechoux C (2011) Role of postoperative radiotherapy in resected non-small cell lung cancer: a reassessment based on new data. Oncologist 16:672–681CrossRefGoogle Scholar
  4. 4.
    Detterbeck FC, Boffa DJ, Tanoue LT (2009) The new lung cancer staging system. Chest 136:260–271CrossRefGoogle Scholar
  5. 5.
    National Comprehensive Cancer Network. NCCN Guidelines in Non-small-cell lung cancer (Version 3. 2019). Accessed 21 March 2019
  6. 6.
    Eberhardt WE, De Ruysscher D, Weder W et al (2015) 2nd ESMO Consensus Conference in Lung Cancer: locally advanced stage III non-small-cell lung cancer. Ann Oncol 26:1573–1588CrossRefGoogle Scholar
  7. 7.
    Andre F, Grunenwald D, Pignon JP et al (2000) Survival of patients with resected N2 non-small-cell lung cancer: evidence for a subclassification and implications. J Clin Oncol 18:2981–2989CrossRefGoogle Scholar
  8. 8.
    Lorent N, De Leyn P, Lievens Y et al (2004) Long-term survival of surgically staged IIIA-N2 non-small-cell lung cancer treated with surgical combined modality approach: analysis of a 7-year prospective experience. Ann Oncol 15:1645–1653CrossRefGoogle Scholar
  9. 9.
    Noone AM, Howlader N, Krapcho M, et al. SEER Cancer Statistics Review, 1975–2015, National Cancer Institute. Bethesda, MD,, based on November 2017 SEER data submission, posted to the SEER web site, April 2018
  10. 10.
    Lally BE, Zelterman D, Colasanto JM et al (2006) Postoperative radiotherapy for stage II or III non-small-cell lung cancer using the surveillance, epidemiology, and end results database. J Clin Oncol 24:2998–3006CrossRefGoogle Scholar
  11. 11.
    Mikell JL, Gillespie TW, Hall WA et al (2015) Postoperative radiotherapy is associated with better survival in non-small cell lung cancer with involved N2 lymph nodes: results of an analysis of the National Cancer Data Base. J Thorac Oncol 10:462–471CrossRefGoogle Scholar
  12. 12.
    Robinson CG, Patel AP, Bradley JD et al (2015) Postoperative radiotherapy for pathologic N2 non-small-cell lung cancer treated with adjuvant chemotherapy: a review of the National Cancer Data Base. J Clin Oncol 33:870–876CrossRefGoogle Scholar
  13. 13.
    Herskovic A, Mauer E, Christos P et al (2017) Role of postoperative radiotherapy in pathologic stage IIIA (N2) non-small cell lung cancer in a prospective nationwide oncology outcomes database. J Thorac Oncol 12:302–313CrossRefGoogle Scholar
  14. 14.
    Douillard JY, Rosell R, De Lena M et al (2008) Impact of postoperative radiation therapy on survival in patients with complete resection and stage I, II, or IIIA non-small-cell lung cancer treated with adjuvant chemotherapy: the Adjuvant Navelbine International Trialist Association (ANITA) randomized trial. Int J Radiat Oncol Biol Phys 72:695–701CrossRefGoogle Scholar
  15. 15.
    Dai H, Hui Z, Ji W et al (2011) Postoperative radiotherapy for resected pathological stage IIIA-N2 non-small cell lung cancer: a retrospective study of 221 cases from a single institution. Oncologist 16:641–650CrossRefGoogle Scholar
  16. 16.
    Mantovani C, Levra NG, Filippi AR et al (2013) Postoperative radiotherapy for patients with completely resected pathologic N2 non-small-cell lung cancer: a retrospective analysis. Clin Lung Cancer 14:194–199CrossRefGoogle Scholar
  17. 17.
    Feng W, Zhang Q, Fu XL et al (2015) The emerging outcome of postoperative radiotherapy for stage IIIA (N2) non-small cell lung cancer patients: based on the three-dimensional conformal radiotherapy technique and institutional standard clinical target volume. BMC Cancer 15:348CrossRefGoogle Scholar
  18. 18.
    PORT Meta-analysis Trialists Group (1998) Postoperative radiotherapy in non-small-cell lung cancer: systematic review and meta-analysis of individual patient data from nine randomised controlled trials. The Lancet 352:257–263CrossRefGoogle Scholar
  19. 19.
    PORT Meta‐analysis Trialists Group (2005) Postoperative radiotherapy for non‐small cell lung cancer. Cochrane Database Syst Rev 2: CD002142Google Scholar
  20. 20.
    Billiet C, Decaluwe H, Peeters S et al (2014) Modern post-operative radiotherapy for stage III non-small cell lung cancer may improve local control and survival: a meta-analysis. Radiother Oncol 110:3–8CrossRefGoogle Scholar
  21. 21.
    Burdett S, Rydzewska L, Tierney J et al (2016) Postoperative radiotherapy for non‐small cell lung cancer. Cochrane Database Syst Rev 10:CD002142Google Scholar
  22. 22.
    Travis WD, Brambilla E, Nicholson AG et al (2015) The 2015 World Health Organization classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol 10:1243–1260CrossRefGoogle Scholar
  23. 23.
    Wagner H (2000) Postoperative adjuvant therapy for patients with resected non-small cell lung cancer: still controversial after all these years. Chest 117:110S–118SCrossRefGoogle Scholar
  24. 24.
    Billiet C, Peeters S, Decaluwe H et al (2016) Postoperative radiotherapy for lung cancer: is it worth the controversy? Cancer Treat Rev 51:10–18CrossRefGoogle Scholar
  25. 25.
    National Cancer Institute, Surveillance, Epidemiology, and End Results Program. Registry Groupings in SEER Data and Statistics. Accessed 21 March 2019
  26. 26.
    Bekelman JE, Rosenzweig KE, Bach PB et al (2006) Trends in the use of postoperative radiotherapy for resected non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 66:492–499CrossRefGoogle Scholar
  27. 27.
    Baumann M, Krause M, Overgaard J et al (2016) Radiation oncology in the era of precision medicine. Nat Rev Cancer 16:234–249CrossRefGoogle Scholar
  28. 28.
    Klapper J, D'Amico TA (2015) VATS versus open surgery for lung cancer resection: moving toward a minimally invasive approach. J Natl Compr Canc Netw 13:162–164CrossRefGoogle Scholar
  29. 29.
    NSCLC Meta-analyses Collaborative Group (2010) Adjuvant chemotherapy, with or without postoperative radiotherapy, in operable non-small-cell lung cancer: two meta-analyses of individual patient data. Lancet 375:1267–1277CrossRefGoogle Scholar
  30. 30.
    Wang J, Zhou Z, Liang J et al (2016) Intensity-modulated radiation therapy may improve local-regional tumor control for locally advanced non-small cell lung cancer compared with three-dimensional conformal radiation therapy. Oncologist 21:1530–1537CrossRefGoogle Scholar
  31. 31.
    Hirsch FR, Scagliotti GV, Mulshine JL et al (2017) Lung cancer: current therapies and new targeted treatments. Lancet 389:299–311CrossRefGoogle Scholar
  32. 32.
    Grootjans W, de Geus-Oei LF, Troost EG et al (2015) PET in the management of locally advanced and metastatic NSCLC. Nat Rev Clin Oncol 12:395–407CrossRefGoogle Scholar
  33. 33.
    Feng W, Fu XL, Cai XW et al (2016) The differential impact of postoperative radiation therapy for completely resected stage IIIA (N2) non-small cell lung cancer: Based on the risk prediction model for locoregional recurrence. Int J Radiat Oncol Biol Phys 96:S69CrossRefGoogle Scholar
  34. 34.
    Vinh-Hung V, Verkooijen HM, Fioretta G et al (2009) Lymph node ratio as an alternative to pN staging in node-positive breast cancer. J Clin Oncol 27:1062–1068CrossRefGoogle Scholar
  35. 35.
    Berger AC, Sigurdson ER, LeVoyer T et al (2005) Colon cancer survival is associated with decreasing ratio of metastatic to examined lymph nodes. J Clin Oncol 23:8706–8712CrossRefGoogle Scholar
  36. 36.
    Kelty CJ, Kennedy CW, Falk GL (2010) Ratio of metastatic lymph nodes to total number of nodes resected is prognostic for survival in esophageal carcinoma. J Thorac Oncol 5:1467–1471CrossRefGoogle Scholar
  37. 37.
    Urban D, Bar J, Solomon B et al (2013) Lymph node ratio may predict the benefit of postoperative radiotherapy in non-small-cell lung cancer. J Thorac Oncol 8:940–946CrossRefGoogle Scholar
  38. 38.
    Corso CD, Rutter CE, Wilson LD et al (2015) Re-evaluation of the role of postoperative radiotherapy and the impact of radiation dose for non-small-cell lung cancer using the National Cancer Database. J Thorac Oncol 10:148–155CrossRefGoogle Scholar
  39. 39.
    Pignon JP, Tribodet H, Scagliotti GV et al (2008) Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol 26:3552–3559CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Department of Radiation Oncology, Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghaiChina
  2. 2.Clinical Research InstituteShanghai Jiao Tong University School of MedicineShanghaiChina

Personalised recommendations