Prognostic Impact of Tumor Doubling Time in Patients with Metachronous Lung Cancer

  • Keisuke AsakuraEmail author
  • Yukihiro Yoshida
  • Hiroyuki Sakurai
  • Kazuo Nakagawa
  • Noriko Motoi
  • Shun-ichi Watanabe
Original Scientific Report



Good prognosis following surgery for metachronous lung cancer has been reported. However, prognostic factors have not been fully investigated. The purpose of this study was to identify the preoperative predictor of survival in metachronous lung cancer.


Patients who underwent a second pulmonary resection for metachronous lung cancer at our institution between 2000 and 2014 were analyzed.


A retrospective chart review identified 86 eligible patients (of 6213; 1.4%). The 5-year overall survival was 77%. All 86 cancers met Martini and Melamed’s criteria for second primary cancer. However, on pathological examination based on morphological concordance between the initial and metachronous cancer, 73 (85%) cases were diagnosed as second primary cancer and 13 (15%) as a possible recurrent tumor. The 5-year overall survivals were 82% for second primary cancers and 52% for possible recurrent tumors. Tumor doubling time > 180 days (p < 0.001), pathological diagnosis of second primary cancer (p = 0.013), pathological stage IA (p = 0.016), interval between resections > 2 years (p = 0.040), and consolidation/tumor diameter ratio ≤ 0.5 (p = 0.045) were associated with superior overall survival. Multivariate Cox regression analysis identified tumor doubling time > 180 days as the only independent predictor of overall survival (hazard ratio 3.600, 95% confidence interval 1.226–10.338; p = 0.0196).


Surgical resection for metachronous lung cancer is effective and feasible. Particularly, a tumor doubling time > 180 days is associated with superior survival in patients with metachronous lung cancer.




Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

The Institutional Ethical Committee approved the study and waived the need for individual patients to provide consent because of the retrospective nature of the study, because consent could not be obtained from all of the patients, and because individual patients were not identified in the study.


  1. 1.
    Lee BE, Port JL, Stiles BM et al (2009) TNM stage is the most important determinant of survival in metachronous lung cancer. Ann Thorac Surg 88:1100–1105CrossRefGoogle Scholar
  2. 2.
    Lou F, Huang J, Sima CS et al (2013) Patterns of recurrence and second primary lung cancer in early-stage lung cancer survivors followed with routine computed tomography surveillance. J Thorac Cardiovasc Surg 145:75–81CrossRefGoogle Scholar
  3. 3.
    Hamaji M, Allen MS, Cassivi SD et al (2013) Surgical treatment of metachronous second primary lung cancer after complete resection of non-small cell lung cancer. J Thorac Cardiovasc Surg 145:683–690CrossRefGoogle Scholar
  4. 4.
    Haraguchi S, Koizumi K, Hirata T et al (2010) Surgical treatment of metachronous nonsmall cell lung cancer. Ann Thorac Cardiovasc Surg 16:319–325Google Scholar
  5. 5.
    Battafarano RJ, Force SD, Meyers BF et al (2004) Benefits of resection for metachronous lung cancer. J Thorac Cardiovasc Surg 127:836–842CrossRefGoogle Scholar
  6. 6.
    Bae MK, Byun CS, Lee CY et al (2011) The role of surgical treatment in second primary lung cancer. Ann Thorac Surg 92:256–262CrossRefGoogle Scholar
  7. 7.
    Martini N, Melamed MR (1975) Multiple primary lung cancers. J Thorac Cardiovasc Surg 70:606–612Google Scholar
  8. 8.
    Sakurai H, Nakagawa K, Watanabe S et al (2015) Clinicopathologic features of resected subcentimeter lung cancer. Ann Thorac Surg 99:1731–1738CrossRefGoogle Scholar
  9. 9.
    Usuda K, Saito Y, Sagawa M et al (1994) Tumor doubling time and prognostic assessment of patients with primary lung cancer. Cancer 74:2239–2244CrossRefGoogle Scholar
  10. 10.
    Wang J, Mahasittiwat P, Wong KK et al (2012) Natural growth and disease progression of non-small cell lung cancer evaluated with 18F-fluorodeoxyglucose PET/CT. Lung Cancer 78:51–56CrossRefGoogle Scholar
  11. 11.
    Travis WD, Colby TV, Corrin B, Shimosato Y, Brambilla E (2012) Histological typing of lung and pleural tumours, World Health Organization International Histological Classification of Tumors. Springer, BerlinGoogle Scholar
  12. 12.
    Sobin LHGM, Wittekind C (2009) International Union Against Cancer (UICC) TNM classification of malignant tumours. Wiley-Liss, New YorkGoogle Scholar
  13. 13.
    Vignot S, Frampton GM, Soria JC et al (2013) Next-generation sequencing reveals high concordance of recurrent somatic alterations between primary tumor and metastases from patients with non-small-cell lung cancer. J Clin Oncol 31:2167–2172CrossRefGoogle Scholar
  14. 14.
    Girard N, Deshpande C, Lau C et al (2009) Comprehensive histologic assessment helps to differentiate multiple lung primary nonsmall cell carcinomas from metastases. Am J Surg Pathol 33:1752–1764CrossRefGoogle Scholar
  15. 15.
    Nicholson AG, Torkko K, Viola P et al (2018) Interobserver variation among pathologists and refinement of criteria in distinguishing separate primary tumors from intrapulmonary metastases in lung. J Thorac Oncol 13:205–217CrossRefGoogle Scholar

Copyright information

© Société Internationale de Chirurgie 2019

Authors and Affiliations

  • Keisuke Asakura
    • 1
    • 2
    Email author
  • Yukihiro Yoshida
    • 1
  • Hiroyuki Sakurai
    • 1
    • 3
  • Kazuo Nakagawa
    • 1
  • Noriko Motoi
    • 4
  • Shun-ichi Watanabe
    • 1
  1. 1.Department of Thoracic SurgeryNational Cancer Center HospitalTokyoJapan
  2. 2.Division of Thoracic SurgeryKeio University School of MedicineTokyoJapan
  3. 3.Division of Respiratory SurgeryNihon University School of MedicineTokyoJapan
  4. 4.Department of Pathology and Clinical LaboratoriesNational Cancer Center HospitalTokyoJapan

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