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Multiple primary lung cancers

Thomas E Stinchcombe, MD
Shamus Carr, MD, FACS
Billy W Loo Jr., MD, PhD
Section Editors
Rogerio C Lilenbaum, MD, FACP
Joseph S Friedberg, MD
Deputy Editor
Sadhna R Vora, MD


Patients with lung cancer may present with more than one primary lesion arising in the lung at the same time (synchronous multiple primary lung cancer) or may develop a second, metachronous, primary lung cancer after treatment of the initial lesion. This is becoming a more common clinical issue and remains a challenge due to how these tumors are classified [1].

Multiple primary lung cancers (MPLC) pose a variety of clinically important diagnostic and therapeutic problems, which may differ from those in patients presenting with a single primary tumor. These issues are reviewed here for both synchronous and metachronous MPLC.


Synchronous MPLC — Patients presenting with more than one pulmonary nodule at the same time must fulfill strict criteria to be classified as having synchronous multiple primary lung cancers (MPLC) [2,3].

Both lesions must be malignant and must arise independently in the lung. The second lesion cannot be assumed to represent a second primary lung cancer. A benign nodule, infectious process, or metastasis from an extrapulmonary site must be excluded.

The second malignant lesion must not represent a metastasis from the first lung lesion. Accepted criteria for this distinction include [4]:

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Literature review current through: Nov 2017. | This topic last updated: Aug 15, 2017.
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  1. Homer RJ. Pathologists' staging of multiple foci of lung cancer: poor concordance in absence of dramatic histologic or molecular differences. Am J Clin Pathol 2015; 143:701.
  2. Kozower BD, Larner JM, Detterbeck FC, Jones DR. Special treatment issues in 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:e369S.
  3. NCCN Guidelines Version 4.2016 Non-small cell lung cancer. http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf.accessed4.5.2016 (Accessed on April 05, 2016).
  4. Detterbeck FC, Franklin WA, Nicholson AG, et al. The IASLC Lung Cancer Staging Project: Background Data and Proposed Criteria to Distinguish Separate Primary Lung Cancers from Metastatic Foci in Patients with Two Lung Tumors in the Forthcoming Eighth Edition of the TNM Classification for Lung Cancer. J Thorac Oncol 2016; 11:651.
  5. Shen KR, Meyers BF, Larner JM, et al. Special treatment issues in lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007; 132:290S.
  6. Goldstraw P. The 7th Edition of TNM in Lung Cancer: what now? J Thorac Oncol 2009; 4:671.
  7. Nakamura H, Saji H. Worldwide trend of increasing primary adenocarcinoma of the lung. Surg Today 2014; 44:1004.
  8. Wakelee HA, Bernardo P, Johnson DH, Schiller JH. Changes in the natural history of nonsmall cell lung cancer (NSCLC)--comparison of outcomes and characteristics in patients with advanced NSCLC entered in Eastern Cooperative Oncology Group trials before and after 1990. Cancer 2006; 106:2208.
  9. Govindan R, Page N, Morgensztern D, et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol 2006; 24:4539.
  10. Girard N, Ostrovnaya I, Lau C, et al. Genomic and mutational profiling to assess clonal relationships between multiple non-small cell lung cancers. Clin Cancer Res 2009; 15:5184.
  11. Travis WD, Brambilla E, Noguchi M, et al. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society: international multidisciplinary classification of lung adenocarcinoma: executive summary. Proc Am Thorac Soc 2011; 8:381.
  12. Barsky SH, Cameron R, Osann KE, et al. Rising incidence of bronchioloalveolar lung carcinoma and its unique clinicopathologic features. Cancer 1994; 73:1163.
  13. Read WL, Page NC, Tierney RM, et al. The epidemiology of bronchioloalveolar carcinoma over the past two decades: analysis of the SEER database. Lung Cancer 2004; 45:137.
  14. Carr SR, Akerley W, Hashibe M, Cannon-Albright LA. Evidence for a genetical contribution to non-smoking-related lung cancer. Thorax 2015; 70:1033.
  15. SLAUGHTER DP, SOUTHWICK HW, SMEJKAL W. Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer 1953; 6:963.
  16. Johnson BE. Second lung cancers in patients after treatment for an initial lung cancer. J Natl Cancer Inst 1998; 90:1335.
  17. Lou F, Huang J, Sima CS, et al. Patterns of recurrence and second primary lung cancer in early-stage lung cancer survivors followed with routine computed tomography surveillance. J Thorac Cardiovasc Surg 2013; 145:75.
  18. Tucker MA, Murray N, Shaw EG, et al. Second primary cancers related to smoking and treatment of small-cell lung cancer. Lung Cancer Working Cadre. J Natl Cancer Inst 1997; 89:1782.
  19. Karp DD, Lee SJ, Shaw Wright GL, et al. A phase III, intergroup, randomized, double-blind, chemoprevention trial of selenium (Se) supplementation in resected stage I non-small cell lung cancer. J Clin Oncol 2010.
  20. Dijkman BG, Schuurbiers OC, Vriens D, et al. The role of (18)F-FDG PET in the differentiation between lung metastases and synchronous second primary lung tumours. Eur J Nucl Med Mol Imaging 2010; 37:2037.
  21. Karp DD, Lee SJ, Keller SM, et al. Randomized, double-blind, placebo-controlled, phase III chemoprevention trial of selenium supplementation in patients with resected stage I non-small-cell lung cancer: ECOG 5597. J Clin Oncol 2013; 31:4179.
  22. Rostad H, Strand TE, Naalsund A, Norstein J. Resected synchronous primary malignant lung tumors: a population-based study. Ann Thorac Surg 2008; 85:204.
  23. Yu YC, Hsu PK, Yeh YC, et al. Surgical results of synchronous multiple primary lung cancers: similar to the stage-matched solitary primary lung cancers? Ann Thorac Surg 2013; 96:1966.
  24. Detterbeck FC, Jantz MA, Wallace M, et al. Invasive mediastinal staging of lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007; 132:202S.
  25. De Leyn P, Lardinois D, Van Schil P, et al. European trends in preoperative and intraoperative nodal staging: ESTS guidelines. J Thorac Oncol 2007; 2:357.
  26. Finley DJ, Yoshizawa A, Travis W, et al. Predictors of outcomes after surgical treatment of synchronous primary lung cancers. J Thorac Oncol 2010; 5:197.
  27. Jiang L, He J, Shi X, et al. Prognosis of synchronous and metachronous multiple primary lung cancers: systematic review and meta-analysis. Lung Cancer 2015; 87:303.
  28. Stella F, Luciano G, Dell'Amore A, et al. Pulmonary Metastases from NSCLC and MPLC (Multiple Primary Lung Cancers): Management and Outcome in a Single Centre Experience. Heart Lung Circ 2016; 25:191.
  29. Haasbeek CJ, Palma D, Visser O, et al. Early-stage lung cancer in elderly patients: a population-based study of changes in treatment patterns and survival in the Netherlands. Ann Oncol 2012; 23:2743.
  30. Shirvani SM, Jiang J, Chang JY, et al. Comparative effectiveness of 5 treatment strategies for early-stage non-small cell lung cancer in the elderly. Int J Radiat Oncol Biol Phys 2012; 84:1060.
  31. Dupuy DE. Treatment of medically inoperable non-small-cell lung cancer with stereotactic body radiation therapy versus image-guided tumor ablation: can interventional radiology compete? J Vasc Interv Radiol 2013; 24:1139.
  32. Shirvani SM, Jiang J, Chang JY, et al. Lobectomy, sublobar resection, and stereotactic ablative radiotherapy for early-stage non-small cell lung cancers in the elderly. JAMA Surg 2014; 149:1244.
  33. Nagata Y, Hiraoka M, Shibata T, et al. Prospective Trial of Stereotactic Body Radiation Therapy for Both Operable and Inoperable T1N0M0 Non-Small Cell Lung Cancer: Japan Clinical Oncology Group Study JCOG0403. Int J Radiat Oncol Biol Phys 2015; 93:989.
  34. 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.
  35. Sinha B, McGarry RC. Stereotactic body radiotherapy for bilateral primary lung cancers: the Indiana University experience. Int J Radiat Oncol Biol Phys 2006; 66:1120.
  36. Matthiesen C, Thompson JS, De La Fuente Herman T, et al. Use of stereotactic body radiation therapy for medically inoperable multiple primary lung cancer. J Med Imaging Radiat Oncol 2012; 56:561.
  37. Creach KM, El Naqa I, Bradley JD, et al. Dosimetric predictors of chest wall pain after lung stereotactic body radiotherapy. Radiother Oncol 2012; 104:23.
  38. Griffioen GH, Lagerwaard FJ, Haasbeek CJ, et al. Treatment of multiple primary lung cancers using stereotactic radiotherapy, either with or without surgery. Radiother Oncol 2013; 107:403.
  39. Chang JY, Liu YH, Zhu Z, et al. Stereotactic ablative radiotherapy: a potentially curable approach to early stage multiple primary lung cancer. Cancer 2013; 119:3402.
  40. Shintani T, Masago K, Takayama K, et al. Stereotactic Body Radiotherapy for Synchronous Primary Lung Cancer: Clinical Outcome of 18 Cases. Clin Lung Cancer 2015; 16:e91.
  41. Owen D, Olivier KR, Mayo CS, et al. Outcomes of stereotactic body radiotherapy (SBRT) treatment of multiple synchronous and recurrent lung nodules. Radiat Oncol 2015; 10:43.
  42. NCCN Guidlines Version 1.2014 Non-Small Cell Lung Cancer http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf (Accessed on October 22, 2013).
  43. Hamaji M, Ali SO, Burt BM. A meta-analysis of resected metachronous second non-small cell lung cancer. Ann Thorac Surg 2015; 99:1470.
  44. Carr SR, Schuchert MJ, Pennathur A, et al. Impact of tumor size on outcomes after anatomic lung resection for stage 1A non-small cell lung cancer based on the current staging system. J Thorac Cardiovasc Surg 2012; 143:390.
  45. van Rens MT, de la Rivière AB, Elbers HR, van Den Bosch JM. Prognostic assessment of 2,361 patients who underwent pulmonary resection for non-small cell lung cancer, stage I, II, and IIIA. Chest 2000; 117:374.
  46. Rea F, Zuin A, Callegaro D, et al. Surgical results for multiple primary lung cancers. Eur J Cardiothorac Surg 2001; 20:489.
  47. Hamaji M, Allen MS, Cassivi SD, et al. Surgical treatment of metachronous second primary lung cancer after complete resection of non-small cell lung cancer. J Thorac Cardiovasc Surg 2013; 145:683.
  48. van Rens MT, Zanen P, Brutel de La Rivière A, et al. Survival in synchronous vs. single lung cancer: upstaging better reflects prognosis. Chest 2000; 118:952.
  49. Tanvetyanon T, Finley DJ, Fabian T, et al. Prognostic factors for survival after complete resections of synchronous lung cancers in multiple lobes: pooled analysis based on individual patient data. Ann Oncol 2013; 24:889.
  50. Creach KM, Bradley JD, Mahasittiwat P, Robinson CG. Stereotactic body radiation therapy in the treatment of multiple primary lung cancers. Radiother Oncol 2012; 104:19.
  51. https://subscriptions.nccn.org/gl_login.aspx?ReturnURL=http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf-accessed 3/21/2013. (Accessed on March 21, 2013).