Related Summaries
Statistics
Histology
Risk Factors
Pathology
Screening
Diagnosis and Treatment
        Surgically resectable disease
        Locally and/or regionally advanced disease
        Distant metastatic disease
Prognostic Factors

Related Summaries

Other PDQ summaries containing information related to lung cancer include:

• Small Cell Lung Cancer Treatment
• Lung Cancer Prevention
• Lung Cancer Screening
• Smoking Cessation and Continued Risk in Cancer Patients.

Estimated new cases and deaths from lung cancer (non-small cell and small cell combined) in the United States in 2009:[1]

• New cases: 219,440.
• Deaths: 159,390.

Lung cancer is the leading cause of cancer-related mortality in the United States.[1] The 5-year relative survival rate for the period of 1995 to 2001 for patients with lung cancer was 15.7%. The 5-year relative survival rate varies markedly depending on the stage at diagnosis, from 49% to 16% to 2% for patients with local, regional, and distant stage disease, respectively.[2]

Patients with resectable disease may be cured by surgery or surgery with adjuvant chemotherapy. Local control can be achieved with radiation therapy in a large number of patients with unresectable disease, but cure is seen only in a small number of patients. Patients with locally advanced, unresectable disease may have long-term survival with radiation therapy combined with chemotherapy. Patients with advanced metastatic disease may achieve improved survival and palliation of symptoms with chemotherapy.

Non-small cell lung cancer (NSCLC) is a heterogeneous aggregate of histologies. The most common histologies are epidermoid or squamous carcinoma, adenocarcinoma, and large cell carcinoma. These histologies are often classified together because approaches to diagnosis, staging, prognosis, and treatment are similar.

Risk factors that contribute to the development of lung cancer include:

• Cigarette, pipe, or cigar smoking.
• Exposure to second-hand smoke, radon, arsenic, asbestos, chromates, chloromethyl ethers, nickel, polycyclic aromatic hydrocarbons, radon progeny, other agents, and air pollution.[3]
• Radiation therapy to the breast or chest.

The single most important risk factor for the development of lung cancer is smoking. For smokers, the risk for lung cancer is on average tenfold higher than in lifetime nonsmokers (defined as a person who has smoked <100 cigarettes in their lifetime). The risk increases with the quantity of cigarettes, duration of smoking, and starting age. Smoking cessation results in a decrease in precancerous lesions and a reduction in the risk of developing lung cancer. Former smokers continue to have an elevated risk for lung cancer for years after quitting. Asbestos exposure may exert a synergistic effect of cigarette smoking on the lung cancer risk.[3]

Smoking-related lung carcinogenesis is a multistep process. Squamous carcinoma and adenocarcinoma have defined premalignant precursor lesions. Before becoming invasive, lung epithelium may undergo morphological changes that include hyperplasia, metaplasia, dysplasia, and carcinoma in situ. Dysplasia and carcinoma in situ are considered the principal premalignant lesions because they are more likely to progress to invasive cancer and less likely to spontaneously regress. In addition, after resection of a lung cancer, there is a 1% to 2% risk for a second lung cancer per patient per year.[4] Screening for early detection of lung cancer and chemoprevention strategies are currently under evaluation for this patient population.

(Refer to the PDQ summary on Lung Cancer Prevention for more information.)

In patients considered at high risk for developing lung cancer, no screening modality for early detection has been shown to alter mortality.[5] Studies of lung cancer screening with chest radiography and sputum cytology have failed to demonstrate that screening lowers lung cancer mortality rates. Published studies of newer screening technologies such as low-dose computed tomography (CT) scans and biomarker screenings report primarily on lung cancer detection rates and do not present sufficient data to determine whether the newer technologies will benefit or harm people. Currently, randomized trials are evaluating low-dose spiral CT scanning.

(Refer to the PDQ summary on Lung Cancer Screening for more information.)

At diagnosis, patients with NSCLC can be divided into three groups that reflect both the extent of the disease and the treatment approach.

The first group of patients has tumors that are surgically resectable (generally stage I, stage II, and selected stage III tumors). This group has the best prognosis, which depends on a variety of tumor and host factors. Patients with resectable disease who have medical contraindications to surgery are candidates for curative radiation therapy. Adjuvant cisplatin-based combination chemotherapy may provide a survival advantage to patients with resected stage II or stage IIIA NSCLC.

The second group includes patients with either locally (T3–T4) and/or regionally (N2–N3) advanced lung cancer. This group has a diverse natural history. Selected patients with locally advanced tumors may benefit from combined modality treatments. Patients with unresectable or N2–N3 disease are treated with radiation therapy in combination with chemotherapy. Selected patients with T3 or N2 disease can be treated effectively with surgical resection and either preoperative or postoperative chemotherapy or chemoradiation therapy.

The final group includes patients with distant metastases (M1) that were found at the time of diagnosis. This group can be treated with radiation therapy or chemotherapy for palliation of symptoms from the primary tumor. Patients with good performance status (PS), women, and patients with distant metastases confined to a single site live longer than others.[6] Platinum-based chemotherapy has been associated with short-term palliation of symptoms and with a survival advantage. Currently, no single chemotherapy regimen can be recommended for routine use. Patients previously treated with platinum combination chemotherapy may derive symptom control and survival benefit from docetaxel, pemetrexed, or epidermal growth factor receptor inhibitor.

Multiple studies have attempted to identify prognostic determinants after surgery and have yielded conflicting evidence as to the prognostic importance of a variety of clinicopathologic factors.[6-10] Factors that have correlated with adverse prognosis include the following:

• Presence of pulmonary symptoms.
• Large tumor size (>3 cm).
• Nonsquamous histology.
• Metastases to multiple lymph nodes within a TNM-defined nodal station.[11-21]
• Vascular invasion.[7,22-24]

Similarly, conflicting results regarding the prognostic importance of aberrant expression of a number of proteins within lung cancers have been reported. For patients with inoperable disease, prognosis is adversely affected by poor PS and weight loss of more than 10%. These patients have been excluded from clinical trials evaluating aggressive multimodality interventions. In multiple retrospective analyses of clinical trial data, advanced age alone has not been shown to influence response or survival with therapy.[25]

Because treatment is not satisfactory for almost all patients with NSCLC, eligible patients should be considered for clinical trials. Information about ongoing clinical trials is available from the NCI Web site.

References

1. American Cancer Society.: Cancer Facts and Figures 2009. Atlanta, Ga: American Cancer Society, 2009. Also available online. Last accessed September 8, 2009. 
   
   
2. Ries L, Eisner M, Kosary C, et al., eds.: Cancer Statistics Review, 1975-2002. Bethesda, Md: National Cancer Institute, 2005 Available online. Last accessed April 9, 2009 . 
   
   
3. Wingo PA, Ries LA, Giovino GA, et al.: Annual report to the nation on the status of cancer, 1973-1996, with a special section on lung cancer and tobacco smoking. J Natl Cancer Inst 91 (8): 675-90, 1999.  [PUBMED Abstract]
   
   
4. Johnson BE: Second lung cancers in patients after treatment for an initial lung cancer. J Natl Cancer Inst 90 (18): 1335-45, 1998.  [PUBMED Abstract]
   
   
5. Bach PB, Silvestri GA, Hanger M, et al.: Screening for lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 132 (3 Suppl): 69S-77S, 2007.  [PUBMED Abstract]
   
   
6. Albain KS, Crowley JJ, LeBlanc M, et al.: Survival determinants in extensive-stage non-small-cell lung cancer: the Southwest Oncology Group experience. J Clin Oncol 9 (9): 1618-26, 1991.  [PUBMED Abstract]
   
   
7. Macchiarini P, Fontanini G, Hardin MJ, et al.: Blood vessel invasion by tumor cells predicts recurrence in completely resected T1 N0 M0 non-small-cell lung cancer. J Thorac Cardiovasc Surg 106 (1): 80-9, 1993.  [PUBMED Abstract]
   
   
8. Ichinose Y, Yano T, Asoh H, et al.: Prognostic factors obtained by a pathologic examination in completely resected non-small-cell lung cancer. An analysis in each pathologic stage. J Thorac Cardiovasc Surg 110 (3): 601-5, 1995.  [PUBMED Abstract]
   
   
9. Martini N, Bains MS, Burt ME, et al.: Incidence of local recurrence and second primary tumors in resected stage I lung cancer. J Thorac Cardiovasc Surg 109 (1): 120-9, 1995.  [PUBMED Abstract]
   
   
10. Fontanini G, Bigini D, Vignati S, et al.: Microvessel count predicts metastatic disease and survival in non-small cell lung cancer. J Pathol 177 (1): 57-63, 1995.  [PUBMED Abstract]
    
    
11. Sayar A, Turna A, Kiliçgün A, et al.: Prognostic significance of surgical-pathologic multiple-station N1 disease in non-small cell carcinoma of the lung. Eur J Cardiothorac Surg 25 (3): 434-8, 2004.  [PUBMED Abstract]
    
    
12. Osaki T, Nagashima A, Yoshimatsu T, et al.: Survival and characteristics of lymph node involvement in patients with N1 non-small cell lung cancer. Lung Cancer 43 (2): 151-7, 2004.  [PUBMED Abstract]
    
    
13. Ichinose Y, Kato H, Koike T, et al.: Overall survival and local recurrence of 406 completely resected stage IIIa-N2 non-small cell lung cancer patients: questionnaire survey of the Japan Clinical Oncology Group to plan for clinical trials. Lung Cancer 34 (1): 29-36, 2001.  [PUBMED Abstract]
    
    
14. Tanaka F, Yanagihara K, Otake Y, et al.: Prognostic factors in patients with resected pathologic (p-) T1-2N1M0 non-small cell lung cancer (NSCLC). Eur J Cardiothorac Surg 19 (5): 555-61, 2001.  [PUBMED Abstract]
    
    
15. Asamura H, Suzuki K, Kondo H, et al.: Where is the boundary between N1 and N2 stations in lung cancer? Ann Thorac Surg 70 (6): 1839-45; discussion 1845-6, 2000.  [PUBMED Abstract]
    
    
16. Riquet M, Manac'h D, Le Pimpec-Barthes F, et al.: Prognostic significance of surgical-pathologic N1 disease in non-small cell carcinoma of the lung. Ann Thorac Surg 67 (6): 1572-6, 1999.  [PUBMED Abstract]
    
    
17. van Velzen E, Snijder RJ, Brutel de la Rivière A, et al.: Lymph node type as a prognostic factor for survival in T2 N1 M0 non-small cell lung carcinoma. Ann Thorac Surg 63 (5): 1436-40, 1997.  [PUBMED Abstract]
    
    
18. Vansteenkiste JF, De Leyn PR, Deneffe GJ, et al.: Survival and prognostic factors in resected N2 non-small cell lung cancer: a study of 140 cases. Leuven Lung Cancer Group. Ann Thorac Surg 63 (5): 1441-50, 1997.  [PUBMED Abstract]
    
    
19. Izbicki JR, Passlick B, Karg O, et al.: Impact of radical systematic mediastinal lymphadenectomy on tumor staging in lung cancer. Ann Thorac Surg 59 (1): 209-14, 1995.  [PUBMED Abstract]
    
    
20. Martini N, Burt ME, Bains MS, et al.: Survival after resection of stage II non-small cell lung cancer. Ann Thorac Surg 54 (3): 460-5; discussion 466, 1992.  [PUBMED Abstract]
    
    
21. Naruke T, Goya T, Tsuchiya R, et al.: Prognosis and survival in resected lung carcinoma based on the new international staging system. J Thorac Cardiovasc Surg 96 (3): 440-7, 1988.  [PUBMED Abstract]
    
    
22. Thomas P, Doddoli C, Thirion X, et al.: Stage I non-small cell lung cancer: a pragmatic approach to prognosis after complete resection. Ann Thorac Surg 73 (4): 1065-70, 2002.  [PUBMED Abstract]
    
    
23. Macchiarini P, Fontanini G, Hardin MJ, et al.: Relation of neovascularisation to metastasis of non-small-cell lung cancer. Lancet 340 (8812): 145-6, 1992.  [PUBMED Abstract]
    
    
24. Khan OA, Fitzgerald JJ, Field ML, et al.: Histological determinants of survival in completely resected T1-2N1M0 nonsmall cell cancer of the lung. Ann Thorac Surg 77 (4): 1173-8, 2004.  [PUBMED Abstract]
    
    
25. Earle CC, Tsai JS, Gelber RD, et al.: Effectiveness of chemotherapy for advanced lung cancer in the elderly: instrumental variable and propensity analysis. J Clin Oncol 19 (4): 1064-70, 2001.  [PUBMED Abstract]
    
    

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