• lung cancer;
  • nonsmall cell lung cancer;
  • multimodality therapy;
  • advanced stage, long-term survival;
  • staging


  1. Top of page
  2. Abstract


The core strategy of American College of Chest Physicians lung cancer guidelines is identification of the earliest symptoms of lung cancer and the immediate initiation of diagnosis and treatment. In the absence of screening, most symptomatic lung cancer is discovered at advanced stages, with the goal of long-term survival entirely dependent on effective treatment of stage III and IV lung cancer.


In a retrospective review, all patients diagnosed with stage IIIA, IIIB, and IV nonsmall cell lung cancer (NSCLC) between the years 1986 and 2001 at City of Hope National Medical Center who survived 5 years or longer were analyzed to identify parameters that might predict long-term survival.


Of 846 patients presenting with stage III or IV disease, 56 (6.6%) survived 5 years or longer. Sixteen patients died of primary tumor progression beyond 5 years. Two 5-year survivors died of second tobacco-caused neoplasms, and 16 died from medical conditions potentially related to prior treatment. A substantial majority of survivors were from specific pathologic subsets including: 1) resectable N2 disease (n = 17, 30.4%), 2) multiple lung tumors (n = 7, 12.5%), 3) T3N0 (n = 5, 8.1%), and 4) single site distant metastasis (n = 8, 14.2%).


Despite aggressive multimodality therapy, 5-year survival in patients with advanced stage NSCLC was very poor and limited to small pathological subsets. Patients with advanced stage NSCLC who did not belong to 1 of these subsets had a small chance of long-term survival. Cancer 2010. © 2010 American Cancer Society.

Lung cancer (LC) is the leading cause of cancer death in the United States.1 Nonsmall cell lung cancer (NSCLC) accounts for 80% to 85% of LC. Patients with early stage NSCLC have relatively high long-term survival rates after surgical resection, but a substantial majority of patients, approximately 80%, present in advanced stages.1 The national focus of management strategy both now and during the years of this study centered upon research-based, aggressive multimodality treatment protocols. Many publications examine short-term survival, but current evidence regarding long-term survival in advanced-stage NSCLC, particularly in stages IIIB and IV, is limited. Few publications have examined the characteristics of advanced-stage survivors. This study focuses on the pathologic and treatment variables in the characterization of 5-year survivors at a National Cancer Institute and National Comprehensive Cancer Network hospital.


  1. Top of page
  2. Abstract

This retrospective study was conducted with the approval of the institutional review board of the City of Hope National Medical Center. The medical records of all patients diagnosed with stage IIIA, IIIB, and IV NSCLC at City of Hope National Medical Center between the years 1986 and 2001 (n = 846) were analyzed. Patients were included in the study population if they had survived 5 years or longer from their time of LC diagnosis (n = 56).

We attempted to identify parameters that might predict long-term survival in these patients. We collected data from the City of Hope National Medical Center Cancer Registry. The City of Hope National Medical Center has been a participant of the Cancer Registry since 1953 and is a recipient of the Approval with Commendation rating by the Commission on Cancer of the American College of Surgeons.

The following data were collected: age; sex; date of diagnosis; presenting symptoms; pulmonary function test results; smoking status; comorbid illnesses; lymph node staging procedure; type of resection; number of surgeries; intraoperative and postoperative complications; tumor size; surgical margin status; lymph node involvement; number of lymph nodes resected; tumor histology; TNM staging; tumor lobe location; invasion of pleura, diaphragm, mediastinum, and chest wall; type of chemotherapy (CT); dosage of radiation; treatment sequencing; number of cycles of treatment; location of metastasis; secondary cancers; recurrent cancer; and date of death.

All second and subsequent lung lesions are considered as metastasis. Unfortunately, there is currently no definitive method to differentiate between a metastasis and a second primary LC of the same cell type in a retrospective study. We have classified our cases strictly according to the staging system in effect, which considers the second lesion to be a metastasis.

TNM classification was incomplete in 11 (18.6%) patients treated before 1997. Where TNM classification was not documented in medical records, we used the overall stage specified in their medical records to classify these patients. The documentation that these patients were staged as IIIA or IIIB was clear in their medical records and the cancer registry files. However, the specific TNM classification was not recorded in their medical records. The characteristics of these patients were not included in specific TNM analysis, but were included in overall interstage comparison.

Descriptive results are reported as mean, standard deviation, number, percentage, or chi-square test where appropriate. The data analyses were performed using SAS 9.1 (SAS Institute Inc., Cary, NC) and Excel 2002 (Microsoft Corporation, Redmond, Wash).


  1. Top of page
  2. Abstract

Advanced stage LC (stage III or IV disease) was diagnosed in 846 patients; 56 (6.6%) survived 5 years or longer. The staging and demographic characteristics of these patients are shown in Table 1. Sixteen 5-year survivors died from progression of the primary LC beyond 5 years; 40 (4.7%) patients ultimately survived the original neoplasm. Two additional patients died of second tobacco-caused cancers, and 18 patients died without identified recurrent malignant disease (in some cases possibly related to prior treatment, eg, progressive respiratory failure after resection and/or radiation therapy (RT) and progressive dementia after whole brain RT).

Table 1. Demographics
CharacteristicsAllStage IIIAStage IIIBStage IV
  1. SD indicates standard deviation.

No. (% of survivors)5684628 (50.0)1999 (16.1)19519 (33.0)452
Sex, No. (%)        
 Men26 (46.4)45615 (53.6)963 (33.3)1108 (42.1)250
 Women30 (53.6)39013 (46.4)1036 (66.7)8511 (57.9)202
Mean age±SD (range), y60.8±10.0  (41-84) 59.8±9.4 (40-77) 65.4±12.1  (51-83) 58.2±9.6  (44-82) 
Malignant pleural effusion, No. (%)1 (1.7) 0 (0.0) 0 (0.0)34 (17.3)1 (5.0) 
Dead, No. (% of survivors)38 (64.4) 18 (51.4) 8 (72.7) 12 (60.0) 
Cause of death        
 No cancer progression18 (48.6) 11 (64.7) 4 (50.0) 3 (25.0) 
 Second primary cancer2 (5.4) 2 (11.8) 0 (0.0) 0 (0.0) 
 Primary cancer progression16 (42.1) 3 (16.6) 4 (50.0) 9 (75.0) 

Pathologic Staging Factors

Specific TNM classification was incomplete in 11 (18.6%) patients treated before 1997. However, their overall stage (IIIA or IIIB) was documented in their medical records. There were 5 patients (8.5% of survivors) treated before 1997 with T3N0M0 disease staged as IIIA before but reclassified as IIB after the 1997 stage reclassification. Of survivors in stage IIIA, 35.7% had left-sided tumors, whereas 67.9% had right-sided tumors (Table 2).

Table 2. Survivors, 1986-2001
  • a

    Reclassified as stage IIB in 1997.

Stage IIIA, No.28
TNM category, No. (%) 
 T1N2M01 (3.4)
 T2N2M08 (27.6)
 T3N0M0a5 (17.2)
 T3N2M03 (10.3)
Affected side, No. (%) 
 Left10 (35.7)
 Right18 (67.9)

One patient (1.8%) with malignant pleural effusion survived 5 years. Seven (12.5%) patients with >1 lung tumor (stages IIIB or stage IV) survived 5 years. Fourteen (73.6%) stage IV survivors had a single site of distant metastasis (oligometastasis); of these, 6 had multiple lung tumors (Tables 3 and 4).

Table 3. Five-Year Survivors, 1986-2001
  • a

    Lymph node status was not evaluable.

Stage IIIB, No.9
Multiple lung tumor, No. (%)1 (11.1)
Same lobe (satellite)1 (11.1)
Different lobe, ipsilateral0 (0.0)
Contralateral0 (0.0)
TNM category, No. (%) 
 Total N2 (in addition to T4N2M0)5 (55.6)
 T47 (77.8)
  N2M03 (42.9)
  NxM0a2 (28.6)
  N1M01 (14.3)
  N3M01 (14.3)
Malignant pleural effusion present0 (0.0)
Table 4. Five-Year Survivors, 1986-2001
  • a

    Three patients with neoplasms in other lobes also had satellite lesions.

Stage IV, No.19
Multiple lung tumor, No. (%)a6 (31.6)
 Different lobe 
Distant metastases, No. (%) 
 Single site distant metastasis14 (73.6)
  LungSee above
  Bone1 (5.3)
  Liver0 (0.0)
  Adrenal0 (0.0)
  Brain3 (15.8)
  Pleural2 (10.5)
  Breast0 (0.0)
  Small bowel1 (5.3)
 Multiple site distant metastasis5 (26.3)
  Brain and pleura2 (10.5)
  Bone and pleura2 (10.5)
  Bone, liver, and pleura1 (5.3)
  Bone, liver, brain, and breast1 (5.3)

Treatment Factors

Table 5 outlines the treatment characteristics stratified by survival status. Thirty-three (89.2%) survivors in stages IIIA and IIIB received aggressive multimodality therapy, including pulmonary resection and systematic mediastinal lymph node dissection in 23 (62.6%) patients. One (1.7%) patient survived 5 years after RT alone for treatment of stage III disease. One (1.7%) stage IV patient survived 5 years with CT alone. Each patient later progressed and died. Six (10.2%) patients survived 5 years with surgery alone. No study patient survived 5 years without treatment.

Table 5. Treatment Factors
Treatment of Lung Cancer, No. (% of Survivors) [% of All Patients]AllStage IIIAStage IIIBStage IV
No treatment0 (0.0) [0.0]65 (7.7)0 (0.0) [0.0]5 (2.5)0 (0.0) [0.0]24 (12.2)0 (0.0) [0.0]37 (8.2)
Surgery only7 (12.5) [25.9]27 (3.2)4 (14.3) [33.3]12 (6.0)1 (11.1) [12.5]8 (4.1)2 (15.8) [33.3]6 (1.3)
Chemotherapy only1 (1.8) [0.8]124 (14.6)0 (0.0) [0.0]7 (3.5)0 (0.0) [0.0]26 (13.3)1 (5.3) [1.1]91 (20.1)
Radiation only2 (3.6) [1.0]191 (22.6)0 (0.0) [0.0]37 (18.6)1 (11.1) [2.6]39 (19.9)1 (5.5) [0.07]115 (25.4)
Radiation and chemotherapy8 (14.2) [3.2]252 (29.8)2 (7.1) [5.6]37 (18.6)4 (44.4) [5.1]79 (40.3)2 (10.5) [1.5]137 (30.3)
Radiation and surgery20 (35.7) [21.9]91 (10.7)15 (53.6) [28.1]57 (28.6)0 (0.0) [0.0]6 (3.1)5 (26.3) [17.2]29 (6.4)
Surgery and chemotherapy6 (10.7) [27.2]22 (2.6)3 (10.7) [50]6 (3.0)1 (11.1) [14.3]7 (3.6)2 (10.0) [22.2]9 (2.0)
Surgery, radiation, and chemotherapy11 (19.5) [14.1]74 (8.7)4 (14.3) [10.3]39 (19.6)2 (22.2) [33.3]6 (3.1)5 (26.3)[55.5]29 (6.4)

National Comprehensive Cancer Network Guidelines state that the best choice for treatment of LC is within the context of a clinical trial, but nationally, only 1% to 5% of adults with new-onset LC participate in such studies.2, 3 Twenty percent (range, 11.2%-32%; n = 1295) of patients treated for LC at City of Hope National Medical Center during the period 1990 to 2001 were enrolled in a clinical trial (Division of Information Sciences, Departments of Cancer Registry and Data Operations, City of Hope Cancer Center).


  1. Top of page
  2. Abstract

Although many authors suggest that development of new treatment regimens is improving the outlook for patients with NSCLC, the long-term survival in patients with advanced stage NSCLC, despite aggressive, research-based treatment at our cancer center, was very poor during the years included in our study. Furthermore, 5-year survival was largely limited to small subgroups of patients.

The prognosis of patients with advanced LC varies by disease characteristics but is generally low, with 5-year survival rates for all stages ranging from 9% to 15%. Our reported survival rates in stages IIIA (14.1%), IIIB (4.6%), and IV (4.2%) are closely comparable to those reported from other centers: IIIA (8%-11%), IIIB (1%-5%), and IV (1%-5%), respectively.4, 5

Pathological Staging Factors

Locally advanced NSCLC includes stages IIIA and IIIB, and represents a heterogeneous group of patients with regard to disease characteristics. A substantial majority of survivors in our series were from specific pathologic subsets, including: 1) resectable N2 disease (n = 17, 30.4%), 2) multiple lung tumors (n = 7, 12.5%), 3) T3N0 (n = 5, 8.1%), and 4) single site distant metastasis (n = 7, 12.5%).

Resectable Disease

Although many authors consider surgical resection of N2 disease “futile,” 17 (28.8%) of the 5-year survivors in our study were patients with resected N2 disease.6 Long-term survival after surgical resection of IIIA NSCLC, including complete and systematic mediastinal lymph node dissection, has been reported in many prior studies.7-12 There are still many questions left unanswered regarding selection of surgical candidates and whether adjuvant CT and/or RT should be provided before or after surgery, as well as the optimal drugs, dose, order, and number of adjuvant treatment modalities.13 After surgical resection, Okada et al found that 48.9% of patients with T3N0 disease and 21.1% of patients with N2 disease survived 5 years.14 Multiple studies have shown that patients with single lymph node, single station, and occult mediastinal lymph node metastases have 5-year survival between 25% and 40% when treated with surgical resection alone or with postoperative adjuvant RT. In contrast, patients with macroscopic, extranodal, multiple lymph node or multiple station N2 disease have lower 5-year survival.15

Riquet reported his experience with primary surgical treatment of 586 patients with N2 NSCLC.16 Cases included both cN0 with pN2 metastasis after mediastinal lymph node dissection, as well as patients with clinical (cN2) disease, and “bulky” cN2 disease (ie, nodes >2 cm). These patients experienced survival >30% at 5 years with single station N2 and 20% in patients with bulky disease, without preoperative mediastinoscopy, preoperative CT, or chemoradiation therapy.


In the current classification system, T4 tumors include malignant pleural effusions, tumors invading vital organs, and satellite tumors within the same lobe.17

Malignant pleural effusions

Thirty-four (17.3%) stage IIIB City of Hope National Medical Center patients had malignant pleural effusion (MPE). None survived 5 years. One patient with stage IV disease and MPE survived 5-years.

Patients with MPE are categorized as stage IIIB, but their prognosis is very poor. Ou reviewed the survival of >23,000 individuals with stage IIIB and IV NSCLC in the International Association for the Study of Lung Cancer International Database. Median and 5-year survival for patients with pleural dissemination were 5 months and 3.9%, respectively.18 Postmus queried the same database and reported very poor survival, suggesting that the staging system be revised to move MPE cases into stage IV.19

Satellite tumors

In the 1997 revision to the International System for Staging Lung Cancer, separate neoplasms in the same lobe are classified as T4, and neoplasms in separate lobes as M1.20

One patient with satellite tumors (11.1% of stage IIIB survivors) survived 5 years. Multiple studies have shown that patients with satellite lesions experience improved survival outcomes.21-23 Five-year survival rates vary from 26.7% to 57% in these patients. On the basis of the International Association for the Study of Lung Cancer database, it has been proposed that patients with satellite lesions and negative nodes be moved to stage IIB in the new staging classification.24


Multiple tumors

Seven (11.9%) patients of the 5-year survivors in this study had multiple lung neoplasms in either the same lobe (satellite) or separate lobes, either ipsilateral or contralateral. Of 6 patients with extralobar or second neoplasms, 3 patients also had satellite tumor nodules. It is not currently possible to determine with certainty whether such neoplasms are metastases as opposed to second primary cancers, if they are of the same cell type. Strand et al concluded that a substantial proportion of survival in stages IIIB and IV was because of higher survival in patients with multiple tumors.25 Pfannschmidt et al found that survival in cases with resected neoplasms in separate lobes (M1) without other distant metastases was comparable to that in stage IIIA disease.26 Our study concurs with other authors who advise that ipsilateral and contralateral lung neoplasm without metastases to other organs should not be denied resection.23, 27, 28

Single site distant metastasis

Three (16.7%) of the stage IV 5-year survivors in our series had solitary brain metastasis.

The brain is a very common site of metastasis in patients with NSCLC.29 Moscetti et al found that 15.5% to 21.9% of patients with NSCLC and synchronous brain metastasis presented with solitary brain metastasis.30 In patients with isolated brain metastasis, resection of a single brain metastasis with or without adjuvant RT can significantly improve long-term survival.31-33 Stereotactic and/or whole brain RT of synchronous brain metastasis can also achieve long-term survival.34 Chang et al found that patients with brain metastasis who received brain tumor resection, whole brain RT, or CT lived significantly longer than their counterparts who did not receive such treatments.35

Treatment Factors

Current approaches to treatment of advanced stage NSCLC achieved low survival in this study, with only 6.6% surviving 5 years or longer, and only 4.7% ultimately surviving the primary tumor. Of these patients, 47 (83%) received aggressive multimodality therapy. Most 5-year survivors received adjuvant RT, CT, or both (Tables 5 and 6)

Table 6. Treatment Factors: Death From Lung Cancer Progression Beyond 5 Years
TreatmentNo. (% of Patients Who Died of Disease Progression) [% of Survivors With Same Treatment]
Total16 (28.6)
Surgery only1 (6.2) [12.5]
Chemotherapy only1 (6.2) [50.0]
Radiation only1 (6.2) [50.0]
Radiation and chemotherapy6 (37.5) [75.0]
Radiation and surgery2 (12.5) [9.5]
Surgery and chemotherapy2 (12.5) [33.3]
Surgery, radiation, and chemotherapy3 (18.8) [25.0]
Single modality treatment

All-stage overall 5-year survival rates range from 46.4% to 50.7% after surgical resection of NSCLC.

Our stage-specific 5-year survival rates for patients who received surgical resection were comparable to literature values as follows: 18.2% versus 15.1%-35.8% for IIIA, 18.2% versus 24.1%-40% for IIIB, and 20.9% versus 0%-21.1% for IV.14, 25, 26

For patients treated with RT alone, we note an overall 5-year survival rate of 1.0% for stages III and IV. Of the 2 survivors, 1 subsequently died of disease progression. Quddus et al reported a 1.3% survival rate for all NSCLC patients treated with palliative RT alone; 0.8% were disease free at the time of death or end of study.36

One stage IV patient survived 5 years with CT alone, but progressed and died beyond 5 years.

Multimodality therapy
Chemoradiation therapy.

Eight patients (13.6%) treated with chemoradiation therapy alone survived 5 years, but 6 of these patients subsequently died of cancer progression beyond 5 years.

When N2 disease is considered unresectable, combination RT and CT is standard. Dillman demonstrated 13% 7-year survival with RT/CT.37 Ohe et al found that 12% of patients treated with CT and RT survived 7 years.38 Kim reported a 10% 6-year survival in 116 patients with stage III disease.39 In each of these series, patients were treated on prospective protocols excluding patients with MPE and restricted to low-risk individuals with good performance status (Eastern Cooperative Oncology Group [ECOG] performance status [PS] 0-1). It must be emphasized that, in clinical trials where eligibility is typically limited to performance Groups 0 and 1 and patients with malignant pleural effusions are generally excluded, higher survival may be expected than in the general population. A sizable percentage of older patients have adverse prognostic factors including malignant effusions, comorbidity, and low PS.

Poor PS is more common in advanced stage NSCLC as well as in patients with comorbid disease. More than 60% of NSCLC patients older than 60 years have a comorbid illness, and a third have 2 or more comorbid diseases.40, 41 The percentage of patients presenting with NSCLC in ECOG PS Groups 2 to 4 has been variously described between 34% and 50% when rated by physicians.42-44 The percentage is even higher when self-rated by patients.

Although the number of cases is small, the observation that 75% of 5-year survivors in our series with IIIA N2 NSCLC died of progressive cancer beyond 5 years after chemoradiation therapy suggests that longer follow-up may be needed to determine cure rates.

Surgery and CT

Of City of Hope National Medical Center patients treated with a combination of CT and surgery, 27.2% survived 5 years. One third of these patients subsequently died from disease progression.

Betticher et al recorded 5-year survival of 30% in patients who received neoadjuvant CT and surgical resection; 60% of patients had local relapse, and 65% of patients had distant metastasis.45 Disease-free survival was not reported. The most common sites of distant metastases were lung (24%) and brain (17%).


We recognize that there may be selection bias in retrospective series, particularly in our patient population, which contains a substantial number of patients seeking second opinions and treatment in research protocols. Analysis of long-term survival in advanced stage patients from other centers, preferably in prospective databases, is needed to provide stronger evidence in this area.

Treatment results may also have improved since our cutoff date of 2002. The report of Gandara on Southwest Oncology Group 9504 raises hopes that addition of consolidation CT after RT/CT may offer improved survival (29% at 5-years) in stage III patients.46 A recent report on 6118 NSCLC patients from Washington University, however, shows only minor improvement of median survival in stage IV NSCLC from 4.5 months before 2000 to 5.8 months after 2000.47 In addition, the Hoosier Oncology Group phase 3 trial showed that consolidation CT after chemoradiation therapy in stage III LC does not improve survival.48


Treatment of symptomatic, advanced-stage NSCLC yields dismal results. A substantial majority (65.2%) of survivors are from minor subsets of patients with favorable pathologic characteristics, including T3N0, resectable N2 disease, multiple tumors (either ipsilateral or contralateral), and single site distant metastasis who are treated with multimodality therapy. We concur with the authors of numerous studies suggesting changes to the current TNM system for LC.18, 19, 21, 22, 49

Finally, screening for LC has the potential to prevent advanced stage LC by detecting LCs before they can reach advanced stage, thus reducing the number of stage III-IV LCs and the associated mortality, morbidity, and expense related to multimodality treatment.50 In discussions of the relative risks and benefits of LC screening, patients should be presented with accurate information regarding treatment results for advanced stage, symptomatic LCs.


  1. Top of page
  2. Abstract

Dr Grannis has been a principal investigator in the International Early Lung Cancer Action Program LC screening trial and in 2001 received $30,000 for data management of this study in addition to travel and accommodation reimbursements for semiannual investigator meetings. In 2006, Dr Grannis provided written testimony in 2 medical monitoring lawsuits in the states of New York and Massachusetts against Philip Morris Corporation and was deposed in the New York case. Fees for this work were approximately $22,000.


  1. Top of page
  2. Abstract
  • 1
    Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2007. CA Cancer J Clin. 2007; 57: 43-66.
  • 2
    Murthy VH, Krumholz HM, Gross CP. Participation in cancer clinical trials: race-, sex-, and age-based disparities. JAMA. 2004; 291: 2720-2726.
  • 3
    Du W, Gadgeel SM, Simon MS. Predictors of enrollment in lung cancer clinical trials. Cancer. 2006; 106: 420-425.
  • 4
    de Cos Escuin JS, Vecentea CD, Penafiel JC, Miranda JAR, Gonzalez MAS, Jimenez JFM. Overall long-term survival in lung cancer analyzed in 610 unselected patients. Arch Bronconeumol. 2004; 40: 268-274.
  • 5
    Fry WA, Phillips JL, Meck HR. Ten-year survey of lung cancer treatment and survival in hospitals in the United States. Cancer Invest. 1999; 86: 1867-1876.
  • 6
    Paulson DL, Urschel HC. Selectivity in the surgical treatment of bronchogenic carcinoma. J Thorac Cardiovasc Surg. 1971; 62: 554-562.
  • 7
    Pearson FG, DeLarue NC, Ilves R, et al. Significance of positive superior mediastinal nodes identified at mediastinoscopy in patients with resectable cancer of the lung. J Thorac Cardiovasc Surg. 1982; 83: 1-11.
  • 8
    Naruke T, Goya T, Tsuchiya R, et al. The importance of surgery to non-small cell carcinoma of the lung with mediastinal lymph node metastasis. Ann Thorac Surg. 1988; 46: 603-610.
  • 9
    Watanabe Y, Shimizu J, Oda M, et al. Results of surgical treatment in patients with stage IIIA non-small-cell lung cancer. Thorac Cardiovasc Surg. 1991; 39: 44-49.
  • 10
    Izbicki JR, Passlick B, Pantel K, et al. Effectiveness of radical systematic mediastinal lymphadenectomy in patients with resectable non-small cell lung cancer. Ann Surg. 1998; 227: 138-144.
  • 11
    Vansteenkiste JF, De Leyn PR, Deneffe GJ, et al. Clinical prognostic factors in surgically treated stage IIIA-N2 non-small cell lung cancer: analysis of the literature. Lung Cancer. 1998; 19: 3-13.
  • 12
    Keller SM, Adak S, Wagner H, et al for the Eastern Cooperative Oncology Group. Mediastinal lymph node dissection improves survival in patients with stages II and IIIa non-small cell lung cancer. Ann Thorac Surg. 2000; 70: 358-366.
  • 13
    Vansteenkiste J, Betticher D, Eberhardt W, et al. Randomized controlled trial of resection versus radiotherapy after induction chemotherapy in stage IIIA-N2 non-small cell lung cancer. J Thorac Oncol. 2007; 2: 684-685.
  • 14
    Okada M, Nishio W, Sakamoto T, et al. Long-term survival and prognostic factors of 5-year survivors with complete resection of non-small cell lung carcinoma. J Thorac Cardiovasc Surg. 2003; 126: 558-562.
  • 15
    Andre F, Grunenwald D, Pignon JP, et al. Survival of patients with resected N2 non-small-cell lung cancer. Evidence for subclassification and implications. J Clin Oncol. 2001; 18: 2981-2989.
  • 16
    Riquet M, Bagan P, Le Pimpec Barthes F, et al. Completely resected non-small cell lung cancer: reconsidering prognostic value and significance of N2 metastases. Ann Thorac Surg. 2007; 84: 1818-1824.
  • 17
    GreeneFL, PageDL, FlemingID, et al eds. AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer; 2002: 157-164.
  • 18
    Ou SH, Zell JA. Validation study of the proposed IASLC staging revisions of the T4 and M non-small cell lung cancer descriptors using data from 23,583 patients in the California Cancer Registry. J Thorac Oncol. 2008; 3: 216-227.
  • 19
    Postmus PE, Brambilla E, Chansky K, et al. The IASLC lung cancer staging project: proposals for revision of the M descriptors in the forthcoming (seventh) edition of the TNM classification of lung cancer. J Thorac Oncol. 2007; 2: 686-693.
  • 20
    Mountain C. Revisions in the international system for staging lung cancer. Chest. 1997; 111: 1710-1717.
  • 21
    Zell JA, Ou SH, Ziogas A, Anton-Culver H. Long-term survival differences for bronchiolo-alveolar carcinoma patients with ipsilateral intrapulmonary metastasis at diagnosis. Ann Oncol. 2006; 17: 1255-1262.
  • 22
    Bryant AS, Pereira SJ, Miller DL, Cerfolio RJ. Satellite pulmonary nodule in the same lobe (T4N0) should not be staged as IIIB non-small cell lung cancer. Ann Thorac Surg. 2006; 82: 1808-1814.
  • 23
    Osaki T, Sugio K, Hanagiri T. Survival and prognostic factors of surgically resected T4 non-small cell lung cancer. Ann Thorac Surg. 2003; 75: 1745-1751.
  • 24
    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 tumors. J Thorac Oncol. 2007; 2: 706-714.
  • 25
    Strand TE, Rostrad H, Moller B, Norstein J. Survival after resection for primary lung cancer: a population based study of 3211 resected patients. Thorax. 2006; 61: 710-715.
  • 26
    Pfannschmidt J, Muley T, Bulzebruck H, et al. Prognostic assessment after surgical resection for non-small cell lung cancer: experiences in 2083 patients. Lung Cancer. 2006; 55: 371-377.
  • 27
    Duchateau CSJ, Stokkel MPM. Second primary tumors involving non-small cell lung cancer: prevalence and its influence on survival. Chest. 2005; 127: 1152-1158.
  • 28
    Okada M, Tsubota N, Yoshimura M, et al. Evaluation of TMN classification for lung carcinoma with ipsilateral intrapulmonary metastasis. Ann Thorac Surg. 1999; 68: 326-330.
  • 29
    Barnholtz-Sloan JS, Sloan AE, Davis FG, et al. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol. 2004; 22: 2865-2872.
  • 30
    Moscetti L, Nelli F, Felici A, et al. Up-front chemotherapy and radiation treatment in newly diagnosed nonsmall cell lung cancer with brain metastases: survey by Outcome Research Network for Evaluation of Treatment Results in Oncology. Cancer. 2007; 109: 274-281.
  • 31
    Burt M, Wronski M, Arbit E, et al. Resection of brain metastases from non-small-cell lung carcinoma. Results of therapy. Memorial Sloan-Kettering Cancer Center Thoracic Surgical Staff. J Thorac Cardiovasc Surg. 1992; 103: 399-410.
  • 32
    Patchell RA, Tibbs PA, Walsh JW, et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med. 1990; 322: 494-500.
  • 33
    Patchell RA, Tibbs PA, Regine WF, et al. Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA. 1998; 280: 1485-1489.
  • 34
    Sneed PK, Suh JH, Goetsch SJ, et al. A multi-institutional review of radiosurgery alone vs. radiosurgery with whole brain radiotherapy as the initial management of brain metastases. Int J Radiat Oncol Biol Phys. 2000; 53: 519-526.
  • 35
    Chang DB, Yang PC, Luh KT, et al. Late survival of non-small cell lung cancer patients with brain metastases. Influence of treatment. Chest. 1992; 101: 1293-1297.
  • 36
    Quddus AM, Kerr GR, Price A, Gregor A. Long-term survival in patients with non-small cell lung cancer treated with palliative radiotherapy. Clin Oncol. 2001; 13: 95-98.
  • 37
    Dillman RO, Herndon J, Seagren SL, et al. Improved survival in stage III non-small-cell lung cancer: 7-year follow-up of cancer and leukemia group B (CALGB) 8433 trial. J Natl Cancer Inst. 1996; 88: 1210-1215.
  • 38
    Ohe Y, Ishizuka N, Tamura T, et al. Long-term follow-up of patients with unresectable locally advanced non-small cell lung cancer treated with chemoradiotherapy: a retrospective analysis of the data from the Japan Clinical Oncology Group trials (JCOG0003A). Cancer Sci. 2003; 94: 729-734.
  • 39
    Kim DW, Shyr Y, Shaktour B, et al. Long term follow up and analysis of long term survivors in patient treated with paclitaxel-based concurrent chemo/radiation therapy for locally advanced non-small cell lung cancer. Lung Cancer. 2005; 50: 235-245.
  • 40
    Janssen-Heijnen MLG, Smulders S, Lemmens VEPP, et al. Effect of comorbidity on the treatment and prognosis of elderly patients with non-small cell lung cancer. Thorax. 2004; 59: 602-607.
  • 41
    Little AG, Gay EG, Gaspar LE, Stewart AK. National survey of non-small cell lung cancer in the United States: epidemiology, pathology and patterns of care. Lung Cancer. 2007; 57: 253-260.
  • 42
    Lilenbaum RC, Cashy J, Hensing TA, et al. Prevalence of poor performance status in lung cancer patients: implications for research. J Thorac Oncol. 2008; 3: 125-134.
  • 43
    Buccieri G, Ferrigno D, Tamburini M. Karnofsky and ECOG performance status scoring in lung cancer: a prospective, longitudinal study of 536 patients from a single institution. Eur J Cancer. 1996; 32A: 1135-1141.
  • 44
    Radzikowska E, Glaz P, Roszkowski K. Lung cancer in women: age, smoking, histology, performance status, stage, initial treatment and survival: population-based study of 20,561 cases. Ann Oncol. 2002; 13: 1087-1093.
  • 45
    Betticher DC, Schmitz SF, Totsch M, et al. Prognostic factors affecting long-term outcomes in patients with resected stage IIIA pN2 non-small-cell lung cancer: 5-year follow-up of a phase II study. Br J Cancer. 2006; 94: 1099-1106.
  • 46
    Gandara DR, Chansky K, Albain KS, et al. Long-term survival with concurrent chemoradiation therapy followed by consolidation docetaxel in stage IIIB non-small cell lung cancer: a phase II Southwest Oncology Group study (S9504). Clin Lung Cancer. 2006; 8: 116-121.
  • 47
    Morgensztern D, Boodgame B, Baggstrom MQ, et al. The effect of FDG-PET on the stage distribution of non-small cell lung cancer. J Thorac Oncol. 2008; 3: 135-139.
  • 48
    Mina LA, Neubauer MA, Ansari RH, et al. Phase III trial of cisplatin (P) plus etoposide (E) plus concurrent chest radiation (XRT) with or without consolidation docetaxel (D) in patients (pts) with inoperable stage III non-small cell lung cancer (NSCLC): HOG LUN 01-24/USO-023—updated results [abstract]. ASCO Meeting Abstracts. 2008; 26: 7519.
  • 49
    Perng RP, Chen CY, Chang GC, et al. Revisit of the 1997 TNM Staging System: survival analysis of 1112 lung cancer patients in Taiwan. Jpn J Clin Oncol. 2007; 37: 9-15.
  • 50
    Henschke CI, Yankelevitz DF, Miettinen OS, et al. The International Early Lung Cancer Action Program Investigators. CT screening for lung cancer: survival upon stage I diagnosis. N Engl J Med. 2006; 355: 1763-1771.