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(Chest. 2005;128:2274-2281.)
© 2005 American College of Chest Physicians

Survival of 2,991 Patients With Surgical Lung Cancer*

The Denominator Effect in Survival

Bronchogenic Carcinoma Cooperative Group of the Spanish Society of Pneumology Thoracic Surgery{dagger}

* From the Pneumology Service, Hospital Universitario 12 de Octubre, Madrid. Spain. {dagger} A complete list of GCCB-S members is given in the Appendix.

Correspondence to: Angel López-Encuentra, MD, PhD, Pneumology Service, Hospital Universitario 12 de Octubre, Ctta. Andalucía 5.4, 28041 Madrid, Spain; e-mail: lencuent{at}h12o.es


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 Appendix
 References
 
Objective: To evaluate the current staging system of lung cancer, taking into account different selection criteria for the studied population.

Population: A total of 2,991 consecutive patients with surgical lung cancer were prospectively compiled from 19 Spanish hospitals (Bronchogenic Carcinoma Cooperative Group of the Spanish Society of Pneumology and Thoracic Surgery) between 1993 and 1997.

Methods: The Kaplan-Meier method was used to calculate survival at 5 years (S5) for each pathologic stage, and the log-rank test was used for comparison purposes. These studies were performed in the total group (population 1, n = 2,972); excluding operative mortality and small cell lung cancer cases (population 2, n = 2,697); excluding cases with induction therapy (population 3, n = 2,542); excluding cases with exploratory thoracotomy (population 4, n = 2,304); and, lastly, excluding cases with incomplete resection (population 5, n = 2082) [70% of the initial population].

Results: The global S5 was similar in populations 1, 2, and 3: 34% (95% confidence interval [CI] 32 to 36%), 37% (95% CI, 35 to 39%), and 38% (95% CI, 35 to 39%), but different from that of populations 4 and 5: 40% (95% CI, 39 to 43%) and 43% (41 to 45%), respectively. For pathologic stage I, pathologic stage II, and pathologic state IIIA (pIIIA), S5 was similar in the five reported populations. In pathologic stage IIIB (pIIIB), there were differences in S5 between populations 1, 2, and 3 (13 to 15%; 95% CI, 10 to 19%) and populations 4 and 5 (26 to 29%; 95% CI, 19 to 38%). In population 4, there was no significant prognostic difference between two specific stage groups, that is between pathologic stage IB (pIB) and pathologic state IIA (pIIA) [p = 0.70] and between pIIIA and pIIIB (p = 0.79); the pathologic T3N2M0 combination has a S5 (13%) lower than that for pIIIB (26%).

Conclusion: The definition of the population that constitutes the denominator for the analysis of survival in surgical lung cancer is important in pIIIB. The inclusion or exclusion of cases without resection is the most important factor for the selection of such population. This study detected that there are no prognostic differences between pIB and pIIA, and between pIIIA and pIIIB.

Key Words: lung cancer • prospective studies • staging • surgery


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 Appendix
 References
 
The staging of lung cancer, or extent of anatomic extension, has been unified worldwide since 1986; the 1997 staging classification is currently in use.12 Since then, different studies from various continents have been reported using this classification,3456789 identifying problems in the prognostic discrimination of some stages,1011 or with differences between series in the survival probability per stages at 5 years.368

Classification after thoracotomy (pathologic staging) provides the maximum possible certainty on which the prognostic stratification of survival is based. To make it simple, survival data are expressed in cases of live cases (patients that are alive [numerator]) during a period of, for example, 5 years over the number of cases selected (denominator).

In theory, different survival data can be obtained depending on the population selected, which could be termed the denominator effect. If populations with conditions associated with a poor prognosis are excluded, the denominator effect may produce an increase in survival.

The study presented herein, conducted on a population of 2,991 patients who underwent thoracotomy for lung cancer, had two main aims: (1) to evaluate the denominator effect from a prognostic point of view by modifying the populations selected for analysis; and (2) after determining the most adequate population for analysis, to decide if the current classification for staging of lung cancer, in force since 1997, was prognostically discriminative in all its stages and TNM groups.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 Appendix
 References
 
Population
All the patients included in the study had lung cancer in initial stages and underwent thoracotomy with intent to cure in hospitals pertaining to the Bronchogenic Carcinoma Cooperative Group of the Spanish Society of Pneumology and Thoracic Surgery (GCCB-S).12 We included prospectively all patients treated surgically from October 1993 to September 1997 in hospitals participating in the GCCB-S. The annual cumulative number of cases was close to 50% of the surgical cases occurring in Spain. The participating GCCB-S centers had a wide variety of activities, including a representative range of number of beds, teaching or research activities (university and nonuniversity hospitals), public and private ownership, and number of interventions per year (from 8 to 100 interventions were performed in participating centers for this disease). The sample was complete, as verified by the inclusion in the registry of all patients undergoing surgery, including incomplete resections and exploratory thoracotomy.

Operative mortality was understood to include all deaths directly related to the surgical act, regardless of time of occurrence (< 30 days or > 30 days, intrahospital or extrahospital occurrence). The initial number of cases included in this study was 2,994. After a new evaluation of the entire series, three registries were ruled out. In the pathologic revision, one of the cases proved to be a carcinosarcoma. The other two registries corresponded to the same person operated on for two different tumors, one on each side, in 1994 and in 1996; this fact became known after confidentiality of the cases was opened in order to determine long-term survival. Thus, the final number of cases was 2,991. Given that the last patient of this GCCB-S series underwent surgery on September 30, 1997, an experience comprising real mortality and/or survival figures with a 7- to 11-year follow-up is now available (December 2004).

Different criteria have been considered to carry out studies on survival in order to progressively select the different populations: the "population denominator." Population 1 includes all patients except those with no survival data. Population 2 also excludes patients with operative mortality and the very small number of patients with small cell lung cancer (SCLC). Population 3 additionally excludes patients who received induction therapy, given the possible downstaging in pathologic staging. Population 4 additionally excludes patients with exploratory thoracotomy. Population 5 additionally excludes patients with residual disease, either microscopic or macroscopic and, therefore, includes patients who underwent complete resection, being the most selective population of this study. This last population meets the characteristics for non-SCLC (NSCLC) treated surgically with survival data, excluding cases with operative mortality, cases with induction therapy, or cases without resection or with incomplete resection.

Methods
The TNM classification currently in use worldwide was approved in 1997.12 Clinical staging is defined as the classification obtained through any means, even surgical, before the definitive therapeutic procedure is applied. Pathologic staging is defined as the classification obtained through findings observed during thoracotomy, after evaluation of the surgical specimen, and in conjunction with the data known from the clinical staging.113

In accordance with the initial design of this study, the period of case recruitment was short (from 1993 to 1997). Similar criteria for the functional operability of patients and oncologic operability of the tumor were used in all the GCCB-S hospitals.14

In the GCCB-S registry, each classificatory component included for different clinical T category groups was considered differentially for each patient. The diagnostic methods were registered using a previously agreed-on code, and the procedure that yielded the best resolution was identified.

The degree of certainty of the TNM stage classification depends on the diagnostic methods used; according to some international organizations, postmortem study yields the maximum certainty factor and clinical findings yield the minimum certainty factor.1 By consensus among the members of the GCCB-S coordinating group (two thoracic surgeons and a pneumologist), we established the methods for affirming maximum classificatory certainty for each component (maximum possible clinical certainty adjusted for each problem).1516 Lymph node categories (N) were evaluated using different diagnostic criteria of classificatory certainty. In order to confirm a clinical N0 classification, the absence of lymph node enlargement or lymph node enlargement of < 1 cm in diameter had to be confirmed by CT scan in lymph node areas 4, 7, and 10.17 Moreover, no lymph nodes must be present in the aortopulmonary window or in the anterior mediastinal area (areas 5 and 6) if the lung cancer involves the left side (upper lobe or main left bronchus). If these criteria were not met, normal results of mediastinoscopy-mediastinotomy or normal results of fine-needle aspiration biopsy (transbronchial, transthoracic, or transesophageal) of these areas was required. The clinical N1 classification was confirmed by cytohistologic evidence (transbronchial fine-needle biopsy, hilioscopy). To confirm a clinical N2 classification, cytohistologic evidence was required (mediastinoscopy, mediastinotomy, fine-needle aspiration biopsy using any approach).

Surgical-pathologic N0 was classified by radical mediastinal lymph node dissection or systematic sampling of at least four lymph node areas (area 2 [only in right lung cancer], and areas 4, 7, and 10 on the same side as the tumor). Moreover, no lymph nodes must be present in the aortopulmonary window or in the anterior mediastinal area (areas 5 and 6) if the lung cancer involves the left side (upper lobe or main left bronchus). For the purpose of classifying the presence or absence of mediastinal lymph node involvement, a randomized study18 demonstrated that systematic sampling has a value similar to that of radical mediastinal lymph node dissection. These minimal requirements (systematic sampling or radical mediastinal lymph node dissection) are indispensable to classify pathologic N0 (pN0), as there are prognostic differences when compared with only random lymph node sampling.19

Internal and external audits were made to survey the ratio between the number of patients undergoing surgery and the cases included in the registry (standard > 95%), and the presence and validity of the data recorded for each case (standard > 70%), including the consistency of tumor staging.1520 The criterion for the validity of the survival data were established as the existence of a known follow-up for ≥ 85% of the cases registered in each hospital. In the hospitals that did not meet all these conditions, the cases corresponding to the period of problems were excluded. Finally, correct data transmission by a single central office from the paper record to the computer database was verified. These procedures were designed to control the selection biases of surgical cases, registered cases out of the total number of surgical cases, sample size, type of hospital, prognostic migration due to the prolonged period of case recruitment, classification with low or deficient degrees of certainty, contamination by data from incomplete series or erroneous data, and loss of long-term follow-up. Given that this series focuses on surgical lung cancer and that the concordance between pathologic and clinical stages in our experience21 is deficient, this article only shows the analysis of the pathologic stages.

Prognostic data are stated in probability of survival at 5 years, with 95% confidence intervals (CIs) and in median (months) using the method of Kaplan-Meier, considering death from any cause as an event. Time zero is the date of the surgery. The log-rank test was used to compare survival curves. The difference is considered to be statistically significant at p < 0.05.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 Appendix
 References
 
General Descriptive Data of the Series
In this study, the patients were male in 2,768 cases (93%). Mean age was 64 years (SD, 9.56 years), and median age was 66 years (interquartile range, 59 to 71 years; minimum, 30 years; maximum, 91 years). At the time of closure of the follow-up study in 2004, 70% of all patients had died. The most common histologic type was squamous tumor (n = 1,775, 59%), followed by adenocarcinoma (n = 759, 25%), large cell carcinoma (n = 188, 6%), nonspecific type carcinoma (n = 136, 5%), bronchioloalveolar carcinoma (n = 84, 3%) and, lastly, SCLC (n = 49, 2%). By pathologic stages, seven cases were classified as occult or in situ carcinoma. There were 290 pathologic stage IA (pIA) cases (9.7%), 995 pathologic stage IB (pIB) cases (33.3%), 43 pathologic stage IIA (pIIA) cases (1.4%), 401 pathologic stage IIB (pIIB) cases (13.4%), 524 pathologic stage IIIA (pIIIA) cases (17.5%), 413 pathologic stage IIIB (pIIIB) cases (13.8%), and 42 pathologic stage IV cases (1.4%). In 276 cases (9.2%), we were unable to determine the pathologic stage either because there was no resection or because the minimal nodal mediastinal staging criteria were not met (refer to "Materials and Methods" section). Comorbidity was a common occurrence in this series of patients.22

Selection of the Populations Under Analysis
Figure 1 details the numeric data of the different populations studied to perform the survival analysis. Population 1 refers to the total initial population with survival data, after exclusion of the 19 cases without follow-up since surgery (0.6%). Population 2 refers to the numbers of cases that were left after cases with operative mortality and the scarce number of cases with SCLC (9%, in total) were excluded; there were 226 cases (7.6%) of operative mortality, the majority of which (90%) occurred within 30 days after surgery. Population 3 excludes the cases with neoadjuvant therapy (6% of population 2). Population 4 excludes the patients who underwent exploratory thoracotomy (9% of the previous population). Lastly, population 5 excludes 10% of population 4 who underwent incomplete resection, resulting in a final number of 2,082 cases (70% of the 2,991 initial total number). All criteria used for defining these populations were collected prospectively.



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  		Figure 1.. Selection of populations for the survival analysis, from the initial (all cases with thoracotomy due to lung cancer) to the most selected population (NSCLC with complete resection, excluding operative mortality and cases with induction therapy).

 
Survival According to Populations
Table 1 shows survival data for each population, identifying among the most extreme populations, a loss of 30% of the cases and a 9% gain in survival at 5 years. The 95% CIs of 5-year survival are similar for populations 1, 2, and 3, and different when compared to populations 4 and 5.


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  		Table 1.. Overall Survival According to Selected Populations

 
When the same comparison is made in surgical lung cancer among the different populations for each pathologic stage, a loss of cases is observed, which increases in percentage in direct relation to the increase in stage. In pathologic stage I (pI), an 11% drop in the number of cases is observed, in pathologic stage II (pII) there is a 23% drop, in pIIIA there is a 34% drop, and in pIIIB there is a 76% drop. However, the 5-year survival gain only represents a 3 to 4% increase in pI, pII, and pIIIA, with practically identical 95% CIs. This behavior is in sharp contrast with that observed in pIIIB, in which a clear prognostic increase is observed when the most extreme populations are compared, with a 16% increase in the 5-year survival for the same stage (Table 2 ).


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  		Table 2.. Survival in pIIIB According to Populations

 
Survival According to Stages
Table 3 states survival data and shows a comparison among the stages, taking into account the different pathologic stages of the total population (population 1, n = 2,972). Neither the 7 cases of occult or in situ carcinomas nor the 42 cases in pathologic stage IV were taken into account. There are 273 cases (9%) in which the pathologic stage is not known either because resection was not performed or because a pN0 classification with sufficient classificatory certainty was not reached (see "Materials and Methods" sections). The only stage without significant difference is pIIA, when compared against the immediate previous stage: pIB.


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  		Table 3.. Survival According to Pathologic Stage, Population 1

 
Population 4 (n = 2,304) was selected to facilitate comparability with other experiences reported in the literature (Fig 1): NSCLC excluding cases with operative mortality, induction therapy, or without resection (exploratory thoracotomy). Table 4 presents detailed survival data by stages in this population 4. As with pIIA, pIIIB does not show a significant prognostic difference when compared with the previous stage, pIIIA (log-rank method or Wilcoxon-Gehan method). Survival figures for all the stages of population 4 (Table 4) are better than the survival figures reported for population 1 (Table 3).


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  		Table 4.. Survival According to Pathologic Stage Population 4

 
Survival According to Pathologic TN Grouping
Table 5 shows for population 4 the survival distribution according to pathologic TN groupings; all are pathologic M0. The order and grouping of the cases were done taking into account punctual values of 5-year survival and the dimensions of the 95% CI for this survival.


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  		Table 5.. Survival According to Pathologic TN Groupings in Pathologic M0, Population 4

 
For each pathologic T category, comparison between pN0 and pathologic N2 (pN2) is statistically significant (p < 0.01); as it is also in pathologic T1, between pathologic N1 (pN1) and pN2 (p = 0.04), in pathologic T2, and also between pN0 and pN1 (p = 0.001) and between pN1 and pN2 (p = 0.01).

Pathologic TN combinations that include pathologic T4 have been excluded, as changes caused by the so-called denominator effect were detected in survival at 5 years (S5) [Tables 234]. Data corresponding to pathologic T1N1 (Table 3) are included between those for pathologic T1N0 and pathologic T2N0 because of its similar survival, although there are statistically significant differences in survival between pathologic T1N0 and pathologic T2N0, and because the S5 rate (95% CI) possibly unstable due to the small number of cases.


   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
Appendix
 References
 
This study was made in a large series of cases collected in a short, recent time interval. The study was multi-institutional and representative of the cases of NSCLC treated surgically in Spain, with an initial design conceived to control the usual biases in prognostic and/or therapeutic studies.23242526

In our study, considering different populations to observe the so-called denominator effect, the most evident criterion to show such effect was the exclusion of exploratory thoracotomy (Fig 1; Table 1). The rest of factors considered also had their own sense of prognostic change although of a lesser magnitude. When considering pathologic stages, the greatest prognostic migration is identified in pIIIB, with a 16% difference in S5 between population 1 and population 5 (Table 2). According to current lung cancer staging classification, and using the total population of the study (population 1), a complete prognostic range is detected justifying all pathologic stages, except for pIIA (Table 3). However, if we select population 4, which excludes, among other criteria, those cases with exploratory thoracotomy, there is no prognostic difference between pIIIA and pIIIB besides what has been reported for pIIA (Table 4).

The literature shows a great variability in the selection criteria used for the selection of the population that constitutes the denominator of the survival equation. Table 6 shows the data corresponding to seven independent experiences with > 500 patients, grouped by continents.3456789 In six of the seven experiences, cases with exploratory thoracotomy were not included in the population under analysis, but incomplete resections were included. The requirement for classificatory certainty for pN0 was also variable. Four studies describe the existence of a systematic sampling or systematic nodal dissection, and in three studies such a description is not given.


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  		Table 6.. Population Characteristics: Different Series of Pathologic Staging Reported in the Literature Grouped by Continents*

 
Population 4 was used to facilitate comparability of the data in our series, which, among other minor criteria, excludes cases without resection from analysis. Data from the eight series, per pathologic stages, are presented in Table 7 , which shows a notable variability among the different experiences despite the fact that a similar population was used as the denominator.


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  		Table 7.. Survival by Pathologic Stages: Different Series Reported in the Literature Grouped by Continents*

 
In the most initial stage, pIA, a significant difference is observed in terms of survival between the Japanese experiences,56 with a 79 to 80% survival at 5 years in comparison with our study, with only a 58% survival for the same period. The same occurs in pIB (60 to 65% vs 51%). In the experience of Naruke et al,6 adenocarcinoma was more frequent than the epidermoid type, being that the survival in pIA was 82% for adenocarcinoma and 72% for epidermoid type. Another possible explanation for the difference is the possible greater frequency of bronchioloalveolar carcinoma in Japan that may be higher than our 3%. Another possible difference is also tumor size. It is well known that the 3-cm cutoff margin in size to differentiate prognosis in lung cancer is debatable and insufficient as a prognostic discriminative criterion.2728293031 The described Japanese experience reports 974 N0M0 cases with complete resection with 241 tumors of < 2 cm in size, 285 tumors between 2 cm and 3 cm, 278 tumors between 3 cm and 5 cm, and 170 tumors > 5 cm.6 Our population of 1,390 N0M0 cases with complete resection includes 99 cases with tumors < 2 cm, 230 tumors between 2 cm and 3 cm, 525 tumors between 3 cm and 5 cm, and 536 tumors > 5 cm. From the comparison between experiences, it is evident that the proportion of cases of larger size within the T1 category (< 3 cm) and the T2 category (> 3 cm) is higher in the Spanish series. A classification as reductional as the one currently in force in relation to tumor size could also serve as explanation for the differences observed in survival.

The comparison of the data shown in Table 7 yields other reflections in the most advanced stages. Other experiences also describe the absence of a prognostic gradient between pIIIA and pIIIB, or a paradoxical behavior (better survival in pIIIB than in pIIIA).79 This observation can be explained by the different prognosis of the heterogeneous clinical situations that are grouped together in the T3 and T4 categories11 or the specific TN combinations that coexist with these stages. Some studies fail to provide survival data for pIIIB (Table 7).

There are some problems in the TN groups. Apart from the already described abnormal and uncertain behavior of pathologic T1N1 (pIIA),1032 the group of TN situations that conform pIIIA (last four TN groups shown in Table 5) also presents a different prognostic behavior. pIIA is very uncommon in all series, making it difficult, among other reasons, to establish a prognostic comparison with adjoining strata; however, in our article, it is in fact different from pIIB (0.03). Between pathologic T1N2 and pathologic T3N2, the eight described experiences are consistent with the difference in survival: Mountain3 reported a big difference at 5 years between pathologic T1N2 and pathologic T3N2: 38% and 12%; Adebonojo et al4 reported a 39% and 15% difference; Inoue et al5 reported a 38% and 11% difference; Padilla et al7 reported a 26% and 10% difference; van Rens et al8 reported a 25% and 7% difference; and Jassem et al9 reported a 35% and 6% difference, respectively. The GCCB-S presented a difference between 22% and 13%.

In conclusion, and mainly for the most advanced stages, the expression of survival in lung cancer must show specifically the population selected for the prognostic analysis. The unification and exact definition of the selection criteria used in the analyzed population for determining the pathologic staging of NSCLC is an absolute must. An accurate classification of the anatomical extension of lung cancer is basic to evaluate new prognostic factors at a time when molecular variables are under intense study worldwide.33 Variability in the prognostic results in the TNM classification has been detected—lung cancer stages among the experiences from different countries and continents—despite the attempt to control homogeneity in the evaluated populations. Given that these studies consist of < 3,500 patients each, it would not be surprising that the International Staging Project of the International Association for the Study of Lung Cancer34 could, with a larger study population, help resolve these problems for the upcoming 2009 lung cancer staging.


   Appendix
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Appendix
References
 
The GCCB-S
Coordinators: José Luis Duque, MD (Hospital Universitario, Valladolid); Angel López-Encuentra, MD, PhD (Hospital Universitario 12 de Octubre, Madrid); Ramón Rami Porta, MD (Hospital Mutua de Terrassa, Barcelona).

Local representatives: Julio Astudillo, MD, Pedro López de Castro, MD (Hospital Germans Trias i Pujol, Barcelona); Emilio Canalís, MD (Hospital Clinic, Barcelona); Antonio Cantó, MD, Arnau Obrer, MD (Hospital Clínico, Valencia); Juan Casanova, MD, Mariñan, MD (Hospital de Cruces, Bilbao); Manuel Castanedo, MD, Jorge Quiroga, MD (Hospital Universitario, Valladolid); Antonio Fernández de Rota, MD, Arrabal Sánchez, MD (Hospital Carlos Haya, Málaga); Federico González Aragoneses, MD, Nicolas Moreno, MD (Hospital Gregorio Marañón, Madrid); Jorge Freixinet, MD, Pedro Rodríguez, MD (Hospital Nuestra Señora del Pino, Las Palmas); Nicolás Llobregat, MD (Hospital Universitario del Aire, Madrid); Nuria Mañes, MD, Helena Hernández, MD (Fundación Jiménez Díaz, Madrid); Mireia Serra Mitjans, MD, José Belda Sanchis, MD (Hospital Mutua de Terrassa, Barcelona); José Luis Martín de Nicolás, MD (Hospital Universitario 12 de Octubre, Madrid); Nuria Novoa (Complejo Hospitalario, Salamanca); Jesús Rodríguez, MD (Complejo Hospitalario, Oviedo); Antonio José Torres García, MD, Ana Gómez, MD (Hospital Universitario San Carlos, Madrid); Mercedes de la Torre (Hospital Juan Canalejo, La Coruña); Abel Sánchez-Palencia, MD, Javier Ruiz, MD (Hospital Virgen de las Nieves, Granada); Andrés Varela Ugarte, MD (Clínica Puerta de Hierro, Madrid); Yat Wah Pun, MD (Hospital de la Princesa, Madrid).

Data analysis: Clinical Epidemiology Unit (Hospital 12 de Octubre): Francisco Pozo Rodríguez, MD, Agustín Gómez de la Cámara, MD.


   Footnotes
 
Abbreviations: CI = confidence interval; GCCB-S = Bronchogenic Carcinoma Cooperative Group of the Spanish Society of Pneumology and Thoracic Surgery; NSCLC = non-small cell lung cancer; pI = pathologic stage I; pIA = pathologic stage IA; pIB = pathologic stage IB; pII = pathologic stage II; pIIA = pathologic stage IIA; pIIB = pathologic stage IIB; pIIIA = pathologic stage IIIA; pIIIB = pathologic stage IIIB; pN0 = pathologic N0; pN1 = pathologic N1; pN2 = pathologic N2; S5 = survival at 5 years; SCLC = small cell lung cancer

Partial funding was provided by Fondo Investigación Sanitaria (FIS) grant 97/0011, Fundación Española del Pulmón-1995 grant, Red Temática Investigación Cooperativa-03/11-ISCIII-Red-Respira grant, FIS grant 03/46, and financial aid from the Castilla-León regional government and the Menarini Foundation.

Received for publication February 14, 2005. Accepted for publication April 21, 2005.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Appendix
 References
 

  1. Sobin, LH, Wittekind, Ch (1997) UICC International Union Against Cancer TNM classification of malignant tumours 5th ed. ,91-97 Wiley-Liss. New York, NY:
  2. Fleming, ID, Cooper, JS, Henson, DE, et al AJCC cancer staging manual 5th ed. 1997,127-137 Lippincott-Raven. Philadelphia, PA:
  3. Mountain, CF Revisions in the international system for staging lung cancer. Chest 1997;111,1710-1717[Abstract/Free Full Text]
  4. Adebonojo, SA, Bowser, AN, Moritz, DM, et al Impact of revised stage classification of lung cancer on survival: a military experience. Chest 1999;115,1507-1513[Abstract/Free Full Text]
  5. Inoue, K, Sato, M, Fujimura, S, et al Prognostic assessment of 1310 patients with non-small-cell lung cancer who underwent complete resection from 1980 to 1993. J Thorac Cardiovasc Surg 1998;116,407-411[Abstract/Free Full Text]
  6. Naruke, T, Tsuchiya, R, Kondo, H, et al Implications of staging in lung cancer: prognosis and survival after resection for bronchogenic carcinoma based on the 1997 TNM-staging classification: the Japanese experience. Ann Thorac Surg 2001;71,1759-1764[Abstract/Free Full Text]
  7. Padilla, J, Calvo, V, Garcia Zarza, A, et al El pronóstico tras resección de carcinoma broncogénico no células pequeñas según la nueva norma de estadificación: un análisis de 1433 pacientes. Arch Bronconeumol 1999;35,483-487[Medline]
  8. van Rens, MT, de la Riviere, AB, Elbers, HR, et al Prognostic assessment of 2,361 patients who underwent pulmonary resection for non-small cell lung cancer, stage I, II, and IIIA. Chest 2000;117,374-379[Abstract/Free Full Text]
  9. Jassem, J, Skokowski, J, Dziadziuszko, R, et al Results of surgical treatment of non-small cell lung cancer: validation of the new postoperative pathologic TNM classification. J Thorac Cardiovasc Surg 2000;119,1141-1146[Abstract/Free Full Text]
  10. Rami Porta R (GCCB-S). Reflections on the revisions in the international system for staging lung cancer. Chest 1998; 113:1728–1729
  11. Kameyama, K, Huang, CL, Liu, D, et al Problems related to TNM staging: patients with stage III non-small cell lung cancer. J Thorac Cardiovasc Surg 2002;124,503-510[Abstract/Free Full Text]
  12. Grupo Cooperativo de Carcinoma Broncogénico de SEPAR (GCCB-S).. Cirugía del carcinoma broncogénico en España: estudio descriptivo. Arch Bronconeumol 1995;31,303-309[Medline]
  13. Rami-Porta, R, Lopez-Encuentra, A, Duque-Medina, JL Caution! The latest AJCC’s rules for lung cancer classification differ from the latest UICC’s. Lung Cancer 2004;43,361-362[Medline]
  14. López Encuentra, A, the Bronchogenic Carcinoma Cooperative Group of the Spanish Society of Pneumology and Thoracic Surgery(GCCB-S).. Criteria of functional and oncological operability in surgery for lung cancer: a multicenter study. Lung Cancer 1998;20,161-168[CrossRef][ISI][Medline]
  15. López Encuentra, A, Gómez de la Cámara, A, for the Bronchogenic Carcinoma Cooperative Group of the Spanish Society of Pneumology and Thoracic Surgery (GCCB-S). Validation of a central review board of staging prior to surgery for non-small-cell lung cancer: impact on prognosis: a multicenter study. Respiration 2002;69,16-24[CrossRef][Medline]
  16. López Encuentra, A, Gómez de la Cámara, A, Varela de Ugarte, A, et al GCCB-S. El "fenómeno Will-Rogers." Migración de estadios en carcinoma broncogénico, tras aplicar criterios de certeza clasificatoria Arch Bronconeumol 2002;38,166-171[Medline]
  17. American Thoracic Society: Clinical staging primary lung cancer.. Am Rev Respir Dis 1983;127,659-664[ISI][Medline]
  18. Izbicki, JR, Passlick, B, Karg, O, et al Impact of radical systematic mediastinal lymphadenectomy on tumor staging in lung cancer. Ann Thorac Surg 1995;59,209-214[Abstract/Free Full Text]
  19. Gajra, A, Newman, N, Gamble, GP, et al Effect of number of lymph nodes sampled on outcome in patients with stage I non-small-cell lung cancer. J Clin Oncol 2003;21,1029-1034[Abstract/Free Full Text]
  20. Grupo Cooperativo de Carcinoma Broncogénico de SEPAR(GCCB-S).. Control de calidad en un registro multiinstitucional de carcinoma broncogénico [abstract]. Arch Bronconeumol 1996;32(suppl 2),70
  21. López-Encuentra, A, García-Luján, R, Rivas, JJ, GCCB-S. et al Comparison between clinical and pathological staging in 2,994 cases of lung cancer. Ann Thorac Surg 2005;79,974-979[Abstract/Free Full Text]
  22. López-Encuentra, A, GCCB-S. Comorbidity in operable lung cancer: a multicenter descriptive study on 2992 patients. Lung Cancer 2002;35,263-269[CrossRef][ISI][Medline]
  23. Nesbitt, JC, Putnam, JB, Walsh, GL, et al Survival in early-stage non-small cell lung cancer. Ann Thorac Surg 1995;60,466-472[Abstract/Free Full Text]
  24. van Meerbeeck, JP Staging of non-small cell lung cancer: consensus, controversies and challenges. Lung Cancer 2001;34(suppl 2),S95-S107
  25. Padilla, J, Calvo, V, Peñalver, JC, et al Carcinoma broncogénico no anaplásico de células pequeñas en estadio I y de diámetro máximo de 3 cm: factores pronósticos. Arch Bronconeumol 2004;40,110-113[Medline]
  26. Okada, M, Nishio, W, Sakamoto, T, et al Evolution of surgical outcomes for non-small cell lung cancer: time trends in 1465 consecutive patients undergoing complete resection. Ann Thorac Surg 2004;77,1926-1930[Abstract/Free Full Text]
  27. Bronchogenic Carcinoma Cooperative Group of the Spanish Society of Pneumology and Thoracic Surgery(GCCB-S).. Clinical tumour size and prognosis in lung cancer. Eur Respir J 1999;14,812-816[Abstract/Free Full Text]
  28. Suzuki, K, Nagai, K, Yoshida, J, et al Conventional clinicopathologic prognostic factors in surgically resected nonsmall cell lung carcinoma: a comparison of prognostic factors for each pathologic TNM stage based on multivariate analyses. Cancer 1999;86,1976-1984[CrossRef][ISI][Medline]
  29. López-Encuentra, A, Duque-Medina, JL, Rami-Porta, R, et al Bronchogenic Carcinoma Co-operative Group of the Spanish Society of Pneumology and Thoracic Surgery. Staging in lung cancer: is 3 cm a prognostic threshold in pathologic stage I non-small cell lung cancer? A multicenter study of 1,020 patients. Chest 2002;121,1515-1520[Abstract/Free Full Text]
  30. Carbone, E, Asamura, H, Takei, H, et al T2 tumors larger than five centimeters in diameter can be upgraded to T3 in non-small cell lung cancer. J Thorac Cardiovasc Surg 2001;122,907-912[Abstract/Free Full Text]
  31. Cangir, AK, Kutlay, H, Akal, M, et al Prognostic value of tumor size in non-small cell lung cancer larger than five centimeters in diameter. Lung Cancer 2004;46,325-331[CrossRef][Medline]
  32. Buccheri, G, Ferrigno, D Prognostic value of stage grouping and TNM descriptors in lung cancer. Chest 2000;117,1247-1255[Abstract/Free Full Text]
  33. Brundage, MD, Davies, D, Mackillop, WJ Prognostic factors in non-small cell lung cancer: a decade of progress. Chest 2002;122,1037-1057[Abstract/Free Full Text]
  34. Goldstraw, P The International Staging Committee of the IASLC: its origins and purpose. Lung Cancer 2002;37,345-348[CrossRef]




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