Lung cancer is the most common overall cause of

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1 GENERAL THORACIC Survival in Primary Lung Cancer Potentially Cured by Operation: Influence of Tumor Stage and Clinical Characteristics Gunnar Myrdal, MD, Mats Lambe, MD, PhD, Gunnar Gustafsson, MD, PhD, Kristina Nilsson, MD, PhD, and Elisabeth Ståhle, MD, PhD Departments of Thoracic and Cardiovascular Surgery and Oncology, Uppsala University Hospital, Uppsala, and Department of Medical Epidemiology, Karolinska Institute, Stockholm, Sweden Background. Surgical resection is currently standard treatment in early stage lung cancer. The aim of the present study was to identify stage-related factors and patient characteristics influencing survival after complete resection. Methods. We identified 395 patients with non-small cell lung cancer who had undergone potentially radical operation during 1987 to 1999 at one thoracic surgery institution in central Sweden. Factors independently related to survival were identified in a multivariate analysis. Survival was analyzed in low-, medium-, and high-risk groups based on a risk score calculated from relative hazards for identified risk factors. Results. Overall 5-year survival among the 395 patients was 51%. The strongest factor predicting prognosis was positive lymph nodes at operation. Higher age, earlier period for operation, impaired lung function, current smoking, and major operative complication were all related to poorer prognosis. Patients with tumor stage Ia had a 5-year survival of 69%, compared to 73% in patients in the low-risk group. Conclusions. Tumor stage is the best prognostic indicator after radical operation. Inclusion of other tumorand patient-related variables did not add prognostic information of clinical relevance beyond that provided by tumor stage alone. (Ann Thorac Surg 2003;75:356 63) 2003 by The Society of Thoracic Surgeons Lung cancer is the most common overall cause of cancer death in Sweden. Moreover, the incidence of lung cancer is increasing, especially in younger birth cohorts of women [1]. Lung cancer has a poorer prognosis than breast, prostate, and colon cancer, with an overall relative 5-year survival rate no higher than 5% to 15% [2]. Approximately 80% of new lung cancer cases are of the non-small cell type [2], with an estimated 5-year overall survival rate of 10% to 18% [3, 4]. At present, surgical resection remains the only therapeutic modality with a curative potential in patients with early stage non-small cell lung cancer (according to the current TNM classification [5]). To ensure that patients with lung cancer receive treatment appropriate for their level of disease, it is necessary to achieve accurate staging by obtaining detailed information about the tumor size, tumor extension, location, and lymph node involvement. Furthermore, little is known about the influences of clinical factors with respect to long-term survival, either separately or in combination with the staging variables. The aim of the present study was to examine the survival in 395 patients with non-small cell lung cancer Accepted for publication Aug 24, Address reprint requests to Dr Myrdal, Uppsala University Hospital, Department of Thoracic and Cardiovascular Surgery, SE Uppsala, Sweden; gunnar.myrdal@thorax.uas.lul.se. potentially cured by operation and to evaluate the impact of different clinical and stage-related factors on the prognosis. Material and Methods Patients Between January 1987 and September 1999, 616 consecutive patients with lung cancer underwent operation with intention to cure at the Department of Thoracic and Cardiovascular Surgery, University Hospital, Uppsala, in central Sweden. After preoperative computed tomographic scan, these patients had been considered to have a locally resectable tumor without signs of metastatic spread, corresponding to tumor stages I and II based on a previous staging system [5]. If signs of metastatic spread were seen on the computed tomographic scan (short axis more than 1 cm), mediastinoscopy was performed (84 patients of 616). Patients with positive mediastinoscopy were excluded from further surgical treatment. Of the 616 patients, 221 patients were excluded from further analyses: 18 died during the first 30 days after operation, 70 patients underwent explorative thoracotomy as the extension of the tumor did not permit resection (of these 70 patients, 44 had a tumor invading mediastinal organs, 19 invading the thoracic wall or a rib, and in 7 patients both); 97 underwent an incomplete 2003 by The Society of Thoracic Surgeons /03/$30.00 Published by Elsevier Science Inc PII S (02)

2 Ann Thorac Surg MYRDAL ET AL 2003;75: SURVIVAL AFTER OPERATION FOR LUNG CANCER resection, defined as either the presence of positive margins at the pathologic examination or residual tumor as judged by the surgeon (of these 97 patients, 68 showed positive margins at pathologic examination and 29 had residual diseases as assessed by the surgeon in 16, invasion of the chest wall or diaphragm and in 13, invasion of a mediastinal organ); 30 had a tumor of the carcinoid type; and 3 patients had a lymphoma in the mediastinum with lung involvement. Three patients living outside Sweden were lost to follow-up. The remaining 395 patients (Table 1) had a completely removed tumor as assessed by the surgeon and showed negative tissue margins at pathologic examination and were considered to be potentially cured by operation. These 395 patients formed the study population. Of these, 255 were men (mean age, 65.8 years; range, 38 to 82 years) and 140 were women (mean age, 63.6 years; range, 27 to 82 years). Preoperative evaluation included spirometry, forced expiratory volume in 1 second (FEV 1% ; percentage of reference values according to age and body size, FEV 1 60% versus FEV 1 60%) [6], and lung perfusion scans. Clinical characteristics included in the analyses were concomitant diseases (diabetes mellitus, chronic obstructive lung disease, ischemic heart disease, or hypertension, all requiring medication) and major complications (postoperative bleeding leading to reoperation, respiratory failure, bronchopleural fistulas, myocardial infarction, major stroke, renal failure, and cardiac failure). Former smokers were defined as patients who had stopped smoking at least 2 months before operation (Table 1). At all operations the standard open posterolateral approach was used. Mediastinal lymph node samples were taken as routine and node stations were classified in anatomic lymph node chains [7]. Since April 1995, 11 patients had been included in a Scandinavian study on adjuvant therapy. No patients received neoadjuvant treatment. Data Collection and Follow-Up Patients potentially eligible for inclusion were identified using an in-hospital database. An individually unique 10-digit national registration number, allocated to all Swedish residents at the time of birth or permanent resident, allowed complete follow-up with respect to survival by computerized linkage to the Swedish Cause of Death Register. These subjects could be assigned a date of death or identified as being alive on 31 December The mean length of follow-up was 46 months (range, 4 to 156 months). Detailed information on each patient was retrieved from medical records. The study was approved by the Ethics Committee at the Uppsala University Hospital. Statistical Methods The observed survival rate for all causes of death was calculated by the actuarial (lifetable) method [8]. The log rank test was used to test for equality of the survival curves in different groups. 357 Univariate and multivariate analyses performed to identify factors related to death (by any cause) were based on the standard Cox proportional hazard model [8]. The relative hazard (RH exp( 1 )) was used as a measure of the risk of death in different categories, where 1 is the basic measure in the Cox model. Continuous variables were tested in their original continuous form, a logarithmic form, and with a set of dummy variables representing ranges, defined by commonly used or standard cutoff points. The RH ratios and their 95% confidence intervals are in general given for the variable in both the optimal continuous form and the dichotomized form, as this way of presenting the results was considered most informative. In the multivariate analyses the variables were used first in their continuous form, the original (year of operation) or logarithmic (age, percent predicted FEV 1, and tumor size) form and then in their optimal dichotomized form with the best discriminatory power. To analyze categorized variables a set of dummy variables was used. Variables significantly related to mortality in the univariate analysis were considered in the multivariate analysis (p 0.05). Variables entered into the analysis are shown in Table 1. On the basis of the results of the multivariate analysis of the influence of different variables on survival (Table 2), a risk score was computed for each patient. Risk Score exp(1.14 {year since 1987} 0.13 {tumor stage Ib} 0.68 {tumor stage II} 0.76 {tumor stage III} 0.05 {ln(age)} 0.57 {ln(percent predicted FEV)} 2.56 {tumor growth in pleura parietal} 0.55 {major complication} 0.26 {active smoker}). Patients were categorized into a low-risk, medium-risk, or high-risk group. The cutoff points were chosen so as to get 25% of the subjects in the low-risk and high-risk groups and 50% in the medium-risk group. Because the basic models used assume that the RH are constant over time, separate models were estimated for follow-up at less than 36 months and 36 months after operation. In an additional step, stratified standard Cox models were used for analysis of the interaction between risk factors. Finally, interaction was tested for by introduction of an interaction variable. Spearman rank correlation was used to test for correlation between tumor size and lymph node involvement. To test for trends in the distribution of risk factors over time the Cochran-Armitage trend test was used. All statistical calculations were performed with the SAS 6.12 statistical procedure (SAS Institute, Cary, NC). Results Survival Patient characteristics and corresponding 5-year survival rates are presented in Table 1. The overall 5-year survival rate in the study population (n 395) was 51% (Fig 1). In addition, survival of patients excluded from the study population, that is, patients who underwent explorative thoracotomy alone and patients with an incomplete resection are also depicted in Figure 1. GENERAL THORACIC

3 GENERAL THORACIC 358 MYRDAL ET AL Ann Thorac Surg SURVIVAL AFTER OPERATION FOR LUNG CANCER 2003;75: Table 1. Patient Characteristics in Relation to Death 5 Years After Operation No. of Patients Total No. of Deaths n (%) n (%) Five-year Survival % [95% CI] a Total 395 (100%) 232 (59%) 51% [46 56] Gender Female 140 (37%) 73 (52%) 54% [45 63] Male 255 (63%) 159 (62%) 50% [44 56] Age 59 years 101 (26%) 48 (47%) 60% [50 70] years 151 (38%) 98 (65%) 49% [40 58] 70 years 143 (36%) 86 (60%) 47% [38 56] Smoking habits b Current smoker 218 (55%) 143 (66%) 46% [39 53] Former smoker 126 (32%) 65 (50%) 61% [51 57] Never smoked 49 (12%) 24 (50%) 50% [35 65] Concomitant disease Yes 140 (35%) 84 (60%) 50% [41 59] No 255 (65%) 148 (58%) 51% [43 60] Measurement of lung function c FEV 1 60% 341 (89%) 192 (56%) 52% [46 58] FEV 1 60% 42 (11%) 35 (83%) 41% [26 56] Time period (30%) 95 (79%) 42% [33 51] (25%) 68 (70%) 53% [44 63] (21%) 44 (52%) 58% [48 68] (23%) 25 (27%) 60% [47 73] Type of operation Pneumonectomy 110 (28%) 75 (68%) 39% [30 48] Lobectomy 257 (65%) 144 (56%) 55% [48 62] Bilobectomy 25 (6%) 11 (45%) 59% [39 79] Segment resection 3 (2%) 2 (67%) 33% [0 66] Major complication Yes 32 (8%) 25 (78%) 32% [16 48] No 363 (92%) 207 (57%) 53% [48 58] Histopathologic type Adenocarcinoma 144 (36%) 76 (53%) 52% [43 61] Squamous cell cancer 183 (46%) 115 (63%) 50% [43 57] Bronchoalveolar cell cancer 31 (8%) 19 (61%) 50% [37 63] Mixed types 37 (9%) 22 (59%) 47% [30 64] Tumor size 10 mm 22 (6%) 11 (50%) 66% [42 90] mm 50 (13%) 24 (48%) 55% [40 70] mm 94 (24%) 56 (60%) 55% [45 65] mm 114 (29%) 71 (62%) 46% [36 56] 50 mm 115 (29%) 70 (61%) 47% [37 57] Tumor growth in lymph nodes d N0 265 (67%) 135 (51%) 62% [56 68] N1 100 (26%) 76 (76%) 28% [19 37] N2 30 (7%) 20 (66%) 34% [16 50] Tumor growth in parietal pleura Yes 4 (1%) 4 (100%) No 391 (99%) 288 (74%) 57% [49 66] Tumor stage e Ia 114 (29%) 53 (46%) 69% [60 77] Ib 142 (36%) 79 (56%) 57% [48 66] IIa IIb 105 (26%) 77 (73%) 31% [22 40] IIIa f 33 (8%) 23 (70%) 29% [13 42] a Confidence Interval. b In 2 patients no information about smoking habits was available. c In 12 patients, no FEV 1 % was available. d Nodal status and e pathological stage (TNM) at time of surgery [5]. f IIIa; 30 patients with T1/T2 N2, and 3 patients with T3 N1.

4 Ann Thorac Surg MYRDAL ET AL 2003;75: SURVIVAL AFTER OPERATION FOR LUNG CANCER Table 2. Variables That Influenced Survival in Patients Potentially Curable by Operation in Univariate and Multivariate Cox Regression Model Variable Univariate Multivariate RH a [95% CI] b RH [95% CI] 359 GENERAL THORACIC a. Stage-related variables considered Tumor size 10 mm 1.0 Reference 1.0 Reference mm 1.0 [ ] 1.0 [ ] mm 1.2 [ ] 1.0 [ ] mm 1.3 [ ] 1.0 [ ] 50 mm 1.4 [ ] 1.1 [ ] Logarithmic 1.2 [ ] 1.1 [ ] Lymph nodes N0 1.0 Reference 1.0 Reference N1 2.1 [ ] 2.0 [ ] N2 1.7 [ ] 1.8 [ ] Tumor growth in parietal pleura No 1.0 Reference 1.0 Reference Yes 16.0 [ ] 17.0 [ ] b. All variables considered Age 59 years 1.0 Reference 1.0 Reference 60 years 1.5 [ ] 1.6 [ ] Logarithmic 2.4 [ ] 3.9 [ ] Time period Reference 1.0 Reference [ ] 0.7 [ ] Linear c 0.94 [ ] 0.95 [ ] Measurement of lung function FEV 1 60% 1.0 Reference 1.0 Reference FEV 1 60% 0.6 [ ] 0.7 [ ] Logarithmic 0.4 [0 0.98] 0.6 [0 1.25] Smoking habits Never/stopped smoking 1.0 Reference 1.0 Reference Current smoker 1.4 [ ] 1.3 [ ] Major complication No 1.0 Reference 1.0 Reference Yes 2.2 [ ] 1.7 [ ] Tumor stage Ia 1.0 Reference 1.0 Reference Ib 1.3 [ ] 1.1 [ ] IIa IIb 2.2 [ ] 2.0 [ ] IIIa 2.3 [ ] 2.1 [ ] Tumor growth in parietal pleura No 1.0 Reference 1.0 Reference Yes 16.0 [ ] 11.0 [ ] a RH relative hazard; b CI confidence interval; c Linear variable, which implies reduction in risk for death for every year from 1987 to In the study population all tumor-related variables were associated with 5-year survival; both tumor size and tumor spread to lymph nodes, locally or in the mediastinum, were inversely related to survival (Fig 2 and Table 1). Risk Factors In univariate explorative analyses, based on stage-related variables, the size of the tumor, the presence and advancement of lymph node metastases were all closely related to the prognosis (Table 2). Any sign of node involvement doubled the risk of death. Tumor size had less impact on prognosis. There was a 40% increase in mortality among patients with tumors larger than 5 cm as compared to those with tumors of 1 cm or less. In the multivariate analysis, stage was chosen and used in the full model including both tumor- and patientrelated variables (Table 2). There was a correlation (Spearman s coefficient 0.17, p 0.001) between tumor size and lymph node involvement; N1 N2 disease being

5 GENERAL THORACIC 360 MYRDAL ET AL Ann Thorac Surg SURVIVAL AFTER OPERATION FOR LUNG CANCER 2003;75: Fig 3. Overall survival and smoking habits at time of operation. Former smokers are defined as those who stopped smoking at least 2 months before operation. Fig 1. Overall survival among all patients undergoing operation for primary lung cancer during the study period 1987 to 1999 in relation to outcome of operation: patients potentially cured by radical operation (study population, n 395), patients in whom lung resection was not radical microscopically (incomplete resection; n 97), and patients who underwent explorative thoracotomy (n 70). The numbers of patients at risk in the three groups after 1 month and after 5 and 10 years are depicted. present in 22% of the patients with T1 (tumor less than 3 cm in diameter) an in 39% of those with T2. Furthermore, 3% of patients with T1 tumors had N2 disease and 9% if T2.. In the full model in which all variables were considered (Table 2), age more than 60 years, earlier time period of operation, impaired lung function, current smoking (Fig 3), and major complication in connection with operation, together with advanced stage, were all significantly related to poorer long-term survival. Also patients who underwent pneumonectomy had decreased survival compared with lobectomy in the univariate analysis (RH 1.5, 95% confidence interval [CI] 1.2 to 1.8). However, after adjustment for other risk factors in the multivariate analysis, pneumonectomy gave no further prognostic information. During the study period the proportion of patients undergoing pneumonectomy decreased significantly (from 38% in 1987 to 1989 to 16% in 1996 to 1999; p 0.001). There was an improvement in survival over calendar time (RH 0.95, 95% CI 0.89 to 0.95 for each year since 1987). There was a significant interaction (p 0.02) between tumor stage and time period. The improvement with time was most pronounced in patients with a limited tumor stage (RH 0.87, CI 0.77 to 0.97 for each year since 1987 for patients in tumor stage Ia, RH 0.97, CI 0.89 to 1.05 for stage Ib, RH 0.96, CI 0.89 to 1.04 for stage II, and RH 0.97, CI 0.83 to 1.1 for those in stage IIIa). A risk score for mortality was calculated for each patient, using the final multivariate model. When patients were categorized according to that risk score, the low-risk group had a 5-year survival rate of 73%, compared to 26% in the high-risk group (Fig 4). Patients characteristics in each risk group are presented in Table 3. Time Trends and Risk Factors As expected, more patients allocated to the low-risk group underwent operation during recent years. During the study period the proportions of patients with impaired lung function and current smokers decreased significantly (p values for trend and 0.003, respectively), The proportion of patients who had never smoked was unchanged. Fig 2. Overall survival according to tumor size (T1 versus T2) [5] and presence or absence of lymph node involvement. (neg. negative; pos. positive.) Risk Factors for Different Time Periods After Operation The effects of the risk factors were virtually the same (year of operation not included) for deaths occurring within or more than 3 years after operation. An exception was major complications in connection with the primary

6 Ann Thorac Surg MYRDAL ET AL 2003;75: SURVIVAL AFTER OPERATION FOR LUNG CANCER Fig 4. Overall survival in patients potentially cured by operation (n 395) in relation to calculated risk score. Twenty-five percent of patients are in low- and high-risk groups and 50% in medium-risk group. Risk score is calculated by results of the multivariate analysis. Characteristics of each risk group are given in Table 2. surgical procedure, which increased the risk only for deaths occurring within 36 months after operation, with RH 2.0 (95% CI 1.5 to 2.5) compared to RH 1.1 (95% CI 0.2 to 2.0) for death after 36 months from operation. A majority of the patients with tumors in an advanced stage died within 36 months, and after that time too few were at risk to allow valid analyses. Comment Our study focused on patients considered to be potentially cured by operation (ie, in whom the tumor had been totally removed microscopically). Thus, the patients included in the analyses represented a selected group, as nonoperable patients and those undergoing incomplete procedures were excluded. Moreover, none of the study patients had received neoadjuvant therapy before operation. Although the survival of patients with non-small Table 3. Characteristics of Risk Groups Low-risk Group Mediumrisk Group High-risk Group n (%) n (%) n (%) Total 95 (25) 192 (50) 95 (25) Time period (77) 75 (39) 27 (28) Age 60 years 55 (58) 148 (77) 86 (91) FEV 1 % 60% 1 (1) 17 (9) 24 (25) Current smoker 24 (25) 115 (60) 73 (77) Major complication 0 (0) 8 (4) 23 (24) Stage I 95 (100) 142 (74) 14 (15) Stage II IIIa 0 (0) 40 (26) 81 (85) Patients categorized into risk groups according to the results from the multivariate model, selecting those 25% with the best survival in the low-risk group. 361 cell lung cancer potentially curable by operation remained poor, the current study points to an improved prognosis over calendar time. The improvement was most apparent in patients with small tumors without lymph node involvement. The improvement in survival during the study period may partly be explained by a decreased summation of risk factors in the most recent time period. During the study period the proportion of patients with impaired lung function and the proportion of those still smoking decreased significantly. Other investigators [9] have also presented an improvement in outcome over time in lung cancer patients and proposed that the improvement was attributable to an increasing number of patients with early disease, female gender, and adenocarcinomas. However, in the present study the prognostic information provided by year of operation could not be explained entirely by alterations in patient and tumor characteristics. Approximately 30% of the patients who were considered to have early stage disease (Ia) died within 5 years after operation. This is likely to reflect the presence of undetected lymph node metastases and verify the notion that large proportions of patients with lung cancer are understaged with current techniques. The finding that as many as 22% of the small tumors (T1) had spread to lymph nodes (N1 or N2) corroborates results from an earlier study [10]. This finding emphasizes the importance of careful lymph node examination, with systematic sampling, also in patients with small tumors, to obtain appropriate staging information [11, 12]. Regardless of the tumor size, lymph node involvement, regional or mediastinal, increased the risk of death by approximately 100%. In comparison, an increased tumor size increased the risk moderately. Earlier studies have also shown that lymph node involvement is strongly associated with decreased survival in patients with small tumors [5]. The present study, in which mediastinoscopy was performed in patients with positive computed tomographic findings, included a small number of patients with N2 disease (n 30). The survival in these patients was poor, but not inferior to that in patients with N1. This finding probably reflects understaging of patients from N2 to N1, which would decrease the observed survival in the N1 group. No doubt more frequent use of mediastinoscopy could have improved the preoperative identification of patients with N2 disease. The accuracy of the staging is of great importance for correct prediction of the prognosis in patients with lymph node involvement [13]. Mediastinoscopy also has the potential to reduce the rate of explorations of unresectable tumors. This rate was quite high in the present study (11%). When mediastinoscopy has been performed routinely in all candidates for radical operation, excluding only small peripheral lesions without enlargement of the mediastinal lymph nodes on computed tomographic scan [14, 15], the incidence of unresectable tumors has been reported to be 4% to 5%. Positron emission tomographic scans have shown high sensitivity but lower specificity for detection of local and distant metastases [16, 17]. Positron emission tomo- GENERAL THORACIC

7 GENERAL THORACIC 362 MYRDAL ET AL Ann Thorac Surg SURVIVAL AFTER OPERATION FOR LUNG CANCER 2003;75: graphic investigations, combined with mediastinoscopy in positive cases, could optimize the preoperative staging further. Operation in older patients has been a subject of concern because of the morbidity and mortality [18]. We found poorer survival among older patients, both before and after adjustment for other risk factors. The use of all causes of mortality may have overestimated the risk of death in older patients, and could have contributed to this finding. Smoking is an established risk factor for early death [6]. In the present study, current smokers had poorer survival than former smokers. We have previously reported an increased early mortality among patients who sustained major complications after lung cancer operation [6]. The present findings indicate that patients with major complications are at increased risk for death up to 3 years after operation. Furthermore, patients with reduced lung function were at increased risk. Thus, optimal medication to prevent complications, cessation of smoking, and physiotherapy may improve the outcome in all patients undergoing lung cancer operation. Of all potential tumor-related prognostic factors only histologic cell type and stage-related variables were considered in this study. Vascular invasion, for example, which is proposed to be the first step toward hematogenous tumor cell dissemination, provides additional prognostic information and may be a rationale for adjuvant treatment [19]. To assess the potential value of additional prognostic information obtained from a combination of tumorrelated factors and clinical variables, compared to tumor stage alone, a risk score was calculated and the patients were categorized accordingly. As many as 27% of the patients in the low-risk group and considered potentially cured by surgery alone died within 5 years after the operation. The corresponding mortality among patients in the high-risk group was 74%. It appears that our expanded predictive model does not add significantly to the information obtained from the staging system alone. The predicted outcome based on the risk score was comparable to that based on tumor stage. Patients with tumor stage Ia had a 5-year mortality of 31%, which is comparable to that in the low-risk group. The overall aim of attempts at prognostic prediction is to identify patients potentially suitable for adjuvant therapy. At present there is no evidence that such therapy is beneficial in patients potentially cured by operation. To improve the prognosis in these patients with NCSLC it is necessary to identify the optimal adjuvant therapy. There are a number of ongoing clinical trials aimed at developing multimodality treatment strategies [20] that might improve survival further in limited disease. In conclusion, this study points at an improvement in prognosis over time, especially among patients with limited disease (stage Ia). Furthermore, this study confirms that the tumor stage is the most important prognostic factor. Patient-related characteristics did not add information of clinical relevance over and above that provided by tumor stage alone. This finding further underlines the importance of accurate staging, both preoperatively and perioperatively. If the current adjuvant therapy alternatives prove to be effective, the staging effort will be valuable in selecting patients for appropriate treatment. This work was supported by the Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden. Financial support was provided by grants from the Swedish Heart and Lung Foundation and the Erik, Karin, and Gösta Selanders Foundation. References 1. Myrdal G, Lambe M, Bergström R, Ekbom A, Wagenius G, Ståhle E. Trends in lung cancer incidence in Sweden with special reference to period and birth cohorts. Cancer Causes and Control 2001;12: Gregor A, Thomson CS, Brewster DH, et al. Management and survival of patients with lung cancer in Scotland diagnosed in 1995: results of a national population based study. Thorax 2001;56: Janssen-Heijnen ML, Schipper RM, Klinkhamer PJ, Crommelin MA, Mooi WJ, Coebergh JW. Divergent changes in survival for histological types of non-small-cell lung cancer in the southeastern area of The Netherlands since Br J Cancer 1998;77: Humphrey EW, Smart CR, Winchester DP, et al. National survey of the pattern of care for carcinoma of the lung. J Thorac Cardiovasc Surg 1990;100: Mountain CF. Revisions in the International System for Staging Lung Cancer. Chest 1997;111: Myrdal G, Gustavsson G, Lambe M, Hörte L, Ståhle E. Outcome after lung cancer surgery. Factors predicting early mortality and major complications. Eur J Cardio-thorac Surg 2001;20: Riquet M, Manac h D, Dupont P, Dujon A, Hidden G, Debesse B. Anatomic basis of lymphatic spread of lung carcinoma to the mediastinum: anatomo-clinical correlations. Surg Radiol Anat 1994;16: Cox D. Regression models and life tables. J R Statist Soc B 1972;34: Yoshino I, Baba H, Fukuyama S, et al. A time trend of profile and surgical results in 1123 patients with non-small cell lung cancer. Surgery 2002;131(suppl 1):S Riquet M, Manac h D, Le Pimpec Barthes F, Dujon A, Debrosse D, Debesse B. Prognostic value of T and N in non small cell lung cancer three centimeters or less in diameter. Eur J Cardiothorac Surg 1997;11: Keller SM, Adak S, Wagner H, Johnson DH. Mediastinal lymph node dissection improves survival in patients with stages II and IIIa non-small cell lung cancer. Eastern Cooperative Oncology Group. Ann Thorac Surg 2000;70: Ohta Y, Oda M, Wu J, et al. Can tumor size be a guide for limited surgical intervention in patients with peripheral non-small cell lung cancer? Assessment from the point of view of nodal micrometastasis. J Thorac Cardiovasc Surg 2001;122: Suzuki K, Nagai K, Yoshida J, Nishimura M, Takahashi K, Nishiwaki Y. The prognosis of surgically resected N2 nonsmall cell lung cancer: the importance of clinical N status. J Thorac Cardiovasc Surg 1999;118: Dillemans B, Deneffe G, Verschakelen J, Decramer M. Value of computed tomography and mediastinoscopy in preoperative evaluation of mediastinal nodes in non-small cell lung cancer. A study of 569 patients. Eur J Cardiothorac Surg 1994;8: Hammoud ZT, Anderson RC, Meyers BF, et al. The current role of mediastinoscopy in the evaluation of thoracic disease. J Thorac Cardiovasc Surg 1999;118:894 9.

8 Ann Thorac Surg MYRDAL ET AL 2003;75: SURVIVAL AFTER OPERATION FOR LUNG CANCER 16. Pieterman RM, van Putten JW, Meuzelaar JJ, et al. Preoperative staging of non-small-cell lung cancer with positronemission tomography. N Engl J Med 2000;343: Gupta NC, Tamim WJ, Graeber GG, Bishop HA, Hobbs GR. Mediastinal lymph node sampling following positron emission tomography with fluorodeoxyglucose imaging in lung cancer staging. Chest 2001;120: Jazieh A, Hussain M, Howington J, et al. Prognostic factors in 363 patients with surgically resected stage I and II non-small cell lung cancer. Ann Thorac Surg 2000;70: 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 2002;73: Manegold C. Chemotherapy in stage I/II NSCLC, and projects of the EORTC-Lung Cancer Group for Early Stage Lung Cancer. Lung Cancer 2001;34(suppl 3):S53 8. GENERAL THORACIC Requirements for Recertification/Maintenance of Certification in 2003 Diplomates of the American Board of Thoracic Surgery who plan to participate in the Recertification/Maintenance of Certification process in 2003 must hold an active medical license and must hold clinical privileges in thoracic surgery. In addition, a valid certificate is an absolute requirement for entrance into the recertification/maintenance of certification process. If your certificate has expired, the only pathway for renewal of a certificate is to take and pass the Part I (written) and the Part II (oral) certifying examinations. The American Board of Thoracic Surgery will no longer publish the names of individuals who have not recertified in the American Board of Medical Specialties directories. The Diplomate s name will be published upon successful completion of the recertification/maintenance of certification process. The CME requirements are 70 Category I credits in either cardiothoracic surgery or general surgery earned during the 2 years prior to application. SESATS and SESAPS are the only self-instructional materials allowed for credit. Category II credits are not allowed. The Physicians Recognition Award for recertifying in general surgery is not allowed in fulfillment of the CME requirements. Interested individuals should refer to the 2003 Booklet of Information for a complete description of acceptable CME credits. Diplomates should maintain a documented list of their major cases performed during the year prior to application for recertification. This practice review should consist of 1 year s consecutive major operative experiences. If more than 100 cases occur in 1 year, only 100 should be listed. Candidates for recertification/maintanance of certification will be required to complete all sections of the SESATS self-assessment examination. It is not necessary for candidates to purchase SESATS individually because it will be sent to candidates after their application has been approved. Diplomates may recertify the year their certificate expires, or if they wish to do so, they may recertify up to two years before it expires. However, the new certificate will be dated 10 years from the date of expiration of their original certificate or most recent recertification certificate. In other words, recertifying early does not alter the 10-year validation. Recertification/maintenance of certification is also open to Diplomates with an unlimited certificate and will in no way affect the validity of their original certificate. The deadline for submission of applications for the recertification/maintenance of certification process is May 10 each year. A brochure outlining the rules and requirements for recertification/maintenance of certification in thoracic surgery is available upon request from the American Board of Thoracic Surgery, One Rotary Center, Suite 803, Evanston, IL 60201; telephone number: (847) ; fax: (847) ; abts_ evanston@msn.com. This booklet is also published on the website: by The Society of Thoracic Surgeons Ann Thorac Surg 2003;75: /03/$30.00 Published by Elsevier Science Inc