The Stage Classification of Lung Cancer
2013; Elsevier BV; Volume: 143; Issue: 5 Linguagem: Inglês
10.1378/chest.12-2354
ISSN1931-3543
AutoresFrank C. Detterbeck, Pieter E. Postmus, L.T. Tanoue,
Tópico(s)Lung Cancer Research Studies
ResumoThe current Lung Cancer Stage Classification system is the seventh edition, which took effect in January 2010. This article reviews the definitions for the TNM descriptors and the stage grouping in this system. The current Lung Cancer Stage Classification system is the seventh edition, which took effect in January 2010. This article reviews the definitions for the TNM descriptors and the stage grouping in this system. atypical adenomatous hyperplasia American College of Chest Physicians American Joint Committee on Cancer bronchioloalveolar carcinoma ground glass opacity International Association for the Study of Lung Cancer isolated tumor cell Union Internationale Contre le Cancer Stage classification is an essential part of the approach to patients with cancer, and there are many things we would like to get from a stage classification. The primary purpose of the classification is to consistently describe the anatomic extent of disease, thus providing a common, consistent language. The anatomic extent of the tumor has a major impact on which treatment we choose and what the outcome will be. However, it is important to recognize that the stage classification does not by itself completely define the prognosis (which depends on multiple factors, eg, comorbidities, performance status, treatment given) or serve as a treatment algorithm (which is driven by data from clinical trials and treatment selection criteria). Efforts to develop a comprehensive prognostic index system are under way. Stage classification is founded on the TNM system, which dates back to 1944. Furthermore, the method of staging is classified as clinical stage (denoted by the prefix c) and pathologic stage (denoted by the prefix p). Clinical stage is determined using all information available prior to any treatment, and pathologic stage is determined after a resection. The extent of clinical staging can vary from a clinical evaluation alone (history and physical examination) to extensive imaging (CT and PET scans) or invasive staging techniques. It must be emphasized that a surgical staging procedure (eg, mediastinoscopy) is still part of clinical staging because surgical resection as a treatment has not taken place. The Union Internationale Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC) are the official bodies that define, review periodically, and refine the stage classification systems. The current seventh edition of the lung cancer staging system was based on a major initiative undertaken by the International Association for the Study of Lung Cancer (IASLC). This 12-year project increased the patient base from 5,319 (collected over several decades predominantly at one institution) to > 100,000 (from around the world, all cases diagnosed between 1990 and 2000). In validating where to make a distinction between one stage descriptor or group and another, the IASLC required that consistent differences in prognosis had to be seen in data sets from different continents, database types, clinical and pathologic staging, and histologic subtypes.2Groome PA Bolejack V Crowley JJ IASLC International Staging Committee Cancer Research and Biostatistics Observers to the Committee; Participating Institutions et al.The IASLC Lung Cancer Staging Project: validation of the proposals for revision of the T, N, and M descriptors and consequent stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours.J Thorac Oncol. 2007; 2: 694-705Abstract Full Text Full Text PDF PubMed Scopus (535) Google Scholar Furthermore, external validation against large databases was done. The statistical analysis was quite sophisticated; in all, the current classification is a quantum leap forward that is unequalled by any other cancer site. However, although the database was large and involved many institutions from 20 countries, the distribution of cases was not uniform. Certain patient subgroups came predominantly from one region or one type of database and were treated in many different ways, and the IASLC database did not report treatment-specific outcomes. This article addresses the official Lung Cancer Stage Classification system. Therefore, the primary sources of information were the AJCC and UICC staging manuals.3Union Internationale Contre le Cancer TNM Classification of Malignant Tumors. 7th ed. Wiley-Blackwell, Hoboken, NJ2009Google Scholar, 4American Joint Committee on Cancer AJCC Cancer Staging. Manual. 7th ed. Springer, New York, NY2009Google Scholar, 5Wittekind C TNM Supplement: A Commentary on Uniform Use. 4th ed. John Wiley & Sons, London, England2012Google Scholar These sources were supplemented by the publications of the IASLC International Staging Committee, which provided the basis for the AJCC/UICC classification,2Groome PA Bolejack V Crowley JJ IASLC International Staging Committee Cancer Research and Biostatistics Observers to the Committee; Participating Institutions et al.The IASLC Lung Cancer Staging Project: validation of the proposals for revision of the T, N, and M descriptors and consequent stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours.J Thorac Oncol. 2007; 2: 694-705Abstract Full Text Full Text PDF PubMed Scopus (535) Google Scholar, 6Goldstraw P IASLC Staging Manual in Thoracic Oncology. Editorial Rx Press, Orange Park, FL2009Google Scholar, 7Rami-Porta R Ball D Crowley J International Staging Committee Cancer Research and Biostatistics Observers to the Committee Participating Institutions et al.The IASLC Lung Cancer Staging Project: proposals for the revision of the T descriptors in the forthcoming (seventh) edition of the TNM classification for lung cancer.J Thorac Oncol. 2007; 2: 593-602Abstract Full Text Full Text PDF PubMed Scopus (611) Google Scholar, 8Rusch VW Crowley J Giroux DJ International Association for the Study of Lung Cancer International Staging Committee Cancer Research and Biostatistics Observers to the Committee Participating Institutions et al.The IASLC Lung Cancer Staging Project: proposals for the revision of the N descriptors in the forthcoming seventh edition of the TNM classification for lung cancer.J Thorac Oncol. 2007; 2: 603-612Abstract Full Text Full Text PDF PubMed Scopus (458) Google Scholar, 9Postmus PE Brambilla E Chansky K International Association for the Study of Lung Cancer International Staging Committee Cancer Research and Biostatistics Observers to the Committee Participating Institutions 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: 686-693Abstract Full Text Full Text PDF PubMed Scopus (335) Google Scholar, 10Goldstraw P Crowley J Chansky K International Association for the Study of Lung Cancer International Staging Committee Participating Institutions 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 tumours.J Thorac Oncol. 2007; 2: 706-714Abstract Full Text Full Text PDF PubMed Scopus (2847) Google Scholar, 11Shepherd FA Crowley J Van Houtte P International Association for the Study of Lung Cancer International Staging Committee and Participating Institutions et al.The International Association for the Study of Lung Cancer lung cancer staging project: proposals regarding the clinical staging of small cell lung cancer in the forthcoming (seventh) edition of the tumor, node, metastasis classification for lung cancer.J Thorac Oncol. 2007; 2: 1067-1077Abstract Full Text Full Text PDF PubMed Scopus (436) Google Scholar, 12Travis WD Giroux DJ Chansky K International Staging Committee and Participating Institutions et al.The IASLC Lung Cancer Staging Project: proposals for the inclusion of broncho-pulmonary carcinoid tumors in the forthcoming (seventh) edition of the TNM Classification for Lung Cancer.J Thorac Oncol. 2008; 3: 1213-1223Abstract Full Text Full Text PDF PubMed Scopus (219) Google Scholar as well as American College of Chest Physicians (ACCP) publications that reviewed and discussed details of the classification.13Detterbeck FC Boffa DJ Tanoue LT The new lung cancer staging system.Chest. 2009; 136: 260-271Abstract Full Text Full Text PDF PubMed Scopus (772) Google Scholar, 14Detterbeck FC Boffa DJ Tanoue LT Wilson LD Details and difficulties regarding the new lung cancer staging system.Chest. 2010; 137: 1172-1180Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar A detailed analysis of tumor size by the IASLC staging committee confirmed that 3 cm was significant as a cut point; thus, the definition of T1 vs T2 was retained. In addition, significant cut points were identified at 2, 5, and 7 cm. Therefore, subgroups were defined for T1 (T1a and T1b) and T2 (T2a and T2b) as shown in Figure 1. The survival differences between each size subgroup were highly statistically significant in pathologically staged patients; among clinically staged patients, the trends were consistent but not always significant (probably because of a more limited data set). Tumors > 7 cm led to survival that tracked with other definitions of T3 (ie, invasion, central location) and were, therefore, placed within this group. The size of a tumor is defined as the greatest dimension, but how this is determined is not addressed by AJCC, UICC, or IASLC. The ACCP panel suggests that for consistency, this measurement be done on an axial CT image using lung windows during inspiration whenever possible (c stage); for p stage, we suggest the greatest dimension (in any direction) of the specimen fixed after inflation or of the unfixed specimen (fixation causes about 20% shrinkage).15Hsu P-K Huang H-C Hsieh C-C et al.Effect of formalin fixation on tumor size determination in stage I non-small cell lung cancer.Ann Thorac Surg. 2007; 84: 1825-1829Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar Further issues arise with semisolid or ground glass opacities (GGOs), which have not been addressed by the AJCC or UICC. One can measure the solid or the ground glass component with either mediastinal or lung windows on a CT image. Emerging data suggest that the size of the solid (invasive) component is of greater prognostic value than the ground glass (lepidic) component.16Yim J Zhu L-C Chiriboga L Watson HN Goldberg JD Moreira AL Histologic features are important prognostic indicators in early stages lung adenocarcinomas.Mod Pathol. 2007; 20: 233-241Crossref PubMed Scopus (124) Google Scholar, 17Suzuki K Yokose T Yoshida J et al.Prognostic significance of the size of central fibrosis in peripheral adenocarcinoma of the lung.Ann Thorac Surg. 2000; 69: 893-897Abstract Full Text Full Text PDF PubMed Scopus (227) Google Scholar, 18Maeshima AM Niki T Maeshima A Yamada T Kondo H Matsuno Y Modified scar grade: a prognostic indicator in small peripheral lung adenocarcinoma.Cancer. 2002; 95: 2546-2554Crossref PubMed Scopus (116) Google Scholar, 19Travis W, Brambilla E, Noguchi M, et al. The new IASLC/ATS/ERS international multidisciplinary lung adenocarcinoma classification. Paper presented at: 13th World Conference on Lung Cancer; August 4, 2009; San Francisco, CA.Google Scholar, 20Yokose T Suzuki K Nagai K Nishiwaki Y Sasaki S Ochiai A Favorable and unfavorable morphological prognostic factors in peripheral adenocarcinoma of the lung 3 cm or less in diameter.Lung Cancer. 2000; 29: 179-188Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar, 21Kerr KM Pulmonary adenocarcinomas: classification and reporting.Histopathology. 2009; 54: 12-27Crossref PubMed Scopus (97) Google Scholar, 22Yoshizawa A Motoi N Riely GJ et al.Impact of proposed IASLC/ATS/ERS classification of lung adenocarcinoma: prognostic subgroups and implications for further revision of staging based on analysis of 514 stage I cases.Mod Pathol. 2011; 24: 653-664Crossref PubMed Scopus (731) Google Scholar The ACCP panel suggests recording the size of both the GGO and the solid component on lung windows (or the percent solid by area) for c stage and both the entire tumor (including lepidic portions) and the invasive component for p stage.14Detterbeck FC Boffa DJ Tanoue LT Wilson LD Details and difficulties regarding the new lung cancer staging system.Chest. 2010; 137: 1172-1180Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar This suggestion is consistent with a recent UICC supplement handbook.5Wittekind C TNM Supplement: A Commentary on Uniform Use. 4th ed. John Wiley & Sons, London, England2012Google Scholar There were insufficient numbers of patients for whom reliable data were available to investigate the validity of other traditional T2, T3, or T4 descriptors (visceral pleural invasion, central location within a lobar or mainstem bronchus, partial or complete atelectasis, direct invasion of particular structures, etc). These traditional definitions were retained even though they could not be confirmed because there were no data to suggest that they are not valid. Invasion beyond the elastic layer of the pleura is defined as T2, including invasion into an adjacent lobe. Elastin stains should be used whenever there is ambiguity.23Travis WDMD Brambilla EMD Rami-Porta RMD International Staging Committee et al.Visceral pleural invasion: pathologic criteria and use of elastic stains: proposal for the 7th edition of the TNM classification for lung cancer.J Thorac Oncol. 2008; 3: 1384-1390Abstract Full Text Full Text PDF PubMed Scopus (214) Google Scholar T3 includes invasion into the parietal or mediastinal pleura or the parietal pericardium. T4 includes invasion of the visceral (inner) pericardial surface and the intrapericardial pulmonary artery and pulmonary veins. Involvement of either the intrapericardial or extrapericardial vena cava or aorta is considered T4. We suggest that involvement of the azygous vein be classified as T3 because it is not counted among the great vessels (but this is not addressed by IASLC, AJCC, or UICC). A Pancoast tumor is classified as T4 if there is unequivocal involvement of C8 or higher nerve roots, cords of the brachial plexus, subclavian vessels, vertebral bodies, lamina, or spinal canal. The tumor is classified as T3 if it involves only thoracic nerve roots (eg, T1 or T2 nerve roots). Left-side recurrent laryngeal nerve paralysis is classified as T4 when directly invaded by the primary tumor but as N2 when invaded by nodal disease. Similarly, infiltration of the superior vena cava, trachea, or esophagus by the primary tumor is defined as T4 but as N2 or N3 when infiltration emanates from the lymph nodes. Difficulties arise in the classification of mediastinal invasion. Although mediastinal pleural invasion is classified as T3, mediastinal fat invasion is T4, and parietal pericardial invasion is T3. Because there is usually some fat between the mediastinal pleura and the pericardium, this classification is confusing. Furthermore, differentiation between hilar fat (considered T2) and mediastinal fat (T4) is difficult. The ACCP panel suggests that only unambiguous mediastinal fat involvement be used as a criterion for T4 status (eg, extensive replacement by tumor on CT scan); otherwise, the lower T3 classification should be chosen.14Detterbeck FC Boffa DJ Tanoue LT Wilson LD Details and difficulties regarding the new lung cancer staging system.Chest. 2010; 137: 1172-1180Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar Analysis of the prognostic influence of the N descriptor resoundingly supported the traditional categorization of N0, N1, N2, and N3; therefore, these definitions were carried forward (Fig 1).8Rusch VW Crowley J Giroux DJ International Association for the Study of Lung Cancer International Staging Committee Cancer Research and Biostatistics Observers to the Committee Participating Institutions et al.The IASLC Lung Cancer Staging Project: proposals for the revision of the N descriptors in the forthcoming seventh edition of the TNM classification for lung cancer.J Thorac Oncol. 2007; 2: 603-612Abstract Full Text Full Text PDF PubMed Scopus (458) Google Scholar Direct extension of a primary tumor into a node is classified as nodal involvement. Station 1 nodes are classified as supraclavicular nodes, which include the low cervical nodes, caudal to the lower margin of the cricoid (N3). Extrathoracic node involvement is designated as M1b (eg, a positive axillary node). Further analyses were done to explore whether particular node stations within an N category had any particular impact. No such relationship could be identified (Fig 2).8Rusch VW Crowley J Giroux DJ International Association for the Study of Lung Cancer International Staging Committee Cancer Research and Biostatistics Observers to the Committee Participating Institutions et al.The IASLC Lung Cancer Staging Project: proposals for the revision of the N descriptors in the forthcoming seventh edition of the TNM classification for lung cancer.J Thorac Oncol. 2007; 2: 603-612Abstract Full Text Full Text PDF PubMed Scopus (458) Google Scholar Specifically, there was no difference in survival among patients with involvement of only peripheral N1 nodes or hilar N1 nodes, and no difference based on which N2 nodal stations were involved. This was true globally as well as within geographic regions. Survival among patients with pN2 right upper lobe tumors with and without N1 involvement (skip metastases) was not different, although there was a slight difference among such patients with a left upper lobe tumor.8Rusch VW Crowley J Giroux DJ International Association for the Study of Lung Cancer International Staging Committee Cancer Research and Biostatistics Observers to the Committee Participating Institutions et al.The IASLC Lung Cancer Staging Project: proposals for the revision of the N descriptors in the forthcoming seventh edition of the TNM classification for lung cancer.J Thorac Oncol. 2007; 2: 603-612Abstract Full Text Full Text PDF PubMed Scopus (458) Google Scholar The IASLC staging committee developed a new node map24Rusch V Asamura H Watanabe H Giroux DJ Rami-Porta R Goldstraw P Members of IASLC Staging Committee The IASLC Lung Cancer Staging Project: a proposal for a new international lymph node map in the forthcoming 7th edition of the TNM classification for lung cancer.J Thorac Oncol. 2009; 4: 568-577Abstract Full Text Full Text PDF PubMed Scopus (809) Google Scholar to overcome ambiguities arising from discrepancies between previous node maps in use in different geographic regions. Furthermore, the committee defined several nodal zones as follows: a supraclavicular zone (station 1), an upper zone (stations 2-4), an aortopulmonary zone (stations 5 and 6), a subcarinal zone (station 7), a lower zone (stations 8 and 9), a hilar zone (stations 10 and 11), and a peripheral zone (stations 12-14). There were no differences in prognosis among involvement of different nodal zones within the N1 or N2 category. Specifically, there was no difference between patients with a left upper lobe tumor and involvement of nodes only in station 5 and 6 and patients with a tumor in a different lobe and involvement of another single N2 nodal zone.8Rusch VW Crowley J Giroux DJ International Association for the Study of Lung Cancer International Staging Committee Cancer Research and Biostatistics Observers to the Committee Participating Institutions et al.The IASLC Lung Cancer Staging Project: proposals for the revision of the N descriptors in the forthcoming seventh edition of the TNM classification for lung cancer.J Thorac Oncol. 2007; 2: 603-612Abstract Full Text Full Text PDF PubMed Scopus (458) Google Scholar The number of involved nodal zones appeared to have a prognostic impact. Patients with pathologic single-zone N1 involvement had better survival than those with pathologic multizone N1 involvement (5-year survival, 48% vs 35%; P < .09). Similarly, patients with pathologic single-zone N2 involvement had better survival than those with pathologic multizone N2 involvement (5-year survival, 34% vs 20%; P < .001). In fact, the survival curves of patients with pathologic multizone N1 and single-zone N2 involvement were almost superimposed.8Rusch VW Crowley J Giroux DJ International Association for the Study of Lung Cancer International Staging Committee Cancer Research and Biostatistics Observers to the Committee Participating Institutions et al.The IASLC Lung Cancer Staging Project: proposals for the revision of the N descriptors in the forthcoming seventh edition of the TNM classification for lung cancer.J Thorac Oncol. 2007; 2: 603-612Abstract Full Text Full Text PDF PubMed Scopus (458) Google Scholar However, the prognostic impact of the number of pathologic nodal zones involved could not be validated within T-stage categories and by geographical region, type of databases, or clinical staging because the number of patients in the subsets was too small.8Rusch VW Crowley J Giroux DJ International Association for the Study of Lung Cancer International Staging Committee Cancer Research and Biostatistics Observers to the Committee Participating Institutions et al.The IASLC Lung Cancer Staging Project: proposals for the revision of the N descriptors in the forthcoming seventh edition of the TNM classification for lung cancer.J Thorac Oncol. 2007; 2: 603-612Abstract Full Text Full Text PDF PubMed Scopus (458) Google Scholar Therefore, the IASLC staging committee decided against subdivision of N categories. The prognostic impact of nodal involvement by direct extension of a primary tumor also could not be validated through the IASLC database because of insufficient sample sizes but was retained because it is consistent with general UICC and AJCC rules. The IASLC node map is shown in Figure 3, Figure 4. Important features include better definition of the subcarinal zone as extending down to the level of origin of the left lower lobe and right middle lobe bronchus.24Rusch V Asamura H Watanabe H Giroux DJ Rami-Porta R Goldstraw P Members of IASLC Staging Committee The IASLC Lung Cancer Staging Project: a proposal for a new international lymph node map in the forthcoming 7th edition of the TNM classification for lung cancer.J Thorac Oncol. 2009; 4: 568-577Abstract Full Text Full Text PDF PubMed Scopus (809) Google Scholar The border between left- and right-side paratracheal nodes is the left lateral border of the trachea (not the midline). The 4R nodal area extends from the lower border of the left innominate vein to the lower border of the azygous vein; the 4L nodal region extends from the level of the top of the aortic arch to the upper border of the left-side pulmonary artery medial to the ligamentum. The level 2 regions extend from the border of level 4 to the upper border of the manubrium in the midline. The supraclavicular nodes extend from the lower border of the clavicles to the lower border of the cricoid. Further details and definitions of all the node stations can be found in Rusch et al.24Rusch V Asamura H Watanabe H Giroux DJ Rami-Porta R Goldstraw P Members of IASLC Staging Committee The IASLC Lung Cancer Staging Project: a proposal for a new international lymph node map in the forthcoming 7th edition of the TNM classification for lung cancer.J Thorac Oncol. 2009; 4: 568-577Abstract Full Text Full Text PDF PubMed Scopus (809) Google ScholarFigure 4[Section 3.1] A-F, Illustrations of how the International Association for the Study of Lung Cancer lymph node map can be applied to clinical staging by CT scan in axial (A-C), coronal (D), and sagittal (E, F) views. A and B, The border between the right- and left-side paratracheal region is shown. Az = azygous vein; InV = innominate vein; LLLB = left lower lobe bronchus; Lt = left; MB = mainstem bronchus; PA = pulmonary artery; Rt = right; SCA = subclavian artery; SPV = superior pulmonary vein. See Figure 2 legend for expansion of other abbreviations. Reproduced with permission from Rusch et al.24Rusch V Asamura H Watanabe H Giroux DJ Rami-Porta R Goldstraw P Members of IASLC Staging Committee The IASLC Lung Cancer Staging Project: a proposal for a new international lymph node map in the forthcoming 7th edition of the TNM classification for lung cancer.J Thorac Oncol. 2009; 4: 568-577Abstract Full Text Full Text PDF PubMed Scopus (809) Google ScholarView Large Image Figure ViewerDownload Hi-res image Download (PPT) The following comments apply to nodal staging at the time of resection. Issues regarding clinical (pretreatment) staging are discussed in section 7.0 of this article, “Type of Stage Classification.” A general AJCC/UICC recommendation is that at least six lymph nodes/stations be sampled for pathologic node staging. The IASLC manual recommends that three mediastinal (including level 7) and three N1 nodes/stations be sampled. Whether the number is supposed to apply to node stations or individual nodes is undefined. Moreover, the pathologist cannot distinguish six nodal fragments from six separate nodes (unless the surgeon is meticulous in how nodes and fragments are labeled and submitted). However, the IASLC staging committee encourages systematic intraoperative node assessment as recommended by clinical guidelines.25Detterbeck F Jantz M Wallace M Vansteenkiste J Silvestri GA American College of Chest Physicians Invasive mediastinal staging of lung cancer: ACCP evidence based clinical practice guidelines (2nd edition).Chest. 2007; 132: 202S-220SAbstract Full Text Full Text PDF PubMed Scopus (621) Google Scholar, 26Lardinois D De Leyn P Van Schil P et al.ESTS guidelines for intraoperative lymph node staging in non-small cell lung cancer.Eur J Cardiothorac Surg. 2006; 30: 787-792Crossref PubMed Scopus (470) Google Scholar Furthermore, the definition of number of nodes/stations needed for pathologic staging by IASLC and AJCC is confusing. If all nodes are negative, the tumor is defined as pN0, regardless of the number sampled, yet if some are positive, it is implied that only cN status be used if fewer than six nodes/stations were sampled. To avoid this awkward inconsistency, the ACCP panel endorses the suggestion14Detterbeck FC Boffa DJ Tanoue LT Wilson LD Details and difficulties regarding the new lung cancer staging system.Chest. 2010; 137: 1172-1180Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar that whenever fewer than six nodes/stations are sampled at resection, the tumor is classified as pN0, pN1, or pN2 with the uncertainty descriptor [eg, pN0(un)], as is described in section 8.0 of this article, “Additional Descriptors.” This descriptor has been suggested by IASLC for further testing relative to the completeness of resection (R) classification; however, extrapolation to address an inconsistency in the formal rules regarding the definition of pN status seems reasonable to the panel. Biopsy of only one sentinel node is considered adequate and is denoted as pN0(sn) if findings are negative and pN1-3(sn) if positive, reflecting the level of the sentinel node. However, sentinel node identification in lung cancer is variable and not widely practiced.27Liptay MJMD D'amico TAMD Nwogu CMD Thoracic Surgery Subcommittee of the Cancer and Leukemia Group B et al.Intraoperative sentinel node mapping with technitium-99 in lung cancer: results of CALGB 140203 multicenter phase II trial.J Thorac Oncol. 2009; 4: 198-202Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar, 28Rzyman W Hagen OM Dziadziuszko R et al.Intraoperative, radio-guided sentinel lymph node mapping in 110 nonsmall cell lung cancer patients.Ann Thorac Surg. 2006; 82: 237-242Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar, 29Ono T Minamiya Y Ito M et al.Sentinel node mapping and micrometastasis in patients with clinical stage IA non-small cell lung cancer.Interact Cardiovasc Thorac Surg. 2009; 9: 659-661Crossref PubMed Scopus (16) Google Scholar The new stage classification system no longer recognizes the term MX because clinical staging information is always available. A history and physical examination are critical parts of clinical staging and often are very reliable without further imaging or biopsy. The presence of distant metastases is classified as M1b.9Postmus PE Brambilla E Chansky K International Association for the Study of Lung Cancer International Staging Committee Cancer Research and Biostatistics Observers to the Committee Participating Institutions 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: 686-693Abstract Full Text Full Text PDF PubMed Scopus (335) Google Scholar Slightly worse survival was seen in patients with multiple vs a solitary distant metastasis (median survival, 5 months vs 6 months; 1 year survival, 20% vs 23%; P = 0,006).9Postmus PE Brambilla E Chansky K International Association for the Study of Lung Cancer International Staging Committee Cancer Research and Biostatistics Observers to the Committee Participating Institutions 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: 686-693Abstract Full Text Full Text PDF PubMed Scopus (335) Google Scholar No differences were noted by the site of a solitary distant metastasis except slightly shorter survival for a solitary brain metastasis. However, the data set was too limited for adequate validation, and further s
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