Chien, Chun-Ru MD, PhD*†; Yang, Su-Tso MD, PhD‡§; Chen, Chih-Yi MD†∥¶; Fang, Hsin-Yuan MD†∥; Tu, Chih-Yen MD†#; Tseng, Guan-Chin MD**; Yu, Yang-Ho MD#; Chen, Hung-Jen MD#; Ho, Chih-Te MD††; Hsieh, Ching-Yun MD‡‡; Chen, Hsiang-Ni MD§§; Chen, Pin-Ru MD∥; Liu, Juhn-Cherng MD‡; Wang, Yao-Ching MD*∥∥; Wu, Hui-Hua MS¶; Hsia, Te-Chun MD§#
*Department of Radiation Oncology, China Medical University Hospital; †School of Medicine, China Medical University; ‡Department of Radiology, China Medical University Hospital; §School of Chinese Medicine, China Medical University; ∥Division of Chest Surgery, Department of Surgery, ¶Cancer Center; #Division of Pulmonary and Critical Care Medicine, **Department of Pathology, ††Department of Family Medicine, ‡‡Division of Hematology and Oncology, §§Division of Internal Medicine, Department of Chinese Medicine, China Medical University Hospital; and ∥∥Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
Disclosure: The authors declare no conflicts of interest.
Address for correspondence: Te-Chun Hsia, MD, Department of Internal Medicine, China Medical University and Hospital, 2nd Yuh-Der Road, Taichung city, Taiwan. E-mail: email@example.com
Presented in part at the 13th World Conference on Lung Cancer, San Francisco, CA, July 31 to August 4, 2009.
Introduction: To investigate the feasibility and clinical impact of the 7th edition of the “Tumor, Node, Metastasis” (TNM) classification scheme in lung cancer as proposed by the International Association for the Study of Lung Cancer (IASLC) for non-small cell lung cancer.
Methods: We evaluated the feasibility of the new staging system in our routine biweekly multidisciplinary lung cancer staging conference compared with the 6th TNM staging in a prospective manner from April 2008 to June 2009. The impact of IASLC staging versus the 6th TNM staging was observed at three levels: change in substaging, staging, and clinical management (based on the discussion within the staging conference).
Results: From 348 patients discussed during these conferences, 226 eligible non-small cell lung cancer patients newly diagnosed within the study period were reviewed and clinically staged. The majority were elderly (median age, 67 years) and men (58%). Of these, 23 patients had different staging, and four patients had different substaging in the IASLC staging compared with the 6th TNM staging. An impact on clinical management was seen in 2.7% (6 of 226) of these patients because of coding ipsilateral different-lobe metastasis as T4 instead of M1.
Conclusions: The new staging system was clinically feasible and resulted in some (27 of 226, 12%) differences in staging. An impact on clinical decision making was occasionally seen within our institutional practice. Further studies are needed to investigate the comprehensive and long-term impact of the new staging system.
Lung cancer is a leading cause of cancer mortality around the world, and non-small cell lung cancer (NSCLC) comprises the majority of lung cancers. Staging is important for prognosis and treatment decision making, and some debate has occurred about the 1997 “tumor, node, metastasis” (TNM) staging system.1–3
The 7th edition of TNM in lung cancer was published by the International Union Against Cancer and the American Joint Committee on Cancer, with changes based primarily on proposals from the International Staging Project of the International Association for the Study of Lung Cancer (IASLC).4,5
This new staging system has been introduced in many medical journals among different medical specialties.6–9 Part of the new staging system has also been externally validated in terms of prognosis in surgical cases of NSCLC or patients with advanced nonbronchioalveolar carcinoma NSCLC.10–12 Some impact may also be observed in pathologic specimen processing due to this new staging system.13 However, to our knowledge, no study related to the clinical implementation, and impact of the new staging system has been reported. Thus, the objective of this study was to investigate the feasibility and clinical impact of this new staging system for NSCLC in a prospective manner.
PATIENTS AND METHODS
As a major tertiary medical center in central Taiwan with about 2000 beds, routine multidisciplinary lung cancer staging conferences have been held in our institute since 2001. All “new” and “treated” patients with lung cancer recorded by the lung cancer case manager (H.H.W.) are reviewed in this biweekly meeting. The “treated” patients list consisted of those patients whose treatment decision making had largely been made. The “new” patients list consisted of those patients whose main treatment had not yet been decided. Generally, the “new” list reflected those diagnosed shortly before the date of the meeting, and the “treated” list reflected those diagnosed shortly after the date of previous meeting. Since April 2008, the feasibility and impact of the new staging system for “new” lung cancer patients were evaluated in a prospective manner in addition to the 6th TNM classification, and feasibility was evaluated based on whether consensus on IASLC staging could be achieved in this meeting. The data we collected and report in this study were the result of our routine records of lung cancer team meeting discussions, which were conducted by department/team head (T.-C.H.).
Demographic (gender and age), tumor (primary site and histology), and patient characteristics (Eastern Cooperative Oncology Group performance status) were collected. Histology was categorized as adenocarcinoma, squamous cell carcinoma, or other. Both 6th TNM and IASLC staging were based on discussion within this meeting, as was suggested treatment. Treatment was categorized as operation or not, systemic anticancer treatment or not, and radiotherapy or not. The staging workup was categorized into (A) conventional (primarily chest computed tomography based), (B) positron emission tomography included, or (C) cytopathological examination other than primary sites, which was primarily decided by the treating physician. The impact of IASLC staging in addition to the 6th TNM staging was observed at three levels: change in substaging (such as from IIA to IIB), change in staging (such as from III to IV), or change in clinical management, which was based on discussions within this conference.
The results were tabulated and described by descriptive analyses. The χ2 test was used for comparisons among different groups. All analyses were done using the Statistical Analysis Software system for Windows, version 9.00 (Statistical Analysis Software Institute, Cary, NC).
Between April 2008 and June 2009, 537 newly diagnosed patients with lung cancer were added, according to institutional cancer registry, including 462 patients with histology-proven NSCLC. During the same period, 348 patient-visits were discussed as “new” patients for further decision making in our biweekly meetings, where “patient-visits” indicates that one patient might be discussed several time over the disease course. Among these “new” patient-visits reviewed and clinically staged in these conference (n = 348), those with no tissue diagnosis yet (n = 66), histology other than NSCLC (n = 24), history of previous treatment (n = 12), further workup needed (n = 15), and double cancer (n = 5) were excluded from our analysis. These exclusion criteria were decided during the first month (April 2008) when we began the study. The remaining 226 newly diagnosed patients with NSCLC constituted our study population (Table 1). Consensus for both 6th TNM and IASLC staging was achieved for these 226 patients at these meetings. Most of these patients were elderly males with adenocarcinomas.
The staging workups were 133 (59%), 50 (22%), and 43 (19%) for workups A, B, and C, respectively. The stage distribution was 14, 8, 56, and 148 for stages I, II, III, and IV, respectively, by the 6th TNM staging. The corresponding numbers were 12, 9, 53, and 152 by the new staging system (Table 2). In total, 23 patients had different staging, and four patients had different substaging using IASLC versus the 6th TNM staging. The reasons for these changes in staging and substaging are shown in Table 3. The predominant reasons for these differences (11 of 27, 41%) were due to coding of malignant effusion as M1 instead of T4, followed by coding of ipsilateral different-lobe nodules as T4 instead of M1 (7 of 27, 26%). Operations were indicated for 38 patients, whereas systemic treatment and radiotherapy were suggested for 156 and 47 patients, respectively. An impact in clinical management was seen in 2.7% (6 of 226) of these patients, including a consideration of operation and radical thoracic radiotherapy for three patients each, in addition to chemotherapy alone. All were due to coding an ipsilateral different-lobe metastasis as T4 instead of M1. The number (percentage) of patients with differences in staging or substaging was 10 (8%), eight (16%), and nine (21%) for work-up methods A, B, and C, respectively (p = 0.038). Use of an advanced staging procedure (work-up B or C) was associated with changes between 6th TNM staging and IASLC staging/substaging (17 of 93 versus 10 of 133; p = 0.014).
The long-awaited new staging system for lung cancer has finally been published.5 Our study revealed that adoption of the 7th TNM staging of lung cancer, as proposed by IASLC, was feasible for newly diagnosed NSCLC in our routine multidisciplinary lung cancer staging conferences.
The objectives of the staging system are to aid clinicians and investigators in planning treatment, assessing prognosis stratification, and facilitating communication.14 There is no doubt that the new staging system, as proposed by IASLC, is a major advance, as revealed by the superior prognostic stratification.4 This achievement was validated by retrospective studies10–12 and was further supported by this study evaluating its clinical feasibility and potential clinical impact. In our study, this clinical impact was seen primarily in patients with ipsilateral different-lobe nodules. Although the justification that we proposed to treat selected patients with ipsilateral different-lobe nodules aggressively as stage III, instead of stage IV, patients deserve further prospective studies; this concept was compatible with the present National Comprehensive Cancer Network guidelines.15
Although this new staging system may also be applied to small-cell lung cancer,16 it was originally based on a database of patients with NSCLC only.4 Thus, only patients with NSCLC were included in our study.
This study has some limitations. First, not all newly diagnosed patients with lung cancer during the study period were included in our analysis; in particular, some early-stage patients might not be included due to the unavailability of a tissue diagnosis before operation. This was also the number one cause (n = 66) of exclusion from our study. Thus, the impact of the new staging system on early-stage NSCLC might not be fully captured by our study. However, because changes in staging primarily occurred in IASLC stages II to IV patients,4 underrepresentation of patients with early-stage NSCLC in our study population might not lead to any significant change in staging result or clinical impact. Additionally, only “new” patients, and not “treated” patients, were included in our study. However, because these two groups only reflected patients diagnosed at times before and after the routine meetings, the omission of “treated” patients should only lead to a reduction in sample size not to limited representation.
Second, our study population was not staged uniformly. However, this made our results more relevant to the real world, where wide variations exist in the pattern of care for staging procedures of lung cancer.1,17 As suggested by the American College of Chest Physicians,18 tissue biopsies for abnormalities are preferred for accurate staging, and positron emission tomography has better sensitivity and specificity than does computed tomography. Thus, staging workups were categorized in three levels in our study. Our results also revealed that the impact of the new staging system might be enhanced if the use of the advanced staging procedures is increased. On the other hand, our results also indicated that conventional investigation alone (work-up group A) might often be sufficient for staging, especially for a predominantly advanced disease patient population.
Another limitation of our study is the moderate sample size, based on data from a single institution. However, for the seven situations where T or M coding was different between the 6th TNM and IASLC staging,4 all seven happened in our study group (Table 3). Thus, we believe our study population was big enough to be representative for a single institution. However, multinational and multiinstitutional experiences are needed for further evaluation of the comprehensive impact of the new staging system, though we believe our findings provide a good starting point.
The lung cancer staging system may be further improved in the future. N staging was not revised in this new staging system, although some subclassification has been suggested.19 Other nonanatomic prognostic factors may also be incorporated in the future.14,20 Currently, a prospective project is underway by IASLC.21
In conclusion, the new staging system was clinically feasible and led to some (27 of 226, 12%) differences in staging. Most of the changes were due to coding of malignant effusion as M1 instead of T4. An impact on clinical decision making was occasionally seen (6 of 226, 2.7%) within our institutional practice. Further studies are needed to investigate the comprehensive and long-term impact of the new staging system.
Partly supported by a grant from the National Science Council, Taiwan (NSC 98-2314-B-039-014-MY3).
1. Alzahouri KY, Martinet S, Briancon S, et al. Staging practices of primary non-small-cell lung cancer: a literature review. Eur J Cancer Care (Engl)
2. Asamura HT, Goya Y, Koshiishi Y, et al. How should the TNM staging system for lung cancer be revised? A simulation based on the Japanese Lung Cancer Registry populations. J Thorac Cardiovasc Surg
3. Marchevsky AM. Problems in pathologic staging of lung cancer. Arch Pathol Lab Med
4. Goldstraw PJ, Crowley K, Chansky, 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
5. Goldstraw P. The 7th edition of TNM in lung cancer: what now? J Thorac Oncol
6. Schneider BJ. Non-small cell lung cancer staging: proposed revisions to the TNM system. Cancer Imaging
7. Rami-Porta R, Crowley JJ, Goldstraw P. The revised TNM staging system for lung cancer. Ann Thorac Cardiovasc Surg
8. Tanoue LT, Detterbeck FC. New TNM classification for non-small-cell lung cancer. Expert Rev Anticancer Ther
9. Milroy R. Staging of lung cancer. Chest
10. Fukui TS, Mori S, Hatooka S, et al. Prognostic evaluation based on a new TNM staging system proposed by the International Association for the Study of Lung Cancer for resected non-small cell lung cancers. J Thorac Cardiovasc Surg
11. Kameyama K, Takahashi M, Ohata K, et al. Evaluation of the new TNM staging system proposed by the International Association for the Study of Lung Cancer at a single institution. J Thorac Cardiovasc Surg
12. Ou SH, Zell JA. Validation study of the proposed IASLC staging revisions of the T4 and M non-small cell lung cancer descriptors using data from 23,583 patients in the California Cancer Registry. J Thorac Oncol
13. Travis WD. Reporting lung cancer pathology specimens. Impact of the anticipated 7th edition TNM classification based on recommendations of the IASLC Staging Committee. Histopathology
14. Greene FL, Sobin LH. The staging of cancer: a retrospective and prospective appraisal. CA Cancer J Clin
15. Zoepf T, Jakobs R, Arnold JC, et al. Palliation of nonresectable bile duct cancer: improved survival after photodynamic therapy. Am J Gastroenterol
16. Ignatius Ou SH, Zell JA. The applicability of the proposed IASLC staging revisions to small cell lung cancer (SCLC) with comparison to the current UICC 6th TNM edition. J Thorac Oncol
17. Chien CR, Tsai CM, Tang ST, et al. Quality of care for lung cancer in Taiwan: a pattern of care based on core measures in the Taiwan cancer database registry. J Formos Med Assoc
18. Silvestri GA, Gould MK, Margolis ML, et al. Noninvasive staging of non-small cell lung cancer: ACCP evidenced-based clinical practice guidelines (2nd edition). Chest
19. Filner JJ, Ost D. Principles of staging as applied to nonsmall cell lung cancer. Curr Opin Pulm Med
20. D'Amico TA. Molecular biologic staging of lung cancer. Ann Thorac Surg
21. Giroux DJ, Rami-Porta R, Chansky K, et al. The IASLC Lung Cancer Staging Project: data elements for the prospective project. J Thorac Oncol