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J Thorac Cardiovasc Surg 2006;132:316-319
© 2006 The American Association for Thoracic Surgery
General Thoracic Surgery |
a Division of Thoracic Surgery, National Cancer Center Hospital, Tokyo
b Department of Surgery, Kyorin University, Tokyo
c Department of Surgery, Jichi Medical School, Tochigi
d Department of Mathematics, Science University of Tokyo, Tokyo, Japan
Received for publication January 31, 2006; revisions received March 9, 2006; accepted for publication March 28, 2006. * Address for reprints: Hisao Asamura, MD, Division of Thoracic Surgery, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan (Email: hasamura{at}ncc.go.jp).
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Abstract |
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METHODS: We revised the T1 descriptor definition and stage grouping for testing as follows. According to the greatest tumor diameter, T1 tumors were divided into T1a tumors (
2.0 cm) and T1b tumors (2.1-3.0 cm). With these descriptors, new IA, IB, and IIA stages were defined as T1a N0 M0, T1b N0 M0, and T2 N0 M0 + T1 N1 M0, respectively. For 6644 patients with histologically non–small cell lung cancers resected in 1994 and reported in the Japanese Lung Cancer Registry Study, the survivals and prognostic difference between neighboring stages were studied.
RESULTS: The 5-year survival of the entire population was 52.6%. In the clinical setting, the 5-year survivals of the new IA, new IB, new IIA, IIB, IIIA, IIIB, and IV stages were 77.5%, 69.3%, 49.8%, 40.6%, 35.8%, 28.0%, and 20.8%, respectively. In the pathologic setting, they were 83.7%, 76.0%, 60.0%, 42.2%, 29.8%, 19.3%, and 20.0%, respectively. For both clinical and pathologic settings, differences between all neighboring stages were statistically significant, except for that between IIIB and IV.
CONCLUSION: Subcategorization of T1 and minor changes in stage grouping results in a system with significant differences in prognosis between neighboring stages. The unification of stages IB and IIA, especially, improves the discriminatory power of the staging system.
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Introduction |
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The sixth edition of the International Union Against Cancer (UICC) TNM staging system for lung cancer has been available worldwide since 1997,
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and the next revision is scheduled for 2009. In a few years, the thoracic oncologic community must finalize a review of the current system and possible changes to it to identify existing and potential problems. As is well known, an important objective of the TNM staging system is to provide a differential prognosis for patients with similar "stages" of the disease, applicable worldwide. As such, overlapping prognoses for patients with different stages must be avoided.
For these purposes, the Japan Lung Cancer Society and the Japanese Association for Chest Surgery established an ad hoc task force, the Japanese Joint Committee of Lung Cancer Registry, and performed a large-scale retrospective study of the primary lung neoplasms resected in 1994 at the 320 certified teaching hospitals in Japan. We received replies from 303 institutions (94.7%) that included data forms from 7408 patients. The results of a detailed analysis of 6644 histologically typed non–small cell lung cancers (NSCLCs) have been published previously, with a critique of the current system.
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An important failing of the current staging system is that no difference in prognosis between stages IB and IIA is seen in either the clinical or the pathologic setting. The survival curves of patients in both groups are essentially superimposed for their entire length. The purpose of this study was therefore to improve the TNM staging system by modifying the T descriptors and stage grouping in the early stages and then to test the new staging retrospectively against the Japanese Lung Cancer Registry.
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Methods |
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The details of this registry study have been published elsewhere.
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In brief, the registry included 7408 patients; among them, data from 6644 patients (89.7%) with histologically typed NSCLC were analyzed. For the preoperative evaluation of the surgical candidates, the standard workup at the time of resection (1994) was performed, in which at least the chest radiography and computed tomography (CT) were performed for all the patients. The use of mediastinoscopy, brain CT (or magnetic resonance imaging), bone scan, or abdominal CT (ultrasonography) was considered if necessary. Positron emission tomography was not routinely used in 1994. The same population was used for this simulation study. The patients included 4601 men (69.6%) and 2010 women (30.4%). Sex was not noted in the records of 33 patients. Patients ranged in age from 19 to 90 years, with an average of 64.5 years. The histologic type of the tumor was described according to the World Health Organization classification.
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The most common histologic type was adenocarcinoma in 3922 patients (59.0%), followed by squamous cell carcinoma in 2300 (34.6%), large cell carcinoma in 245 (3.7%), and adenosquamous carcinoma in 177 (2.7%).
Simulation
In the previous study, the 5-year survivals by stage for clinical and pathologic settings were as follows: stage IA, 72.1% and 79.5%; IB, 49.9% and 60.1%); IIA, 48.7% and 59.9%; IIB, 40.6% and 42.2%; IIIA, 35.8% and 29.8%; IIIB, 28.0% and 19.3%; and IV, 20.8% and 20.0%.
2
No statistically significant difference in survival was observed between stages IB and IIA in either the clinical or the pathologic setting. On the basis of these results, we have proposed the following new definition of T descriptors and stage grouping. All the other definitions of T, N, and M descriptors, as well as the stage groupings, remained unchanged.
T descriptors
T1 tumors were originally defined as those 3 cm or smaller in greatest diameter, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus (not in the main bronchus).
1
In our revision to the staging system, T1 tumors were divided into T1a and T1b subcategories according to size. T1a tumors were defined as 2.0 cm or smaller in greatest diameter; T1b tumors were defined as 2.1 to 3.0 cm in greatest diameter. Other T descriptors remained unchanged.
Stage grouping
In our revised system, we defined T1a N0 M0 as new stage IA and T1b N0 M0 as new stage IB. T2 N0 M0 (stage IB) and T1 N1 M0 (stage IIA) were merged as new stage IIA. All other stage groupings remained unchanged.
Statistical Analysis
The survival time was defined as the date of surgery to the last follow-up date. The survival curves were estimated according to these new stage definitions for the same population with histologically typed NSCLC as in the previous study, and the differences in survival between neighboring stages was tested to evaluate the appropriateness of stage distribution. The survival curves were estimated by the Kaplan-Meier method, and the difference in survival was tested by the log-rank test.
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Results |
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Discussion |
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For NSCLC histologic types, the demographic and prognostic data of 6644 patients were analyzed. The most remarkable finding in that study was the overlapping prognoses of patients with stage IB and IIA cancer. Despite the different stage categories, the survival curves of stages IB and IIA were almost identical, with 5-year survivals of 49.9% versus 48.7% (clinical stage) and 60.1% versus 59.9% (pathologic stage), respectively. No significant difference in survival was observed in either the clinical or the pathologic setting. Similar results have been reported in the past, raising a concern about the current TNM staging system.
4-7
These findings clearly indicated that the current stages IB and IIA should be merged together, either as a new stage IB or a new stage IIA. There would be two alternative ways to name the merged IB + IIA category, as new IB or new IIA. Considering that this merged category has a 5-year survival of only approximately 50% in a clinical setting, it should be a part of stage II and not of stage I.
Separation of the subgroup of patients with worse prognoses in stage IB (T2 N0 M0) has been attempted previously. Larger tumors, such as those at least 5 or 6 cm in diameter, have been proposed for an upgrade to T3.
8,9
Tumors larger than 6 cm in our current data set comprised 12.1% (n = 341) of the entire group of T2 lesions (n = 2809), so even if these tumors were transferred to the T3 category, the prognostic difference between stages IB and IIA would remain unchanged. Considering the small percentage of large tumors in T2 category, the impact of the exclusion of the larger T2 subgroup on the prognostic difference between stages IB and IIA seemed to be limited as a whole.
According to the UICC TNM staging system, T1 tumors were originally defined as those 3 cm or smaller in greatest diameter, surrounded by lung or visceral pleura, and without bronchoscopic evidence of invasion more proximal than the lobar bronchus (not in the main bronchus). However, the T1 category is heterogeneous. Many groups have performed retrospective studies examining the effect of tumor size on stage, curability, and patient survival, although controversy remains as to the role of size within the T1 category. Ishida and colleagues,
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Read and coworkers,
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Warren and Faber,
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Padilla and colleagues,
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Koike and associates,
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and Gajra and coworkers
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uniformly reported a significant difference in survival between patients with tumors no larger than 2.0 cm and those with tumors 2.1 to 3.0 cm. Flieder and colleagues
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found that NSCLC larger than 2.0 cm was twice as likely to have nodal metastases than carcinomas no larger than 2.0 cm. Most of the reports used the 2.0-cm cutoff point. This study also identified a significant difference in survival between T1a N0 M0 and T1b N0 M0 for both clinical and pathologic settings in larger populations, and thus the subdivision of the T1 N0 M0 stage group according to the 2.0-cm cutoff point might be well justified. Although a numeric imbalance between T1a (2.0 cm) and T1b (2.0-3.0 cm) might be expected, the actual numbers of patients in this study were well balanced: 1204 T1a N0 M0 versus 993 T1b N0 M0 for the clinical setting and 1065 T1a N0 M0 versus 886 T1b N0 M0 for the pathologic setting. Therefore the subdivision of stage I by tumor size at a 2.0-cm cutoff point seems to be realistic.
However, because of the recent improvement of CT images and the advent of low-dose CT screening programs, the noninvasive form of adenocarcinoma, bronchioloalveolar carcinoma (BAC), is often included in the smaller T category. According to the World Health Organization histologic classification, BAC is defined as an adenocarcinoma with a pure bronchioloalveolar growth pattern and no evidence of stromal, vascular, or pleural invasion. The superb prognosis after adequate resection of BAC is already well recognized.
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These noninvasive BACs should therefore be newly termed as Tis and excluded from the T1 category. The prognostic difference between T1a N0 M0 and T1b N0 M0 thus might change in the future.
In conclusion, stages IB and IIA in the existing UICC TNM system should be merged (as a new stage IIA) because they have essentially the same prognosis. Stage IA tumors should be divided into stages new IA and new IB with a tumor cutoff size of 2.0 cm (T1a tumors 2.0 cm, T1b tumors 2.1-3.0 cm). BAC should be considered Tis and excluded from the T1 category. With these minor revisions, the prognostic distribution by stage would be better balanced, with significant differences between neighboring stages.
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References |
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