Descriptor
Subgroup
Definition
T (tumor)
T0
No evidence of primary tumor
T1
Tumor ≤3 cm, surrounded by the lung or visceral pleura, not more central than the lobar bronchus
T1a (mi)
Minimally invasive adenocarcinoma (solitary adenocarcinoma <3 cm, with predominant lepidic pattern and <5 mm invasion)
T1a
≤1 cm
T1b
>1 cm and ≤2 cm
T1c
>2 cm and ≤3 cm
T2
Tumors >3 cm and ≤5 cm or with any of the following features:
– Involves main bronchus without invading main carina, regardless distance to main carina
– Involves visceral pleura
– Associated atelectasis or pneumonitis of part or all the lung
T2a
>3 cm and ≤4 cm
T2b
>4 cm and ≤5 cm
T3
Tumors >5 cm and ≤7 cm (prior T2b) or with separate nodule(s) in same lobe, invading chest wall, phrenic nerve, or parietal pericardium
T4
Tumors >7 cm (prior T3) or with separate nodule(s) in a different ipsilateral lobe, invading diaphragm (prior T3), mediastinum, heart, great vessels, trachea, carina, recurrent laryngeal nerve, esophagus, or vertebral body
N (regional LN)
N0
No regional metastases
N1
Metastases to ipsilateral peribronchial, perihilar, or intrapulmonary LN
N2
Metastases to subcarinal or ipsilateral mediastinal LN
N3
Metastases to contralateral hilar or mediastinal LN or involvement of any scalene or supraclavicular LN
M (metastasis)
M0
No metastasis
M1
Metastasis present
M1a
Separate nodule(s) in contralateral lung, malignant pleural/pericardial effusion, or pleural/pericardial nodule
M1b
Single extrathoracic metastasis
M1c
Multiple extrathoracic metastases in one or more organs
Involvement of the Main Bronchus
Involvement of the main bronchus less than 2 cm from the main carina, without invasion of the carina (currently a T3 descriptor), was found to have better prognosis than other T3 descriptors. The distance from the carina (up to 2 cm or >2 cm) does not seem to increase risk of death after adjusting for tumor size. Hence, it was proposed to group all tumors invading the main bronchi regardless of the distance to the carina—as long as the carina is not invaded—as T2.
Involvement of the Diaphragm
Involvement of the diaphragm, a current T3 descriptor, was found to confer a worse prognosis than other T3 descriptors both in clinical and pathological settings. Hence, it is proposed to reclassify involvement of the diaphragm as T4.
Atelectasis/Pneumonitis
This new analysis showed that complete atelectasis/pneumonitis may have a better prognosis than other T3 descriptors, and besides the small number of patients with this characteristics, it is proposed to reclassify these patients from T3 to T2. The new proposal is to include in T2 category patients with any degree of atelectasis or pneumonitis.
Ground Glass/Lepidic Features and Pneumonic-Type Tumors
Tumors presenting with ground glass/lepidic pattern (GG/L) and “pneumonic” type infiltrates are typically multifocal and have different biologic behavior, and they are difficult to classify with our current TNM. A subcommittee of the IASLC was created to provide a consistent nomenclature for these particular presentations of lung cancer [21]. Since the IASLC database did not capture information on GG/L and pneumonic-type tumors, an evidence-based approach was taken, systematically reviewing the literature from 1995 to 2015. Multifocal GG/L lung adenocarcinoma should be classified by the T category of the lesion with the highest T, with the number (#) of lesions or simply (m) for multiple indicated in parentheses. The size is determined by the largest diameter of the solid component (by CT) or the invasive component under the microscope. The designation of T should be used for adenocarcinomas in situ (AIS) and T1a (mi) for minimally invasive adenocarcinomas (MIA) (e.g., T1a (mi) (m) N0 M0). The (#) or (m) is applied regardless of location (e.g., same lobe, different lobe of the lung). The T component should include all tumors whether resected or not that are thought to be malignant (either suspected or proved), as well as to those that are only discovered on pathological examination [20]. A single N and M category is applied to all GG/L tumors. Pneumonic-type lung cancer has a worse prognosis than GG/L type, yet nodal or extrathoracic metastases are rare. In cases of pneumonic-type cancers with a single area of tumor, the current TNM is easily applied. Unlike with GG/L tumors, in cases of multiple areas of involvement, the T or M category will be applied: T3 within same lobe, T4 within different lobe of same lung, and M1a in contralateral lung. This classification applies to both grossly and microscopically found tumors. If a tumor crosses a boundary between two lobes, a T4 classification should be applied. If a tumor is confined to one lobe but hard to measure, a T3 classification is given.
Summary of “Proposed” T Changes for the Eighth Edition of the TNM Classification of Lung Cancer
The subclassification of T1 into:
T1a: tumor 1 cm or less in greatest dimension
T1b: tumor more than 1 cm but not more than 2 cm in greatest dimension
T1c: tumor more than 2 cm but not more than 3 cm in greatest dimension
The subclassification of T2 into:
T2a: tumor more than 3 cm but not more than 4 cm in greatest dimension
T2b: tumor more than 4 cm but not more than 5 cm in greatest dimension
The reclassification of tumors more than 5 cm but not more than 7 cm in greatest dimension as T3.
The reclassification of tumors more than 7 cm in greatest dimension as T4.
The grouping of the involvement of the main bronchus as a T2 descriptor, regardless of distance from the carina, but without invasion of the carina.
The grouping of partial and total atelectasis or pneumonitis as a T2 descriptor.
The reclassification of diaphragm invasion as T4.
Multiple GG/L tumors should be given the T category of the largest lesion with the number of lesions between parenthesis or simply (m) next to the T category, with bilateral lesions not considered as M1a.
Both clinical and pathological information (when available) should be applied to GG/L tumors when describing the TNM.
Pneumonic-type tumors are classified according to the size of the involved area, and they follow the standard definitions of T3, T4, and M1a for lesions in different lobes.
Proposal for the Revision of N Descriptors
Nodal status continues to be one of the most reliable indicators of prognosis in lung cancer, and it is a major determinant of the optimal therapeutic option. The seventh edition of the TNM staging categorized the N status based on the location of the involved lymph nodes (LN) as N0 (no LN involved), N1 (ipsilateral hilar LN involvement), N2 (ipsilateral mediastinal LN involvement), and N3 (contralateral hilar or mediastinal or ipsilateral/contralateral supraclavicular LN involvement), regardless the number of LN involved. This seventh edition of the TNM also accepted the IASLC nodal map as the standard of care to describe LN involvement in lung cancer [11, 13]. The new database was analyzed to corroborate the prognostic ability of the current N categorization and to explore if there is a more sophisticated method for describing LN involvement [22]. Among 70,976 patients with NSCLC, data on the “N component” were available in 38,910 (54.8%) patients for “clinical” nodal (cN) status and in 31,426 (44.3%) patients for pathological nodal (pN) status. Of note, Japan submitted the most data, which consisted of 23,012 (59.1%) patients for cN status and 23,463 (74.7%) patients for pN status, in which the “Naruke-Japanese map” was exclusively used to designate the location of metastatic lymph nodes and to determine the nodal status [23]. Despite the fact that in 2009 the new international lymph node map (IASLC map) was promulgated by the IASLC and recommended by the seventh edition of the TNM, this map was rarely utilized. With the collected data, it was not possible to reconcile the discrepancies between the two maps.
Nodal Staging
Clear differences in overall survival were evidenced again in the new database for both clinically and pathologically staged cases, supporting the traditional classification of N0, N1, N2, and N3, without changes from the seventh TNM (new 5-year survival rates were 60%/75% for cN0/pN0, 37%/49% for cN1/pN1, 23%/36% for cN2/pN2, and 9%/20% for cN3/pN3). For T1 and T2 tumors, cN status continued to show a difference in prognosis for each category. For T3 and T4 tumors, there was no statistically significant difference between cN0 and cN1, but there was a difference between cN1 and cN2 and cN2 and cN3. Further analyses were performed to explore the prognostic impact of combining the number of involved LN stations with the current nodal categories in T—any M0 patients. Unfortunately this specific data on the number of involved stations was only available on pathological data and not clinical. Pathological N categories were further subdivided: pN1 was divided into pN1 single (pN1a) and pN1 multiple (pN1b), and pN2 was divided into pN2 single (pN2a) and pN2 multiple (pN2b). The survival curves for pN1b and pN2a overlapped, with 5-year survival rates of 50% and 49% for R0 resections, respectively (Fig. 22.1). The presence of skip metastasis was further taken into consideration: pN2a was divided into pN2 single with skip (no pN1 involvement, pN2a1), pN2 single without skip (pN1 involvement as well, pN2a2), and pN2b. There was a statistically significant difference in 5-year survival between pN2a1 (skip) and pN2a2 (no skip) (54% vs. 43%, respectively). However, there was no significant difference in prognosis between pN1b and pN2a1 (50% vs. 52%, respectively). These results indicated that the prognosis of pN2a1 (skip metastasis) was close to that of pN1b (multiple N1 stations). Since these interesting findings derived from pathological data and could not be corroborated in clinical staging, they could not be utilized to propose modifications in the N descriptors. Moreover, the analysis on the N descriptor was thought to be partly hampered by differences between the Naruke and the MD-ATS nodal maps.
Fig. 22.1
Analysis of survival in patients with pN1 and pN2 disease with single and multiple station involvement, both for R0 and any R resections. R0 = complete resection. Any R = complete and incomplete resections. Copyright IASCL 2015
Summary of “Proposed” N Changes for the Eighth Edition of the TNM Classification of Lung Cancer
No changes were made in N descriptors, retaining the traditional N0, N1, N2, and N3.
Further N category classification based on single versus multiple involved stations and presence or absence of skip metastases needs further prospective evaluation before it can be applied to our TNM system.
The IASLC nodal map recommended by the seventh edition of TNM continues to be recommended to provide precise anatomic definitions for all LN stations.
Proposal for the Revision of M Descriptors
Since the database generated for the seventh edition of the TNM, there have been multiple advances in diagnosis, staging, and management of lung cancer. The widespread use of PET-CT and MRI, the more precise local radiation therapies, the advent of minimally invasive surgery, and the individualized molecular-targeted oncologic treatments have changed our approach to patients with advanced disease. With the new and prospectively collected database being much richer than the prior one, the IASLC Staging and Prognostic Factors Committee has revised the M descriptors focusing on the burden of metastatic disease [24]. While data from 2411 non-resected M1 patients was available for analysis, only 1059 patients submitted through EDC had the specific data required to assess the objectives set out by IASLC, and the analysis was restricted to this group of patients. Median follow-up for M1a and M1b cases in the EDC was 29.3 months. Overall survival was measured since the day of diagnosis for clinically staged patients, and survival was estimated with Kaplan-Meier method. The analysis corroborated the difference in prognosis between the seventh edition TNM M1a (pleural/pericardial effusions, contralateral/bilateral tumor nodules, pleural/pericardial nodules) and M1b patients (extrathoracic metastases). The former category is showing a median survival of 11.5 months and the latter 7.5 months. In addition, the new database showed that patients with a single extrathoracic metastatic site had a similar survival to patients with M1a disease (median survival of 11.4 months) and much better survival than those patients with multiple extrathoracic metastases (median of 6.3 months). This prompted the reclassification of extrathoracic disease into M1b (single metastasis) and M1c (multiple metastatic disease in one organ or metastasis in multiple organs).
Summary of “Proposed” M Changes for the Eighth Edition of the TNM Classification of Lung Cancer
Maintain M1a category (pleural/pericardial effusions, contralateral/bilateral tumor nodules, pleural/pericardial nodules).
Reclassify current M1b category for patients with a single extrathoracic metastatic lesion.
Introduce the new category M1c for patients with extrathoracic metastatic disease characterized by either multiple lesions in a single organ or lesions in multiple organs.
Proposal for the Revision of Stage Groupings
Based on the previously described proposed changes to T and M descriptors (Table 22.1), new subsets of group stages were also developed [25]. Proposed TNM stage groupings were evaluated for survival based on clinical, pathologic, and best stage. Survival was calculated with Kaplan-Meier method, and it was measured from the date of diagnosis for clinically staged tumors to the date of surgery for pathologically staged tumors. The newly proposed stage groupings are summarized in Table 22.2. The proposed changes in T or M categories are translated into multiple migrations between stage groups. These migrations are highlighted with up or down arrows in Table 22.2. The overall survival for clinical and pathologically stage in the proposed stage grouping of the eighth edition of TNM is summarized in Table 22.3.
Table 22.2
Proposed stage groupings for the eighth TNM classification of lung cancer
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