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New TNM Classification for Lung Cancer - Part I: The changes

Author: Dr. A. De la Guerra | Submitted: February 01, 2010. Updated: February 01, 2010.

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Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

 

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ABSTRACT: Appropriate staging of lung cancer is fundamental for determining the best treatment approach and defining prognosis. After ten years of labor the IASLC has modernized the lung cancer TNM staging system. Revisions to the TNM were determined by differences in the overall survival of 81,015 patients; after meticulous validation the proposals for changes were submitted to the AJCC and UICC, and accepted. The 7th edition of the “TNM Classification of Malignant Tumors” was launched recently, including the new lung cancer staging system. This article review and discusses the changes that appear in this new edition, which took effect for all new diagnosis of cancer on the first day of 2010.

Introduction

"Systems do not exist in Nature
but only in men’s minds."
Claude Bernard (1813-1878).

Following microscopic confirmation of lung cancer the anatomic extent of disease must be assessed to (1) separate patients who are candidates for surgical resection from those who are not, and will benefit from chemotherapy and/or radiotherapy, (2) determine prognosis. Staging also offers a common language to evaluate, compare and exchange information of treatment results and clinical research (1).

The basis for lung cancer staging is the tumor, node, and metastasis (TNM) classification developed and maintained collaboratively by the American Joint Committee on Cancer (AJCC) and the Union Internationale Contre le Cancer (UICC). The current system, the sixth edition of the TNM Classification of Malignant Tumors, was published in 2002. The last revision of the staging system for lung cancer was presented by Mountain in 1997 (2), which remained unaltered on the 2002 manual (3).

The staging system developed by Mountain was based on data collected from 5,319 patients with NSCLC, and was validated by Naruke in 2001 (4).

Proposals for a new Staging System

A staging system is not a static science; it requires periodic modifications to reflect new knowledge on cancer etiology, advances in diagnostic capabilities and staging procedures, along with improvements in therapy.

The current staging system has held up very well for 12 years, but has clear limitations. Several publications revealed problems in the T and N definitions, as well as variability of prognosis within the subsets of the stage groups (5-8). Revision of T, N, and M descriptors and the consequent stage groupings must be defined by the outcome measure of survival to improve the alignment of TNM stage with prognosis (9) to facilitate decisions about treatment options. Mountain’s revision was based on a relatively small population of patients who underwent surgical treatment in a single geographic area, and no validation was presented to justify the individual descriptors (10). Therefore, a revision was necessary (11-13).

In order to overcome the limitations of the present TNM classification, the International Association for the Study of Lung Cancer (IASLC) launched the Lung Cancer Staging Project in 1996 and, in 1998 created an International Staging Committee (ISC) of multidisciplinary members to conduct revisions (14).

Now, after a decade of work the IASLC has updated the lung cancer staging system. Changes to the sixth edition were proposed by the ISC based on an international collection and review of 100,869 patients from 46 sources of 20 countries. Data were drawn from lung cancer cases treated by all modalities between 1990 and 2000. After exclusion of ineligible cases, 81,015 patients (67,725 nsclc and 13,290 sclc) remained for investigation (15, 16). Data management and statistical analysis was carried out by the Cancer Research And Biostatistics “CRAB” (17).

Proposals for revision were submitted to the AJCC and UICC for consideration in the new edition of the staging manual and both accepted the recommendations. In the last months of 2009, the Seventh Edition of the TNM Classification of Malignant Tumors was published, with a new lung cancer staging system. The new edition took effect on January 1, 2010 (18, 19).

Changes in lung cancer staging

"One enlarges science in two ways: by adding new facts
and by simplifying what already exists."
Claude Bernard (1813-1878).

The changes recommended by the IASLC for the future 7th edition of TNM classification for lung cancer were based on differences in survival (20), and the results of the data analysis were internally and externally validated (21). These changes include new T and M definitions and consequent new stage groupings, a new lymph node map, a novel definition on pleural invasion, as well as recommendations to apply the TNM system to broncho-pulmonary carcinoid tumors and SCLC.

Changes to T Descriptors (22, 23). See table 1.

  • New tumor size cut points at 2, 3, 5, and 7 cm subclassify and reclassify the T component as follows:
  • T1 subclassified: T1a: tumors = 2 cms.

T1b: tumors: > 2 cms and = 3 cms.

  • T2 subclassified: T2a: > 3cms and = 5cms.

T2b: > 5 cms and = 7 cms.

  • T2 reclassified: T2 > 7 cms. became T3.
  • Multicentric tumors of similar histology reclassifies the T component as follows:
  • Separate nodule(s) in the primary lobe: became T3.
  • Separate nodule(s) in a different ipsilateral lobe: became T4.
  • T4 descriptors reclassified to a new component:
  • Pleural dissemination (nodules or malignant effusion): became M1a.
  • Malignant pericardial effusion: became M1a.

Table 1. T descriptor changes: comparison between 6th and 7th edition of the TNM Classification of Malignant Tumors.

T definitions

6th ed. descriptor

7th ed. descriptor

Tumors = 2 cms.

T1

T1a

Tumors > 2 cms and = 3 cms.

T1

T1b

Tumors > 3cms and = 5cms.

T2

T2a

Tumors > 5 cms and = 7 cms.

T2

T2b

Tumors > 7 cms.

T2

T3

Separate nodule(s) in the primary lobe.

T4

T3

Separate nodule(s) in a different ipsilateral lobe.

M1

T4

Malignant pericardial effusion.

T4

M1a

Pleural dissemination.

T4

M1a

Changes to N Descriptors (24, 25).

  • No changes were made to N descriptors.
  • New International Lymph Node Map: The ISC has developed a new lymph node chart to resolve disagreements in nomenclature between Naruke’s (The Japan Lung Cancer Society) and Mountain-Dresler’s maps (American Thoracic Society).
  • New classification of lymph nodes by grouping stations into “Nodal Zones” for prognostic analysis (Table 2); this proposal needs to be validated with prospective studies and will not be effective in the new TNM system.
  • Proposal to subdivide the N component according to the extent of involvement of regional lymph nodes into N1a (single-zone N1), N1b (multiple-zone N1), N2a (single-zone N2), and N2b (multiple-zone N2). This needs further validation and will not be part of the new TNM changes.

Table 2. Grouping of lymph node stations into “zones”.

Nodal Zone

Lymph node station

Upper zone

Low cervical, supraclavicular, sternal notch (1R – 1L)

Upper paratracheal (2R – 2L)

Prevascular (3a) and retrotracheal (3p)

Lower paratracheal (4R – 4L)

Aortopulmonary zone

Subaortic (aortopulmonary window - 5)

Para-aortic (ascending aorta or phrenic nerve - 6)

Subcarinal zone

Subcarinal (7)

Lower zone

Paraesophageal (8)

Pulmonary ligament (9)

Hilar zone

Hilar (10)

Interlobar superior (11s) and inferior (11i)

Peripheral zone

Lobar (12)

Segmental (13)

Subsegmental (14)

Changes to M Descriptors (9, 23). See table 3.

  • Subclassify the M1 component in:
  • M1a: Intrathoracic metastasis.
  1. M1b: Extrathoracic (distant) metastasis.
  • Reclassify pleural dissemination (malignant pleural effusions, pleural nodules) and malignant pericardial effusions as a metastasis descriptor: from T4 to M1a.
  • Subclassify M1 by additional nodules in the contralateral lung as M1a.
  • Subclassify M1 by distant metastases as M1b.
  • The MX and pM0 designation has been eliminated from the AJCC/UICC TNM system.

Table 3. M descriptor changes: comparison between 6th and 7th edition of the TNM Classification of Malignant Tumors.

M factor definitions

6th ed descriptor

7th ed descriptor

Metastasis cannot be assessed.

MX

M0

Malignant pericardial effusion.

T4

M1a

Pleural dissemination (malignant pleural effusions, pleural nodules).

T4

M1a

Additional nodules in the contralateral lung (same histology).

M1

M1a

Distant metastasis.

M1

M1b

Additional changes.

  • Introduction of a new accurate definition of visceral pleural invasion (VPI); VPI is a pT2 descriptor (Table 4). To avoid confusion, the abbreviation PL is employed instead of P which is also used for designation of pTNM in distinction from cTNM. The IASLC also recommends the use of elastic stains to distinguish between PL0 and PL1 when hematoxylin and eosin (H&E) sections are not helpful (26).
  • Clinical TNM staging now is valid for SCLC, and stratification by stage I to III should be included in clinical trials of early stage disease (27).
  • Pathologic TNM staging must be used for all SCLC cases (28).
  • Carcinoid tumors are now included within the TNM classification (29), a new staging system for neuroendocrine tumors. Lung carcinoids are staged in the same way as carcinomas.
In summary, the new TNM staging system is applicable to NSCLC, SCLC and broncho-pulmonary carcinoid tumors.

Table 4.  Classification of visceral pleural invasion (VPI): Proposed modification of Hammar Classification (30).

PL category

Definition

T status

PL0

Tumor within the subpleural parenchyma or, invading superficially into the pleural connective tissue below the elastic layer.

PL0 is not a T descriptor and the T component should be assigned on other features.

PL1

Tumor invades beyond the elastic layer.

pT2

Indicates VPI

PL2

Tumor invades to visceral pleural surface.

PL3

Tumor invades the parietal pleura.

pT3

Changes to Stage Groups (31).

Stage groupings were modified due to changes to the TNM descriptors (Table 5).

  • TNM grouping categories that were down-staged:
  1. T2 smaller tumors, now T2a (>3 cm =5 cm), N1M0 are down-staged from IIB to IIA.
  1. T4 tumors due to additional nodules in primary lobe, now T3, are down-staged from IIIB to IIB (N0) or to IIIA (N1-2).
  1. M1 cases due to additional nodules in other ipsilateral lobe(s), now T4, are down-staged from IV to IIIB (N2-3) or to IIIA (N0-1).
  1. T4 tumors due to other factors, N0-1 are down-staged from IIIB to IIIA.
  • TNM grouping categories that were up-staged:
  1. T2 larger tumors, now T2b (>5 cm =7 cm), N0M0 are up-staged from IB to IIA.
  1. T2 tumors >7 cm, now T3, are up-staged: T3N0M0 from IB to IIB and T3N1M0 from IIB to IIIA.
  1. Tumors with pleural nodules or malignant pleural (or pericardial) effusion were reclassified from T4 to M1a, therefore are up-staged from stage IIIB to IV.

Table 5. TNM staging groups changes: comparison between 6th and 7th edition of the TNM Classification of Malignant Tumors.

6th ed

7th ed

N0

N1

N2

N3

T/M descriptors

T1 (=2cm)

T1a

IA

IIA

IIIA

IIIB

T1 (>2 cm =3 cm)

T1b

IA

IIA

IIIA

IIIB

T2 (>3 cm =5 cm)

T2a

IB

IIA

IIIA

IIIB

T2 (>5 cm = 7 cm)

T2b

IIA

IIB

IIIA

IIIB

T2 (>7 cm)

T3

IIB

IIIA

IIIA

IIIB

T3 (direct invasion)

IIB

IIIA

IIIA

IIIB

T4 (same lobe nodules)

IIB

IIIA

IIIA

IIIB

T4 (extension)

T4

IIIA

IIIA

IIIB

IIIB

M1 (ipsilateral nodules)

IIIA

IIIA

IIIB

IIIB

T4 (pleural effusion)

M1a

IV

IV

IV

IV

M1 (contralateral nodules)

IV

IV

IV

IV

M1 (distant)

M1b

IV

IV

IV

IV

= Change in TNM classification.

Conclusions

So, what makes this latest review of the TNM system for lung cancer unique?

  • The size of the database, the largest ever collected for any cancer type.
  • For the first time, data was collected from different countries.
  • The timeframe of 10 years allowed for 5 years follow-up.
  • Cases included all treatment modalities.
  • Pathologic and clinical staging where considered in survival analysis.
  • The statistical analysis included meticulous internal and external validation.
  • Changes to the TNM descriptors and stage groups were derived strictly from the outcome measure of overall survival.

The new TNM system is less intuitive and more complex than the 6th edition, and will be more difficult to learn. The oncology community needs to overcome the higher learning curve in order to offer patients the most appropriate treatment choices based on more accurate prognostic information.

Perfection is achieved, not when there is nothing more to add,
but when there is nothing left to take away.
—Antoine de Saint-Exupéry

Conflict of interest statement

No financial conflicts or disclosures to report.

CITE THIS ARTICLE:
Dr. A. De la Guerra. New TNM Classification for Lung Cancer - Part I: The changes. Doctors Lounge Website. Available at: http://www.doctorslounge.com/index.php/articles/page/340. Accessed August 30 2014.

References



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