Predicting the Prognosis of Lung Cancer: The Evolution of Tumor, Node and Metastasis in the Molecular Age—Challenges and Opportunities

Ramón Rami-Porta; Hisao Asamura; Peter Goldstraw


Transl Lung Cancer Res. 2015;4(4):415-423. 

In This Article

Towards the 8th Edition

The modifications in the T and the M components of the classification, the recognition of the relevance of the quantification of nodal disease, the new stage groupings, and the application of the TNM classification to small-cell lung cancer improved our capacity to indicate prognosis, but the 7th edition of the TNM classification for lung cancer has limitations derived, mainly, from its retrospective nature.[67] Not all databases contained the necessary staging details to validate all descriptors, and over half of the registered patients underwent surgical treatment either alone or in combination.[11] This high proportion of surgical cases does not reflect common clinical practice and there is the need of a wider representation in the range of therapeutic modalities. To achieve this, the IASLC made a worldwide call to build a new international database to inform the 8th edition of the TNM classification of lung cancer.[68] Amazing as it may seem, the call was answered with the submission of more than 90,000 new patients from 35 databases in 16 countries, diagnosed from 1999 to 2010; and 77,156 (70,967 with non-small cell lung cancer and 6,189 with small-cell lung cancer) met the requirements for analysis.[69] Table 2 shows the geographical origin of the data. Europe maintains its leadership in submitting patients, while there was an important drop in contributions from North America and a very relevant increase in cases from Asia, thanks to the massive submission of Japanese registries. Although modest, for the first time there are some patients from South America. Another characteristic of this database is that nearly 4,000 patients were prospectively registered online through the electronic data capture system established by CRAB. These cases have very complete information and have been very useful for certain analyses for which detail matters, such as the number of metastases in patients with M1b disease. Table 3 shows the types of submitted databases. Clinical trials were in the lead in the database used for the 7th edition, while none was submitted for the 8th. The absence of clinical trials and the surgical cases submitted by Japan account for the relative scarcity of advanced cases in the database used for the 8th edition. Table 4 shows the types of treatments for each database. In both, there is a predominance of surgical cases, which is more evident in the database for the 8th edition. This fact may question the generalizability of the recommendations for changes derived from the analyses of the database, as it has been shown that some descriptions, for example tumor size, do not have the same prognostic impact in the populations of patients treated with radiotherapy.[70]

At the moment of this writing, the members of the IASLC Staging and Prognostic Factors Committee already have analyzed the database and decided on the changes to be recommended in the 8th edition. The original papers describing these analyses and the recommendations for changes already are submitted to the Journal of Thoracic Oncology or are in the process of being submitted.

Pending the scrutiny from the international oncological community and the acceptance from the UICC and the AJCC, the most important recommended changes affect tumor size, the relevance of which is greater than it was thought from the analyses of the previous database. Consequently, the recommendation is to define more groups of tumors based on size and to include tumor size as a descriptor in all T categories, from Tis to T4. The recommendation for the N component is to retain the 7th edition descriptors, but to propose the quantification of nodal disease by number of involved nodal stations for prospective registration of data. For the M component, the recommendation is to separate extrathoracic single metastasis from multiple metastases, as they have different prognosis. The stage grouping will be slightly modify, as the suggested changes in the T and the M components lead to the creation of more stages both in early and advanced disease. There will also be recommendations to code the new adenocarcinoma subtypes, especially adenocarcinoma in situ and minimally invasive adenocarcinoma; the recommendation to apply the TNM classification to small-cell lung cancer will be emphasized; and an attempt will be made to clarify the classification of lung cancers with multiple lesions: second primary tumors, separate tumor nodules, and multiple nodules with ground glass/lepidic features.