Staging of cancer is designed to provide prognosis and treatment framework. It should be able to provide meaningful comparisons between different treatment modalities and the same treatment modality between different investigators. The AJCC has published the eighth edition of TNM classification of lung cancer which has adopted several newer modifications based on the database collected between 1999 and 2010 from 16 different countries and 35 sources.4
This edition has assimilated certain new descriptors including 23 non-anatomical elements viz. patient related elements such as smoking and demographics, tumor related factors such as standard uptake value (SUV) on PET for T and N, grade of tumor and environment related factors.25 The new staging system has been analyzed in both eastern and western countries and drew inconclusive results. This meta-analysis was done to evaluate the new classification.
With respect to the survival discrimination, the eighth edition seemed to fare better than the seventh edition. In this study, the HR for each 7th edition TNM classification were 1.36 in IB, 1.88 in IIA, 1.89 in IIB, 1.50 in IIIA and 3.45 in IIIB compared with IA. HRs for the seventh edition was found to be showing an erratic pattern. On the other hand, HRs of each 8th edition TNM classification showed linear progression with 1.52 in IB, 1.82 in IIA, 1.97 in IIB, 2.19 in IIIA, 5.03 in IIIB, and 7.15 in IIIC compared with IA. It showed a steady and reasonable increase in HRs signifying a better ability to characterize disease according to its survival curve.
Sensitivity analysis indicated that heterogeneity owing to different sample size and population. It might also be attributed to widespread lung cancer screening program mostly in western population with an earlier presentation than the eastern studies.
Most of the validation studies included in the analysis have fared toward a clear prognostic advantage towards the eighth edition individually but the meta-analysis based on four studies showed almost similar prognostic value with only slight superiority to the new edition.5,12−14 (C-index 0.688 vs 0.690)
The new edition has finessed a number of issues which were lacking in the previous edition. It allowed the evaluation of several descriptors that is expected to help stratify patients and prognosis more accurately. It also promotes the importance of multidisciplinary meetings as a standard of practice. This is the first time when characterization of sub-solid nodules and multiple pulmonary nodules has been clarified with a distinct role of difference in clinical, radiological and pathological staging.26
Even though this edition has incorporated some of the vital components as per the advent of scientific innovations, but still has several limitations. One of the major drawbacks is that a lot of data collected was still not necessarily designed for TNM classification similar to its predecessor. This leads to a lack of necessary details and clarifications required for a specific descriptor. One of those descriptors is lymphangitis carcinomatosis which has still not found its place in the classification due to lack of representation in the dataset. Agencies like NCCN and American College of Chest Physicians have recommended PET scan for the initial characterization of clinically indeterminate pulmonary nodule > 8 mm with a probability of malignancy (5–65%) as well as for pretreatment evaluation of lung cancer but SUV uptake of individual tumors have not been included in the stage.27,28 Modern medicine has evolved from radical to a more personalized way of treating cancer. Some of the malignancies have incorporated methods of precision medicine into its staging system such as breast cancer in the recent update but lung cancer staging has still not incorporated factors like immunohistochemistry and mutation genetics e.g. EGFR which can impact on treatment response and outcome.29
Like its predecessor, the eighth edition has been marred by the lack of representation of patients who were treated other than surgery. (12% to 4.7%) Owing to that generalizability of the new staging system for nonsurgical treatment modalities might affect the prognostic impact of the TNM descriptors.30 This meta-analysis has taken that into consideration with the incorporation of validation studies which have used radiotherapy and chemotherapy as their treatment modalities and came to the conclusion that prognostic ability of the new stage is almost same as its predecessor. The validity of the prognostic ability of the staging system is under scrutiny and should be further investigated.
In conclusion, the application of the eighth edition of the TNM classification in survival discrimination is valid but the prediction of prognosis needs further evaluation. The future staging system should be based on the dataset which is designed for TNM classification with the incorporation of elements of precision medicine and more representation of non-surgically treated patients.