This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
From TNM 8 to TNM 9: Stage Migration and Histology-Specific Patterns in Lung Cancer
by
, , , ,
Amalia Constantinescu
1,2
,
Radu-Nicolae Căprariu
2,*, 
Emil-Robert Stoicescu
2,3,4,5,*
,
Roxana Iacob
3,5,6,
Marius Mânzatu
7,
Janet Camelia Drimus
1,7
,
Alessia-Stephania Roșian
1,
Alexandre Ionescu
1,7,
Cristian Oancea
8,9 and
Diana Manolescu
2,7,8 1
Doctoral School, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
2
Department of Radiology and Medical Imaging, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
3
Research Center for Medical Communication, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
4
Research Center for Pharmaco-Toxicological Evaluations, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
5
Field of Applied Engineering Sciences, Specialization Statistical Methods and Techniques in Health and Clinical Research, Faculty of Mechanics, “Politehnica” University Timisoara, Mihai Viteazul Boulevard No. 1, 300222 Timișoara, Romania
6
Department of Anatomy and Embryology, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
7
Clinical Hospital of Infectious Diseases and Pneumophthisiology “Dr. Victor Babeș” Timișoara, Gheorghe Adam No. 13, 300226 Timisoara, Romania
8
Center for Research and Innovation in Precision Medicine of Respiratory Diseases (CRIPMRD), “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
9
Department of Pulmonology, “Victor Babeș” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania
*
Authors to whom correspondence should be addressed.
Cancers 2025, 17(20), 3290; https://doi.org/10.3390/cancers17203290
Submission received: 25 August 2025
/
Revised: 28 September 2025
/
Accepted: 8 October 2025
/
Published: 10 October 2025
(This article belongs to the Section Methods and Technologies Development)
Simple Summary
The TNM classification is an essential instrument for assessing the stage of lung cancer, informing prognosis and therapy strategies. In 2024, the 9th edition implemented significant modifications, notably the division of the N2 category into single-station (N2a) and multi-station (N2b) nodal illness, as well as the clarification of the concept of distant metastases (M1c1 vs. M1c2). Specifically, M1c1 refers to multiple metastatic deposits confined to a single extrathoracic organ, whereas M1c2 designates multiple metastatic deposits involving different extrathoracic organs. Our study examined lung cancer staging according to the 8th and 9th editions. The revised system resulted in considerable stage migration, with an increased number of patients categorized into advanced stages, particularly stage IIIA. Adenocarcinoma was the predominant histological type and showed an increased risk for progression to later stages relative to other subtypes. These findings correspond with international research and support the 9th edition as a more accurate and biologically relevant staging system, enhancing the consistency of prognostic evaluation and clinical decision-making.
Abstract
Introduction: The 9th edition of the TNM classification for lung cancer implemented significant revisions, notably the subdivision of the N2 and M1c categories, to enhance anatomical precision and prognostic accuracy. Nonetheless, the actual effects of these modifications on stage distribution, histology-specific patterns, and clinical interpretation remain to be fully evaluated. Objectives: To compare lung cancer staging distributions between the 8th and 9th TNM editions, analyze patterns of stage migration, and evaluate histology-specific reclassification trends. Although TNM 9 applies the same descriptors across all histological subtypes, the magnitude of stage migration varies. In our cohort and in international datasets, adenocarcinoma demonstrated a higher likelihood of reclassification into advanced stages compared to other subtypes. Methods: A retrospective analysis was performed on a cohort of lung cancer patients staged according to the 8th and 9th editions of the TNM classification. Stage distribution alterations were analyzed by chi-squared tests, whereas McNemar’s test examined the directional shifts in upstaging and downstaging. Further investigations evaluated the correlation between histological subtype and stage reclassification. Results: A statistically significant redistribution of stages was noted (χ2 = 1013.03, df = 64, p < 0.0001), with a notable prevalence of upstaging (p = 0.0019). The most significant proportional increase was observed in stage IIIA, mostly attributable to the N2 subdivision (N2a vs. N2b). Adenocarcinoma was the predominant histological subtype at all stages and showed a greater tendency for reclassification into advanced stages, specifically IIIA and IIIB. Squamous cell carcinoma was predominantly observed in stages IIB and IIIA, whereas small cell and large cell carcinomas were concentrated in advanced stages. These histology-specific patterns correspond with international findings, including research confirming the prognostic relevance of N2 subdivision. Conclusions: The 9th edition of the TNM classification results in significant stage migration, particularly in adenocarcinoma cases, indicating the improved sensitivity of the updated criteria in identifying advanced nodal disease. These modifications significantly impact prognostic evaluation and global comparability of clinical cohorts, supporting the implementation of TNM 9 as a more anatomically and biologically relevant staging system.
