Lung cancer staging: is TNM still enough?

Lung cancer staging has traditionally been based on anatomy: the size and location of the tumour, whether cancer has reached the lymph nodes and whether it has spread to other parts of the body.

That information remains central to diagnosis, treatment decisions and prognosis.

But our understanding of lung cancer has changed considerably. Biomarker testing can now identify molecular differences between cancers that may look very similar on a scan. Blood tests such as circulating tumour DNA (ctDNA) are also being studied as a way to detect very small amounts of cancer that cannot be seen on imaging.

Researchers are now asking whether future staging systems could use some of this biological information alongside the anatomical information already captured by TNM.

How TNM lung cancer staging works

TNM is the internationally recognised system used to describe the anatomical extent of many cancers, including lung cancer.

It records three main features:

T - Tumour: the size of the primary tumour and whether it has grown into nearby structures.

N - Nodes: whether cancer has spread to nearby lymph nodes.

M - Metastasis: whether cancer has spread to other parts of the body.

These findings are combined to give an overall stage. For non-small cell lung cancer, this ranges from stage I, where the cancer is relatively localised, to stage IV, where it has spread to distant parts of the body.

TNM provides a common language for clinicians, researchers and cancer registries around the world. It also helps guide treatment and provides information about likely outcomes.

Why the same lung cancer stage can describe very different cancers

TNM describes where cancer is in the body. It does not describe all the biological characteristics of that cancer.

Two people with lung cancer can have the same TNM stage but have cancers with different molecular drivers, different responses to treatment and different risks of recurrence.

This has become increasingly relevant as biomarker testing and targeted treatments have developed.

An EGFR-positive lung cancer, for example, can be treated differently from an ALK-positive lung cancer or a cancer without an identified actionable biomarker. These differences are already influencing treatment decisions even though they are not part of the TNM stage itself.

Biomarkers are already adding information beyond lung cancer stage

Biomarker testing is now an established part of care for many people with non-small cell lung cancer.

Tests can identify changes in genes or proteins that help clinicians understand the cancer and, in some cases, select a targeted treatment or immunotherapy.

This means clinicians may now know considerably more about a cancer than its TNM classification records.

The development of targeted treatments in earlier-stage lung cancer has made this particularly relevant. Molecular information can influence treatment after surgery, while the formal stage remains based on anatomical findings.

Could ctDNA and MRD provide more information after treatment?

Researchers are also studying whether blood tests could provide information about cancer that remains in the body after treatment.

Tumours can release small fragments of DNA into the bloodstream. This is known as circulating tumour DNA, or ctDNA.

Highly sensitive tests may sometimes detect ctDNA when there is no cancer visible on a scan. When evidence of cancer remains after treatment but cannot be detected using conventional imaging, it may be described as molecular residual disease or minimal residual disease (MRD).

Studies in lung cancer are investigating whether ctDNA detected after surgery or other curative-intent treatment can help identify people with a higher risk of recurrence.

This remains an active area of research. ctDNA and MRD testing are not currently part of the standard TNM staging system.

The proposed TNM + DB staging model

A new JAMA Oncology Viewpoint proposes keeping TNM and adding two further descriptors.

D - Driver: whether the cancer has an actionable molecular alteration that has been validated at that stage of disease.

B - Biology/burden: molecular burden measured through circulating tumour DNA (ctDNA) or minimal residual disease (MRD).

Under the proposed model, a cancer could still be described by its existing TNM stage, with D and B added to provide further information about its molecular biology.

For example, the authors describe stage IIIB (D-positive, B-positive) as locoregionally advanced cancer with a targetable driver and detectable molecular burden.

This is a proposal published as a Viewpoint. TNM + DB is not a staging system currently used in clinical practice.

Molecular data are already being studied in lung cancer staging

Lung cancer provides a strong setting for this discussion because molecular testing is already closely linked to treatment.

Researchers can now study whether genomic information, ctDNA results and other biomarkers provide useful prognostic information in addition to TNM stage.

For example, research is examining whether ctDNA after treatment can identify a higher risk of recurrence before that recurrence becomes visible on a scan.

The important question for staging is whether these measures are sufficiently accurate, reproducible and clinically useful to become part of a system used across different hospitals and countries.

What would need to change before biology could become part of staging?

A staging system needs to work consistently across large and diverse populations.

Any molecular or blood-based measure added to TNM would therefore need strong evidence that it provides useful information beyond existing staging.

There would also need to be agreement on how tests are performed, which biomarkers are included, when samples are taken and how results are interpreted.

Technology is developing quickly. A staging system also needs enough stability to remain useful as tests and treatments change.

For now, TNM remains the standard system for staging lung cancer.

Access to biomarker testing will be part of the discussion

Any move towards biologically informed staging would also raise questions about access.

Biomarker testing is not equally available across Europe. Differences exist between countries and between centres within the same country.

Adding molecular information to staging would only be useful if people could access the testing needed to provide that information.

Without equitable access, a more detailed staging system could introduce another source of variation rather than improve consistency.

For Lung Cancer Europe, access to timely, accurate biomarker testing therefore remains an important part of this wider discussion.

Where could lung cancer staging go next?

TNM has evolved repeatedly as evidence and diagnostic technology have improved. Future versions may also need to reflect the growing amount of biological information available in cancer care.

For lung cancer, the direction of research is clear. Scientists are studying how anatomical stage, tumour biology and blood-based biomarkers can provide a more detailed understanding of an individual cancer.

There is not yet enough evidence to replace or formally expand TNM with these measures.

For now, TNM tells us where lung cancer is in the body. Biomarker testing can tell us more about the cancer itself. Research into ctDNA may provide further information about cancer that remains after treatment or the risk of recurrence.

How these different types of information should be brought together is likely to be an important area of lung cancer research over the coming years.

Sources

Subbiah V, Nabhan C. When TNM Staging Is Not Sufficient. JAMA Oncology. Published online 30 July 2026.

Carbone DP, Hirsch FR, Osarogiagbon RU, et al. The International Association for the Study of Lung Cancer Staging Project: The Impact of Common Molecular Alterations on Overall Survival in NSCLC in Initial Analyses of the IASLC Ninth Edition Staging Database. Journal of Thoracic Oncology. 2025;20(10):1423–1440.

International Association for the Study of Lung Cancer. IASLC Staging Project: Lung Cancer, Thymic Tumors, and Mesothelioma.

Further reading from Lung Cancer Europe

Lung cancer biomarker testing is moving faster than ever. Is Europe keeping up?

Why biomarker testing should be routine in all NSCLC

When care happens is as important as what happens: the case for timed targets in lung cancer