Key takeaways

  • Non-small cell lung cancer (NSCLC) tumor markers are signs of specific types of tumors. Routine tumor markers doctors may test for after an NSCLC diagnosis include EGFR, ALK, and ROS1.
  • Tumor markers can help a doctor diagnose NSCLC or differentiate between different types of NSCLC. However, doctors will not typically use tumor markers alone to provide a diagnosis.
  • Testing for tumor markers can also help to guide treatment decisions, including monitoring treatment progression and the aggressiveness of the cancer.

Doctors use several tests to measure cancer and tumor markers during diagnosis and throughout treatment. Regular testing can help measure the presence and stage of cancer in certain areas and gauge a person’s response to treatment.

This article looks at tumor markers, how they relate to NSCLC, types of NSCLC tumor markers, tests and normal ranges for tumor markers, and whether they are a reliable diagnostic tool.

A tumor marker is a specific compound related to a tumor cell doctors are testing for.

Tumor markers are proteins or other compounds that cancer cells excrete or create faster than healthy cells. They differ from healthy cells, which allows doctors to get an accurate reading.

In NSCLC, testing for these tumor markers may help doctors identify the following:

  • cancer sites and stage
  • a person’s response to cancer treatment
  • specific mutations from the tumor, which may help with treatment

A doctor may take many samples to check tumor marker concentrations in a person’s blood, urine, or stool to get a better overall picture.

Knowing specific details about tumor markers for a particular cancer can help doctors immensely. This information may help them screen for cancer before other tests and differentiate NSCLC from other conditions that cause similar symptoms.

When a person has a known cancer, measuring tumor markers may help determine the disease course, such as estimating how aggressive the cancer will be. Doctors may also test for tumor markers in different tissues to check if the cancer has spread.

This information may also help a doctor determine what treatments could be effective against the specific type of cancer. Regular monitoring of tumor markers may also help identify the response to cancer treatment.

NSCLC is the most common form of lung cancer, accounting for about 87% of all lung cancer cases.

Several types of cancerous cells may occur with NSCLC, including the three main types:

Depending on the type of cancerous cell and the cancer itself, doctors may look for several tumor markers.

Diagnosis and differentiation

They may use markers such as thyroid transcription factor 1, napsin A, p40, p63, and cytokeratin 5/6 to help differentiate between adenocarcinoma and squamous cell carcinoma.

Tumor markers that may help a doctor diagnose NSCLC include:

  • carcinoembryonic antigen (CEA)
  • cytokeratin 19 fragment antigen (CYFRA21-1)
  • squamous cell carcinoma antigen (SCC-Ag)

People with NSCLC may have increased levels of other markers, including various carbohydrate antigens (CA), such as CA125. Although these carbohydrate antigens are not diagnostic tools, rising levels and other tumor markers may signify NSCLC.

Tumor markers that may help differentiate NSCLC from small cell lung cancer (SCLC) include neuron-specific enolase (NSE).

Some tumor markers will come from testing the tumor itself, including:

  • anaplastic lymphoma kinase gene rearrangement and overexpression
  • BRAF gene mutation
  • mutations in epidermal growth factor receptor genes
  • KRAS gene mutations
  • ROS1 gene rearrangement
  • programmed death-ligand

Treatment progression

Doctors may also use tumor markers, such as CYFRA21-1, to monitor the progress of treatment or the recurrence of cancer.

Doctors may use a few different methods to test for tumor markers, including:

A doctor will take a sample of the appropriate fluid or tissue and send it to a lab for testing.

The most suitable type of test may vary from person to person, depending on factors such as the type of tumor, the stage a doctor suspects a person’s cancer is at, and how far it may have spread.

The ranges of different tumor markers may help doctors diagnose NSCLC or differentiate it from other types of cancer or noncancerous lung diseases.

A 2024 article uses the following upper limits for “normal” levels of tumor markers:

  • CEA — 5 nanograms (ng) per milliliter (ml)
  • CA125 — 35 units per ml
  • CA19-9 — 35 units per ml

None of these individual factors is enough to make a diagnosis. Doctors will consider many factors during both diagnosis and treatment.

People should speak with their healthcare team to understand their tumor marker ranges and what the results may mean.

Doctors may use tumor markers as a guide throughout diagnosis and treatment. They can provide useful information about cancer’s presence in tissues, its stage, and the effectiveness of treatment.

Tissue biopsies of the tumor can help doctors identify the type of tumor by its mutations. Knowing what mutations caused the tumor may help doctors recommend targeted therapy for lung cancer if available for the type of tumor markers a person’s cancer has.

As a diagnostic tool

Tumor markers may be helpful diagnostic tools for lung cancer.

A 2025 study suggests that using a combination of tumor markers may be the most helpful when diagnosing lung cancers. In particular, CA-62 is highly sensitive in detecting early stage lung cancer.

The three routine tumor markers doctors use to diagnose NSCLC are EGFR, ALK, and ROS1. However, guidelines recommend testing at least seven biomarkers following NSCLC diagnosis.

Differentiating between cancer types and subtypes

Tumor markers may also help differentiate between types of lung cancer. For example, marker tests for CD56, chromogranin, or synaptophysin can help a doctor determine if the lung cancer is a small cell carcinoma or another type.

They may also help differentiate between types of NSCLC. Older research from 2017 suggests specific markers may be higher in different types of NSCLC, including:

  • higher levels of CEA and CA125 in adenocarcinoma
  • higher levels of SCC in squamous tumor
  • higher levels of CA125 in large cell lung cancer

Disease course

Tumor markers may also provide some idea of the disease course.

For example, a 2020 research article suggests that high levels of CYFRA21-1 in people with advanced NSCLC indicated an unfavorable disease course and survival rate.

Potential issues

With this said, tumor markers are not a certainty. There are some possible issues with using tumor markers.

For example, people may have cancer without having notable changes in tumor markers, and some conditions have few reliable tumor markers to check for.

Additionally, some other health conditions can cause similar increases in the levels of some tumor markers. Depending on the markers doctors are looking for, this may create a false positive for cancer.

Because of these possible limitations, doctors will not rely on tumor markers alone to gather the information they need to confirm a diagnosis of cancer.

They may use tumor marker results with other tests, such as imaging tests, to get more comprehensive results to help guide their diagnosis and treatment.

Testing for tumor markers can provide doctors with helpful information to help them identify non-small cell lung cancer.

Doctors may use the results of tumor marker tests, along with results from other tests, to guide diagnosis and treatment. More research into the reliability of tumor markers may improve understanding of how these markers can help guide a diagnosis.