Can Lung Cancer Be Detected Through Blood Tests?

Lung cancer is the most common cause of cancer deaths for people of any sex in the United States, causing more deaths than breast cancer, colon cancer, and prostate cancer combined. Unfortunately, lung cancer is often diagnosed in the later stages of the disease when treatment is less effective.

The gold standard for finding lung cancer early is computed tomography (CT) lung cancer screening. However, this is limited to people who have smoked. Currently, there are more non-smokers (never smokers and past smokers) who develop lung cancer than current smokers.

Available laboratory tests may help diagnose lung cancer, though this is more likely with advanced tumors. Research offers hope that blood tests (biomarkers) will assist in the diagnosis or even screening for early stage lung cancer in the future.

Laboratory professionals doing blood tests

PonyWang / Getty Images

This article explores how different types of blood tests/biomarkers may be used in two different situations. One involves using blood tests as a primary screening test to find lung cancer early. The other addresses the ability of blood tests to determine if a nodule found on a CT scan is likely to be malignant (cancerous).

This can help you understand why your doctor may recommend certain blood tests or why others may be recommended in the future.

Current Screening Methods

Screening for a condition refers to looking for and finding a condition before symptoms are present. If a test is done to evaluate symptoms, it is not considered a screening test but rather a diagnostic test.

After many years of hoping for a screening test for lung cancer that can find lung cancer early, one is now available. Unfortunately, the test is only recommended for certain people, is relatively expensive, and can result in false positives (positive tests in people who do not have the condition being screened for).

That said, when used appropriately, screening can reduce lung cancer deaths.

Imaging Tests

Low-dose CT screening is the only imaging test that can detect lung cancer early enough to change outcomes.

Chest X-Ray

For many years physicians recommended yearly chest X-rays to look for lung cancer in people who had smoked heavily. While chest X-rays can find some lung cancers, screening chest X-rays do not appear to save lives.

This can sound confusing, but the reason is that by the time tumors are large enough to be detected by a chest X-ray, they have already grown to a size at which survival would be similar if the tumor was found by chance alone.

Even after a lung cancer diagnosis is made, a chest X-ray can remain normal. In a review of studies in which people had symptoms of lung cancer and had been diagnosed, chest X-rays were negative 20% to 25% of the time.

Computed Tomography (CT)

Computed tomography (CT) can detect lung nodules that are much smaller than those that can be picked up on chest X-rays, as well as nodules that are difficult to see on chest X-rays due to location.

Low-dose CT is similar to conventional CT of the chest but involves roughly 90% less radiation. Due to this early detection, a 2021 review of studies found that, on average, annual low-dose CT screening can reduce the mortality rate of lung cancer by 25%.

When detected in the earliest stage, many of these cancers can be removed surgically (often with minimally invasive surgery) with good long-term outcomes.

Due to this reduced mortality, the U.S. Preventive Task Force now recommends yearly low-dose CT (LDCT) lung cancer screening for people who meet all three of these criteria:

  • Between the ages of 50 and 80
  • Have smoked for 20 pack years or more (pack years are calculated by multiplying the number of years smoked by how many packages of cigarettes are/were smoked daily)
  • Currently smoke or quit smoking in the past 15 years

For people who do not meet these criteria but have additional risk factors, such as radon exposure in the home, occupational exposures, or family history, the option of screening can be discussed with your doctor.

False Positives

In addition to being relatively expensive (though usually covered by insurance or Medicare) and involving a small exposure to radiation, the major drawback to CT screening is false positives. A false positive in cancer screening occurs when a test finds something that could be cancer, but no cancer is present.

In a well-designed Veterans Health Administration study, the false positive rate for CT lung cancer screening was 28.9%. This was similar to what other studies have found.

Out of this 28.9%, some people will require invasive tests to rule out cancer. The previous review found that 17 out of 1,000 people who were screened (and not found to have lung cancer) underwent an invasive test to rule out cancer.

(The false positive rate and detection rate can vary between different clinics and medical centers.)

Low-dose CT is designed to screen people who do not have any symptoms of lung cancer. If a person has symptoms, such as a cough, shortness of breath, or fatigue, a full dose CT should be done.

CT Lung Cancer Screening Can Lower Lung Cancer Deaths

While CT lung cancer screening can reduce mortality from lung cancer, only 6% of people who meet the criteria are receiving regular screening.

While LDCT screening can find some lung cancers early enough to improve survival, it's hoped that a blood test (biomarker test) will be developed to use alongside of CT screening to reduce the false positive rate (see below).

Biopsy

If a nodule or mass is found on a CT scan, a lung biopsy is most often needed to determine whether the abnormality is cancerous or not. In a biopsy, a tissue sample is removed from the lung and examined in the lab to look for cancer and other disease processes.

The type of biopsy that is done will depend on the location of the nodule, the size, and other factors but may include a needle biopsy, a biopsy during bronchoscopy, or a biopsy during surgery.

A biopsy will often be able to rule out or confirm the diagnosis, though repeat procedures or another type of biopsy may sometimes be needed.

Bronchoscopy

Early lung cancers can sometimes be detected on a bronchoscopy. A bronchoscopy is a test in which a thin tube is inserted through the mouth or nose and down into the large airways (bronchi) of the lungs.

It is most often ordered if a person has symptoms suggestive of lung cancer or to follow-up on a lung nodule seen on CT. That said, specialized bronchoscopy techniques (such as autofluorescence bronchoscopy) are being evaluated to see if they can detect precancerous or cancerous changes in the lungs.

Tumors in the large airways may be visualized via a light and camera attached to the end of the bronchoscope. An ultrasound device attached to the scope (endobronchial ultrasound) may also be used to identify tumors that are not in the airways but are in the tissues directly beneath the airways.

If an abnormality is seen on bronchoscopy, an instrument at the end of the bronchoscope can be used to take a biopsy of the abnormality for confirmation.

Unfortunately, bronchoscopy is primarily of use in identifying cancers that occur in or near the large airways. But the type of lung cancer that is becoming more common, lung adenocarcinoma, tends to grow in the outer regions of the lungs.

In one study, bronchoscopy was able to detect 69% of cancers. Bronchoscopy may be able to detect cancers in the uppermost part of the bronchi (CT is not as effective at detecting these tumors), but its low detection rate currently limits its value as a screening test.

Sputum Cytology

Once hoped to be a screening test for lung cancer, sputum cytology is a test in which cells are coughed up from the lungs and examined under the microscope.

At the current time, the test may still have some uses. If cancer cells are seen, it can confirm that a cancer is present (there are few false positives since cancer cells aren't ordinarily present in lungs without lung cancer). Even then, however, it doesn't indicate where the cancer may be in the lungs.

But if the test is negative, it means very little. In one study, sputum cytology was normal in 42% of people who had lung cancer.

Blood Tests for Lung Cancer

The results of non-biomarker blood tests (tests that aren't specifically looking for lung cancer) are usually nonspecific (meaning that the finding could be due to many different medical conditions) with lung cancer and frequently normal in the early stages of the disease.

Complete Blood Count

The complete blood count (CBC) includes counts and other analyses of red blood cells, white blood cells, and platelets. It is usually normal in the early stages of lung cancer (or if it is abnormal, it is for another reason).

Researchers have looked at the ratio of some types of white blood cells to predict prognosis with early stage tumors, but thus far it does not have a clear benefit in screening for or diagnosing lung cancer. However, changes seen on a CBC may provide clues in cases of advanced lung cancer.

With metastatic lung cancer that has spread to the brain or bones (between 25% and 40% of lung cancers at the time of diagnosis), there may be characteristic changes. These include a low level of one type of white blood cell (lymphocytes), an increased level of a different kind of white blood cell (neutrophils), and a low platelet count.

Blood Chemistry Tests

There are two primary settings where blood chemistry tests may be abnormal with lung cancer. One is if cancer has spread to other organs, such as the liver. The second occurs with the paraneoplastic syndromes that occur with some cancers.

Paraneoplastic Syndromes

Paraneoplastic syndromes are signs and symptoms caused by hormones or hormone-like substances produced by cancer (or by the body in response to cancer).

These symptoms/lab findings may occur at any stage of lung cancer, and the severity of the symptoms does not correlate with the seriousness or stage of the cancer. For this reason, there has been some hope that laboratory changes related to paraneoplastic syndromes may help diagnose at least some early stage lung cancer.

They are most commonly found with small cell lung cancers and squamous cell lung cancers, which often arise in the large airways. As noted earlier, lung adenocarcinoma is increasing while the incidence of small cell and squamous cell lung cancers is decreasing. Hence, there is a lower incidence of paraneoplastic syndromes than in the past.

Some of the findings may include:

  • High calcium levels: The most common sign of paraneoplastic syndrome is hypercalcemia (elevated blood calcium). Elevated calcium levels may also be seen when lung cancer spreads to bones.
  • Low sodium levels: Hyponatremia (low sodium level in the blood) occurs with a paraneoplastic syndrome called syndrome of inappropriate antidiuretic hormone secretion.
  • Increased uric acid levels: This is usually seen with squamous cell cancers.

In some cases, other labs may be abnormal, such as the kidney tests including blood urea nitrogen (BUN) and creatinine (Cr) and magnesium (Mg) levels.

Metastatic Lung Cancer

With liver metastases (spread of cancer to the liver), liver function tests may be abnormal, including aspartate aminotransaminase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), prothrombin time (PT), and bilirubin.

With bone metastases, alkaline phosphatase (ALP) is often elevated.

The State of Lung Cancer Research

When looking at newer techniques to detect lung cancer early, it's important to note that these are two different issues:

  • Can the test screen for lung cancer by itself?
  • Could the test be used along with a CT scan or when a nodule is found on CT to determine the likelihood that a nodule is cancerous?

Some of the newer techniques may address both concerns, whereas others are being studied primarily to assess whether a nodule should be biopsied.

Since most lung cancer diagnoses are preceded by discovering a nodule on a chest CT, a test that could be combined with CT screening could provide great guidance in the diagnostic process.

Lung nodules are common, and the number found on CT will likely increase as more people follow guidelines for lung cancer screening. Currently, it's estimated that 1.5 million lung nodules are detected each year in the U.S. Fortunately, the majority of these nodules are not cancer.

The downfall is that a significant number of nodules are in the indeterminate zone; they could be cancer, or they could be benign. So which of these indeterminate nodules should be biopsied?.

Biomarkers and Cancer Risk

Biomarkers are used commonly in medicine to guide diagnosis in treatment. A well-known example is the A1C test used with diabetes.

Biomarkers to assist in evaluating some cancers (tumor markers) have also been used for a long time. Perhaps best known is the prostate-specific antigen (PSA) test used to screen for or monitor the treatment of prostate cancer.

Categories of biomarkers being evaluated to assist in the diagnosis of lung cancer include protein markers and DNA (liquid biopsy).

Protein Biomarkers

Protein biomarkers may be nonspecific or specific to cancer.

Nonspecific biomarkers are proteins that aren't specific to a tumor but are often markers of inflammation. They may be increased in the blood when cancer is present. Several have been studied alone or in combination or panels. Examples include C-reactive protein (CRP), carcinoembryonic antigen (CEA), and alpha-1-antitrypsin.

A 2018 study was promising. By measuring two different proteins in the blood (LG3BP and C163A), researchers estimated that combining the biomarker with low-dose CT screening could result in 40% fewer invasive diagnostic procedures.

Tumor-specific biomarkers also hold some promise when combined with CT lung cancer screening. When a tumor is present in the body, B lymphocytes (the white blood cells that make antibodies) enter the tumor and "see" markings on the cells (antigens) that appear unique.

The lymphocytes then make antibodies (autoantibodies since they are essentially "against self") against these antigens. The antibodies can then be measured in a blood sample. A panel of 13 autoantibodies that were isolated were found to detect around 50% of lung cancers.

DNA Biomarkers (Liquid Biopsy)

A liquid biopsy is a test that looks for cancer cells or fragments of cancer cells that break off from a tumor and enter the bloodstream. These cells or portions of DNA can be distinguished from normal cells by the presence of the mutations that are characteristic of cancer.

Circulating Tumor Cells

Cells from a tumor may break off and enter the bloodstream, and researchers postulated that measuring these circulating tumor cells (CTCs) may help diagnose lung cancer. Unfortunately, whole tumor cells are found infrequently in the early stages of cancer and are considered unsuitable for lung cancer screening.

Cell-free DNA (ctDNA)

Unlike circulating tumor cells (whole tumor cells), small portions of the DNA from tumor cells are found frequently, even in the early stages of cancer.

In a 2020 study, researchers developed a test based on common molecular features of non-small cell lung cancers. This panel was called Lung-CLiP, which stands for "lung cancer likelihood in plasma." The test was able to detect between 40% and 70% of early stage lung cancers.

While the test is less sensitive than a low-dose CT scan, it is also less invasive and less expensive. It could play a role as a primary screening test for those who decline CT screening. (Researchers have likened this to stool tests for blood to screen for colon cancer which are less reliable than a colonoscopy but may be helpful for those who decline a colonoscopy.)

While less sensitive than CT screening, Lung-CLiP is much more specific, meaning the false positive rate is very low. For this reason, it might be helpful when combined with CT screening to guide when a nodule should be biopsied.

Cell-free DNA Fragmentomes

Another new approach has been to test for cell-free DNA in a different way. In a 2021 study, researchers looked at DNA fragmentation features (fragmentomes).

The hope is that this approach may provide a screening test for both people at a higher risk (e.g., smokers) and the general population. Currently, only 6% of people who meet the criteria for CT screening have the test done, and there is no test for people who have not smoked.

In this approach, scientists look at millions of fragments of cell-free DNA to look for abnormal patterns in different regions (DNA fragmentomes) via artificial intelligence. Due to how this is conducted, it's thought it could be more cost-effective than traditional cell-free DNA approaches.

In the study, evaluation of cell-free DNA fragmentomes detected over 91% of early stage (stage 1 and stage 2) lung cancers.

Summary

Currently, almost half of lung cancers are found when they have grown or spread too far to cure the disease. While CT lung cancer screening can reduce lung cancer deaths, it's only recommended for current or former smokers, and it has a high false positive rate.

Conventional blood tests are usually normal in the early stages of the disease, but newer biomarker tests could change this. Both protein and DNA biomarkers (liquid biopsy) may provide a way to guide the evaluation of lung nodules in the near future and possibly even offer a way to screen the general population for early stage lung cancer.

Also, a breath test is currently being developed that may increase the sensitivity and specificity of low-dose CTs in detecting lung cancers at an early phase.

A Word From Verywell

Unlike several medical conditions and even cancers that have biomarkers to aid in diagnosis, a blood test for early lung cancer has been lacking. Newer techniques, especially those now possible due to the completion of the Human Genome Project, offer solid hope that the early detection of lung cancer for everyone could be possible in the future.

Being aware of the symptoms and undergoing CT screening if you smoke or have smoked is the best option. Don't dismiss the risk if you've never smoked. Lung cancer is increasing in never smokers. Sometimes it is a wise patient that reminds a doctor that anyone who has lungs can get lung cancer.

Frequently Asked Questions

  • Is there a gold standard test for lung cancer?

    The gold standard for lung cancer detection at this time is a CT scan. As a screening test, low-dose CT screening can improve survival rates from lung cancer.

    Unfortunately, the test is recommended only for people who have smoked, and we do not have a screening test for never smokers. For people who have symptoms of lung cancer, a conventional (full dose) rather than a low-dose CT should be done.

  • Does lung cancer affect blood cell counts?

    Lung cancer may affect white blood cell counts or platelet levels, but not usually until it has spread to distant regions of the body such as the brain or bones.

  • What labs are elevated with lung cancer?

    Lab tests are often all normal in the early stages of lung cancer. An exception is with some tumors that make hormone-like substances. These may affect the calcium, magnesium, or sodium levels or affect kidney function tests such as BUN and creatinine.

    Lung cancer can raise AST and ALT levels when it spreads to the liver and an elevated ALP if it spreads to bones.

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