How Fast Does Lung Cancer Develop, Grow, and Spread?

Learn about doubling time and its role in progression and treatment

In This Article

Many people wonder how fast lung cancer grows and how long it takes to spread. As a related question, some people wonder about how long lung cancer takes to develop, or when it first started. Understanding the growth rate and doubling time of lung cancer is not just an academic curiosity, but could affect decisions on the timing of treatment. These questions are being asked more frequently than in the past. For example, you may be wondering:

  • Is it OK to wait for the results of genomic testing before starting treatment?
  • Do you have time to do pulmonary rehabilitation before you have lung cancer surgery?
  • If you have a lung nodule found on lung cancer screening, is it OK to wait and watch it for the time being?
  • Does the size of your cancer mean it's more likely to recur or spread?

While imagining a cancer growing can be disheartening, we will talk about how factors other than growth rate are often important in both the spread and recurrence of lung cancer.

Every Cancer is Different

When discussing anything surrounding lung cancer it's important to note that every person is different, and every cancer is different on a molecular level. Even two lung cancers of the same type and stage may behave quite differently. Not every cancer grows at the same rate.

Even being able to estimate the growth rate is not enough, however, to make decisions in cancer care. When making decisions about timing of treatments it's important to look at how the timing between diagnosis and treatment affects outcomes, not just the growth rate of a tumor. In some cases, especially with lung cancers that have targetable mutations, waiting a month for results of testing may lead to better outcomes than beginning treatment right away.

How Fast Lung Cancer Grows (Proliferation)

To get an idea about how fast lung cancer grows, it's helpful to look at doubling time. But it's also important to look at the biology of cancer cell growth, as this places limitations on the estimates used. These limitations may lead to both overestimates and underestimates of the true growth rate.

The Biology of Lung Cancer Cell Growth

A normal lung cell becomes a cancer cell after a series of mutations in genes that control cell growth (often both oncogenes and tumor suppressor genes) results in a cell that behaves very differently than a normal cell. These mutations do not usually all happen at once, but accumulate over a significant period of time, sometimes decades. On average, a typical cancer cell must divide roughly 30 times before a tumor is 1 centimeter in diameter (roughly half an inch). At this point, the cell has multiplied to become 10 billion to 100 billion cells, and is just barely detectable (if at all) on a chest X-ray.

Not All Cells Divide at the Same Time/Growth Fractions

While growth rates and doubling time are important, in real life there are exceptions to every rule. Estimates of growth rate are based on the exponential growth of cells. For example, one cell becomes two, two become four, four then become eight, and so on. In real life, however, not all cells are dividing at the same time.

Different types of cancer have different "growth fractions," a measure of the proportion of cells that are in an active cell cycle. Some cancers, such as childhood leukemias, have a very high growth fraction in which a large number of cells are dividing at a specific time. Other cancers, such as breast cancer, have a low growth fraction.

Growth Rate Varies at Different Stages in Tumor Growth

In addition, the growth can also be different at different stages of development and progression. Tumors are not simply a clone of abnormal cells that grow in an out-of-control manner. As a cancer grows, the cells develop further mutations that can change the behavior of a tumor. Many people are familiar with this phenomenon as it is often the new mutations in a tumor that make it resistant to a treatment that had previously worked. Some of the added mutations in a tumor may result in the cancer cells growing and dividing more rapidly than when it first developed.

Specific Growth Rate

In measuring the growth of a tumor, researchers now often look at both tumor doubling time and specific growth rate (since tumor doubling time can result in rates faster or slower than real growth). The specific growth rate is calculated as the change in volume of a tumor in a certain period of time. The result estimates the percentage growth of a tumor in a particular period of time (such as daily growth).

Lung Cancer Doubling Time

The doubling of a lung tumor may be reported as volume doubling time (the time it takes for the cancer to double in size) or metabolic doubling time.

Limitations

There are a number of limitations in estimating doubling time in studies.

  • They are based on a continuous rate of growth (and this is not the case)
  • Difficulty designing studies: It wouldn't be ethical to observe cancers in people to see how rapidly their tumors doubled in size. Studies done on cancer cells in the lab or in animals don't necessarily reflect what happens in people. And estimates based on radiological measurements (such as PET or CT) are subject to limitations in estimating the size of tumors.

Overall Doubling Time

Some studies have looked at the doubling time of lung cancer in general; including tumors in people with different types and stages of the disease. A study comparing the doubling time of breast cancer with that of non-small cell lung cancer found that the volume doubling time for lung cancer (134 days) was significantly faster than that of breast cancer (252 days).

Lung cancers, on average, double in size in four months to five months.

Doubling Time Non-Small Cell Lung Cancer (NSCLC)

The doubling time of non-small cell lung cancer can vary significantly based on several factors, including the subtype and smoking history.

One study looked at growth rate by measuring growth with CT scans taken an average of 25 days apart, followed by surgery in which the tumors were removed. The average doubling time was 191 days, with non-small cell tumors growing significantly slower than small cell lung tumors. Tumors in people who smoked had a more rapid doubling time than those from people who never smoked or had quit smoking. An important finding was that tumors with a slower doubling time (greater than 400 days) did not necessarily have a better prognosis, and 1/3 of people with these tumors developed metastases to distant regions of the body.

Doubling Time CT-Detected Lung Cancer

A different study (the Pittsburgh Lung Screening Study) looked at the doubling time of CT-detected lung cancer, and separated the tumors into three categories:

  • Rapid growing (doubling time of less than 183 days): 15.8%
  • Typical (doubling time of 183 to 365 days): 36.5%
  • Slow growing (doubling time of over 365 days): 47.6%

They then compared these doubling times with subtypes. Lung adenocarcinoma (and the subtype of lung adenocarcinoma formerly referred to as bronchioloalveolar carcinoma) made up a significant proportion of the slow-growing group (86.7%) with only 20% in the rapid doubling time group. In contrast, squamous cell carcinoma of the lung made up 60% of the rapid doubling time tumors and only 3.3% of the slow doubling time group.

Squamous cell carcinoma of the lung tends to have a more rapid doubling time than lung adenocarcinoma.

Studies have also looked at the doubling time of adenocarcinomas that are EGFR positive, with some showing a longer doubling time and others not.

Doubling Time Small Cell Lung Cancer

Doubling time with small cell lung cancer has been studied less than that of non-small cell lung cancer, but appears to be both rapid and dependent on stage. Unlike non-small cell lung cancer that is divided into four stages, small cell lung cancer has only two stages: limited stage and extensive stage. In a study looking at initial CT scans (and the CT component of PET/CT), the mean diameter doubling time for small cell lung cancer was 70 days for the primary tumor, and 51.1 days for involved lymph nodes.

The doubling time was much more rapid, however with extensive stage disease (24 days) relative to limited stage disease (97.6 days). Looking at all people in this study and all lesions (primary tumor plus metastases), the mean diameter doubling time was 59.6 days and the mean volume doubling time was 50.5 days.

Factors That Affect Growth Rate

There are a number of factors that may affect the growth rate of lung cancer, including:

  • The type and subtype of lung cancer
  • Genomic alterations (for example, EGFR mutations)
  • Smoking status
  • Sex: Several studies have found that lung cancers in women have a longer average doubling times than lung cancers in men (roughly twice as long on average)
  • Volume doubling time tends to be longer in tumors diagnosed by CT screening than tumors that are discovered clinically

Predicting the Natural History of Cancer From Doubling Times

Looking at doubling times of tumors is helpful only if estimated doubling times can be used to predict the growth of a person's tumor. One study looked at predicted survival times of people who had inoperable lung cancers (before recent advances in targeted therapies and immunotherapy) and found that there was a close correlation between survival predicted from doubling time and actual survival.

Survival Without Treatment

Researchers sometimes look to doubling time when asked a heartwrenching question: How long can a person survive without treatment. Overall, it's thought that current models are inadequate to accurately estimate this answer.

Time to Spread (Metastasis)

Another common question concerns how long it takes lung cancer to spread (metastasize) to other regions of the body. Does a lung tumor have to first reach a particular size? Since metastases are responsible for the majority of deaths from cancer, this is an important question to address.

The answer is that it may depend, and how quickly a lung cancer spreads may be tied closely with the type of lung cancer. While there are differences, it's important to note that any lung cancer (other than stage 0 lung cancer or carcinoma in situ) has the potential to spread.

Any stage or size lung cancer has the potential to spread.

Overall, small cell lung cancer has the potential to spread very early. Even very tiny small cell lung cancers may spread, for example, to the brain, and symptoms related to brain metastases are not uncommonly the first symptoms of the disease. Squamous cell carcinomas of the lung, in contrast, may become quite large before they spread; even to lymph nodes. Lung adenocarcinomas appear to be somewhere in the middle, and where and when they spread varies with the molecular profile of the tumor (genomic mutations and other alterations).

Overall, the most common sites of lung cancer metastases incude:

Factors Other Than Growth Rate are Often Key in Metastases

The chance that a tumor will metastasize often depends on factors other than the growth rate or doubling time. Old theories about the natural history of lung cancer have been tossed aside as knowledge about the natural history of lung cancer expands.

In the older concept, it was thought that a tumor had to reach a particular size, first spread to lymph nodes, and then onward from there. We know now that this simply isn't the case. Instead, it may be particular mutations in the cells, or the tumor microenvironment (the normal cells surrounding a tumor) that allow cancer cells to begin to grow in that organ or tissue.

First, the cancer cells need to "escape." Normal cells have adhesion molecules that hold them together. Different mutations in cancer cells can make it easier or harder to break free.

Then they have to travel via either the blood, lymphatic system, or airways. Spreading through the lymphatics (with which people are often more familiar) takes longer, whereas spread through the bloodstream can "seed" cancer cells to other regions much more rapidly, sometimes long before a tumor is detected. Studies have found that tumor cells in the bloodstream (cells that break off and circulate through the body) are common even in very early-stage non-small cell lung cancers.

Most cancer cells that arrive at a new destination do not turn into a metastasis but instead die off. For growth to occur, the cells need to establish a blood supply (angiogenesis) as well as change the environment so that the immune system doesn't attack (establish immune tolerance). To do this, they need to communicate with normal cells nearby. Rather than reaching a particular size or spreading to lymph nodes, it could be that some lung cancer cells develop new mutations that allow them to more readily develop a blood supply in a new region.

What this means is that rather than catching cancers as early as possible to prevent metastases or recurrence (although that is still important), it's important to find ways to prevent cancer cells from taking up residence in other areas. This may also be somewhat helpful for those who are anxiously awaiting the results of their next-generation sequencing (or other test) for lung cancer.

An example of how this works is with the recent approval of bisphosphonates for early stage breast cancer to lower the risk of recurrence. These medications appear to work by changing the microenvironment of bone so that cancer cells that arrive (usually via the bloodsteam) can't set up a home base and instead die off.

Time to Recurrence

A related question concerns how long it takes for lung cancer to recur. While the size of a tumor at diagnosis and the number of positive lymph nodes are correlated with recurrence, they can't predict what will happen with individual people. Newer research is finding that the heterogeneity of a tumor (how different the parts of a tumor are, or how much variety in cells is present) may be linked with recurrence (tumors that are more chaotic may be more likely to come back).

Time to Develop (When Does Lung Cancer Begin)

A different question looks at when lung cancer may have first begun. People may think of a stressful time in their life or some specific exposure and wonder if it could have been the "cause" of their cancer. Certainly there isn't a precise answer, but some estimates have been made.

In 2011 in response to the common question, "how long have I had my cancer," an estimate of the typical "age" of a lung cancer when diagnosed was made (using an extension of Collin's law). In order to make the estimate, researchers looked at the time it took a cancer to recur. The conclusion was that it took 3 years to 4 years for cancer to go from a cancer cell to a detectable cancer (breast cancer was 5 to 6 years).

Other estimates have been done looking at the doubling time. For example, a cancer with a doubling time of 200 days would take 20 years to grow to the size where it would be detected, a doubling time of 100 days, 10 years, and so on. But we know that doubling time is not constant.

More recent studies have addressed the same question by looking at the mutational signature of tumors (the mutations and other changes present in tumors). A 2017 study published in the New England Journal of Medicine suggested that it takes a long time for a lung cancer to develop, perhaps decades, especially lung adenocarcinomas. (Even though lung cancers are commonly found in non-smokers, and non-smokers tend to be diagnosed at an earlier age.)

When Can Lung Cancer First Be Detected?

Talking about doubling size raises the question about when lung cancer can first be detected. Lung cancer is most treatable in the early stages, and unfortunately, at the current time the majority of people have an advanced stage tumor at the time of diagnosis.

It's thought that the average size at which lung cancers can be detected on a chest X-ray is 10 mm to 20 mm. On chest CT, tumors as small as 6 mm, however, can often be seen (sometimes as small as 4 mm).

The difference has become evident as we've learned that while screening chest X-rays didn't save lives, screening chest CT scans clearly do save lives.

When Does Lung Cancer Need to Be Detected for a Cure?

The option of lung cancer screening has raised the question about what size a tumor must be detected at for it to be cured. In 2017, researchers created a simulation model in which for the most aggressive non-small cell lung cancers, they would need to be diagnosed at only 10 mm in size in males and 15 mm in females. The average size of a lung tumor at diagnosis without screening is 33 mm.

A Word From Verywell

With the relatively new recommendation (especially with advanced lung adenocarcnoma) that results of genomic testing be evaluated prior to begininng treatment, concerns about the growth rate of lung cancer are likely to increase. Genomic testing results, whether done on tumor biopsy samples, a liquid biopsy, or both, can sometimes take up to two to four weeks.

Understanding the limitations of looking at growth rate, and how factors other than growth rate often play a role in tumor progression, may offer some reassurance during this waiting period. After all, outcomes (how a person does with the disease) are what is most important, and starting treatment right away without knowing the best treatment options can sometimes do more harm than good.

As more options are available and with cancer treatment changing so rapidly, it's important to find a physican who you can trust deeply. Becoming involved in the lung cancer community is another way to learn about your disease and obtain support while facing uncertainty.

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