Why Does Cancer Come Back?

Reasons Why Cancer Recurs After Years of Remission

Despite treatments such as surgery, chemotherapy, and radiation therapy, too often a cancer comes back. And while many cancers recur in the first five years, many of us know of someone who remained cancer-free for years or even decades before their cancer returned. Why do some cancers come back, and how does this happen?

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Importance of Knowing Why Cancers Recur

In asking why cancers recur, we are asking one of the most important questions in oncology today. Often, a recurrence, such as with breast cancer, is metastatic. An initial cancer that was stage 1 or stage 2 is now stage 4 or metastatic. Since more than 90% of cancer deaths occur due to metastases, why this happens is a crucial question.

Much of the treatment we use for cancer is to prevent cancer cells from persisting and "finding a chance to hide." This is the reason behind "adjuvant chemotherapy" given for early stage breast and lung cancers, since chemotherapy is a systemic treatment that is designed to attack these errant cells. But for some reason, all too often, cells are left behind.

When cancer cells remain, where do they stay? Why do some cancer cells appear to do nothing for 20 years and then grow again? Let's look at some of these questions, but first it helps to define the terminology we will be using.

Brief Review of Cancer Terminology

When talking about a cancer coming back, it helps to define exactly what a recurrence is, as well as a few other terms.

  • Remission: Remission does not mean a cancer is cured, but instead refers to the absence of disease. There are two types of remission. In complete remission, a cancer is unable to be detected through physical examination or through radiological studies. In partial remission, a cancer is still detectable but has decreased in size.
  • No evidence of disease (NED): NED is defined the same way as a complete remission, that a cancer cannot be detected by any tests or examination
  • Recurrence: A cancer recurrence refers to a cancer that returns (comes back, relapses, or recurs) after a period of time during which a cancer has been in remission (usually meaning that there is no evidence of disease and the cancer is not detected on scans).
  • Relapse: The term relapse is usually used interchangeably with recurrence.
  • Metastatic disease: Metastatic cancer refers to the spread of cancerous cells from their original (primary) location to another part of the body. Cancer cells can travel to distant areas of the body through the lymphatic system or the bloodstream.
  • Progression (progressive disease, or PD): Cancer progression refers to a cancer that is worsening and has increased at least 20% in size or has spread after treatment. Many oncologists believe that cancers that recur within three months are a progression, not a recurrence.
  • Partial response: A partial response to treatment means that a tumor decreases at least 30% in size, but does not go away completely as noted on clinical exam or scans. This is also called partial regression.
  • Stable (static) disease: Stable disease means a tumor has not changed much. It also means that there are no new tumors and that the tumor has not spread to any new regions of the body. The tumor has not increased enough to be called progressive disease (a 20% increase or more) or decreased enough to be called a partial response (at least a 30% decrease.)
  • Complete response: Complete response or complete regression means the same thing as a complete remission or NED (no evidence of disease). This means that no residual tumor can be detected by a physical exam, scans, or blood tests, but does not mean a cancer is cured.

Why Do Some Cancers Come Back?

Since recurrence is a significant cause of morbidity (sickness) and mortality (death) from cancer, understanding why cancers return is critical in improving survival rates for cancer patients. It's hoped that, as knowledge improves in this area, the survival rate for many cancers will increase.

Sometimes, patients who were successfully treated for cancer are diagnosed with a recurrence. This does not mean that their treatment was incorrect or unsuccessful. Rather, it is important to understand that some cancers are more likely to return than others.

It only takes a few cancer cells left over after treatment for that cancer to grow again. It takes many millions of cancer cells together to form a tumor that can be detected with even the most advanced imaging techniques.

Surgery and Radiation Therapy

If you have surgery with clear margins on your pathology report, and if a scan shows no evidence of cancer, it can be hard to understand why a cancer would come back. Yet even when no cancerous cells are seen at the edges of a tumor, some cancerous cells may have already spread via the lymphatic system, to nearby tissues or through the bloodstream to other regions of the body. These undetectable cells are referred to as micrometastases.

Both surgery and radiation therapy are considered "local treatments." As such, they do not treat cancer cells that have traveled beyond the treatment region. In addition, radiation therapy may not kill all cancer cells. Radiation works by damaging DNA in both cancer cells and normal cells. Just as normal cells may recover following radiation, some cancer cells may "recover" as well. 

The possibility of micrometastases is the reason that some people receive adjuvant chemotherapy (chemotherapy that is given after the completion of the local treatment with surgery or radiotherapy) to ensure that micrometastases are eradicated.

Chemotherapy

Chemotherapy, unlike surgery and radiation therapy, is considered a systemic therapy. It is designed to treat not just cancer cells in or near a tumor but also those that have spread beyond the areas that are treated with surgery and radiation. So why wouldn't chemotherapy kill all cancer cells in the body?

To understand the answer to this question, it’s important to understand a bit about how chemotherapy works. Most chemotherapy drugs work at a particular point in the process of cell division, and different chemotherapy drugs work at different points in that process.

Not all cancer cells are dividing at all times, though, and cells that are not dividing, or are at a different stage in cell division than the one a specific chemotherapy drug addresses, may survive. This is one of the reasons that people are often treated with more than one chemotherapy drug and why chemotherapy is usually given in several sessions spaced out over time.

Cancer Cells Can Hide

There are a few theories that have been proposed to account for what seems to be a cancer cell's ability to "hide" for an extended period of time. For example, 20% to 45% of estrogen-receptor positive breast cancer recurrences occur years or even decades after the cancer has been successfully treated. 

One theory is the idea of cancer stem cells, a subset of cancer cells. Simplistically, we might think of cancer cells as having a hierarchy. In this case, cancer stem cells would be at the top. They are stronger than other cancer cells and divide more slowly than regular cancer cells. This makes them more resistant to treatments such as chemotherapy. While cancer treatments may kill off many regular cells, these stronger stem cells could remain alive, ready to grow again. 

Another concept is dormancy. For some reason, a cancer cell can lie dormant (like a plant during winter, or a fungal spore) and, given the right circumstances, begin to grow again. These dormant cancer cells (which may be stem cells) may "sleep" for long periods of time before "waking up" and entering a rapid growth phase.

A strong immune system, or a lack of angiogenesis (the ability of a cancer to make blood vessels to feed it and allow it to grow) can make cancer cells go dormant. Likewise, if the immune system is not functioning as well (immunosuppression) or if angiogenesis takes place, the cells can wake up.

Cancer Recurrence

Doctors don't usually use the word "cured," because most tumors have the ability to come back. Exceptions include some early stage cancers that have very low risk of coming back (for example, early thyroid cancer).

Cancer does not always recur in the same area of the body as the original tumor. Some patients can experience recurrence in different organs or body systems. For instance, a prostate cancer patient whose prostate was removed during treatment could experience a recurrence in their bones if cancer cells traveled there and did not respond to treatment.

There are three main types of cancer recurrence:

  • Local recurrence: When a cancer comes back in the same location or near the original location
  • Regional recurrence: When a cancer returns in the nearby lymph nodes or tissues.
  • Distant recurrence (also called metastatic disease): When a cancer returns in a separate organ or a distant part of the body (like prostate cancer in the bones)

Doctors and researchers have determined that certain cancers are more likely to recur in specific sites of the body. For instance, a distant recurrence of breast cancer is most likely to be found in the bones, brain, liver, or lungs, whereas a distant recurrence of colon cancer is more likely to be found in the liver, lung, or peritoneum.

Which Cancers Recur?

Some cancers are more likely to recur than others. For instance, glioblastoma (which forms in the brain or spinal cord) recurs in more than 90% of patients. Estimates indicate that 85% of ovarian cancer patients will develop recurrent disease following successful treatment. Certain types of lymphomas also recur at higher rates.

Cancers that are diagnosed at more advanced stages are more likely to recur after treatment than those that are diagnosed at the earliest stages of development.

Treating Recurrent Cancer

Some cancers can be more difficult to treat when they recur. This is because, for most tumors, the first line of treatment used is often considered to be the most effective. But that does not mean your cancer cannot be treated a second time.

Treatment for recurrent cancer depends on the type of recurrence, how much time has passed since your original treatment, the location of the new growth, and your general health. A local recurrence of prostate cancer, for instance, may be treatable with radiation therapy. Likewise, breast cancer that has metastasized to the liver (a distant recurrence) may still be treatable with surgery, radiation, or chemotherapy.

Some forms of cancer, such as testicular cancer, may still be curable even after they recur.

Coping with Recurrent Cancer

Receiving news from your doctor that cancer has returned can be devastating. Some patients may question whether they could have prevented the recurrence, but often that is not the case. If you are coping with a cancer recurrence, it is important to talk with your doctor about your concerns and to ask questions about what treatments may be available to you for your specific cancer.

Coping with recurrent cancer isn't just about understanding how your case will be managed with your medical provider. There are a number of things to consider as you navigate your recurrence:

  • Manage emotions: Many people feel depressed or angry about their diagnosis, and these strong feelings can impact quality of life. It can be helpful to talk with a professional if depression, anger or anxiety are overwhelming.
  • Eat well and exercise: Not only will this improve your mood, but it can also help ensure that you are physically able to withstand treatments that your doctor may suggest.
  • Keep stress in check: Cancer is stressful, so it is important to take steps to minimize how stress impacts you. Taking time for yourself with activities such as meditation, a favorite book or movie, or time with family and friends, can help reduce your stress level.

Frequently Asked Questions

Which cancers have the highest recurrence rates?

Certain cancers are harder to treat and have higher recurrence rates such as glioblastoma, which has a recurrence rate of almost 100%. Ovarian cancer has a recurrence rate of approximately 85%. Other cancers with recurrence rates of 30% to 50% include soft tissue sarcomas, bladder cancer, and non-Hodgkin lymphoma.

Which cancers have the lowest recurrence rates?

Cancers that have relatively low recurrence rates (in part because they respond well to treatment) include estrogen receptor-positive breast cancer, kidney cancer, and Hodgkin lymphoma.

How is recurrence different from a second cancer?

Being diagnosed with a second cancer is different from a recurrence because the second cancer begins in a different set of cells in your body and is not a metastasis of the original cancer. This would mean you have or had two separate cancers rather than one type that metastasized to another area of the body.

A Word from Verywell

A cancer diagnosis can be frightening and confusing, and this is even more so for patients whose cancers have come back after successful treatment. As doctors and researchers continue to make progress in understanding how recurrent cancers can be actively treated or managed, a growing number of options are available to treat advanced disease.

If you have been diagnosed with a cancer recurrence, it's important to talk with your doctor about your specific cancer, the location of the recurrence, and what treatments are available to you.

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  1. American Cancer Society. Treating prostate cancer that doesn't go away or comes back after treatment. Updated June 11, 2020.

  2. National Cancer Institute. Recurrent cancer: When cancer comes back. Updated December 2, 2020.

  3. National Cancer Institute. Metastatic cancer: When cancer spreads. Updated November 10, 2020.

  4. Fabian D, guillermo Prieto Eibll MDP, Alnahhas I, et al. Treatment of glioblastoma (GBM) with the addition of tumor-treating Fields (TTF): A review. Cancers. 2019;11(2).pii:E174. doi:10.3390/cancers11020174

  5. Corrado G, Salutari V, Palluzzi E, Distefano MG, Scambia G, Ferrandina G. Optimizing treatment in recurrent epithelial ovarian cancerExpert Review of Anticancer Therapy. 2017;17(12):1147-1158. doi: 10.1080/14737140.2017.1398088

  6. American Cancer Society. Coping with cancer recurrence. Updated February 12, 2016.

  7. BreastCancer.org. Liver metastasis: Local treatments. Updated March 9, 2019.

  8. Cancer Therapy Advisor. Cancer recurrence statistics. Published November 30, 2018.

  9. American Cancer Society. What is cancer recurrence? Updated February 12, 2016.