Why Does Cancer Come Back?

Despite treatments such as surgery, chemotherapy, and radiation therapy, sometimes cancer comes back. And while many cancers recur in the first five years, some can recur decades later. Why do some cancers come back, and how does this happen?

Importance of Knowing Why Cancers Recur

Often, cancer recurrence is metastatic. An initial cancer that was stage 1 or stage 2 can recur in stage 4 with metastases. More than 90% of cancer deaths occur due to metastases.

Cancer treatments are intended to prevent cancer cells from growing or persisting in the body. This is why adjuvant chemotherapy is part of the treatment for early-stage breast and lung cancers.

Brief Review of Cancer Terminology

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

• Remission: Remission does not mean the cancer is cured, but instead refers to the absence of disease. There are two types of remission:
• In complete remission, a cancer is undetectable detected through physical examination, imaging studies, or laboratory tests.
• In partial remission, the cancer is still detectable but has decreased in size.
• No evidence of disease (NED): NED is defined the same way as complete remission.
• Recurrence: A cancer recurrence refers to cancer that returns (comes back, relapses, or recurs) after a period of remission.
• 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 cancer that is worsening and has increased at least 20% in size or has spread after treatment. Many oncologists believe that cancers that seem to 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 can still be detected and has not gone away completely. 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 that cancer is cured.

Why Do Some Cancers Come Back?

Sometimes, people 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.

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 your 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.

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. 

Chemotherapy

Chemotherapy, unlike surgery and radiation therapy, is considered a systemic therapy. It is designed to treat cancer cells in or near a tumor as well as 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?

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, 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 cancer has been successfully treated. 

• One theory is the idea of cancer stem cells, a subset of cancer cells. These cells divide more slowly than regular cancer cells, which makes them more resistant to treatments such as chemotherapy. While cancer treatments may kill off many regular cells, stem cells could remain alive, ready to grow again. 
• Another concept is dormancy. Sometimes cancer cells can lie dormant (like a plant during winter) and, given the right circumstances, begin to grow again. These dormant cancer cells (which may be stem cells) may remain inactive for long periods of time before entering a rapid growth phase.

A strong immune system can help keep cancer cells dormant. If the immune system is not functioning well (immunosuppression).

Angiogenesis, which is the ability of a tumor to make blood vessels to feed it and allow it to grow, promotes cancer survival.

Cancer Recurrence

Healthcare providers don't usually say that cancer is cured because most tumors could come back. Exceptions include some early-stage cancers that have a 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 people can experience recurrence in different organs or body systems. For instance, after prostate removal for treatment of prostate cancer, the same cancer can recur in the bones if cancer cells traveled there and did not respond to treatment.

There are three main types of cancer recurrence:

• Local recurrence: When cancer comes back in the same location or near the original location
• Regional recurrence: When 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)

Healthcare providers 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 more than 90% of the time. Estimates indicate that 85% of ovarian cancer will recur 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 healthcare provider that your cancer has returned can be devastating. Some people 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 healthcare provider about your concerns and to ask questions about what treatments may be available to you.

Coping with recurrent cancer isn't just about the medical aspects.

There are a number of things to consider as you navigate your recurrence:

• Manage emotions: You may feel depressed or angry about your diagnosis, and these strong feelings can impact your 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 you to be physically able to withstand treatments that your healthcare provider 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 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 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 when cancer comes back after successful treatment. As healthcare providers 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 healthcare provider about your specific cancer, the location of the recurrence, and what treatments are available to you.