Understanding No Evidence of Disease (NED)

What NED Means Your Life Long-Term

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What exactly does it mean to be NED - no evidence of disease?. Istockphoto.com/Stock Photo©MCCAIG

The term "no evidence of disease" (NED) is often used with cancer when there is no physical evidence of the disease on examination or imaging tests after treatment. The term means the same thing as complete remission or complete response. NED does not, however, mean that a cancer is cured, and, with most cancers, there is a chance the cancer could recur or relapse at a later date.

Certainly, being NED, as the term is often used, is very positive, and means that the treatment was effective. Since the recurrence of cancer, and metastases (when cancer spreads to other sites in the body), are responsible for the majority of cancer deaths, there is currently a lot of research focusing on how to keep a cancer NED.

It's also important to note people with cancer who are NED need tremendous support. Not only do many people who have achieved a complete remission need to cope with the fear of recurrence and survivor guilt, but late effects of cancer treatment can sometimes reduce quality of life.

Definitions

The National Cancer Institute defines remission as, “[a] decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although cancer still may be in the body." NED means the cancer cannot be seen on scans or in blood work, although this does not mean the cancer isn’t there. Essentially, these two definitions describe the same medical understanding. 

People may be NED after an early stage cancer is treated, or may be NED even with metastatic cancer. With metastatic cancer, however, the disease will almost inevitably recur at some time. NED describes a point in time—where you are today—having no signs or symptoms of cancer nor any evidence of cancer on blood tests, such as tumor marker tests, or imaging studies, including CT scans, MRI, bone scans, or PET scans. NED may be temporary, or it could be permanent.

When speaking of breast cancer, the term no evidence of disease (NED) does not mean the disease had been cured. In fact, and especially with estrogen-receptor positive tumors, the disease may recur many years, or even decades, after it appears to have been eradicated.

NED vs Cure

Doctors rarely use the term "cure" when talking about solid tumors—even if there is a 99 percent likelihood a cancer will never come back. It is impossible to know if there are "micrometastases" present in your body—that is, metastases which are too small to be seen on imaging studies.

Researchers know how how breast cancer spreads, but they don't know exactly why some cancers return (recur) years, or even decades later. There are theories that describe dormant cells or stem cells having the ability to hide and evade treatment, but as yet we aren't entirely sure. Until then it's likely that the word "cure' will mostly remain reserved for only the smallest "pre-" cancers or some childhood blood-related cancers.

Very recently, however, some people with stage 4 cancer who have been treated with immunotherapy drugs appear to have what is being called a "durable response." We also know that, unlike treatments such as chemotherapy, the benefits of some immunotherapy drugs persist after treatment has been stopped. It will be some time before we know whether or not these drugs are actually curing some people with advanced cancer.

Metastatic Breast Cancer

NED can occur in people with metastatic cancer (MBC), not just those who have early stage potentially curable cancers. With breast cancer, NED is associated with longer survival than that of people who are never NED with metastatic breast cancer. MBC requires treatment to control the disease for the rest of a person’s life.  

One study reported in 2015 of patients with metastatic breast cancer with no evidence of disease after treatment finds NED status means “significantly prolonged survival.” The study of 570 MBC patients were treated from January 2003 to December 2005 found 16 percent (90 patients) achieved NED, which the researchers defined as a “complete metabolic response” and “healing of bone metastases” seen on PET scans and MRIs. The follow-up period for the NED patients was 14-134 months. The three- and five-year overall rates were 44 percent and 24 percent, respectively for the NED patients. 

The researchers determined HER2 positivity was a strong factor associated with overall survival and estrogen-receptor positivity was significantly connected to progression‐free survival. Interestingly, one drug in particular seemed to be connected to progression-free survival, Herceptin (trastuzumab), a medication often used in cancers that are HER2 positive. Thirty-four of the NED patients remained in remission at the last follow-up, around eight to 10 years following the last treatment. 

Recurrence

With the recommendation of a new treatment options for some people with early-stage breast comes a slightly better understanding of how breast cancer cells may hide and then begin to grow again many years later.

For women who have early stage postmenopausal estrogen receptor-positive breast cancer, the bisphosphonate medication Zometa (zoledronic acid) is now recommended as adjuvant therapy. This medication which has been used for osteoporosis and bone metastases appears to affect the microenvironment in bone. The microenvironment is the characteristics of tissue surrounding a cancer. As such it may reduce the risk of bone metastases occurring in the first place. Such findings have led researchers to question whether dormant breast cancer cells (when it is NED) hang out in the bone marrow. Since 90 percent of breast cancer deaths are related to metastases, research into this mechanism is critically important.

One 2018 study shows certain protein markers indicate if a person will develop a recurrence of lethal, metastatic breast cancer. When cells from the original breast cancer tumor metastasize into the patient’s bone marrow, either with no, or only a small amount, of the protein NR2F1, the patient eventually died. However, the patients who had high concentrations of NR2F1 in their bone marrow did not frequently develop metastatic breast cancer and lived longer. Researchers believe NR2F1 promoted dormancy in cancer cells, eventually deactivating them, thus improving survival and decreasing the risk for recurrence. 

If you are NED with breast cancer, check out the symptoms and learn more about breast cancer recurrence.

You may wonder why you aren't scheduled for regular imaging exams, including PET scans, as with other cancers. The reason is that even though these scans may show a recurrence slightly earlier than would be possible based on symptoms alone, there is no evidence survival is improved by detecting signs of a recurrence before any symptoms are present.

Concerns

Being NED can be a frightening place. It may sound a little odd, but many people feel a bit depressed when they reach this step. It may seem like everyone you know is going back to their life before cancer but you. There might be some specific reasons for why you are feeling this way.

Late Effects of Cancer Treatment

The majority of people who are NED are still coping with some side effects from the treatments it took to get to NED. Symptoms, such as annoying cancer fatigue, pain, hot flashes, and more, linger far past the last dose of chemotherapy or radiation.

Fear of Recurrence

The fear of recurrence is very real and it doesn't matter if you had a very early stage cancer or advanced cancer. Life is much different than before cancer. What once was a mild headache, you may fear is cancer reappearing in your brain. What was once a tickle in your throat from seasonal allergies, you may now fear is cancer returning in your lungs.

Fear of recurrence is universal. Some people find it helpful to talk with an oncology counselor to develop ways to best cope with this fear.

Survivor Guilt

Many people are involved in local or online support groups with others facing breast cancer. People are often surprised to realize the mortality rate from breast cancer really hasn't changed that much. Certainly, the treatment options for early-stage disease are reducing the risk of recurrence, but recurrences still occur.

When distant recurrences happen (metastatic or stage 4 breast cancer) there is no longer a possibility of a cure. What this means is that if you have people in your support group facing metastatic breast cancer, you will lose friends. The term survivor guilt has been coined to describe this sometimes heart-wrenching guilt that hits when you survive, but your friends and loved ones do not.

Survivorship Needs

You are going to be anxious about the future and a possibility of recurrence.  Therefore, it may help to look into a survivorship program to help you get the psychological and medical support you need. Your oncologist likely has more information about locating such a program.

Additional ways to manage your concerns include:

Enjoying a healthy lifestyle: There is some evidence that eating a healthy diet, as well as exercising regularly, may lower the risk of recurrence.

Getting enough sleep: If you suffer from sleep difficulties, talk to your doctor. Some evidence suggests breast cancer may be more likely to recur in women who suffer from insomnia.

Finding ways to reduce stress: Much like insomnia, it has been suggested that stress can play a role in some people going from NED to recurrence.

Journaling: There are many benefits to journaling, including stress relief, clarifying thoughts, chronicling your journey, and even making sense of everything that has happened to help you let go.

On a positive note, think of all you have gained from your experience. In addition to stress, going through cancer can lead to post-traumatic growth. In other words, cancer really can change people for the better!

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