Stage 4 to No Evidence of Disease

This page is for people living with stage 4 cancer, and those close to them, who have heard stories of people reaching "no evidence of disease." It explains what the terms mean, why rare exceptional responses happen, and which questions are worth asking.

No evidence of disease, or NED, means that scans, examination and blood tests currently find no cancer. It is a statement about the limits of measurement. Imaging cannot see microscopic disease. So NED is not automatically the same as cure. For some cancers, though, a long enough NED interval does become strong evidence of one. What NED means in your case depends on three things: the cancer type, the treatment given, and how long the interval has lasted. That is a question worth asking directly.

Complete response is the related term used during treatment. It means all measurable disease has gone. It can be short-lived or lasting.

NCI ran an Exceptional Responders Initiative to study people who did far better than the trial they were in predicted. The working definition was concrete. It meant a complete or partial response that lasted at least six months. The treatment had to be one where fewer than one in ten similar patients respond. A response lasting more than three times the usual length also counted. A feasibility search of phase 2 trials from 2002 to 2012 found about 100 cases. They are rare, but there are enough to learn from.

The case that prompted the work makes the point. A person with high-grade bladder cancer had a remarkable response to everolimus. Sequencing found mutations in TSC1 and NF2. Researchers then checked 13 other bladder cancer patients treated with everolimus. Three of four with a TSC1 mutation had some tumor shrinkage. Of the nine whose tumors progressed, eight had no such mutation. The unusual outcome had a molecular reason. Finding it produced information useful to other people.

Where explanations exist, they are biological.

NCI reports that changes in DNA repair genes were a significant finding. One breast cancer patient had a complete response lasting 84 months and carried several such changes. NCI also says that 10% to 20% of exceptional responder tumors had unusually high mutation rates. That may make them easier for the immune system to attack. Sometimes a tumor carries a mutation that matches a drug, as in the bladder cancer case above.

Some people have cancer that has spread to only a small number of sites. This is called oligometastatic disease. Ask your team whether local treatment could be added to drug treatment in your case.

Some people have long-lasting responses to immunotherapy. They are a minority, and most people do not have that outcome.

None of the mechanisms above involve the patient's attitude, determination, diet, stress levels or refusal to give up. There is no evidence that positivity affects who responds exceptionally. The belief that it does has two costs. It burdens people who are already ill with responsibility for their own scan results. And it tells the bereaved that their person did not want it enough. That is both false and unkind.

Exceptional responses happen to people who were frightened, exhausted and pessimistic as often as to anyone else.

Access, not attitude. Questions to ask your care team:

• Is comprehensive molecular or genomic profiling of my tumor available, and could it change my options?
• Is testing for mismatch repair status and tumor mutational burden relevant for me?
• Would a second opinion at a center running trials in my disease help?
• Is my disease oligometastatic, and is local therapy being considered?
• Am I eligible for any clinical trials?

Then ask again later. Disease changes, and so does the list of open trials.

These are the questions with something behind them.

• NCI: Exceptional Responders Initiative Moving Forward
• NCI: Exceptional Responders Initiative Q&A