What causes cancer relapse after full remission at 50?

Question

Hello doctor,

I hope you are doing well.

I am writing to seek your advice on my mother's situation.

My mother is 50 years old and completed therapy for stage IIIA non-small cell lung cancer around 18 months ago. She got concomitant chemoradiation and Durvalumab maintenance therapy. Her follow-up scans stayed absolutely free for almost a year, and both she, her oncology staff, and I were hopeful about her prognosis.

However, during a recent follow-up CT scan last month, new nodules were identified in the contralateral lung along with an enlarged supraclavicular lymph node. Her oncologist has confirmed that this represents a recurrence rather than a new primary tumor, based on molecular profiling that showed the same KRAS G12C mutation as her original cancer.

This recurrence has been distressing, especially given her positive response to treatment. We would appreciate clarification on how recurrence can occur after a period of remission, despite aggressive initial therapy. Concepts such as minimal residual disease and cancer stem cells were mentioned, and we would like to understand these better.

Is it possible that microscopic cancer cells persisted undetected during this time?
Her circulating tumor DNA (ctDNA) was not monitored during remission. Could earlier monitoring have identified the recurrence sooner?

She is currently being evaluated for Adagrasib, and her performance status is good (ECOG 0). Her LDH and CEA levels have increased compared to remission.

We would appreciate your insights into how this recurrence may have developed, especially after such a favorable response and period of stability.

Thank you for your time and support.

Answer 1

Hello,

Welcome to icliniq.com.

I have read your message and understand your concerns.

I know this situation is very difficult for you and your family, especially after things seemed to be going well. When scans are clear for a long time, it is reassuring, so having the disease return can feel sudden and overwhelming.

What you are experiencing, however, is something that can occur in lung cancer, even after very effective treatment. When we use the term “complete remission,” it means that no disease is visible on imaging. However, current scans can only detect tumors above a certain size. In some cases, a very small number of cancer cells may remain in the body at a microscopic level, which cannot be detected at that time.

These leftover cells can stay inactive, or “dormant,” for a long time. In some people, they do not cause problems right away. Later, for reasons we cannot fully control, these cells may start to grow again and show up on scans. This is called minimal residual disease.

Some cancer cells are naturally more resistant to treatments like chemotherapy, radiation, or immunotherapy. These cells can survive the first round of treatment and, over time, may cause the cancer to come back. This is due to the nature of the cancer itself, not a problem with the treatment.

Because the new lesions have the same KRAS G12C mutation, we know this is a return of the original cancer, not a new tumor. Simply put, a few original cancer cells likely stayed hidden, were inactive for a while, and have now started to grow again.

Circulating tumor DNA (ctDNA) is a promising tool and can sometimes detect recurrence earlier than scans. However, it is not used everywhere yet and is not perfect. Even if ctDNA shows early changes, treatment decisions are usually based on scan results. Please know that no important step was missed.

The increase in lactate dehydrogenase (LDH) and carcinoembryonic antigen (CEA) levels matches what we see on the scans, but these markers are only supportive and not the main way we diagnose.

One positive thing is your mother’s current health. An Eastern Cooperative Oncology Group (ECOG) performance status of 0 means she is physically well, which helps her handle and respond to more treatment. For patients like her with a KRAS G12C mutation, targeted therapies such as Adagrasib have shown good results and offer real options for the future.

To answer your question directly, it is likely that a few cancer cells stayed in the body in a way we could not detect, remained inactive for some time, and then started to grow again. This is a known pattern in lung cancer and could not have been fully prevented.

I hope this explanation helps.

If you have more questions, please feel free to ask.

Thank you.