What If I Do Everything Right and It Still Comes Back?
Agency, recurrence, and the importance of understanding what may remain when the scans say everything looks clear.
There is a question that sits quietly beneath almost every conversation about recurrence. Sometimes it is spoken directly. Sometimes it is hidden inside questions about food, supplements, exercise, scans, blood tests or treatment options. Sometimes it is there in the person who has become incredibly disciplined with their health and still finds themselves lying awake in the week before a scan.
The question is simple, but emotionally enormous: What if I do everything right and it still comes back?
It is an uncomfortable question because it forces us to confront one of the hardest truths in cancer care: there is a difference between influence and control.
I believe deeply in agency. I believe there are many things we can influence around cancer, including metabolic health, nutrition, inflammation, insulin signalling, immune function, physical activity, sleep, stress physiology, treatment tolerance, recovery, treatment preparation and nutritional status. I also believe there is enormous value in understanding your diagnosis properly, knowing why each treatment is being recommended, asking better questions and becoming an active participant in your care rather than simply handing your body over to a system and hoping for the best.
But agency is not the same thing as certainty.
Taking responsibility for the things you can influence does not mean accepting blame for the things you cannot. You can eat beautifully, exercise, meditate, regulate your nervous system, follow treatment carefully, take every supplement at exactly the right time and still experience recurrence. That does not mean you failed. It does not mean you were not positive enough. It does not mean you ate the wrong food at Christmas. And it certainly does not mean you somehow created your cancer through an incorrect thought, emotion or lifestyle choice.
Cancer biology is complicated.
The reason I talk so much about agency is not because I believe we can control every outcome. It is because I know how damaging the opposite belief can be: the idea that there is nothing meaningful you can do beyond turning up for treatment and waiting for the next scan. There is a very large space between “I control everything” and “I can influence nothing.” That space is where I believe good cancer care lives.
And nowhere is that distinction more important than in understanding what happens after treatment.
When “No Evidence of Disease” Does Not Necessarily Mean Nothing Is There
One of the most emotionally powerful moments in a cancer journey can be hearing that the scans are clear. No evidence of disease. NED. For obvious reasons, those words can feel like someone has finally opened the door of a room you have been trapped inside.
They matter, and they should be celebrated.
But they also need to be understood accurately.
A scan can only detect disease once it reaches a certain size or creates a sufficiently obvious structural change. Conventional imaging is extraordinarily valuable, but it is not a microscope capable of locating every remaining malignant cell in the body. There can therefore be an important difference between no detectable disease on imaging and no malignant cells remaining anywhere in the body.
That difference is the world of minimal residual disease, often shortened to MRD.
MRD describes cancer cells, cancer-derived material or microscopic disease that remains after treatment but exists below the detection threshold of conventional imaging and traditional monitoring. In solid tumours, the term molecular residual disease is also increasingly used when this hidden disease is identified through circulating tumour DNA or other liquid-biopsy technologies.
This is not an obscure theoretical idea. It is one of the central reasons recurrence can occur.
Surgery may remove everything surgeons can see. Chemotherapy may dramatically reduce the burden of disease. Radiotherapy may sterilise a defined area. A scan may then show no remaining tumour. Yet somewhere, a very small population of cells may survive. They may remain dormant for months or years. They may survive because they possess characteristics that made them less vulnerable to treatment. They may exist in tissues or biological niches that provided protection. Eventually, under the right conditions, some of those cells may begin growing again.
By the time a new lesion becomes visible on imaging, that biological process has often been underway for some time.
This is why I think one of the most important questions after successful treatment is not simply, “Is my scan clear?” It is also, “What do we know about what might still be happening microscopically?”
Those are different questions.
The Microscopic Lie of the Land
I often describe this as understanding the microscopic lie of the land.
A CT scan, MRI or PET scan gives us an enormously useful picture of the visible landscape. It tells us whether there is measurable disease, where it is, whether it has changed and whether treatment appears to be working.
But imagine looking across an enormous paddock from a helicopter. You can see the trees, the buildings, the major roads and the fires. What you cannot necessarily see are a handful of seeds sitting beneath the soil.
Minimal residual disease asks us to look for the seeds.
One of the most rapidly developing ways of doing this is through liquid biopsy—looking in blood for biological evidence that cancer may still be present. There are several different things researchers can look for, and each tells us something slightly different.
Circulating tumour DNA, or ctDNA, consists of fragments of genetic material released from tumour cells into the bloodstream. Increasingly sensitive assays can search for tumour-associated mutations or other molecular signatures after apparently successful treatment. Across multiple solid cancers, detectable ctDNA after curative-intent treatment has repeatedly been associated with a substantially higher risk of recurrence.
In colorectal cancer, for example, meta-analyses have found that detectable postoperative ctDNA is strongly associated with subsequent recurrence, with some studies showing molecular evidence of recurrence months before disease becomes visible through conventional surveillance.
That is an extraordinary development.
For the first time, we are beginning to move from waiting for a tumour to become large enough to see towards asking whether there is evidence of disease while it is still microscopic.
But ctDNA is only one window into that world.
Another is the circulating tumour cell.
Circulating Tumour Cells: Cancer Cells Caught in Transit
Tumours are not always completely contained structures. Cancer cells can detach from a primary tumour or metastatic deposit, enter blood vessels and travel through the circulation. These are known as circulating tumour cells, or CTCs.
Most of these cells will never successfully establish a new tumour. The bloodstream is actually a remarkably hostile environment. Circulating cancer cells must survive physical forces, immune attack, oxidative stress and the loss of the tissue environment that previously supported them.
But some survive.
And these surviving cells matter because metastasis—the spread of cancer to distant organs—is responsible for the majority of cancer-related deaths.
CTCs are therefore more than interesting debris. They represent living tumour cells caught in transit.
Research has repeatedly shown that higher CTC counts can carry prognostic information in several cancers. The CellSearch system, for example, has regulatory clearance for CTC enumeration in metastatic breast, colorectal and prostate cancers, where counts have been associated with progression-free and overall survival.
Modern CTC technologies are increasingly attempting not only to count these cells but to characterise them, to understand what mutations they carry, which proteins they express and potentially what they reveal about treatment resistance or metastatic behaviour.
This matters because a tumour is not biologically static. The disease present after several rounds of treatment may not be identical to the disease present at diagnosis. Certain populations may have been eliminated while more resistant populations survived. A circulating tumour cell can therefore potentially give us a small biological snapshot of what remains.
But there is another population that interests me even more.
The Cells With the Capacity to Start Again
Not every cancer cell appears equally capable of recreating a tumour.
Within many cancers, researchers have identified populations of cells with stem-like properties. These are commonly called cancer stem cells, although the biology is more complex than the name sometimes suggests.
These cells can possess characteristics associated with self-renewal, treatment resistance, adaptation and the ability to generate new populations of tumour cells. This makes them particularly relevant to recurrence.
Conventional treatment can dramatically reduce the bulk of a tumour, yet if a small treatment-resistant population with strong tumour-initiating capacity survives, that population may contribute to future regrowth.
This is one reason a tumour shrinking substantially does not always tell us everything we need to know about its future behaviour.
Imagine removing almost every weed from a garden but leaving behind a small number of hardy roots capable of producing the entire plant again. The garden looks clear, but the biology capable of rebuilding it may not be.
Cancer stem-cell biology is an active and evolving area of research, but there is good evidence linking stem-like cancer-cell populations with treatment resistance, metastatic capacity and recurrence.
Researchers have also identified circulating tumour cells displaying stem-like characteristics. A systematic review and meta-analysis found that the presence of stem-like circulating tumour cells was associated with poorer overall, progression-free and disease-free survival across multiple cancers.
This is why, in my own work, I am interested not only in how many circulating tumour cells can be detected, but also whether there is evidence of circulating cancer stem-cell populations.
That information does not provide a crystal ball. It does not tell us with certainty whether recurrence will or will not happen. But it may add another layer of information about the microscopic state of disease.
And when someone has already experienced cancer, I believe information about what may be happening below the threshold of imaging can be enormously valuable when interpreted responsibly.
Why Is This Not Standard Everywhere?
This is where the conversation needs some nuance.
It would be easy to say mainstream oncology simply ignores minimal residual disease. That would not be accurate.
MRD is already a central part of management in several blood cancers, and molecular residual disease testing in solid tumours is now one of the fastest-moving areas of oncology research. Circulating tumour DNA is increasingly being studied across colorectal, breast, lung and other cancers. Evidence that ctDNA positivity after treatment predicts recurrence is now substantial. New clinical trials are investigating whether using this information to escalate, de-escalate or change treatment actually improves outcomes.
But this is the important distinction: being able to predict recurrence risk is not automatically the same as knowing what to do about that information.
A test may tell us that microscopic disease is probably present before a scan can see it. The next question is much harder: does starting or changing treatment at that moment improve survival?
For many solid tumours, that question is still being answered.
Even in colorectal cancer, one of the most advanced areas for ctDNA MRD research, recent trials continue to show how difficult it is to translate powerful prognostic information into proven treatment decisions.
CTC testing faces similar challenges. We have strong evidence that CTC counts can carry prognostic information in certain metastatic cancers, but evidence that changing treatment purely because the count changes improves outcomes is less established. Different laboratories also use different technologies, markers and definitions, making standardisation difficult.
Circulating cancer stem-cell testing is earlier again. The biology is compelling and prognostic associations exist, but standardised assays, thresholds and treatment algorithms are not yet established across routine oncology.
This distinction matters because I never want new technology to become another form of false certainty.
A result is only useful when we understand what it can—and cannot—tell us.
What I Wish I Had Known During My Own Cancer Journey
This subject is personal for me.
When I was going through cancer, these technologies were either in their infancy or simply were not realistically available to me in the way they are now.
My own journey involved relapse after relapse. Each time, we responded when disease became detectable again. There were scans, treatments, periods when things appeared clear, and then another recurrence, another treatment decision and another chapter I would much rather not have had to live through.
Hindsight is an extraordinary thing.
I cannot honestly say that sophisticated microscopic disease monitoring would definitely have prevented my relapses. Nobody can know that. Maybe my journey would still have unfolded exactly as it did.
But I often wonder how different things might have looked if I had possessed more information about what was happening between those scans.
What if we had been able to see evidence of residual disease when the tumour burden was microscopic rather than waiting for it to become structurally obvious? What if we had understood whether circulating tumour-cell numbers were falling, stable or increasing? What if we could have identified a persistent population of stem-like tumour cells after treatment?
Would we have changed something earlier? Would we have monitored differently? Could we have reduced the amount of treatment I eventually needed?
I will never know.
And I am careful not to rewrite history with technologies that did not yet have the evidence or accessibility they have today.
But one of the gifts of surviving something difficult is that you get to turn around and hold a torch for the people walking behind you.
The testing I wish I could have accessed more meaningfully during my own journey is now something I have incorporated into the way I think about long-term cancer management. Not because a blood test can guarantee that cancer will never return. It cannot. But because I would rather have more meaningful information about the microscopic landscape than simply wait for something large enough to appear on a scan.
Monitoring Should Be a Process, Not an Event
One of the things cancer teaches you very quickly is that one result is only one moment in time.
This applies to scans. It applies to tumour markers. And it applies to liquid-biopsy testing.
A single CTC or stem-cell result can provide information, but what often interests me more is the direction of travel.
Are circulating tumour-cell numbers reducing over time? Are they stable? Have they begun to rise? Are stem-like populations detectable after treatment? Do they disappear with intervention? Do they reappear? How does this information sit alongside imaging, tumour markers, symptoms and everything else we know about the disease?
This is where monitoring becomes much more powerful.
Instead of thinking of cancer surveillance as waiting several months and then taking another photograph, we begin to think about gathering different forms of information that may describe the disease from different angles.
Imaging tells us what can be seen structurally. Tumour markers may provide biochemical clues in cancers where they are useful. ctDNA may reveal tumour-derived genetic material. CTCs may tell us whether intact tumour cells are present in circulation. Stem-like CTC populations may provide information about particularly resilient or tumour-initiating cells.
None of these should be interpreted alone.
The goal is to build a richer picture.
That is what I mean when I talk about understanding the microscopic lie of the land.
Agency Without Fear
There is a danger with all of this.
Monitoring can become obsessive.
More information does not automatically create more peace. Sometimes it creates more anxiety.
The answer is not to spend every waking moment hunting for cancer. The purpose of monitoring is not to turn your body into a crime scene that must constantly be investigated. It is to replace unnecessary blindness with appropriately interpreted information.
Agency should make you feel more informed, not more frightened.
The goal is to create a sensible surveillance strategy appropriate to the diagnosis, stage of disease, treatment history and personal circumstances.
For one person, conventional imaging and routine blood markers may be entirely appropriate. For another, there may be a strong rationale to explore additional molecular or cellular monitoring. For someone at high risk of recurrence, someone who has already relapsed, or someone trying to understand the effectiveness of a broader metabolic strategy, additional information about circulating tumour cells or microscopic disease may be particularly valuable.
But the result has to be interpreted in context.
A positive result does not mean catastrophe is inevitable. A negative result does not guarantee that every malignant cell has disappeared. Every test has limits.
The real value lies in combining information, watching trends and making thoughtful decisions rather than reacting emotionally to a single number.
What If It Still Comes Back?
So we return to the original question.
What if I do everything right and it still comes back?
Then it comes back, and we deal with what is in front of us.
That may sound almost too simple, but there is freedom in it.
Agency is not a bargain you make with the universe in which perfect behaviour earns you immunity from recurrence. It is not, “If I do everything correctly, cancer owes me a good outcome.”
Agency means using every reasonable opportunity to influence the outcome while accepting that biology still contains uncertainty. It means preparing well for treatment, understanding your disease, supporting your metabolic and immune health, asking better questions and monitoring intelligently.
And increasingly, I believe that means looking beyond only what can be seen on a scan and considering what information may be available about the microscopic state of disease.
Because recurrence is rarely born on the day a scan discovers it.
The scan is simply the day we finally become able to see it.
The biological process may have begun long before.
If we can learn more about that period, when disease may be microscopic, when tumour burden may be low and when there may potentially be opportunities to respond differently, then that deserves serious attention.
This is where I believe the future of long-term cancer management is heading.
Not towards abandoning imaging, oncology or conventional follow-up, but towards adding resolution.
Looking at visible disease and invisible disease. Looking at the tumour and the circulation. Looking at what happened yesterday and what the biology may be telling us today. Most importantly, moving from passive waiting towards informed observation.
My own cancer journey taught me many things I would have preferred to learn from a textbook.
I cannot go backwards and change what happened.
But I can use what I learned.
The technologies available today allow us to ask questions that were barely possible when I was going through my own relapses. They are not perfect. They are not magic. And they do not replace standard oncology.
But in the right circumstances, they can provide another window into the biology of disease.
That window matters to me.
Because when someone has fought hard to reach remission, I do not simply want to celebrate the fact that we cannot currently see cancer. Where appropriate, I also want to ask: What can we learn about what may still be there?
That is not fear.
That is agency.
.
.
Exploring Microscopic Disease Monitoring
I use specialised circulating tumour-cell and circulating cancer stem-cell testing as part of long-term cancer management in selected cases. Whether this type of testing is useful depends on the cancer type, stage, treatment history, current disease status and what question we are trying to answer.
It is not a replacement for imaging, pathology, tumour markers or oncology follow-up. It is another potential layer of information that can sometimes help us better understand the microscopic landscape of disease and monitor how that landscape changes over time.
If you would like to explore whether circulating tumour-cell, cancer stem-cell or other minimal residual disease testing may be appropriate in your situation, you can make an appointment with me and we can look at your diagnosis, treatment history and current monitoring strategy together.
The purpose is not to order more tests simply because they exist.
The purpose is to decide whether the information a test may provide is meaningful enough to help guide the way we think about your long-term care.
Important Disclaimer
This article is provided for educational and informational purposes only. It is not medical advice and should not be used to diagnose cancer, determine recurrence risk, alter treatment, or replace the advice of your treating oncology team.
Minimal residual disease, circulating tumour DNA, circulating tumour-cell and circulating cancer stem-cell technologies are rapidly evolving fields. Their level of clinical validation and usefulness varies considerably between cancer types, stages of disease, testing platforms and clinical situations. A positive or negative result should never be interpreted in isolation.
Any decision to undertake additional cancer monitoring should be made with appropriate professional guidance and integrated with conventional oncology follow-up, imaging, pathology and other clinically relevant information.
For individual advice, seek the support of a qualified and experienced practitioner in metabolic oncology who can consider your diagnosis, treatment history, current therapies, medications, overall health and the limitations of the particular test being considered.
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