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Immunotherapy · When It Stops Working & Difficult Decisions
Some Tumours Shrinking, Others Growing — Understanding a Mixed Response
The report says some deposits are smaller and one is bigger, and nobody has explained what that means. It is a recognised pattern called a mixed or dissociated response. It is not automatically failure, and where one site is escaping while the rest stays controlled, that single site can often be treated on its own.
Medically reviewed by Dr. T. Raghavender Reddy, Medical Oncologist, MBBS · DM (Medical Oncology) · MD (Radiation Oncology) · Last reviewed August 2026
- Deposits are not identical to each other — Different tissues, different blood supply, different immune traffic — and often different genetic changes.
- Not automatically failure — Part of the disease is still being controlled, and the criteria may record the growth as unconfirmed.
- One escaping site can often be treated — Focused radiotherapy or surgery to that site while the systemic treatment continues.
- Count the growing sites out loud — How many, and where, changes the options more than any other question in the appointment.
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The short answer
What Does a Mixed Response on Immunotherapy Mean?
It means the disease is not behaving the same way everywhere. Some deposits are shrinking or stable while at least one is growing, on the same treatment at the same time. It is a recognised pattern with immunotherapy, and it is a different situation from every site growing together.
It is a recognised pattern, not a reporting error. Radiologists sometimes call it a mixed or dissociated response. It is described more often with immunotherapy than with chemotherapy, which is one reason immune-specific response criteria were developed at all.
Deposits of the same cancer are not identical to one another. They sit in different tissues with different blood supply, different immune cell traffic and different local conditions. A liver deposit and a lung deposit are treated by the immune system very differently, and they have often accumulated different genetic changes over time.
The brain is a special case. Deposits inside the skull sit behind a barrier that many systemic treatments cross poorly, so brain disease can progress while everything else responds. That is usually a reason to treat the brain locally rather than to abandon the systemic treatment.
Ask how many sites are growing, and where. The answer changes the options more than anything else in the conversation, and it is a question that often goes unasked because families hear the word progression and stop there.
The question that decides the mood of the appointment
Is a Mixed Response the Same as Treatment Failure?
Not automatically, and it is worth asking in exactly those words. A mixed response means part of the disease is still being controlled by the treatment. Whether it counts as formal progression depends on how much has grown, whether that growth is confirmed on a repeat scan, and how you are clinically.
Part of the disease is still being controlled. That is a real and useful piece of information. It says the treatment is doing something in most of the body, which is a different starting point from a treatment that is controlling nothing.
The formal criteria may not call it progression at all. Response assessment totals up measured lesions rather than reacting to any single one, and under the immune-specific iRECIST framework growth may be recorded as unconfirmed, with a repeat scan commonly four to eight weeks later to establish whether it is real. Ask whether your report says confirmed or unconfirmed progression.
How you feel counts as data. Radiological change in a person who is well, eating and active is read differently from the same change in a person who has new pain, breathlessness or weight loss. Say clearly how you have actually been since the last scan.
What it does mean is that a decision is due. A mixed response is a fork rather than a verdict. It opens the question of whether one site can be treated on its own, whether to confirm before changing anything, or whether the overall plan should change. Being told it is not necessarily failure is not the same as being told to do nothing.
Did you know?
Not every enlarging lesion on immunotherapy is cancer. Checkpoint inhibitors can provoke an inflammatory reaction that enlarges lymph nodes and produces new nodules on a scan, closely mimicking progression, and occasionally a growing spot turns out to be infection or a separate condition altogether. This is one of the situations where sampling the one discordant lesion can change the whole plan — ask whether a biopsy of that specific site is worth doing.
Reading the scan before the prognosis
What Does Each Pattern Usually Lead To?
This is a general map to help you follow the conversation. Only your own team can read your scan against your history, and none of these routes is a recommendation for your case.
| What the scan shows | What it usually suggests | The conversation it usually opens |
|---|---|---|
| One site growing, everything else controlled | Localised escape, sometimes called oligoprogression. | Treating that single site with radiotherapy or surgery while the systemic treatment continues. |
| Two or three sites growing, the rest controlled | Limited escape rather than whole-disease resistance. | Whether local treatment to those sites is technically feasible, or whether a systemic change is the better move. |
| Brain deposits growing, body disease controlled | A site many systemic treatments reach poorly, rather than a failing treatment. | Local treatment to the brain, usually with a radiation oncologist, while the systemic plan is often continued. |
| Growth in most sites | Broader loss of control across the disease. | Switching class, considering a trial, or shifting the emphasis to symptom control. |
| Enlarging lymph nodes with no other change | Possible inflammatory reaction to the treatment rather than cancer growth. | Whether to sample the node, or to repeat imaging after a short interval before changing anything. |
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One Deposit Growing While the Rest Responds?
That pattern has a name and it has options. A medical oncologist can compare the scan against the baseline images and say whether local treatment to the escaping site belongs in the plan.
The row angle, step by step
Can the One Growing Spot Be Treated on Its Own?
Often it can be considered, and this is the option most often left unmentioned. Where one or a small number of sites are escaping while the rest of the disease stays controlled, treating those sites locally with radiotherapy or surgery while continuing the systemic treatment is a recognised approach in selected patients. Five things decide whether it applies to you.
NCCN and ESMO both describe local treatment of a limited number of progressing sites as an approach that may be considered in selected patients. It is not appropriate for everyone, and feasibility is a radiation oncology and surgical judgement rather than a general rule.
1
Establish that the growing lesion is what everyone assumes it is
Not every enlarging spot on immunotherapy is cancer. Enlarged lymph nodes and new nodules can also reflect an inflammatory reaction to the treatment itself, and occasionally a growing lesion turns out to be infection or a separate condition. Ask whether a biopsy of that specific site would change the plan.
2
Confirm the pattern against the earlier images, not the earlier report
Ask for the new scan to be read side by side with the baseline and interim images. Response-assessment imaging is coordinated at partner imaging centres, so ask that the earlier images travel with the new ones rather than assuming they will.
3
Count the growing sites, out loud
One or two escaping sites with the rest controlled is a different situation from disease progressing everywhere, and it is the pattern that most often opens the option of local treatment. Ask your oncologist how many sites are involved, in those words.
4
Involve a radiation oncologist early if local treatment is on the table
Whether a site can be treated locally depends on where it is, how big it is, what is next to it and what radiation that area has already received. That is a radiation oncology assessment, and it is better made before a systemic switch is decided than after.
5
Agree what happens to the systemic treatment while the site is treated
Continued, paused or changed? And what would trigger a review afterwards? Write the answer down. This is the part of the plan that most often stays vague and then causes confusion at the next appointment.
Described, not prescribed
What Local Treatments Are Usually Discussed?
Four are usually on the table, plus the option of doing nothing yet. Focused radiotherapy to a single deposit, surgery where the site is safely reachable, targeted treatment to brain deposits, and sampling the growing lesion to find out what it is. Which of these is feasible depends on where the site is and what has been treated before.
| Approach | What it involves | What it is usually for |
|---|---|---|
| Focused radiotherapy | A precisely targeted course of radiation aimed at one deposit, planned by a radiation oncologist. | A single accessible site, particularly where it is causing pain or pressure, or where it is the only area escaping. |
| Surgery to one deposit | Removal of a single lesion where it is safely reachable and the rest of the disease is controlled. | Selected patients, usually where the site is technically straightforward and the person is fit for an operation. |
| Local treatment to brain deposits | Targeted radiation to deposits inside the skull, sometimes with surgery. | Brain disease progressing while the rest responds, because many systemic treatments reach the brain poorly. |
| Biopsy of the discordant lesion | Sampling the one growing site to establish what it actually is. | Where inflammation, infection or a second condition is a real possibility, or where a new biomarker result could change the plan. |
| No local treatment for now | Repeating imaging after a short interval before anything is changed. | Borderline or unconfirmed growth in a patient who feels well. |
Five sentences worth taking with you
What to Ask at the Appointment
Alongside any of these answers, ask about palliative care by name. It is symptom and quality-of-life support that runs in parallel with cancer treatment rather than after it, and ASCO and WHO both describe it as a service to introduce early. You can have focused radiotherapy to one site, continue immunotherapy and see a palliative care team in the same month. Asking for it does not remove your oncologist and does not signal that you have stopped considering treatment.
A fork in the road, not a verdict
Ask How Many Sites Are Growing Before You Accept a Change of Plan
The answer is often narrower than the word progression suggests, and it is what decides whether treating one site locally is on the table at all.
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Common questions
Mixed Response on Immunotherapy — Your Questions Answered
What does mixed response mean on an immunotherapy scan?
It means the disease is not behaving the same way everywhere. Some deposits are shrinking or staying stable while at least one is growing, on the same treatment at the same time. Radiologists sometimes call it a mixed or dissociated response. It happens because deposits of the same cancer are not identical to one another: they sit in different tissues with different blood supply and different immune cell traffic, and they have often accumulated different genetic changes over time. Brain deposits are a particular case, because many systemic treatments reach the brain poorly, so disease there can grow while everything else responds.
Is a mixed response the same as immunotherapy failing?
Not automatically, and it is worth asking your oncologist in exactly those words. Part of the disease is still being controlled by the treatment, which is a different starting point from a treatment that is controlling nothing. Formal response assessment adds up measured lesions rather than reacting to any single one, and under the immune-specific iRECIST framework growth may be recorded as unconfirmed, with a repeat scan commonly four to eight weeks later to establish whether it is real. How you feel counts too: the same radiological change is read differently in someone who is well and active than in someone with new pain, breathlessness or weight loss.
Can the one tumour that is growing be treated on its own?
It can often be considered, and this is the option most often left unmentioned. Where one or a small number of sites are escaping while the rest of the disease stays controlled, treating those sites locally with focused radiotherapy or surgery while continuing the systemic treatment is an approach that NCCN and ESMO both describe as reasonable to consider in selected patients. Whether it applies to you depends on where the site is, how big it is, what is next to it, whether that area has been irradiated before, and how fit you are. That is a radiation oncology and surgical judgement, so ask for a radiation oncologist to be involved before a systemic switch is decided rather than after.
What is oligoprogression?
It is the term for progression at a limited number of sites while the rest of the disease remains controlled on the same treatment. It matters because it is the pattern that most often opens the option of local treatment. Instead of abandoning a systemic treatment that is working nearly everywhere, the escaping sites are treated directly and the systemic treatment continues. There is no single number of sites that defines it, and different teams use it slightly differently, so the useful question is not whether your case fits a label but how many sites are actually growing and whether each of them could be treated locally.
Why would one deposit grow while others shrink?
Because a cancer is not one uniform thing and neither is the body it sits in. Deposits in different organs have different blood supply, different oxygen levels and different amounts of immune cell traffic, so a checkpoint inhibitor can produce a strong effect in one place and little in another. Deposits also evolve separately over time, so one may have acquired changes that let it escape while others have not. And some sites are physically harder for treatment to reach, the brain being the clearest example. None of this means the treatment has stopped working everywhere, which is why the number and location of the growing sites is the question to ask.
Should the growing spot be biopsied again?
Sometimes, and it is a decision rather than a routine. The reason it can be valuable here is that not every enlarging lesion on immunotherapy is cancer. Checkpoint inhibitors can provoke an inflammatory reaction that enlarges lymph nodes and produces new nodules closely resembling progression, and occasionally a growing site turns out to be infection or a separate condition. A biopsy can also supply tissue for biomarker testing that was never done. The question worth putting to your oncologist is what would change if the result came back different. If the honest answer is nothing, the biopsy is unlikely to help you, and it carries its own risk, delay and cost.
This page is general patient-education information, not a substitute for the written guidance your own oncology team gives you based on your specific diagnosis, scans and treatment history.