How Do Doctors Know If Cancer Treatment Is Working?

01. What Does It Actually Mean When Cancer Treatment Is Working?

After starting cancer treatment, one of the most important questions a patient may ask is:

“How will we know if my treatment is working?”

You might expect the answer to be straightforward: if a tumor gets smaller, the treatment is working. If it stays the same size or grows, perhaps it isn't.

But cancer treatment is not always that simple.

A treatment does not necessarily have to make a tumor disappear to provide meaningful benefit.

To understand whether a cancer treatment is working, doctors must first consider a fundamental question:

What was the treatment intended to achieve?

Different Treatments Have Different Goals

Cancer treatments are used for different reasons, depending on the type of cancer, how far it has spread, its biological characteristics, and the patient's overall situation.

Understanding the original treatment goal is essential to interpreting the results.

1. Treating Cancer With the Goal of Cure

Some treatments are given with the intention of eliminating cancer completely and achieving a cure.

This is called curative-intent treatment.

It may involve surgery, radiation therapy, systemic treatments such as chemotherapy, or a combination of approaches.

In certain situations, doctors can assess how much a tumor shrinks during treatment. In others, particularly after surgery, there may be no visible cancer remaining to measure.

Importantly, receiving treatment with curative intent does not guarantee that a cure will be achieved.

2. Reducing the Risk of Cancer Coming Back

Sometimes, a patient receives additional treatment after surgery, even when there is no visible evidence of cancer.

This is called adjuvant treatment.

Its purpose is to reduce the risk that cancer will return, potentially by eliminating cancer cells that are too small to be detected by current tests.

But this creates an important distinction:

If there is no visible tumor, there may be nothing to measure on a scan.

In this situation, doctors cannot determine whether the treatment is working simply by looking for tumor shrinkage.

Instead, the expected benefit of adjuvant treatment is established through clinical studies that compare outcomes, including cancer recurrence, between groups of patients.

Follow-up examinations and tests can help detect a recurrence, but they generally cannot prove whether adjuvant treatment prevented cancer from returning in one particular person.

3. Controlling Cancer Over Time

When cancer cannot be cured, treatment may still provide important benefits.

The goal may be to slow its growth, prevent further progression, prolong life, reduce complications, or preserve quality of life.

In these situations, keeping cancer from growing may itself be a meaningful treatment outcome.

For example, imagine a patient receiving treatment for advanced cancer.

After several months, a CT scan shows that the tumors have not significantly changed in size.

At first, this might sound disappointing.

However, depending on the cancer's characteristics, how long it has remained controlled, and how the patient is feeling, this result may be encouraging.

Doctors may describe this as stable disease.

Stable disease does not automatically mean that treatment is successful, but it does not necessarily mean that treatment has failed.

We will explore this important distinction later.

4. Improving Symptoms and Quality of Life

In some situations, an important goal of cancer treatment is to reduce symptoms or complications caused by the disease.

For example, treatment may help relieve cancer-related pain, improve breathing, or reduce symptoms caused by a tumor pressing on nearby structures.

These benefits can be meaningful even when imaging changes are modest.

Supportive and palliative care can also help manage symptoms, improve quality of life, and support patients and families throughout the cancer journey.

Importantly, palliative care is not limited to end-of-life care. It can be provided alongside treatments intended to control cancer or even achieve a cure.

Why the Whole Picture Matters

A CT scan may show that a tumor is shrinking, but that is not the only information doctors need.

They must also consider how the patient is feeling, whether symptoms are improving, how well the treatment is tolerated, and whether it is helping achieve the original treatment goals.

A treatment that substantially reduces tumor size may still cause significant side effects.

Another treatment may produce little visible change in tumor size while maintaining disease control and allowing the patient to continue important daily activities.

These situations require different clinical interpretations.

Tumor response, disease control, and clinical benefit are related, but they are not exactly the same thing.

That is why evaluating cancer treatment involves much more than measuring tumors.

The most useful starting question is not simply:

“Did the tumor get smaller?”

It is:

“What were we hoping this treatment would accomplish, and are we achieving that goal?”

Understanding this distinction is the first step toward making sense of cancer treatment results.

02. How Do Doctors Evaluate Cancer Treatment?

Imagine two patients receiving treatment for cancer.

The first patient feels considerably better. Their pain has decreased, their appetite has improved, and they have returned to many of their usual activities.

The second patient feels increasingly tired and has developed new symptoms.

Does this mean the treatment is working for the first patient but failing for the second?

Not necessarily.

Symptoms provide valuable information, but they do not always reflect what is happening to the cancer itself.

A patient may feel better because treatment is controlling the disease, but also because pain medication or supportive care has improved their symptoms.

Another patient may feel worse because of treatment-related side effects, even while their cancer is responding.

This is why oncologists use several complementary methods to evaluate treatment effectiveness.

Each provides a different piece of information.

1. Clinical Evaluation: How Is the Patient Feeling?

One of the most important parts of evaluating cancer treatment happens during a conversation.

Your oncology team may ask questions such as:

• Have your symptoms improved, worsened, or remained unchanged?
• Are you experiencing new or unusual symptoms?
• Has your appetite or weight changed?
• Are you able to perform your usual daily activities?
• How is treatment affecting your quality of life?

These questions help doctors understand how both the cancer and its treatment may be affecting your everyday life.

For example, a patient receiving treatment for lung cancer may notice that breathing has become easier.

This could be an encouraging sign, particularly if the cancer was contributing to breathing difficulties.

However, improvement in symptoms does not necessarily prove that tumors have decreased in size.

Similarly, worsening symptoms do not automatically indicate cancer progression.

Doctors must consider other explanations, including treatment side effects, infections, other medical conditions, and complications that may require attention.

Importantly, new or rapidly worsening symptoms should be reported to the oncology team rather than waiting for the next scheduled scan.

2. Physical Examination: What Can Doctors Observe?

A physical examination can provide additional information.

Depending on the type and location of the cancer, doctors may assess:

• Changes in a tumor or lymph node that can be felt.
• Swelling or fluid accumulation.
• Breathing and other physical findings.
• Changes in strength, mobility, or general physical condition.

For example, if a patient has an enlarged lymph node that was detectable during previous examinations, a decrease in its size may suggest a response to treatment.

However, many cancers develop in areas that cannot be examined directly.

A normal physical examination does not necessarily mean that cancer is absent.

This is one reason imaging and other investigations may be necessary.

3. Medical Imaging: What Is Happening Inside the Body?

Imaging studies are among the most important tools for evaluating many cancers during treatment.

They allow doctors to examine areas of the body that cannot be assessed through a physical examination alone.

Common imaging methods include:

CT scans (Computed Tomography)

CT scans produce detailed cross-sectional images of the body.

They are frequently used to evaluate changes in the size of tumors and to look for new areas of disease.

MRI (Magnetic Resonance Imaging)

MRI provides detailed images of soft tissues and certain organs.

It is particularly useful in selected situations, including the evaluation of tumors involving the brain, spinal cord, liver, and other anatomical structures.

PET scans (Positron Emission Tomography)

PET imaging can provide information about tissue metabolic activity.

In certain cancers, such as some lymphomas, changes in metabolic activity can be particularly useful when evaluating treatment response.

However, PET is not required or appropriate for every cancer.

Why Are Previous Scans So Important?

When reviewing new imaging results, doctors usually compare them with earlier studies.

They may look for:

• Tumors that have become smaller.
• Tumors that have remained approximately the same size.
• Tumors that have increased in size.
• New suspicious lesions.
• Other changes that may help determine whether treatment is achieving its goals.

But imaging also has limitations.

Not every cancer can be measured reliably using the same methods.

Some abnormalities may represent inflammation, treatment-related changes, or scar tissue rather than active cancer.

And even when a scan shows no detectable cancer, microscopic disease may still be present.

Imaging shows what current technology can detect. It cannot always tell us everything about the cancer's biological activity or whether every cancer cell has disappeared.

We will explore how doctors compare scans and measure treatment response in the next sections.

4. Blood Tests: What Additional Information Can They Provide?

Blood tests are another important part of cancer treatment monitoring.

However, different blood tests answer different questions.

Routine Blood Tests

Tests such as complete blood counts, kidney function tests, and liver function tests help doctors understand how the body is tolerating treatment.

For example, chemotherapy may cause a decrease in blood cell counts.

This is important for treatment safety, but it does not necessarily indicate whether the cancer is responding.

Similarly, changes in liver function tests may have several possible explanations, including treatment effects, other medical conditions, or cancer-related complications.

Many routine blood tests are used primarily to monitor treatment safety, not to measure whether tumors are shrinking.

Tumor Markers

Certain cancers produce or are associated with substances that can sometimes be measured in blood.

These substances are commonly called tumor markers.

Examples include:

• CEA (Carcinoembryonic Antigen): sometimes used to help monitor colorectal cancer and selected other cancers.
• PSA (Prostate-Specific Antigen): commonly used in the evaluation and monitoring of prostate cancer.
• CA 15-3: sometimes used as an additional monitoring tool in metastatic breast cancer.
• CA-125 (Cancer Antigen 125): commonly used to help monitor treatment response and follow-up in certain types of ovarian cancer, particularly epithelial ovarian cancer.

In appropriate clinical situations, changes in these markers can provide useful information.

For example, a tumor marker that was elevated before treatment and subsequently decreases may support other evidence suggesting a response.

However, tumor markers have important limitations.

Not every cancer produces a useful measurable marker.

Some markers can rise for reasons unrelated to cancer progression.

And a normal tumor marker does not necessarily mean that cancer is absent.

For these reasons, tumor markers generally should not be interpreted in isolation.

Their usefulness depends on the particular cancer, the clinical situation, and the evidence supporting that marker.

5. Pathology: What Can Tissue Tell Us After Treatment?

Sometimes, doctors can examine cancer tissue after treatment to evaluate how the tumor has responded.

This is particularly relevant when treatment is given before surgery, an approach known as neoadjuvant treatment.

For example, a patient with breast cancer may receive systemic treatment before undergoing an operation.

After surgery, a pathologist examines the removed tissue under a microscope.

The examination may reveal remaining cancer cells, signs of treatment effect, or, in certain circumstances, a pathological complete response.

A pathological complete response means that no residual cancer is identified according to the specific pathological criteria used for that cancer.

This can provide important information about treatment response and prognosis.

However, its significance varies depending on the type of cancer and the clinical context.

A pathological complete response does not automatically guarantee that cancer will never return.

Importantly, not every patient needs another biopsy or an operation to determine whether treatment is working.

Pathological response assessment is used when clinically appropriate, rather than as a routine requirement during every treatment.

6. Putting Everything Together

No single test provides a complete picture of cancer treatment effectiveness in every situation.

Consider a patient whose latest CT scan shows that their tumors have become smaller.

That may be encouraging.

But their oncology team must also consider whether the patient is experiencing significant treatment-related complications, whether symptoms have improved, and whether the treatment continues to support the patient's goals.

Now consider another patient whose tumors have remained approximately the same size.

If the disease has been controlled for a meaningful period, symptoms are manageable, and treatment is well tolerated, continuing the current approach may be appropriate.

The interpretation depends on the complete clinical situation.

That is why cancer treatment evaluation is not simply about asking whether a test result is better or worse.

It involves understanding what each result means, how the different findings fit together, and whether treatment is providing meaningful benefit.

How Often Do Doctors Check Whether Treatment Is Working?

There is no single monitoring schedule that applies to every patient.

The frequency of medical visits, blood tests, and imaging depends on several factors, including the type of cancer, treatment being used, original treatment goal, previous results, symptoms, and overall clinical condition.

Some treatments require frequent laboratory monitoring, while imaging studies may be performed at longer intervals.

Your oncology team determines which evaluations are appropriate and when they should be performed.

And importantly, experiencing more side effects does not mean that cancer treatment is working better.

The absence of side effects does not mean that treatment is ineffective.

The Key Takeaway

Doctors evaluate cancer treatment by combining several sources of information.

Symptoms help us understand how a patient is feeling.

Physical examinations reveal changes that can be observed directly.

Imaging allows us to assess many tumors inside the body.

Blood tests provide information about treatment safety and, in selected situations, cancer activity.

Pathology can reveal how tumors have responded when tissue is available for examination.

Each method answers a different question. Together, they help doctors understand whether treatment is achieving its intended goals.

But when cancer can be measured on imaging, another important question arises:

How do doctors determine whether a tumor has shrunk enough to be considered a response, remained stable, or grown enough to be classified as progression?

To answer that, we first need to understand how cancer scans are compared.

03. Why Do Doctors Compare Cancer Scans?

Imagine looking at a CT scan that shows a tumor measuring 3 centimeters.

Is that good news or bad news?

The measurement alone cannot tell us.

If the tumor measured 5 centimeters before treatment, it has become smaller.

But if it previously measured 1 centimeter, it has grown.

To understand whether cancer is responding to treatment, doctors need to know what has changed over time.

This is why comparing current scans with previous examinations is such an important part of cancer care.

1. Baseline Imaging: Establishing the Starting Point

Before starting treatment, doctors often perform imaging studies to understand the location and extent of the cancer.

When these studies are used as the starting reference for evaluating treatment response, they are called baseline imaging.

Baseline scans help establish:

• Where cancer is currently detectable.
• How large certain tumors are.
• Which organs or anatomical structures are involved.
• Which lesions can be measured reliably.
• What findings should be monitored during treatment.

For example, a patient with colorectal cancer may have two measurable metastases in the liver.

One measures 4 centimeters and the other measures 3 centimeters.

These measurements provide a starting point for evaluating changes during treatment.

However, not every abnormality visible on imaging is necessarily cancer, and not every cancer lesion can be measured accurately.

This is why radiologists and oncologists carefully interpret the findings before deciding which abnormalities should be followed.

2. Follow-Up Imaging: Looking for Changes

After treatment begins, imaging studies may be repeated at intervals determined by the oncology team.

These are called follow-up scans.

Doctors compare the new images with previous studies to determine whether the cancer has changed.

They may observe that some lesions have become smaller, others have remained approximately the same size, or certain areas have increased in size.

They also look for new findings that were not visible previously.

Whenever possible, doctors use comparable imaging techniques during follow-up.

For example, comparing CT scans obtained using similar technical methods can help make measurements more consistent.

Different imaging methods, scan settings, or the way measurements are performed can sometimes influence the apparent size of a lesion.

A small difference between two measurements does not always represent a meaningful biological change.

This is one reason doctors interpret imaging results within the broader clinical context.

3. Target Lesions: Which Tumors Do Doctors Measure?

When evaluating treatment response, doctors may select particular cancer lesions that can be measured reliably over time.

These are called target lesions.

They are usually chosen because their boundaries can be identified clearly and their dimensions can be measured consistently.

In many solid tumors, a standardized system called RECIST 1.1 helps define how these lesions should be selected and evaluated.

Under RECIST 1.1, doctors can select up to five target lesions in total, with a maximum of two per organ.

For most non-lymph-node lesions evaluated using an appropriate CT technique, a lesion generally needs to measure at least 10 millimeters in its longest diameter to qualify as measurable.

Lymph nodes are evaluated differently: their shorter diameter, called the short axis, is used. A lymph node generally needs a short-axis measurement of at least 15 millimeters to qualify as a measurable target lesion.

These technical requirements help ensure that measurements are sufficiently reliable for standardized comparisons.

An Example

Imagine that a patient has two measurable liver metastases.

At baseline:

Lesion A: 40 mm

Lesion B: 30 mm

The combined measurement is:

40 mm + 30 mm = 70 mm

This is called the sum of diameters.

During follow-up, doctors can compare this sum with measurements obtained at different time points.

Importantly, RECIST uses the diameters of selected lesions, not their total volume.

And selecting target lesions does not mean that other areas of cancer are ignored.

4. Non-Target Lesions: What About the Other Tumors?

Not every cancer lesion is selected as a target lesion.

Some abnormalities may be too small, difficult to measure consistently, or otherwise unsuitable for standardized measurements.

Others may represent disease that can be identified but not reliably quantified using the same approach.

These findings may be classified as non-target lesions.

For example, a patient may have multiple small lesions or certain types of cancer involvement that are difficult to measure accurately.

Doctors still document and evaluate these findings during treatment.

Instead of calculating their contribution to the sum of target-lesion diameters, the evaluation focuses on whether the non-target disease has disappeared, persists, or shows unequivocal progression.

This distinction is important.

A patient's overall response cannot always be determined by measuring only the selected target lesions.

Changes in non-target disease may also influence the interpretation.

5. New Lesions: Why Do They Matter?

When reviewing a follow-up scan, doctors also look for new abnormalities.

A new lesion is a finding that was not identified on the previous relevant examination.

But not every new abnormality represents cancer.

Inflammation, infections, treatment-related changes, and other benign conditions can sometimes produce findings that appear suspicious.

Doctors must determine whether the new finding is likely to represent malignant disease.

Under RECIST 1.1, the appearance of an unequivocally new malignant lesion is considered evidence of progressive disease.

This can be true even when previously measured tumors have become smaller.

Consider This Example

A patient begins treatment with two measurable liver metastases.

After several months, both lesions have decreased substantially in size.

That sounds encouraging.

However, the follow-up scan also reveals a new lesion that is clearly identified as metastatic disease.

Although the original tumors have responded, the appearance of new metastatic disease changes the overall assessment.

Under conventional RECIST 1.1, this would be classified as progressive disease.

This does not mean that every new or uncertain imaging finding should automatically trigger a treatment change.

The oncologist must consider the certainty of the finding, the clinical circumstances, and the appropriate response criteria.

We will explore this situation in greater detail when discussing progressive disease.

6. Why Doctors Sometimes Compare More Than Two Scans

It may seem natural to compare the most recent scan with the one obtained before treatment.

But oncologists may also need to examine what happened between those two studies.

Imagine the following sequence:

Before treatment: a tumor measures 5 cm.

After several months: it decreases to 2 cm.

On a later scan: it increases to 3 cm.

The tumor is still smaller than it was before treatment.

However, it has grown compared with its smallest previously recorded measurement.

This distinction matters because standardized response criteria do not always use the same reference measurement.

Under RECIST 1.1, the nadir is the smallest recorded sum of target-lesion diameters, including the baseline measurement if it is the smallest recorded value.

The nadir plays an important role when determining whether measurable disease has progressed.

This is why doctors may review the entire imaging history rather than looking only at the first and most recent scans.

A tumor can remain smaller than it was initially and still show clinically important growth.

7. Why Imaging Results Need Interpretation

Cancer scans provide essential information, but interpreting them is not simply a matter of comparing numbers.

Several factors may influence what doctors see:

• Differences in imaging technique or measurement.
• Treatment-related inflammation.
• Scar tissue or other changes following treatment.
• Lesions that are difficult to measure consistently.
• Different patterns of response among tumors.
• The appearance of findings whose nature is initially uncertain.

Furthermore, some treatments can affect tumor characteristics without producing an immediate or proportional reduction in size.

For these reasons, a radiology report is an essential part of response assessment, but it is not always the final word on whether treatment is providing meaningful benefit.

The oncology team combines imaging findings with symptoms, physical examination, laboratory results, treatment toxicity, and the original therapeutic goals.

The Key Takeaway

Doctors compare cancer scans because the direction and significance of change matter more than a single measurement taken in isolation.

Baseline imaging establishes a reference point.

Follow-up imaging shows how findings evolve.

Target lesions provide standardized measurements.

Non-target lesions contribute additional information.

New malignant lesions may change the overall assessment.

And the smallest measurement previously recorded — the nadir — can become particularly important when evaluating progression.

But how much must a tumor shrink to be considered a response?

And how much must it grow before doctors classify the disease as progressing?

To answer these questions, oncologists use standardized response categories.

Let's explore what they actually mean.

04. Understanding Cancer Response: CR, PR, SD and PD

After reviewing a patient's follow-up scans, an oncologist might say:

"Your cancer is responding to treatment."

"The disease is stable."

"Unfortunately, the scans show progression."

But what do these expressions actually mean?

And how do doctors decide whether a tumor has shrunk enough to be considered a response, or grown enough to be classified as progression?

To make these assessments more consistent, oncologists and researchers use standardized response criteria.

One of the most widely used systems for evaluating measurable solid tumors is called RECIST.

What Is RECIST?

RECIST stands for Response Evaluation Criteria in Solid Tumours.

The current widely established conventional version is RECIST 1.1, published in 2009.

It provides standardized rules for evaluating changes in cancer lesions over time, particularly in clinical trials.

Rather than relying exclusively on descriptions such as "slightly smaller" or "somewhat larger," RECIST allows doctors and researchers to classify tumor response using defined measurements.

The system includes four main categories:

• Complete Response (CR)
• Partial Response (PR)
• Stable Disease (SD)
• Progressive Disease (PD)

These categories help describe what is happening to measurable cancer during treatment.

However, RECIST does not apply to every cancer or clinical situation, and a RECIST classification does not automatically determine whether treatment should be continued or changed.

Let's understand each category.

1. Complete Response (CR): When Cancer Is No Longer Detectable

A Complete Response, often abbreviated as CR, means that the cancer findings being evaluated have disappeared according to the applicable response criteria.

Under RECIST 1.1, a complete response of target lesions requires the disappearance of all target lesions.

Lymph nodes are assessed slightly differently.

A lymph node previously considered abnormal must decrease to a short-axis measurement of less than 10 millimeters to be considered normal under these criteria.

To classify the patient's overall response as complete, doctors must also consider non-target lesions and confirm that no new malignant lesions have appeared.

An Example

Imagine a patient with two measurable liver metastases.

Before treatment:

Lesion A: 40 mm

Lesion B: 30 mm

After treatment, neither lesion is detectable on the follow-up CT scan.

If there are no other findings that prevent an overall complete response classification, the patient may meet RECIST criteria for CR.

This is an encouraging result.

However, there is an essential distinction:

Complete Response does not necessarily mean that cancer has been cured.

Imaging can show that previously detectable cancer has disappeared, but it cannot always establish whether microscopic cancer cells remain.

The significance of a complete response depends on the type of cancer, treatment received, disease characteristics, and subsequent clinical course.

We will explore this distinction in greater detail later.

2. Partial Response (PR): When Cancer Shrinks Significantly

A Partial Response, or PR, means that measurable cancer has decreased sufficiently in size to meet established criteria.

Under RECIST 1.1, partial response requires:

At least a 30% decrease in the sum of target-lesion diameters compared with baseline.

This is an important point.

Doctors do not necessarily calculate a percentage change for every individual tumor and then average those percentages.

Instead, they calculate the sum of the selected target-lesion diameters and compare that sum with the original baseline measurement.

An Example

Let's return to our patient with two liver metastases.

Before treatment:

Lesion A: 40 mm

Lesion B: 30 mm

Total: 70 mm

After treatment:

Lesion A: 25 mm

Lesion B: 19 mm

Total: 44 mm

The combined measurement has decreased from 70 mm to 44 mm.

That represents a reduction of approximately 37.1%.

Because the reduction exceeds the 30% threshold, the measurable target lesions meet the criteria for Partial Response.

Provided there is no new malignant disease or other finding that changes the overall assessment, this may represent an overall PR.

Does a Partial Response Mean Treatment Is Successful?

A partial response demonstrates that measurable tumors have decreased substantially in size.

This can be an encouraging indication of treatment activity.

However, the clinical significance depends on the cancer, treatment goal, duration of response, symptoms, and overall condition of the patient.

A partial response does not necessarily mean the cancer has been eliminated.

It also does not automatically guarantee longer survival.

Tumor shrinkage is an important measure of treatment activity, but it is not the same thing as measuring every aspect of clinical benefit.

3. Stable Disease (SD): When Cancer Has Not Changed Enough to Meet Other Criteria

A Stable Disease classification, abbreviated SD, means that measurable cancer has neither decreased sufficiently to qualify as a partial response nor increased sufficiently to meet the criteria for progressive disease.

Under RECIST 1.1, these assessments use different reference measurements.

To determine whether there has been enough shrinkage for PR, doctors compare measurements with baseline.

To determine whether there has been enough growth for PD, they compare measurements with the smallest recorded sum during treatment.

An Example

Consider our patient again.

Before treatment:

Total target-lesion measurement: 70 mm

First follow-up scan:

Total target-lesion measurement: 63 mm

This represents a decrease of 10%.

The tumors have become somewhat smaller, but the reduction does not reach the 30% threshold required for Partial Response.

The findings also do not meet the criteria for progression.

In this simplified first-follow-up scenario, the result is classified as Stable Disease.

Does Stable Disease Mean Treatment Is Not Working?

Not necessarily.

Some cancers grow rapidly without effective treatment. Others may progress more slowly.

Depending on the circumstances, maintaining disease stability can represent an important treatment outcome.

However, stable disease does not automatically mean treatment is providing meaningful benefit.

The duration of disease control, cancer biology, treatment toxicity, symptoms, and original therapeutic goals all matter.

Stable Disease is a description of the cancer's behavior under defined criteria, not a universal judgment about treatment success or failure.

We will explore why this distinction matters in the next section.

4. Progressive Disease (PD): When Cancer Has Progressed

Progressive Disease, or PD, indicates that cancer has progressed according to the applicable response criteria.

Under RECIST 1.1, measurable target lesions meet the criteria for progression when BOTH of the following occur:

1. The sum of target-lesion diameters increases by at least 20%.

2. The absolute increase is at least 5 millimeters.

Importantly, this increase is calculated relative to the smallest sum previously recorded during treatment, known as the nadir.

The baseline measurement is used if it remains the smallest recorded sum.

An Example

Let's return to our original measurements.

Before treatment:

Lesion A: 40 mm

Lesion B: 30 mm

Total: 70 mm

First follow-up scan:

Lesion A: 52 mm

Lesion B: 38 mm

Total: 90 mm

In this example, the baseline measurement of 70 mm is also the nadir.

The increase from 70 mm to 90 mm represents approximately 28.6%.

The absolute increase is 20 mm.

Because both thresholds are met, the target-lesion measurements qualify as Progressive Disease.

Why Is There Also a 5 mm Requirement?

Small tumors can show large percentage changes even when their actual measurements differ by only a few millimeters.

For example, consider a combined target-lesion measurement that increases from 20 mm to 24 mm.

This represents a 20% increase.

However, the absolute increase is only 4 mm.

Under RECIST 1.1, this would not meet the target-lesion progression criteria because the additional 5 mm requirement has not been reached.

This safeguard helps reduce the risk of classifying small measurement differences as disease progression.

Can Cancer Progress Even Without a 20% Increase?

Yes.

RECIST 1.1 also considers other findings.

For example, progression may be identified when:

• A new lesion is unequivocally identified as malignant.
• Previously documented non-target disease shows unequivocal progression.

This means that a patient may have shrinking target lesions but still be classified as having overall Progressive Disease if a new metastatic lesion appears.

However, suspicious or uncertain findings require careful interpretation.

Not every new abnormality on a scan represents cancer progression.

5. An Important Detail: Baseline Is Not Always the Reference for Progression

This is one of the most important concepts in RECIST 1.1.

For Partial Response, the reference is the baseline measurement.

For Progressive Disease involving target lesions, the reference is the nadir.

These measurements are not necessarily the same.

Consider This Situation

A patient begins treatment with a combined tumor measurement of:

70 mm

After several months, the tumors decrease to:

42 mm

Later, a follow-up scan shows:

54 mm

At first glance, this might seem reassuring.

After all, the tumors are still smaller than they were before treatment.

But there are two different comparisons.

Compared with baseline:

The tumors remain approximately 22.9% smaller.

Compared with the nadir:

The tumors have increased approximately 28.6%, with an absolute increase of 12 mm.

That increase meets both RECIST 1.1 criteria for target-lesion progression.

Therefore, in this example, the target lesions are classified as Progressive Disease.

A tumor can still be smaller than it was before treatment and nevertheless meet the criteria for progression.

This is why reviewing the complete imaging history is so important.

It also helps explain why comparing only the first and most recent scans can sometimes produce a misleading impression.

6. Target-Lesion Response Is Not Always the Same as Overall Response

So far, our examples have focused primarily on measurements of selected target lesions.

But doctors must also consider the rest of the disease.

RECIST 1.1 evaluates three components:

Target lesions: the selected lesions measured over time.

Non-target lesions: other documented cancer findings that are evaluated without being included in the same sum of diameters.

New lesions: abnormalities that may represent newly developed malignant disease.

These findings contribute to the overall response classification.

One Last Example

Imagine that a patient's target lesions have decreased by 40%.

Based on the measured tumors alone, this would meet the threshold for Partial Response.

However, the same follow-up scan reveals a new, unequivocally malignant liver metastasis.

Under conventional RECIST 1.1, the appearance of that new lesion establishes overall Progressive Disease.

The measured tumors have responded, but the disease as a whole has progressed.

This illustrates an essential principle:

The response of individual tumors does not always represent the response of all the cancer in the body.

7. Do These Categories Tell Doctors Whether to Continue Treatment?

RECIST classifications provide valuable information, but they are not automatic treatment instructions.

A Partial Response may support continuing treatment when the patient is benefiting and tolerating therapy.

Stable Disease may represent meaningful control in certain settings.

Progressive Disease often leads the oncology team to reconsider the treatment strategy.

However, decisions depend on additional factors, including:

• The type of cancer and its biological behavior.
• The original goal of treatment.
• The patient's symptoms and overall condition.
• Treatment-related side effects.
• The duration and pattern of response.
• Available treatment alternatives.
• The patient's preferences and priorities.

Furthermore, not every cancer can be evaluated using conventional RECIST criteria.

And certain treatments, particularly immunotherapy, can occasionally produce unusual imaging patterns that require additional interpretation.

We will discuss these situations later.

The Key Takeaway

RECIST 1.1 provides standardized categories that describe how measurable cancer changes during treatment.

Complete Response (CR): Cancer findings disappear according to the applicable criteria.

Partial Response (PR): The sum of target-lesion diameters decreases by at least 30% from baseline.

Stable Disease (SD): The measurements do not meet the criteria for partial response or progression.

Progressive Disease (PD): The sum of target-lesion diameters increases by at least 20% from the nadir, with an absolute increase of at least 5 mm, or other qualifying evidence of progression is present.

These percentages refer to changes in the sum of measured diameters, not tumor volume.

And while the categories are valuable, they are only one part of understanding the effectiveness of cancer treatment.

A response classification tells us what has happened to the cancer according to defined criteria. Understanding what that response means for the patient requires a broader clinical assessment.

05. Why Can Stable Disease Be Good News?

Imagine receiving the results of your latest CT scan.

You have been undergoing cancer treatment for several months, and your oncologist tells you:

"Your scans show stable disease."

You might feel uncertain about what that means.

Perhaps you were hoping to hear that the tumors had become smaller.

You might wonder:

"If the cancer hasn't shrunk, does that mean my treatment isn't working?"

The answer is not necessarily.

Sometimes, preventing cancer from growing can be an important treatment achievement.

But understanding when stable disease represents good news requires looking beyond the scan itself.

1. Cancer Does Not Always Need to Shrink to Be Controlled

Cancer treatments can have different effects on tumors.

Some treatments cause substantial tumor shrinkage.

Others may slow tumor growth or help maintain disease control without producing a major reduction in size.

As we discussed earlier, RECIST 1.1 classifies disease as stable when the findings do not meet the criteria for partial response or progressive disease.

This means that stable disease is a defined category of tumor response assessment.

It does not necessarily mean that the tumors have remained exactly the same size.

A small decrease or increase may still fall within the stable disease category.

For example, imagine a patient whose measurable tumors have a combined diameter of 70 mm before treatment.

At the first follow-up scan, the combined measurement is 63 mm.

This represents a 10% decrease.

Although the tumors have become somewhat smaller, they have not decreased sufficiently to meet the 30% threshold for a partial response.

Assuming there are no other findings that change the overall assessment, the result is classified as Stable Disease.

The disease has not disappeared, and it has not met the criteria for partial response.

But it also has not met the criteria for progression.

Depending on the patient's circumstances, this may be encouraging.

2. The Biology of the Cancer Matters

Not all cancers behave in the same way.

Some cancers tend to grow relatively quickly.

Others may develop or progress more slowly, sometimes over extended periods.

This difference is important when interpreting stable disease.

Consider Two Different Situations

Patient A

A patient has an advanced cancer that demonstrated rapid growth before treatment.

After starting systemic therapy, subsequent scans show that the disease has remained approximately the same size for several months.

In this situation, sustained stability may be an encouraging indication of disease control.

Patient B

Another patient has a slowly growing cancer that had shown very little change over a long period, even before treatment began.

After starting therapy, the scans continue to show minimal change.

Although the disease is stable, it may be more difficult to determine how much of that stability is attributable to the treatment.

Both patients may receive the same radiological classification.

However, the clinical interpretation can be quite different.

The same imaging result does not necessarily have the same meaning in every type of cancer.

This is also why clinical trials are important.

Comparing appropriately selected groups of patients helps researchers determine whether a treatment genuinely delays progression or improves outcomes, rather than simply observing the natural behavior of a disease.

3. How Long Has the Disease Remained Stable?

Time is another important consideration.

Stable disease observed at a single early evaluation may not have the same clinical significance as disease that remains controlled over many months.

Imagine two patients receiving treatment for advanced cancer.

One patient's first follow-up scan shows stable disease, but progression is identified shortly afterward.

Another patient continues to have stable disease during several consecutive evaluations over a much longer period.

Although both patients may initially receive the same response classification, the duration of disease control is different.

This distinction can be clinically meaningful.

Why Does Duration Matter?

In certain cancers, prolonged disease control may indicate that the current treatment strategy is helping achieve its intended goal.

However, there is no universal period of stability that automatically proves treatment success.

The significance of stable disease depends on the cancer type, its expected natural history, the treatment being used, and the patient's individual circumstances.

In clinical trials, researchers often specify minimum observation periods when evaluating stable disease.

This helps prevent an isolated early scan from being interpreted as evidence of meaningful disease control without sufficient follow-up.

Stable disease describes what has been observed. The duration and clinical context help determine what that observation means.

4. What If the Patient Feels Better?

Imaging findings are only one part of treatment evaluation.

Doctors also consider symptoms, physical functioning, treatment side effects, and quality of life.

Imagine a patient receiving treatment for advanced lung cancer.

The follow-up CT scan shows that the tumors have remained approximately the same size.

However, the patient reports less shortness of breath, improved appetite, and greater ability to perform everyday activities.

These changes may represent meaningful clinical improvements.

Even without major tumor shrinkage, the patient's overall situation may have improved.

However, we must be careful about interpreting these findings.

Symptoms can improve because of cancer-directed treatment, supportive care, or other interventions.

Therefore, symptom improvement does not necessarily prove that stable disease was caused by the anticancer treatment.

Similarly, a patient may have radiologically stable cancer but continue to experience significant symptoms.

Clinical benefit is not determined by imaging measurements alone.

The oncology team must consider how the patient is doing as a whole.

5. What About Treatment Side Effects?

A treatment may help control cancer while also causing unwanted effects.

Some side effects are mild and manageable.

Others may significantly affect daily activities, physical functioning, or quality of life.

Imagine a patient whose cancer has remained stable during treatment, but who develops severe fatigue, persistent nausea, or other significant complications.

Even if the scans are encouraging, the treatment may need to be reassessed.

Doctors may consider supportive measures, treatment adjustments, or alternative approaches, depending on the circumstances.

The goal is not simply to maintain favorable imaging results at any cost.

The potential benefits of treatment must be considered alongside its risks and burdens.

This is particularly important when treatment is intended to control an advanced cancer over an extended period.

For some patients, maintaining daily functioning and quality of life may be among the most important treatment priorities.

For others, different goals may take precedence.

These priorities should be discussed with the oncology team.

6. Does Stable Disease Mean Treatment Should Continue?

Not automatically.

Stable disease may support continuing a treatment when the clinical circumstances are favorable.

For example, continuing the current approach may be reasonable when:

• The disease remains controlled over a meaningful period.
• The patient is tolerating treatment adequately.
• Symptoms and functional status are acceptable.
• The treatment remains consistent with the patient's goals.
• The expected benefits continue to outweigh the risks.

However, stable disease does not guarantee that continuing the same treatment is always the best decision.

Changes in treatment tolerance, overall health, patient preferences, or other clinical factors may lead the oncology team to reconsider the plan.

Likewise, a treatment may sometimes be modified or discontinued despite radiological disease control.

These decisions depend on the individual situation.

A stable scan is important information, but it is not an automatic instruction to continue treatment indefinitely.

7. Stable Disease Is Not the Same as Cure

There is another important distinction.

Stable disease means that the cancer has not demonstrated sufficient change to meet the applicable criteria for response or progression.

It does not mean that the cancer has disappeared.

It does not establish that treatment has eliminated all malignant cells.

And it does not guarantee that the disease will remain controlled permanently.

Cancer can remain stable for a period and subsequently progress.

This is one reason follow-up evaluations remain important, even when treatment appears to be controlling the disease.

However, uncertainty about the future does not make disease control meaningless.

For patients receiving treatment for advanced cancer, maintaining control while preserving quality of life can be a valuable outcome.

The Key Takeaway

Hearing that cancer is stable can produce mixed emotions.

It may not be the result a patient was hoping for.

But stable disease does not automatically mean that treatment has failed.

In some situations, preventing or delaying cancer progression is an important therapeutic goal.

The meaning of stable disease depends on several factors:

What type of cancer is being treated?

How was the cancer behaving before treatment?

How long has the disease remained stable?

How is the patient feeling and functioning?

What side effects is the treatment causing?

Is the treatment helping achieve the original goals?

These questions help doctors interpret the significance of a stable scan.

Stable Disease is a radiological response category. Whether it represents meaningful treatment benefit depends on the broader clinical picture.

And what happens when the next scan shows that a tumor has started growing?

Does an increase in size always mean that treatment has stopped working?

That question introduces another important part of cancer response assessment.

06. What Happens If a Tumor Gets Bigger?

Imagine receiving the results of a follow-up CT scan.

Your oncologist explains that one of your tumors has increased in size.

For many patients, hearing this can be frightening.

You might immediately wonder:

"Does this mean my treatment has stopped working?"

An increase in tumor size is an important finding, but its meaning depends on several factors.

Doctors need to understand how much the tumor has grown, how the measurements compare with previous scans, whether other cancer lesions have changed, and how the patient is doing clinically.

Not every increase in tumor size meets the criteria for progressive disease.

However, when cancer progression is established, it is important to reassess whether the current treatment remains appropriate.

Let's explore how doctors approach these situations.

1. Does Every Increase in Tumor Size Mean Cancer Is Progressing?

Not necessarily.

Medical imaging allows doctors to measure cancer lesions, but these measurements are not perfectly precise.

Imagine that a tumor measures 30 millimeters on one CT scan.

On the next examination, it measures 32 millimeters.

Does this mean the cancer has definitely grown?

Not always.

Several factors can influence measurements, including:

• Differences in how the scan was performed.
• The position or shape of the lesion.
• How clearly its boundaries can be identified.
• Differences in the timing of contrast administration.
• Small variations in where the measurement is taken.
• Differences between the professionals interpreting the images.

Some tumors have well-defined borders and can be measured relatively consistently.

Others have irregular shapes or poorly defined boundaries, making accurate measurements more challenging.

These differences are one reason standardized response criteria exist.

Why Do Standardized Criteria Matter?

RECIST 1.1 establishes thresholds that help distinguish meaningful changes in measurable cancer from smaller variations.

For target lesions, progression requires an increase of at least 20% in their combined diameters, together with an absolute increase of at least 5 millimeters, compared with the smallest previously recorded sum.

These requirements help reduce the risk of classifying minor measurement differences as progression.

However, they do not eliminate every source of uncertainty.

A change in a measurement is an observation. Determining what that change means requires interpretation.

Importantly, measurement variability should not be used to dismiss a concerning new finding or delay the assessment of worsening symptoms.

2. A Tumor Can Grow Without Meeting the Criteria for Progressive Disease

Let's return to our fictional patient with two liver metastases.

Before treatment, the combined measurement of the selected lesions was:

70 mm

After several months of treatment, the combined measurement decreased to:

42 mm

This represents a 40% reduction from baseline.

The patient therefore met the target-lesion threshold for Partial Response.

Now imagine that the next scan shows a combined measurement of:

48 mm

The tumors have increased in size compared with the previous examination.

But have they progressed according to RECIST 1.1?

Let's compare the measurements.

Change from the smallest recorded measurement (nadir):

42 mm → 48 mm

This represents an increase of approximately 14.3%.

Although the tumors have grown, the increase does not reach the 20% threshold required for target-lesion progression.

Assuming the other disease assessments remain unchanged, this finding does not meet the criteria for Progressive Disease.

Furthermore, under RECIST 1.1, a previously established Partial Response can continue to be classified as PR at subsequent evaluations when there is some increase in measurable disease but the criteria for progression have not been met.

This illustrates an important distinction:

Tumor growth and formally defined Progressive Disease are not always the same thing.

Doctors still pay attention to these changes, particularly if there is a consistent pattern of growth over several examinations.

But a small increase does not automatically mean that treatment must be changed.

3. Why the Smallest Previous Measurement Matters

Now imagine that the same patient's next scan shows further growth.

Their measurements have changed as follows:

Before treatment: 70 mm

Best response: 42 mm

Later scan: 48 mm

Most recent scan: 54 mm

At first glance, the tumors are still smaller than they were before treatment.

However, RECIST 1.1 evaluates target-lesion progression using the nadir — the smallest previously recorded sum of diameters.

In this example, the nadir is 42 mm.

The increase from 42 mm to 54 mm represents approximately 28.6%, with an absolute increase of 12 mm.

Both requirements for target-lesion progression are satisfied.

Therefore, the latest measurement meets the criteria for Progressive Disease.

Why Is This Important?

If we compared only the baseline and most recent scans, we might conclude that the cancer had improved because its combined measurement decreased from 70 mm to 54 mm.

But that comparison would overlook what happened in between.

The cancer initially responded substantially and then began growing again.

Cancer can remain smaller than it was before treatment and still meet the criteria for progression.

This is why doctors often review the complete imaging history rather than comparing only two examinations.

It also explains why your oncology team may refer to your "best previous response" when discussing treatment results.

4. What If Some Tumors Shrink While Others Grow?

Cancer does not always respond uniformly throughout the body.

Sometimes, different lesions behave differently during treatment.

For example, a patient with metastatic cancer may have:

• A liver metastasis that becomes considerably smaller.
• A lung metastasis that remains approximately the same size.
• Another lesion that increases in size.

This is sometimes described as a mixed response or heterogeneous response.

Why Can This Happen?

Cancer is biologically complex.

Even within the same patient, different cancer lesions may contain populations of cells with different characteristics.

Some cancer cells may be more sensitive to a particular treatment than others.

Over time, certain cancer-cell populations may develop or demonstrate resistance to treatment while other populations remain sensitive.

However, not every difference between lesions is necessarily caused by treatment resistance.

Imaging variability, anatomical characteristics, and treatment-related changes may also contribute.

How Do Doctors Interpret a Mixed Response?

Under conventional RECIST 1.1, doctors evaluate the combined measurements of target lesions, non-target disease, and the appearance of new lesions.

Consider a simplified example.

Before treatment, two target lesions measure:

Lesion A: 40 mm

Lesion B: 30 mm

Total: 70 mm

At the first follow-up:

Lesion A: 20 mm

Lesion B: 45 mm

Total: 65 mm

One lesion has decreased substantially, while the other has increased.

However, the combined measurement has decreased by approximately 7.1%.

Assuming there are no new lesions or unequivocal progression of non-target disease, this first follow-up assessment would be classified as Stable Disease.

Yet the individual lesions are behaving differently.

A single overall response category does not always capture every important detail of how cancer is behaving.

This is why oncologists examine both the overall results and the behavior of individual lesions.

In selected clinical situations, progression confined to a small number of sites may also lead doctors to consider whether local treatments have a role while reassessing the systemic treatment strategy.

Such decisions depend on the cancer type, its biology, available evidence, and the patient's overall circumstances.

5. What If a New Tumor Appears?

Another important situation occurs when previously known tumors are shrinking, but imaging reveals a new lesion.

Imagine a patient whose measurable liver metastases have decreased substantially during treatment.

The combined measurements suggest a Partial Response.

However, a follow-up scan also identifies a new lesion that is clearly established as metastatic cancer.

Under conventional RECIST 1.1, the appearance of an unequivocally malignant new lesion indicates overall Progressive Disease.

This is true even when the previously measured tumors have become smaller.

Why Does a New Lesion Matter So Much?

A new metastatic lesion may indicate that cancer has developed in an additional location despite ongoing treatment.

It can therefore change the overall assessment of disease control.

However, there is an important distinction.

A new abnormality on imaging is not necessarily a new cancer lesion.

Inflammation, infection, benign lesions, and treatment-related changes can sometimes resemble malignancy.

When a finding is uncertain, doctors may review previous examinations, obtain additional imaging, or consider other investigations.

In selected circumstances, follow-up imaging can help clarify whether a suspicious finding truly represents new malignant disease.

This does not mean that every unequivocal progression requires a second scan before it can be classified as progression.

Under conventional RECIST 1.1, clearly established progression does not universally require confirmation on another examination.

The need for further testing depends on the uncertainty of the finding, the clinical circumstances, and the response criteria being used.

6. Can Treatment-Related Changes Make a Tumor Look Bigger?

Sometimes, changes in the appearance of a lesion do not correspond directly to an increase in active cancer.

For example, treatment may produce inflammation, tissue damage, or changes in the internal structure of a tumor.

Certain tumors may undergo necrosis, meaning that some of their cells die.

A lesion may therefore change in appearance or internal composition without its dimensions reflecting every aspect of its biological response.

However, doctors cannot assume that a growing lesion is responding simply because treatment-related changes are possible.

In many situations, enlargement does represent genuine cancer progression.

There are also particular circumstances in which treatment-related changes can complicate imaging interpretation.

One important example is pseudoprogression during immunotherapy.

In this uncommon phenomenon, tumors may initially appear larger, or new lesions may become apparent, before subsequent examinations demonstrate a response or disease control.

Pseudoprogression requires careful evaluation and must not be assumed whenever a tumor enlarges.

We will explore this phenomenon, including how doctors distinguish possible pseudoprogression from true progression, in the next section.

7. What Happens When Doctors Confirm Cancer Progression?

When disease progression is established, the oncology team reassesses the treatment strategy.

Progression may indicate that the current therapy is no longer adequately controlling the cancer.

However, radiological progression and the decision to stop treatment are not always identical events.

Doctors consider several factors before deciding what should happen next.

How Much Has the Cancer Progressed?

Progression affecting multiple organs or causing significant complications may require a different approach from limited progression involving only one or a few sites.

The location of progression also matters.

For example, growth involving a critical anatomical structure may require urgent attention, even when the overall increase in measurable disease is relatively small.

How Is the Patient Doing Clinically?

Symptoms, functional status, organ function, and overall health help guide treatment decisions.

A patient whose disease has progressed and who is developing significant symptoms may require prompt reassessment.

Importantly, feeling well does not invalidate a clear finding of cancer progression.

Some cancers can progress without immediately causing noticeable symptoms.

What Treatment Options Are Available?

Depending on the cancer type and clinical circumstances, the oncology team may consider:

• Changing to another systemic treatment.
• Reassessing the cancer's biological characteristics or relevant biomarkers.
• Considering local treatment for selected sites of progression.
• Exploring appropriate clinical trial opportunities.
• Adjusting the overall treatment plan according to expected benefits, risks, and patient preferences.

In some carefully selected situations, continuing a systemic treatment despite limited radiological progression may be considered, particularly when there is ongoing clinical benefit and an evidence-supported strategy.

However, this is not appropriate for every patient or every treatment.

Progression generally requires a thoughtful reassessment rather than an automatic assumption that the same treatment should continue.

Does Progression Mean That No More Treatments Are Available?

No.

Progression on one treatment does not necessarily mean that all treatment options have been exhausted.

Many cancers have multiple possible treatment approaches, although the available options and their expected benefits vary considerably.

For some patients, another effective treatment may be available.

For others, the priority may shift toward symptom control, quality of life, and supportive care.

These decisions should be individualized and discussed openly with the oncology team.

8. When Should Patients Contact Their Oncology Team?

Routine response assessments are usually scheduled in advance.

However, patients should not wait for their next scan if they develop concerning new symptoms.

For example, new or rapidly worsening pain, breathing difficulties, neurological symptoms, or significant deterioration in general condition should be reported promptly.

Some symptoms may require urgent medical evaluation.

They do not necessarily mean that the cancer is progressing, but they may indicate complications that need attention.

Imaging schedules are important, but patient safety should never depend exclusively on the date of the next scan.

The Key Takeaway

Discovering that a tumor has increased in size can be distressing.

However, understanding what that increase means requires more than comparing two measurements.

Doctors consider:

How much has the tumor grown?

Has the increase met established criteria for progression?

How does the measurement compare with the smallest previous measurement?

Are other lesions shrinking, remaining stable, or growing?

Have new malignant lesions appeared?

How is the patient feeling and functioning?

Is the current treatment still providing meaningful benefit?

Small measurement changes do not always represent progressive disease.

Different cancer lesions may respond differently.

A new unequivocally malignant lesion can establish overall progression even when other tumors have shrunk.

And progression on one treatment does not necessarily mean that no further treatment options exist.

Progressive Disease is an important finding that prompts clinical reassessment. What happens next depends on the complete clinical situation.

But there is one particularly interesting situation we have not yet explored.

What if a tumor appears to grow during treatment, but later becomes smaller without changing that treatment?

Although uncommon, this can occur with certain immunotherapies.

Understanding why requires exploring a phenomenon called pseudoprogression.

07. Can Cancer Sometimes Look Worse Before It Gets Better?

Imagine a patient receiving immunotherapy for advanced cancer.

After several weeks of treatment, the patient undergoes a follow-up CT scan.

The results show that some tumors have become larger.

New suspicious lesions may even have appeared.

Naturally, this raises an important concern:

"Does this mean the immunotherapy isn't working?"

In many situations, cancer growth during treatment does represent disease progression.

However, immunotherapy has introduced an unusual phenomenon that can sometimes make the interpretation more complicated.

It is called pseudoprogression.

In this uncommon situation, cancer may initially appear to worsen on imaging, but subsequent examinations reveal tumor shrinkage or disease control without a change in the anticancer treatment.

Understanding why this can happen requires knowing a little about how immunotherapy works.

1. Why Can Immunotherapy Produce Unusual Response Patterns?

Many traditional anticancer treatments act by directly damaging cancer cells or interfering with processes necessary for their survival and growth.

Immunotherapy can work differently.

Certain immunotherapies, particularly medications known as immune checkpoint inhibitors, help the immune system recognize and attack cancer cells more effectively.

These treatments target regulatory pathways involving proteins such as PD-1, PD-L1, or CTLA-4.

Under normal circumstances, immune checkpoints help regulate immune responses and prevent excessive immune activity.

Some cancers exploit these pathways to avoid immune destruction.

By blocking selected checkpoints, immunotherapy can restore or enhance the ability of immune cells to attack malignant cells.

However, this process does not always produce immediate tumor shrinkage.

The interaction between cancer cells, immune cells, and surrounding tissues can create changes that are visible on medical imaging.

In certain situations, these changes may temporarily make a lesion appear larger.

But why would that happen?

2. What Is Pseudoprogression?

Pseudoprogression is an apparent worsening of cancer on imaging that is subsequently followed by tumor response or disease control without changing the anticancer treatment.

It can occur during treatment with immune checkpoint inhibitors, although it is uncommon.

Imagine that a tumor measures 4 centimeters before treatment.

After several weeks of immunotherapy, a follow-up scan shows that it measures 5 centimeters.

At first, this increase appears concerning.

However, the patient remains clinically stable, and the oncology team determines that continued treatment with close reassessment is appropriate.

Several weeks later, another scan shows that the lesion has decreased to 3 centimeters.

The initial enlargement may have represented pseudoprogression.

The important point is that doctors generally cannot identify pseudoprogression with certainty from the initial scan alone.

Pseudoprogression is usually recognized by examining how the disease evolves over time.

What Might Cause a Tumor to Look Larger?

Several biological mechanisms have been proposed.

Immune-cell infiltration

As immunotherapy stimulates anticancer immune activity, immune cells may accumulate within or around tumor tissue.

This increased cellular presence may contribute to an apparent increase in lesion size.

Inflammation and tissue swelling

Immune activity can produce inflammatory changes and fluid accumulation within the tumor microenvironment.

These changes may temporarily affect the appearance or dimensions of a lesion.

Changes within tumor tissue

As cancer cells are damaged or destroyed, changes such as tissue necrosis and inflammatory reactions may alter the appearance of the treated area.

These processes can occur alongside genuine anticancer activity.

However, they do not necessarily explain every case of apparent pseudoprogression.

And importantly, a conventional CT scan cannot reliably determine how much of an enlarging lesion consists of active cancer, inflammation, immune cells, or treatment-related tissue changes.

A tumor that becomes larger during immunotherapy may be progressing, even when immune-related changes are biologically possible.

This distinction is essential.

3. How Common Is Pseudoprogression?

Pseudoprogression is a recognized phenomenon, but it occurs in a minority of patients receiving immune checkpoint inhibitors.

A systematic review and meta-analysis published in Radiology in 2020 evaluated 17 studies involving 3,402 patients with solid tumors treated with these medications.

The researchers found a pooled incidence of pseudoprogression of approximately 6%.

This means that pseudoprogression was uncommon in the populations included in those studies.

However, the exact frequency varies depending on several factors:

• The type of cancer being treated.
• The immunotherapy regimen.
• How pseudoprogression is defined.
• The response criteria used in the study.
• The population being evaluated.

Pseudoprogression has been described in several malignancies, including melanoma, non-small cell lung cancer, and other solid tumors.

However, it is not equally common across all cancers or treatment settings.

What Does the 6% Figure Actually Mean?

It is important not to misinterpret this number.

The reported incidence does not mean that a patient whose tumor grows during immunotherapy has a 6% probability of experiencing pseudoprogression.

Those are two different questions.

The first asks how frequently pseudoprogression occurred among all patients evaluated in the included studies.

The second asks how likely pseudoprogression is in an individual patient who has already developed concerning imaging findings.

That individual probability depends on additional clinical factors and cannot be determined simply from the pooled incidence.

The central message is:

Most apparent progression during immunotherapy is not pseudoprogression.

For this reason, doctors must take concerning imaging findings seriously.

4. Why Can a Single CT Scan Be Difficult to Interpret?

As we discussed earlier, conventional RECIST 1.1 criteria classify progressive disease when established measurements or other findings meet specific thresholds.

For example, the sum of target-lesion diameters may increase by at least 20% from the nadir, with an absolute increase of at least 5 millimeters.

Alternatively, unequivocal progression of non-target disease or the appearance of a new malignant lesion can establish progression.

These rules are valuable because they provide a standardized way to describe changes in measurable cancer.

However, they were not originally designed to account fully for the unusual response patterns sometimes observed with immunotherapy.

Consider two patients whose tumors become larger during treatment.

Patient A

The cancer is genuinely growing despite immunotherapy.

The treatment is no longer controlling the disease adequately.

Patient B

The initial enlargement is followed by tumor shrinkage while the patient continues receiving immunotherapy.

The initial findings may represent pseudoprogression.

At the first scan, both situations may look similar.

The difference becomes apparent only after considering subsequent imaging and the broader clinical course.

This creates an important challenge.

Doctors want to avoid stopping an effective treatment prematurely.

But they must also avoid continuing an ineffective treatment while the cancer progresses and potentially causes harm.

This challenge led researchers to develop response criteria specifically adapted to immunotherapy trials.

5. What Is iRECIST?

In 2017, an international working group published a framework called iRECIST.

The name stands for immune Response Evaluation Criteria in Solid Tumours.

It was developed primarily to standardize response assessment in clinical trials evaluating immunotherapies.

iRECIST builds upon conventional RECIST 1.1 but introduces an important distinction when disease progression is first identified.

Instead of treating every initial progression event as permanently confirmed, it allows certain findings to be classified as unconfirmed progression, pending further evaluation.

This does not mean that the progression is harmless or that treatment should automatically continue.

It means that the framework recognizes the possibility of atypical immune-related response patterns.

iUPD — Immune Unconfirmed Progressive Disease

Under iRECIST, the first imaging assessment that meets the conventional RECIST 1.1 criteria for progression is generally classified as:

iUPD — Immune Unconfirmed Progressive Disease.

This classification indicates that the imaging findings meet the criteria for progression, but progression has not yet been confirmed under the additional rules of iRECIST.

For example, a patient receiving immunotherapy might develop a sufficient increase in measurable tumor size to meet conventional progression criteria.

Under standard RECIST 1.1, this would be classified as Progressive Disease.

Under iRECIST, the initial finding would instead be labeled iUPD.

Importantly, iUPD does not mean pseudoprogression has been diagnosed.

It simply identifies a progression event that has not yet undergone the additional confirmation process.

iCPD — Immune Confirmed Progressive Disease

If a subsequent examination demonstrates additional progression according to the specific rules of iRECIST, the classification becomes:

iCPD — Immune Confirmed Progressive Disease.

For example, after an initial iUPD classification based on measurable tumor growth, further enlargement may confirm progression.

Additional new malignant lesions or further progression in other disease categories may also contribute to confirmation.

The exact requirements depend on which findings originally established iUPD and what changes occur afterward.

Importantly, a subsequent scan that does not show additional worsening does not automatically establish pseudoprogression.

Depending on the findings, the disease may remain classified as iUPD.

If the subsequent evaluation instead meets the applicable criteria for stable disease, partial response, or complete response, iRECIST can assign the corresponding response category without confirming progression.

Why Is This Distinction Important?

It allows clinical trials to document situations in which an initial appearance of progression is not followed by continued worsening.

This helps researchers evaluate immunotherapy response patterns more consistently.

However, iRECIST is primarily a research framework, not a universal instruction for treating individual patients.

Decisions about continuing treatment must still be made according to the patient's clinical situation.

6. When Might Doctors Consider Repeating Imaging Before Changing Treatment?

In selected circumstances, an oncology team may consider obtaining another imaging study after an initial finding of progression during immunotherapy.

Under the original iRECIST recommendations, clinical trials that permit treatment beyond iUPD generally recommend reassessment approximately 4 to 8 weeks later.

However, this approach is intended for appropriately selected patients.

A crucial consideration is whether the patient remains clinically stable.

What Does Clinically Stable Mean?

Clinical stability involves more than simply feeling reasonably well.

Doctors consider whether there has been:

• A meaningful deterioration in the patient's general condition or ability to perform daily activities.
• Worsening symptoms that may be related to cancer progression.
• Increasing pain or breathing difficulties.
• A need for substantially more treatment to control cancer-related symptoms.
• Other developments suggesting that continued disease growth could place the patient at risk.

A clinically stable patient with an initial finding of progression may, in selected circumstances, be considered for close reassessment.

But even in this situation, the decision depends on the cancer type, treatment being used, extent of progression, available alternatives, and other clinical factors.

When Might Waiting Be Dangerous?

Imagine a patient receiving immunotherapy whose scan shows tumor enlargement.

At the same time, the patient develops rapidly worsening shortness of breath, significant pain, or neurological symptoms.

In this situation, assuming that the imaging changes represent pseudoprogression could be dangerous.

Progression involving critical organs or anatomical structures may require urgent evaluation and treatment.

Continuing an ineffective therapy could also delay access to another potentially beneficial treatment.

For these reasons, the possibility of pseudoprogression should never be used to dismiss worsening symptoms.

Patients should not continue or discontinue immunotherapy based on their own interpretation of scan findings.

These decisions require individualized assessment by the treating oncology team.

7. Two Patients, Two Very Different Outcomes

Let's return to our fictional patients.

Both are receiving immune checkpoint inhibitor treatment for advanced cancer.

Both have two measurable tumors.

Before treatment, their combined target-lesion measurement is:

70 mm

At the first follow-up examination, the combined measurement increases to:

90 mm

This represents an increase of approximately 28.6% from baseline, with an absolute increase of 20 mm.

Assuming baseline is also the nadir, these measurements meet conventional RECIST 1.1 criteria for progression.

Under iRECIST, the initial finding can be classified as iUPD.

Now imagine two different possible outcomes.

Scenario A — True Progression

The patient's next scan shows that the combined tumor measurement has increased further.

Additional findings also support continued cancer growth.

The subsequent examination meets the relevant criteria for confirmed progression.

In this situation, the imaging pattern is consistent with genuine disease progression despite treatment.

The oncology team must reassess the strategy and determine what treatment options remain appropriate.

Scenario B — Possible Pseudoprogression

The patient remains clinically stable.

After carefully considering the clinical circumstances, the oncology team continues immunotherapy with close monitoring.

On the next scan, the combined tumor measurement decreases substantially.

The disease now meets the applicable criteria for Partial Response.

Because the initial apparent progression was followed by a response without changing the anticancer treatment, this evolution is compatible with pseudoprogression.

However, the initial scan alone could not have established that conclusion.

What Do These Scenarios Teach Us?

The initial imaging results were similar.

The subsequent clinical courses were not.

The possibility of pseudoprogression becomes clearer through the pattern of change over time, not through one isolated measurement.

These examples are simplified educational scenarios.

They do not mean that patients with similar measurements should receive identical treatment decisions.

8. Can New Lesions Also Be Part of Pseudoprogression?

Yes.

Pseudoprogression does not necessarily involve enlargement of previously identified tumors alone.

In some reported cases, new lesions have appeared during immunotherapy and were followed by subsequent tumor regression or disease control.

However, this situation requires particular caution.

A new lesion that is unequivocally malignant represents progression under conventional RECIST 1.1.

Under iRECIST, its initial appearance may establish iUPD, with additional evaluation used to determine whether progression becomes confirmed.

This distinction allows researchers to capture atypical patterns without immediately treating every initial progression event as definitive under the immunotherapy-specific framework.

However, the appearance of new malignant lesions must always be taken seriously.

A new lesion cannot be assumed to represent immune-related inflammation simply because the patient is receiving immunotherapy.

Its location, appearance, clinical significance, and subsequent evolution all matter.

9. Can Doctors Use Other Tests to Distinguish Pseudoprogression From True Progression?

Sometimes, additional investigations may help clarify an uncertain situation.

However, no single routinely used test can reliably distinguish pseudoprogression from true progression in every patient.

Additional Imaging

Doctors may compare multiple CT or MRI examinations to evaluate how lesions change over time.

In selected circumstances, additional imaging techniques may provide useful information.

However, inflammation and active cancer can sometimes produce overlapping imaging findings.

For example, increased metabolic activity on a PET scan may occur in both malignant tissue and inflammatory processes.

Therefore, PET imaging does not universally resolve the uncertainty.

Biopsy

Occasionally, a biopsy may be considered if obtaining tissue would meaningfully influence clinical management.

A tissue sample may reveal cancer cells, inflammatory infiltrates, or treatment-related changes.

However, biopsies have limitations.

A sample represents only a portion of the lesion.

Different areas of the same tumor may contain different proportions of viable cancer and inflammatory tissue.

Some lesions are also difficult or unsafe to biopsy.

Consequently, biopsy is not routinely required to establish pseudoprogression.

Blood Tests and Tumor Markers

Laboratory tests and selected tumor markers may contribute additional clinical information in certain cancers.

However, their changes are not sufficiently reliable to establish pseudoprogression across all malignancies.

Research is also investigating whether circulating tumor DNA and other molecular tools could help distinguish treatment response from progression.

These approaches are promising in selected contexts, but they are not universally validated for this specific purpose.

The interpretation usually requires combining imaging findings, the patient's clinical course, the characteristics of the cancer, and the treatment being administered.

10. Does Pseudoprogression Mean Immunotherapy Is Working Better?

Not necessarily.

Although pseudoprogression can be followed by a favorable treatment response, its occurrence does not automatically establish a better prognosis.

It also does not mean that patients must experience pseudoprogression for immunotherapy to be effective.

Many patients who benefit from immune checkpoint inhibitors never experience this phenomenon.

Their tumors may shrink without any initial enlargement.

Others may experience prolonged disease control without substantial tumor shrinkage.

And some patients may not benefit from immunotherapy despite receiving an appropriate treatment.

The effectiveness of immunotherapy cannot be determined simply by whether pseudoprogression occurs.

Pseudoprogression is an unusual response pattern, not a requirement for treatment success.

11. What Should Patients Ask Their Oncology Team?

If imaging suggests cancer progression during immunotherapy, patients may find it helpful to ask:

"Do my scans meet established criteria for progression?"

Understanding whether the findings represent definite progression or remain uncertain can help clarify the discussion.

"Could pseudoprogression be considered in my situation?"

The answer depends on the type of cancer, treatment, clinical condition, and imaging findings.

"How does my overall condition influence the decision?"

Symptoms and functional status are essential considerations.

"Would another scan provide useful information?"

In selected situations, additional imaging may help clarify the pattern of response.

"What are the risks of continuing treatment compared with changing it?"

This question helps bring the discussion back to the patient's overall treatment goals.

"Are there symptoms that should prompt me to contact the oncology team immediately?"

Patients should understand which changes require attention before the next scheduled evaluation.

These conversations can help patients participate more confidently in decisions without feeling responsible for independently interpreting complex imaging results.

The Key Takeaway

During treatment with certain immunotherapies, cancer can occasionally appear to worsen on imaging before later showing a response or disease control.

This phenomenon is called pseudoprogression.

It may involve temporary enlargement of existing lesions or the appearance of new lesions.

However, pseudoprogression is uncommon.

An initial scan cannot reliably distinguish it from genuine cancer progression.

iRECIST provides a standardized framework used primarily in clinical trials to evaluate these unusual response patterns, including the distinction between unconfirmed and confirmed progression.

In carefully selected, clinically stable patients, an oncology team may consider continued treatment with close reassessment when appropriate.

But this is not a universal approach.

True cancer progression is more common than pseudoprogression, and delaying necessary treatment changes can be harmful.

The most important lesson is that imaging findings must always be interpreted alongside the patient's symptoms, overall condition, cancer characteristics, and treatment goals.

And although pseudoprogression can occur, it should never be assumed simply because a tumor becomes larger during immunotherapy.

08. Does Every Type of Cancer Respond in the Same Way?

So far, we have explored how doctors use imaging studies and standardized measurements to determine whether cancer is responding to treatment.

We have also learned about RECIST 1.1, a widely used system that classifies treatment response based on changes in measurable tumors.

But this raises another important question:

Can doctors use the same measurements to evaluate every type of cancer?

The answer is no.

Different cancers can behave differently, affect different tissues, and respond to treatment in ways that cannot always be captured by measuring tumor size alone.

For example, a tumor in the liver may become smaller during effective treatment.

A bone metastasis may become denser without shrinking.

A lymphoma may leave behind a visible mass even after its metabolic activity has disappeared.

And a brain tumor may produce imaging changes that are difficult to distinguish from the effects of radiation treatment.

The best way to evaluate cancer treatment depends partly on the type of cancer, where it is located, and how it responds to therapy.

Let's explore some important examples.

1. Bone Metastases: When Cancer Response Is Difficult to Measure

Bone metastases occur when cancer cells spread from their original location to the bones.

They can develop in several types of cancer, including breast, prostate, and lung cancer.

However, bone metastases do not always behave like tumors located in soft tissues.

Some cause destruction of normal bone.

Others stimulate the formation of abnormal new bone.

And some produce a combination of both processes.

Doctors often describe these patterns using two terms:

Osteolytic lesions: areas in which cancer is associated with bone destruction.

Osteoblastic or sclerotic lesions: areas associated with increased bone formation or density.

These differences are important because changes in bone density do not necessarily correspond directly to changes in the amount of active cancer.

Why Are Bone Metastases Difficult to Measure?

Under RECIST 1.1, many bone metastases cannot be used as measurable target lesions.

For example, purely osteoblastic lesions are considered non-measurable.

However, certain osteolytic or mixed bone lesions may qualify as measurable if they contain a clearly identifiable soft-tissue component that meets the appropriate measurement requirements.

This means that doctors cannot simply apply the same diameter measurements to every bone metastasis.

When Healing Can Look Like Worsening

Consider a patient with metastatic breast cancer involving the bones.

Before treatment, a CT scan shows an area of bone destruction caused by a metastasis.

After treatment, the same area becomes denser and appears more sclerotic.

Does this necessarily mean that the cancer has progressed?

Not necessarily.

In certain situations, increased sclerosis may reflect a healing response as bone tissue reacts to successful treatment.

This can sometimes create a confusing appearance on follow-up imaging.

Similarly, bone scans may demonstrate temporarily increased uptake or more conspicuous lesions during a healing reaction.

This phenomenon is often called bone flare.

Bone flare is not the same phenomenon as the immune-related pseudoprogression discussed in the previous section.

It reflects the complex relationship between bone remodeling, healing, and the imaging techniques used to assess skeletal disease.

However, increased sclerosis or bone-scan activity cannot automatically be interpreted as healing.

Genuine disease progression can sometimes produce similar findings.

Doctors consider the pattern of changes, previous imaging, symptoms, laboratory results, and the overall clinical situation.

A bone lesion that looks different after treatment is not necessarily a bone lesion that contains more active cancer.

This is one reason bone metastases often require a more specialized approach to response assessment.

2. Brain Tumors: Why MRI Requires Special Interpretation

Primary brain tumors present another important challenge.

The brain has unique anatomical characteristics, and tumor-related changes can affect both the brain tissue itself and the surrounding structures.

MRI is particularly important when evaluating many brain tumors.

However, interpreting changes on MRI can be complicated.

For example, a contrast-enhancing area may become larger because of tumor progression.

But changes in contrast enhancement can also occur following radiation therapy or other treatments.

Treatment-related inflammation, alterations in the blood-brain barrier, and tissue injury can influence the appearance of the affected area.

What Is RANO?

For certain brain tumors, particularly gliomas, researchers developed specialized criteria known as:

RANO — Response Assessment in Neuro-Oncology.

The updated RANO 2.0 framework incorporates features specific to glioma assessment.

Depending on the tumor type and clinical context, these may include:

• Changes in tumor measurements on MRI.
• Contrast-enhancing and selected non-enhancing tumor components.
• The patient's neurological condition.
• Corticosteroid use.
• The timing and effects of previous treatments.

These factors help interpret changes that may not be adequately described using conventional RECIST measurements.

An Important Example: Changes After Radiotherapy

Consider a patient who has received surgery, radiation therapy, and systemic treatment for a glioma.

A follow-up MRI shows an increase in contrast enhancement near the treated area.

This finding may raise concern for tumor progression.

However, treatment-related changes can sometimes create a similar appearance.

In particular, pseudoprogression following radiation-based treatment can complicate the interpretation of early follow-up imaging.

This situation is related to treatment effects in brain tissue and should not automatically be considered identical to the immune-related pseudoprogression discussed earlier.

Depending on the circumstances, doctors may need additional imaging, further observation, or other investigations to clarify the findings.

In brain tumors, a change in MRI appearance does not always provide a straightforward answer about tumor activity.

The appropriate interpretation depends on the type of tumor, treatment history, imaging characteristics, and clinical condition.

3. Lymphoma: When Metabolic Activity Matters More Than Tumor Size

Lymphoma is a type of cancer that develops from cells of the lymphatic system.

Unlike many solid tumors, certain lymphomas are particularly well suited to response assessment using metabolic imaging.

One commonly used technique is:

FDG-PET/CT.

This examination combines anatomical information from CT with metabolic information obtained using a radioactive glucose-like tracer called FDG.

Many lymphoma cells demonstrate increased uptake of this tracer.

However, inflammatory and other non-malignant processes can also produce FDG uptake, so the findings must be interpreted carefully.

Why Can a Mass Remain Visible After Successful Treatment?

Imagine a patient with lymphoma who has a large mass in the chest before treatment.

After completing therapy, the mass becomes smaller but does not disappear completely.

On a CT scan, some tissue remains visible.

Does this necessarily mean that active lymphoma is still present?

No.

The remaining tissue may include scar tissue, fibrosis, or other changes following treatment.

In appropriate types of lymphoma, PET imaging can help determine whether the residual mass continues to demonstrate abnormal metabolic activity.

A patient may therefore have a persistent anatomical mass but meet the criteria for Complete Metabolic Response.

What Is the Lugano Classification?

The Lugano classification provides standardized approaches to staging and evaluating treatment response in lymphoma.

For many FDG-avid lymphomas, it incorporates PET/CT findings and a scoring method called the Deauville five-point scale.

The scale compares FDG uptake in suspected lymphoma sites with reference activity in normal tissues, including the mediastinum and liver.

This helps classify metabolic response.

For example, under conventional Lugano criteria, a Deauville score of 1, 2, or 3 generally corresponds to a complete metabolic response in the appropriate clinical context, even when a residual mass remains visible.

However, not every lymphoma is assessed using PET in the same way.

The most appropriate evaluation depends on the lymphoma subtype, its FDG avidity, treatment, and clinical circumstances.

A visible residual mass does not always mean that active cancer remains.

This is one of the clearest examples of why tumor size alone cannot fully describe treatment response.

4. Prostate Cancer: Why Bone Scans, PSA, and Imaging Must Be Considered Together

Prostate cancer provides another important example.

Advanced prostate cancer frequently involves the bones.

As we discussed earlier, many bone metastases are difficult to measure using conventional RECIST criteria.

This creates particular challenges when monitoring treatment response.

The Role of PSA

PSA, or Prostate-Specific Antigen, is a blood marker commonly used in the management of prostate cancer.

In appropriate settings, changes in PSA can provide valuable information about disease activity.

For example, a substantial PSA decrease during systemic treatment may be encouraging.

However, PSA does not always reflect the complete behavior of the cancer.

Some patients may experience important changes in imaging or symptoms that are not accurately represented by PSA alone.

Conversely, an isolated PSA increase does not necessarily establish that treatment should be stopped immediately.

PSA is an important monitoring tool, but it is not a complete measure of treatment effectiveness.

Why Are Bone Scans Sometimes Difficult to Interpret?

Bone scans detect changes in bone activity rather than directly measuring cancer cells.

After treatment, healing reactions can sometimes make bone lesions appear more active or reveal areas that were previously less conspicuous.

This is another example of bone flare.

In certain settings, researchers use specific confirmation rules to help distinguish these effects from genuine progression.

What Is PCWG?

The Prostate Cancer Clinical Trials Working Group developed recommendations for evaluating treatment outcomes in advanced prostate cancer.

The PCWG3 framework, for example, addresses several important dimensions of treatment evaluation, including:

• PSA changes.
• Radiological progression.
• Bone metastases.
• Symptoms and clinical status.
• The distinction between documented progression and the point at which treatment is no longer providing sufficient clinical benefit.

These recommendations are particularly relevant to clinical trials involving castration-resistant prostate cancer.

They do not mean that every patient with prostate cancer requires the same imaging schedule or monitoring strategy.

Rather, they illustrate why doctors need to consider several sources of information when evaluating this disease.

5. Sometimes Treatment Changes the Tumor Without Making It Much Smaller

There is another reason measuring tumor size alone may not tell the whole story.

Some treatments can produce important changes in the internal characteristics of tumors without causing an immediate or proportional reduction in their dimensions.

A tumor may become less metabolically active.

Its density may change.

Parts of the tumor may become necrotic.

Or the surrounding tissues may respond to treatment in ways that affect its appearance.

These changes are particularly relevant in selected tumor types and treatment settings.

For example, certain gastrointestinal stromal tumors, known as GISTs, can demonstrate changes in CT density during effective targeted therapy before a substantial reduction in size becomes apparent.

Specialized approaches, such as Choi criteria, have been developed to evaluate these characteristics in appropriate contexts.

However, these alternative criteria are not applicable to every cancer or treatment.

Changes in density, metabolism, or tissue characteristics do not automatically prove that a tumor is responding.

The appropriate interpretation depends on the specific cancer and the evidence supporting the assessment method.

Different treatments may produce different patterns of response, and different cancers may require different tools to evaluate them.

6. Does This Mean RECIST Is Not Useful?

Not at all.

RECIST 1.1 remains an important, widely established system for standardized assessment of treatment response in many solid tumors.

Its strengths include providing consistent definitions and allowing investigators to compare treatment activity across appropriately designed clinical studies.

However, like every medical tool, it has limitations.

It was not designed to capture every possible biological change occurring within every cancer.

It also does not independently establish how a treatment affects survival, quality of life, or other outcomes important to patients.

Specialized response criteria exist because some diseases require additional information or different methods of assessment.

The central principle remains the same:

Doctors choose the most appropriate way to evaluate treatment based on the cancer, the treatment, and the clinical situation.

The Key Takeaway

Not every cancer responds to treatment in the same way.

And not every cancer can be evaluated using the same measurements.

Bone metastases may demonstrate healing changes that complicate imaging interpretation.

Brain tumors may produce MRI changes related to both cancer and treatment effects.

Certain lymphomas can achieve complete metabolic response even when a residual mass remains visible.

Prostate cancer often requires integrating PSA, imaging, symptoms, and specialized assessment of bone disease.

And some treatments can change tumor characteristics without producing substantial early shrinkage.

These examples illustrate an important lesson:

Tumor size is valuable information, but it does not always tell the complete story of treatment response.

This is why oncologists use different assessment methods for different diseases and why clinical judgment remains essential.

But there is another question that deserves careful explanation.

What happens when doctors say that cancer has completely disappeared?

Does a Complete Response mean the same thing as remission?

What does No Evidence of Disease actually mean?

And when can we say that cancer has been cured?

These expressions are often used interchangeably, but their meanings are not always identical.

Understanding the differences can help patients interpret some of the most important conversations they will have during cancer care.

09. Does Complete Response Mean Cancer Is Cured?

Imagine receiving the results of your latest cancer tests.

Your oncologist looks at you and says:

"We can no longer detect any evidence of your cancer."

For many patients, these are words they have been hoping to hear since the day of their diagnosis.

They may bring enormous relief, excitement, and hope.

But they can also raise another question:

"Does this mean I'm cured?"

The answer depends on several factors, including the type of cancer, the treatment received, the tests performed, and how the disease behaves over time.

During cancer care, patients may encounter expressions such as:

Complete Response.

Complete Remission.

No Evidence of Disease.

Cancer-free.

Cured.

These terms are sometimes used interchangeably in everyday conversations.

Some genuinely overlap in their medical definitions.

Others describe different aspects of cancer treatment and recovery.

Understanding these distinctions can help patients interpret encouraging results without misunderstanding what those results can—and cannot—tell us.

1. Complete Response: When Cancer Is No Longer Detectable After Treatment

A Complete Response (CR) means that the detectable signs of cancer have disappeared in response to treatment, according to the assessment methods being used.

For example, imagine a patient receiving systemic treatment for metastatic cancer.

Before treatment, CT scans show several measurable tumors.

During treatment, those tumors become progressively smaller.

Eventually, follow-up imaging no longer identifies the previously visible cancer.

If the remaining assessments also meet the applicable response criteria, the oncology team may describe this result as a Complete Response.

This can be an excellent outcome.

However, there is an important limitation.

A Complete Response does not necessarily mean that every cancer cell has been eliminated.

Medical tests can identify cancer only within the limits of their sensitivity.

Cancer cells may occasionally remain at levels too small to be detected by the assessments performed.

This does not mean that microscopic disease is always present after a complete response.

It means that the available tests cannot establish its absence with absolute certainty.

Complete Radiological Response

When doctors specifically refer to a complete radiological response, they are describing the disappearance of detectable cancer findings according to the imaging criteria being used.

For example, under RECIST 1.1, Complete Response requires the disappearance of target lesions, appropriate resolution of non-target disease, and no new malignant lesions.

Previously abnormal lymph nodes are assessed using specific measurement requirements.

Importantly, a complete radiological response is based on imaging.

It does not necessarily mean that a pathologist has examined tissue and confirmed the absence of cancer cells.

Radiological response describes what imaging can demonstrate, not necessarily everything that may be happening at the microscopic level.

2. Complete Remission: Is It Different From Complete Response?

This is where cancer terminology can become confusing.

The expressions Complete Response and Complete Remission are frequently used as synonyms.

In fact, the National Cancer Institute defines them interchangeably.

Both generally describe the disappearance of detectable signs of cancer following treatment.

However, their use can vary according to the type of cancer and the clinical setting.

For example, oncologists treating solid tumors may frequently describe treatment results using response categories such as CR, PR, SD, and PD.

In hematological cancers, including leukemias and certain lymphomas, the term remission is particularly common.

The exact criteria used to establish remission may differ between diseases.

For example, complete remission in leukemia may involve specific findings in blood and bone marrow, rather than relying on CT measurements.

Therefore, although Complete Response and Complete Remission often mean the same thing conceptually, the tests and criteria used to establish them may be different.

The important question is not simply which term your doctor uses, but what examinations and findings support that conclusion.

And remember:

Complete Remission does not automatically mean cure.

3. Partial Remission: When Cancer Has Improved but Has Not Completely Disappeared

The term Partial Remission describes a reduction in the signs or manifestations of cancer without their complete disappearance.

It is closely related to the concept of Partial Response.

However, the precise meaning depends on the disease and the response criteria being used.

For measurable solid tumors evaluated using RECIST 1.1, Partial Response requires at least a 30% reduction in the sum of target-lesion diameters compared with baseline, provided the other response requirements are satisfied.

But this numerical threshold should not be applied to every use of the expression partial remission.

For example, hematological cancers may use different laboratory, pathological, or disease-specific criteria.

An Example

A patient begins treatment with several measurable tumors.

After treatment, the tumors become significantly smaller but remain detectable.

The patient may meet the criteria for Partial Response.

This means that treatment has produced a measurable reduction in cancer burden.

It does not mean that the cancer has disappeared completely.

And, as we discussed earlier, tumor shrinkage alone does not establish the full clinical benefit of treatment.

4. No Evidence of Disease (NED): What Does It Actually Mean?

Another expression patients may hear is:

"No Evidence of Disease."

Often abbreviated as NED, this means that the evaluations performed do not currently identify evidence of cancer.

It describes what doctors can establish based on the available examinations.

However, NED is not necessarily the same as a formal RECIST Complete Response.

Consider Two Different Patients

Patient A: After Surgery

A patient is diagnosed with localized colon cancer.

The tumor is surgically removed.

Subsequent evaluation reveals no evidence of remaining or metastatic disease.

The oncology team may describe the patient as having No Evidence of Disease.

However, the patient has not necessarily experienced a radiological Complete Response to systemic treatment.

There was no measurable tumor left for that treatment to shrink.

Depending on the stage and other risk factors, additional treatment may still be recommended to reduce the risk of recurrence.

Patient B: After Systemic Treatment

Another patient has measurable metastatic cancer.

After receiving systemic therapy, the previously detectable lesions disappear.

The patient meets the relevant criteria for Complete Response.

In appropriate circumstances, the oncology team may also describe the current status as No Evidence of Disease.

Both patients may be considered NED, despite reaching that status through very different clinical situations.

Does NED Mean Cancer Cannot Return?

No.

NED means that cancer is not currently detectable using the evaluations performed.

It does not provide an absolute guarantee that recurrence is impossible.

However, this distinction should not diminish the importance of achieving NED.

For many patients, particularly those treated for localized cancer with curative intent, remaining free of detectable disease is an important and encouraging outcome.

NED describes the present assessment. The likelihood of remaining disease-free depends on the individual cancer and its clinical characteristics.

5. Pathological Complete Response (pCR): What Can Tissue Tell Us?

So far, we have discussed response based mainly on clinical examinations and imaging.

But sometimes, doctors can examine tissue after cancer treatment.

This provides another way to evaluate response.

A Pathological Complete Response (pCR) means that no residual cancer is identified according to the pathological criteria applied to tissue examined after treatment.

This concept is particularly relevant when patients receive treatment before surgery, known as neoadjuvant treatment.

An Example: Breast Cancer

Imagine a patient diagnosed with breast cancer who receives chemotherapy, sometimes combined with other systemic treatments, before surgery.

The purpose may include treating microscopic disease and reducing the size or extent of the tumor.

After completing the preoperative treatment, the patient undergoes surgery.

A pathologist examines the removed breast tissue and, when applicable, the regional lymph nodes.

The examination determines whether residual cancer remains.

In breast cancer, one commonly used definition of pCR is:

No residual invasive cancer in the breast or sampled regional lymph nodes after neoadjuvant treatment.

Under this definition, residual ductal carcinoma in situ may still be present.

This is sometimes described using the pathological classification ypT0/is ypN0.

Importantly, different studies and clinical settings may use slightly different definitions of pCR.

Why Is pCR Important?

In several breast cancer settings, achieving a pCR is associated with more favorable long-term outcomes.

This association is particularly relevant in certain biologically aggressive subtypes, including triple-negative and HER2-positive breast cancers.

However, the prognostic significance varies across cancer subtypes and treatment contexts.

Does pCR Mean Cure?

Not necessarily.

A pCR provides important information about the tissue examined after treatment.

But it cannot always exclude malignant cells that may exist outside the surgically evaluated area.

Patients who achieve pCR can still experience cancer recurrence, although their risk may be lower in certain clinical contexts.

Likewise, patients who do not achieve pCR are not necessarily destined to experience recurrence.

Pathological response contributes valuable prognostic information, but it does not predict an individual patient's future with certainty.

6. Curative Intent: Treating Cancer With the Goal of Cure

Another expression that deserves careful explanation is Curative Intent.

This describes the purpose of a treatment rather than a response category.

When doctors recommend treatment with curative intent, their objective is to eliminate the cancer and achieve a cure.

For example, a patient with localized cancer may undergo surgery with curative intent.

Another patient may receive a combination of chemotherapy and radiation therapy intended to eradicate the disease.

In some situations, systemic treatment is given before or after surgery as part of an overall curative strategy.

Does Curative Intent Mean Cure Is Guaranteed?

No.

A treatment can be administered with the goal of cure even when there is a possibility that the cancer may return.

The probability of achieving cure depends on several factors, including:

• The type and stage of cancer.
• Its biological characteristics.
• The effectiveness of available treatments.
• The patient's overall clinical situation.
• The presence or absence of disease after treatment.
• The subsequent course over time.

The distinction is important:

Curative Intent describes what treatment is trying to achieve. Cure describes the outcome we hope to accomplish.

These concepts should not be confused.

7. What Does It Mean to Be Cured of Cancer?

The word cure carries enormous emotional significance.

It is also a concept that requires careful interpretation in oncology.

Broadly, curing cancer means successfully eliminating the disease so that it will not return.

And it is important to say something clearly:

Many cancers can be cured.

Some patients are cured through surgery alone.

Others are cured through radiation therapy, systemic treatment, or combinations of different approaches.

The possibility of cure depends heavily on the type of cancer and the clinical circumstances.

However, determining whether a particular patient has been cured is not always straightforward.

Why Is Cure Sometimes Difficult to Establish?

Even when treatment has eliminated all detectable cancer, doctors may not be able to prove immediately that recurrence will never occur.

Medical tests have detection limits.

And certain cancers can recur months or years after treatment.

For this reason, the likelihood of cure is often assessed using information about the cancer's natural history, treatment outcomes, and the length of time a patient remains free of recurrence.

In some cancers, the probability of recurrence becomes very low after a prolonged disease-free interval.

In other cancers, a meaningful risk of late recurrence can persist for many years.

Therefore, there is no universal timeline that establishes cure for every cancer.

What About the Five-Year Rule?

Patients sometimes hear that if cancer has not returned after five years, they are considered cured.

But this is an oversimplification.

Five-year survival statistics are commonly used in oncology research.

However, being alive five years after diagnosis is not the same as being cured.

And remaining free of detectable disease for five years does not establish an identical recurrence risk across all cancers.

For some malignancies, a prolonged disease-free interval is strongly associated with a very low probability of recurrence.

For others, particularly certain hormone receptor-positive breast cancers, the risk of recurrence can extend beyond five years.

This is why doctors interpret disease-free intervals according to the specific cancer rather than applying one universal rule.

Can Doctors Ever Say That Someone Is Cured?

Yes.

Depending on the diagnosis, treatment history, and long-term course, physicians may reasonably consider a patient cured.

However, the degree of certainty and the terminology used vary across cancer types and clinical circumstances.

The inability to guarantee the future with absolute certainty does not mean that cure is impossible.

Cure is a genuine outcome of cancer treatment, even though medicine cannot always establish it immediately or with absolute certainty.

8. What About Measurable Residual Disease (MRD)?

There is another concept that helps explain why a patient can appear to have no detectable cancer while more sensitive tests may still identify evidence of disease.

It is called Measurable Residual Disease, or MRD.

The term minimal residual disease is also commonly encountered.

MRD testing uses specialized methods to detect very small amounts of remaining cancer that may not be identified by conventional assessments.

It is particularly well established in selected hematological malignancies, including certain leukemias.

For example, a patient with leukemia may achieve complete remission according to standard blood and bone marrow criteria.

However, specialized molecular or flow cytometry testing may still detect residual malignant cells.

This can provide additional information about disease status and prognosis.

Does MRD-Negative Mean Cure?

Not necessarily.

An MRD-negative result means that residual cancer was not detected by the particular test used, at that time, within the limits of its sensitivity.

It does not universally establish that every malignant cell has been eliminated.

The significance of MRD testing depends on the type of cancer, testing method, and clinical setting.

In solid tumors, circulating tumor DNA is being investigated and increasingly used in selected settings to identify molecular evidence of residual disease.

However, the clinical role of these approaches varies considerably.

Not every MRD or circulating tumor DNA assay has been validated to guide treatment decisions.

And a negative result should not automatically be interpreted as proof of cure.

More sensitive tests can provide additional information, but every test still has limitations.

9. Why Do Patients Still Need Follow-Up After a Complete Response or NED?

This is one of the most important practical questions.

If the cancer is no longer detectable, why are additional appointments or examinations sometimes necessary?

The answer is that follow-up serves several purposes.

Monitoring for Recurrence

For patients who have completed treatment with curative intent, follow-up may help identify evidence of cancer recurrence when appropriate.

The recommended examinations depend on the type of cancer, the treatments received, and the evidence supporting different surveillance strategies.

Not every patient requires frequent CT scans or tumor-marker testing.

Managing Long-Term Treatment Effects

Some treatments can produce side effects that persist or develop after treatment has finished.

Follow-up care provides an opportunity to identify and manage these problems.

Supporting Recovery and Survivorship

Cancer survivorship involves more than checking whether cancer has returned.

It may include managing fatigue, physical rehabilitation, emotional well-being, cardiovascular health, fertility concerns, and other aspects of long-term health.

Follow-up can also address the risk of second primary cancers and recommended screening, when relevant.

Why Follow-Up Is Not a Sign That Doctors Expect Cancer to Return

The need for follow-up does not necessarily mean that recurrence is likely.

Surveillance is part of responsible cancer care.

Its frequency and duration should be adapted to the individual cancer and patient.

Being followed after cancer treatment does not mean that treatment has failed or that recurrence is inevitable.

10. Different Terms, Different Questions

Let's bring these concepts together.

Although some expressions overlap, they do not all answer the same question.

Complete Response

Did the detectable cancer disappear in response to treatment?

Complete Remission

Have the detectable signs of cancer disappeared?

This term is often synonymous with Complete Response.

Partial Remission

Has the cancer improved without disappearing completely?

No Evidence of Disease

Can doctors currently detect any cancer using the examinations performed?

Pathological Complete Response

Does the tissue examined after treatment meet the criteria for absence of residual cancer?

Curative Intent

Was the treatment designed to eliminate the cancer and achieve cure?

Cure

Has the cancer been successfully eradicated so that it will not return?

These questions are related, but they are not interchangeable.

And the terminology alone cannot describe every aspect of a patient's condition.

A patient may be NED after surgery without ever having measurable disease that could be assessed for response to systemic treatment.

Another patient may achieve complete radiological response during treatment for metastatic cancer.

A third may achieve pathological complete response after neoadjuvant treatment.

All three results may be encouraging.

But they describe different clinical situations and may have different implications for prognosis and follow-up.

The Key Takeaway

Hearing that cancer is no longer detectable can be an extraordinary moment.

It may represent a major treatment achievement and an important step forward.

But understanding exactly what that result means requires distinguishing several related concepts.

Complete Response and Complete Remission generally describe the disappearance of detectable signs of cancer following treatment.

No Evidence of Disease describes a current state in which cancer cannot be detected by the examinations performed.

Pathological Complete Response describes findings in tissue evaluated after treatment, according to specific pathological criteria.

Curative Intent describes the goal of treatment.

Cure describes the successful eradication of cancer.

These terms may overlap, but they are not always interchangeable.

And none of the tests used to evaluate cancer can predict every patient's future with absolute certainty.

However, uncertainty should not overshadow an important reality:

Many patients are cured of cancer, and many others achieve meaningful, sometimes prolonged periods of remission or disease control.

The most useful question to ask your oncology team is:

"What does this result mean for my particular type of cancer, and what should I expect next?"

Understanding the answer can help patients recognize the significance of their treatment results while making informed decisions about ongoing care.

10. Questions to Ask Your Oncology Team

Understanding whether cancer treatment is working can be complicated.

A CT scan may show that tumors are shrinking, but that does not always tell the complete story.

A report of stable disease may be encouraging in one situation and less reassuring in another.

And even when cancer is no longer detectable, questions about treatment, follow-up, and the future may remain.

The good news is that you do not need to understand every medical measurement or response criterion to have a meaningful conversation with your oncology team.

Knowing which questions to ask can help you better understand your results and what they mean for your care.

1. Understanding the Goal of Treatment

"What are we hoping this treatment will achieve?"

This is one of the most important questions you can ask.

Is the goal to cure the cancer?

Reduce the risk of recurrence?

Control the disease for as long as possible?

Improve symptoms or quality of life?

Understanding the original goal helps you interpret future treatment results.

"How will we know whether we are achieving that goal?"

Depending on your situation, your oncology team may evaluate imaging findings, symptoms, blood tests, pathological results, or other outcomes.

If you are receiving treatment after surgery and there is no visible cancer remaining, your team can explain how treatment benefit is assessed when there is no tumor to measure.

2. Understanding Your Scan Results

"What has changed compared with my previous scans?"

Ask whether the cancer has become smaller, remained stable, or increased in size.

Your oncologist can explain which findings are most important.

"Are we comparing this scan with my first scan or with my best previous response?"

This question is particularly relevant when you have been receiving treatment for an extended period.

A tumor may still be smaller than it was before treatment but have grown compared with its smallest previous measurement.

"Does my scan show Complete Response, Partial Response, Stable Disease, or Progressive Disease?"

If these categories apply to your cancer, your oncology team can explain which classification best describes the findings.

Remember that not every cancer is evaluated using conventional RECIST criteria.

"Are all areas of cancer behaving similarly?"

Sometimes, different tumors respond differently.

Some may shrink while others remain stable or grow.

Understanding these differences can help clarify the overall assessment.

3. Understanding What the Results Mean

"Is this result encouraging for my particular type of cancer?"

A response classification is not the same as a prediction of what will happen next.

The significance of your results depends on your cancer, the treatment being used, and your overall clinical situation.

"If my cancer is stable, what does that mean for me?"

Stable disease can represent meaningful disease control in certain circumstances.

Your oncologist can explain how long the cancer has remained stable and whether the current treatment appears to be helping achieve its intended goals.

"If my tumors are growing, how certain are we that this represents progression?"

Imaging changes sometimes require additional interpretation.

Your oncology team can explain whether the findings are clear, whether further investigation is necessary, and what the results mean for treatment.

If you are receiving immunotherapy, they can also explain whether unusual response patterns are relevant to your situation.

4. Understanding the Next Steps

"Do these results change my treatment plan?"

A scan result may support continuing treatment, modifying it, or considering another approach.

The decision depends on more than tumor measurements alone.

"What are the benefits and risks of continuing the current treatment?"

This question is particularly important when treatment is controlling the cancer but causing significant side effects.

You and your oncology team can discuss the balance between disease control, treatment tolerability, and quality of life.

"When will we evaluate my cancer again, and why?"

Understanding the follow-up schedule can help you know what to expect.

The timing of scans and other tests depends on the cancer type, treatment, previous findings, and clinical circumstances.

"What symptoms should prompt me to contact the oncology team before my next appointment?"

Do not assume that important changes can wait until the next scheduled scan.

Ask your team which symptoms require prompt attention and how to contact them if a problem develops.

5. Understanding Remission and Long-Term Expectations

"If my cancer is no longer detectable, what does that mean in my situation?"

Your oncology team can explain whether your results represent Complete Response, Complete Remission, No Evidence of Disease, or another disease-specific assessment.

"Does this change my treatment or follow-up plan?"

Some patients require additional treatment or surveillance even when no cancer is detectable.

Others may have completed their planned cancer treatment.

The appropriate approach depends on the individual circumstances.

"What can we say about the possibility of cure or recurrence?"

This can be a difficult question, but it is an important one.

Your oncologist can explain what is known about your type of cancer, which factors influence prognosis, and what remains uncertain.

You may also choose how much prognostic information you would like to discuss.

There is no requirement to explore every uncertainty in a single appointment.

A Simple Way to Prepare for Your Appointment

Before your next oncology visit, consider writing down three things:

1. What has changed since my last appointment?

Think about symptoms, energy levels, daily activities, and any new concerns.

2. What do I most want to understand about my results?

This might be a measurement, a medical term, or what the latest scan means for your treatment.

3. What is my most important question about what happens next?

Perhaps you want to understand whether treatment will continue, when the next scan is scheduled, or what changes you should watch for.

You do not need to ask every question in this guide.

Choose the ones that matter most to you.

It may also help to bring a trusted family member or caregiver, take notes, or ask whether your team can provide a written summary.

If an explanation is unclear, it is reasonable to ask your clinician to explain it another way.

You deserve to understand the information being used to guide your care.

One Final Thought

Cancer treatment response is not always a simple answer of working or not working.

Sometimes tumors shrink.

Sometimes the disease remains stable.

Sometimes cancer progresses despite treatment.

And sometimes the meaning of a test result is uncertain until additional information becomes available.

Throughout this process, your oncology team considers not only what is happening to the cancer but also how treatment is affecting you.

The most important question is not always:

"Did my tumor get smaller?"

It is:

"Is this treatment helping us achieve the goals that matter for my care?"

Understanding that answer can help you participate in decisions about treatment, follow-up, and the next steps in your cancer journey.

Your scan is an important part of your story. It is not the whole story.