When you’ve been diagnosed with cancer, the last thing you want to hear is that your tumor has grown or new lesions have appeared. But it may come as a surprise to many patients that, with some cancer treatments, especially immunotherapy, tumor growth may actually be a good sign.
Consider what happens when you get sick: The lymph nodes in your neck often swell as your body prepares to fight the infection by increasing its production of white blood cells. After the infection passes, the swelling goes down.
Researchers have discovered that certain cancer drugs can work similarly—by activating an immune response that temporarily stimulates tumor growth.
This phenomenon, called pseudoprogression, actually means cancer is may be responding to treatment. In some cases, however, it’s possible that the tumor growth may be interpreted as a sign that treatment isn’t working, and the care team may be tempted to stop treatment early. That’s why education about pseudoprogression is key.
In this article, we’ll explore:
- What is pseudoprogression?
- Pseudoprogression vs. true progression
- Signs immunotherapy is working
- Pseudoprogression timelines
- Coping with pseudoprogression
If you’ve been diagnosed with cancer and are interested in a second opinion on your diagnosis and treatment plan, call us or chat online with a member of our team.
What is pseudoprogression?
It’s been more than a decade since the U.S. Food and Drug Administration (FDA) approved the first immune checkpoint inhibitor—a class of immunotherapy drug that helps the immune system find and attack cancer cells.
The FDA approved ipilimumab (Yervoy®) to treat metastatic melanoma in 2011. The drug works by blocking CTLA-4, a checkpoint protein, from binding with its partner protein, preventing it from turning “off” an immune response and allowing the body’s T-cells to target and kill cancer cells.
Since 2011, the FDA has approved a handful of other checkpoint inhibitors to treat a range of solid-tumor cancers, among them:
Most of these drugs, including nivolumab (Opdivo®), pembrolizumab (Keytruda®), atezolizumab (Tecentriq®), durvalumab (Imfinizi®) and avelumab (Bavencio®), block PD1 or its companion protein PD-L1.
Researchers herald this drug class as a game-changer that has revolutionized the landscape of cancer treatment in recent years. Yet, in some patients, the drugs’ activation of an immune response can cause pseudoprogression, when a tumor temporarily grows or new cancer lesions appear. In fact, some studies have found that it occurs in up to 15 percent of cancers treated with checkpoint inhibitors.
Most often, oncologists discover evidence of pseudoprogression during follow-up imaging scans used to determine the cancer’s response to treatment.
Pseudoprogression vs. true progression
For most of the past quarter century, the gold standard for measuring tumor response has been a rubric called Response Evaluation Criteria in Solid Tumors (RECIST). Oncologists use RECIST to guide treatment decisions. But under RECIST, pseudoprogression may be considered progressive disease, which may lead some oncologists to stop an otherwise effective treatment early.
That’s why newer guidelines have since been proposed, including immune-modified response evaluation criteria in solid tumors (imRECIST) that account for pseudoprogression and responses to treatment that may be consider atypical.
Using criteria outlined by these newer rules allows for treatment to continue even with the appearance of disease progression. Still, doctors don’t currently have any ways to predict who may develop pseudoprogression or to identify consistent criteria for monitoring it when it occurs.
Signs immunotherapy is working
Instead of relying solely on repeated imaging tests to determine whether a tumor is truly growing, oncologists often use one or all of the below to help confirm the presence of pseudoprogression.
Biopsies
Biopsies may help determine the difference between pseudoprogression and true progression in certain cancers because they can show which cells are infiltrating the tumor: normal immune cells or cancer cells.
Biomarkers
Oncologists may use biomarkers like the cytokine interleukin-8 (IL-8) and circulating tumor DNA (ctDNA), which comes from cancer cells and tumors, to identify pseudoprogression. When levels of these biomarkers are low, it generally means immunotherapy is working.
Imaging tests
Researchers have found that PET/CT scans can help identify pseudoprogression in immunotherapy because they use radiotracers—molecules linked to a small amount of radioactive material that accumulate in tumors.
Patient health
Pseudoprogression is often accompanied by improved overall health. But true tumor progression typically goes hand in hand with worsening health.
Pseudoprogression timelines
Pseudoprogression is most common in the first few weeks after immunotherapy has started, but it may also show up later.
Tumor growth that occurs within the first 12 weeks after treatment starts is called early pseudoprogression.
Tumor growth that happens after the first 12 weeks is known as delayed pseudoprogression.
The average time it takes for a tumor to begin to decrease in size on imaging scans is six months.
Coping with pseudoprogression
Even if psuedoprogression may be a good sign that your immunotherapy treatment is working, it still may be difficult to hear that your tumor is growing.
It may be especially taxing if you’re already dealing with cancer-related anxiety, one of the most common behavioral side effects of the disease. The National Behavioral Health Network estimates that up to half of cancer survivors experience some level of anxiety.
Many patients may also experience what’s become known as “scanxiety,” anxiousness that escalates around the time they’re due for diagnostic testing or post-treatment imaging tests or scans.
“It’s a real thing, no question,” Anthony Perre, MD, New Patient Intake Physician at City of Hope Atlanta and a Hodgkin lymphoma survivor, says in a CancerCenter360 blog on the topic. “I’ve experienced it, and I'm usually a pretty calm person. Everything gets ratcheted up.”
Even though it can sometimes take weeks to determine whether cancer is, indeed, growing or if it’s just temporary growth, patience is important.
Here are some steps you can take to help relieve stress from the waiting game:
- Talk to family and friends about your anxiety.
- Consider behavioral health therapy.
- Seek out spiritual support.
- Join a support group.
- Get some exercise.
Remember that, with immunotherapy drugs, it’s important to continue treatment until you know the full picture of how it’s working. And even if imaging scans show tumor growth, it could very well be a good sign.
If you’re interested in getting screened for cancer or if you’ve been diagnosed with cancer and want a second opinion, call us or chat online with a member of our team.
