Why Some Tumors Appear to Grow During Immunotherapy - and Why That Can Be a Good Sign

New immune-based treatments are changing how we fight cancer in dogs. These therapies don’t attack tumors directly; instead, they train the dog’s immune system to recognize and destroy cancer cells. But as powerful as they are, immune therapies can sometimes confuse both owners and veterinarians about early treatment outcomes.

One puzzling phenomenon is called pseudoprogression, when a tumor appears to grow before it actually begins to shrink.

What Is Pseudoprogression?

Pseudoprogression means a temporary increase in tumor size or inflammation after starting an immune-based therapy, even though the cancer is actually responding.

It happens because the dog’s immune system floods the tumor area with activated T cells, macrophages, and other immune cells. These immune cells infiltrate the tumor, causing swelling, fluid accumulation, and inflammation. On imaging, or even by touch, the tumor can feel larger or look worse.

Later, as those activated cells destroy cancer cells and inflammation subsides, the tumor often shrinks or becomes inactive.

So what looks like the cancer “getting worse” can actually be the immune system at work.

Why It Happens With Immunotherapy

Traditional chemotherapy kills cancer cells directly, so tumor shrinkage often appears quickly. Immunotherapy works differently: it needs time to activate the immune response and train immune cells to target cancer antigens.

During that process, several things can make the tumor look bigger:

• Immune cell infiltration: activated T-cells and macrophages enter the tumor site.

• Edema and inflammation: blood vessels leak as immune activity increases.

• Necrosis and debris: dead tumor cells and immune remnants can increase measured volume.

  
  

In other words, pseudoprogression isn’t the cancer growing. It’s the immune battle being waged inside the tumor.

How Common Is It?

In human oncology, pseudoprogression occurs in about 5–10% of patients treated with checkpoint inhibitors or other immune activation therapies

Incidence of Pseudoprogression during Immune Checkpoint Inhibitor Therapy for Solid Tumors: A Systematic Review and Meta-Analysis

In dogs, we’re just starting to recognize it. Because most veterinary immunotherapy studies are small, it may have been missed or misclassified as “disease progression.”

As more dogs receive immune-based treatments, such as intratumoral immune stimulants, cytokine gene therapies, or personalized immune cell treatments, clinicians are learning to watch for this early swelling pattern.

How to Tell the Difference Between Pseudoprogression and True Progression

Distinguishing pseudoprogression from real tumor growth is challenging. But several clues can help:

Feature	Pseudoprogression	True Progression
Timing	Usually within 2–8 weeks after therapy begins	Can occur anytime
Symptoms	Dog often feels stable or slightly better	Dog shows new pain, lethargy, or appetite loss
Imaging	Temporary enlargement, later stabilization or shrinkage	Continuous rapid growth on follow-up

Veterinarians may recommend a short-interval recheck scan (e.g., 3–4 weeks later) instead of declaring the treatment ineffective right away. 

This “pause and reassess” approach mirrors what’s done in human immunotherapy trials.

Why It Matters

Misinterpreting pseudoprogression can have serious consequences. If a promising immune therapy is stopped too early, the dog might lose the chance for a meaningful response. Conversely, if the tumor is truly progressing, waiting too long can let the disease spread.

If your dog is receiving an immune-based cancer therapy and the tumor looks temporarily larger, don’t panic. This swelling can sometimes signal that the immune system is finally recognizing the cancer.

Stay in close contact with your veterinary oncologist. Ask about re-imaging timelines and whether your dog’s overall condition suggests inflammation or true progression. Most importantly, remember that the success of immunotherapy often takes time to appear, sometimes weeks or months.

Get Your Free Immunotherapy Guide

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Check out other articles and videos

• Could the Right Time of Day Boost Cancer Treatment Response in Dogs??

  
  

  

• 8 Things Pet Parents Should Know About Elias Immunotherapy for Canine Cancer

• A New Immunotherapy Trial for Dogs with Lung Metastases: The CAALM Study

Questions? Email us at info@ccralliance, and we'll get back to you as soon as we can!

Canine Cancer Alliance is a non-profit organization supporting research for canine cancer cures.

All information on the Canine Cancer Alliance website is for educational purposes only. It is not intended to be a substitute for professional veterinary advice.

Always seek guidance from your veterinarian with any questions regarding your pet’s health and medical condition.