When you get sick, the lymph nodes in your neck may swell as your body amps up its production of white blood cells to fight the infection. The swelling is usually temporary, and once the threat has passed and the infection heals, the lymph nodes return to their normal, bean-shaped size. In a similar way, when an immunotherapy drug is used to treat cancer, it stimulates the production of immune cells to locate and destroy cancer cells, which may cause the tumor to temporarily grow. That may be confusing to doctors and patients who don’t understand that it’s not a sign of disease progression, but, instead, a symptom of what researchers call pseudoprogression—tumor growth from the treatment rather than from the disease itself.
“ Pseudoprogression is a not-uncommon side effect of immunotherapy that's still being studied to be better understood. In the past, the popular belief was that the tumor was getting bigger and treatment should be stopped. Now we know that it's actually a sign that the immunotherapy may be working.” - Pamela Crilley, DO - Department of Medical Oncology Chair at Cancer Treatment Centers of America® (CTCA)
Most of the time, oncologists discover evidence of pseudoprogression during follow-up tests used to determine the cancer’s response to treatment. “Immunotherapy drugs cause the tumor to flare up initially and get bigger, but that’s only temporary,” says Ashish Sangal, MD, Medical Director of the Lung Cancer Center and Medical Oncologist at our hospital in Phoenix. “So anything that looks bigger in the first three to six months after treatment doesn’t mean it’s a progression.”
For that reason, multiple follow-up tests may be required for patients undergoing immunotherapy treatment. “Immunotherapy may take a longer time to determine results than other therapies,” Dr. Crilley says. That’s why it’s important to be patient when evaluating immunotherapy’s effect. “Patients and physicians are coming to understand that, sometimes, you have to do more than one or two evaluations to really be sure of what’s happening,” she says.
Since 2000, oncologists have largely relied on a system called Response Evaluation Criteria in Standard Tumors (RECIST) to measure cancer’s response to a certain therapy and guide treatment decisions. But a newer rubric, called the immune-related Response Criteria (irRC), accounts for the pseudoprogression phenomenon and is being used in many clinical trials for immunotherapy drugs. “It’s important to know that this is still in evolution, but that we’re working to more properly understand the patterns of response,” Dr. Crilley says.
Some studies have found that pseudoprogression indicates a better outcome, though more studies are needed. While researchers work to learn more about what causes pseudoprogression and what it may mean for patients who experience it, communication between doctors and patients is critical. “Because immunotherapy is still so new, more information is coming out all the time,” Dr. Crilley says. “Oncologists need to educate their patients on what is known at the time and, when new information comes out, communicate that to them in as timely a manner as possible.”