Tumor pseudoprogression during nivolumab immunotherapy for lung cancer

Immunotherapy is a new treatment in advanced lung cancer that works by modulating the immune response against malignant cells. One aspect that is challenging for radiologists in the evaluation of the response to immunotherapy is the phenomenon of pseudoprogression, in which the infiltration of inflammatory cells causes lesions to increase in size or new lesions to appear and then decrease in size or disappear. Pseudoprogression actually represents a response to treatment. We aimed to determine the frequency of pseudoprogression in patients with advanced stages of lung cancer treated with nivolumab.

We included 56 patients with advanced stages of lung cancer treated with nivolumab as a second-line or later treatment. We analyzed CT studies done while patients were undergoing nivolumab treatment. Tumor pseudoprogression was defined as an increase in the size of lesions or appearance of new lesions followed by a decrease in size or disappearance of these lesions on follow-up CT studies 4 to 8 weeks later. We did a descriptive analysis.

In 15 patients, it was impossible to evaluate possible pseudoprogression because a second CT study was unavailable due to change of treatment or death. Tumor pseudoprogression was observed in 5 (12.2%) of the 41 patients, in most cases within 12 weeks of treatment initiation (in the fourth cycle). A second episode of pseudoprogression occurred in 2 (40%) of the 5 patients with an initial episode; the second episode occurred more than 12 weeks after treatment initiation.

Tumor pseudoprogression occurred in 12.2% of patients with advanced stage lung cancer treated with nivolumab. An increase in lesion size or the appearance of new lesions must be assessed over time to avoid mistaking pseudoprogression for true progression of disease.