Pseudoprogression Manifesting as Recurrent Ascites with Anti-PD-1 Immunotherapy in Urothelial Bladder Cancer - Beyond the Abstract

Five anti-PD-1/L1 immunotherapies have been approved for advanced/metastatic urothelial bladder cancer since 2016, which has shifted drastically the way in which patients are treated. Longstanding experience with chemotherapy led to clinician and patient familiarity with expected toxicities, including their timing and physical manifestations. In contrast, immunotherapies are relatively newer, and as their use has become widespread, less common findings are now being observed in terms of toxicities and patterns of response. 

In our paper, we highlight a previously unreported clinical finding in a patient with urothelial bladder cancer metastatic to the peritoneum who was treated with anti-PD1 immunotherapy. Notably, the patient developed recurrent large-volume ascites. While this finding is typically highly concerning for disease progression, this patient was found to have a significant reduction in size of peritoneal nodules on imaging, and no malignant cells could be recovered from the fluid upon repeated paracenteses.

Immune checkpoint blockade is now the standard-of-care multiple genitourinary malignancies, and radiographic pseudoprogression has emerged as a real, albeit rare, phenomenon. Emerging literature, including this report, indicate that clinical pseudoprogression is another important phenomenon that occurs when manifestations typical of clinical progression occur in the context of a patient having an anti-tumor immune response. With both radiographic and clinical pseudoprogression, the findings are caused by rapid proliferation of activated T lymphocytes. In this study, flow cytometry revealed a high proportion of activated CD8+ T lymphocytes based on surface markers (Figure 1), and cytokine analysis indicated high levels of IL-6 and IL-15. In summary, ascites during immune checkpoint therapy, particularly in the setting of peritoneal metastases, can result from T cell expansion. Pseudoprogression is rare, so clinical judgement remains paramount in deciding a course of action. 

 anti PD 1 immunotherapy

Written by: Randy F. Sweis, M.D. Department of Medicine, Section of Hematology/Oncology, Comprehensive Cancer Center, University of Chicago Medicine, Chicago, IL

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