Incidence and Clinical Impact of Inflammatory Fluorodeoxyglucose Positron Emission Tomography Uptake After Neoadjuvant Pembrolizumab in Patients with Organ-confined Bladder Cancer Undergoing Radical Cystectomy

Data regarding the incidence and prognostic impact of immune-related imaging changes, assessed by 18[F] fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scan, in patients receiving immune-checkpoint inhibitors (ICIs) are lacking. We relied on the population of patients enrolled in the PURE-01 study to evaluate such changes. To evaluate the role of PET/CT to visualize the immune-related adverse events (irAEs) following pembrolizumab. From February 2017 to August 2019, in 103 patients with nonmetastatic, clinical T2–4aN0M0 bladder cancer, PET/CT scan was performed before and after neoadjuvant pembrolizumab (N = 206 scans), before radical cystectomy. PET/CT before and after neoadjuvant pembrolizumab, before radical cystectomy. We analyzed the occurrence of irAEs, evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, against the development of inflammatory FDG uptake described at PET/CT (irAEs + PET/CT). Logistic regression analyses evaluated the association between irAEs + PET/CT and the pathological response to pembrolizumab. Kaplan-Meier curves tested their association with progression-free survival (PFS) after pembrolizumab and radical cystectomy. Forty patients (39%) developed irAEs + PET/CT in several target organs. The most frequent target organs were the thyroid (N = 18), stomach (N = 14), mediastinal lymph nodes (N = 9), and lung (N = 5). These changes were clinically evident in 18 (45%) and were not associated with the pathological response, neither in terms of complete response (ypT0N0, p = 0.07) nor as downstaging to ypT≤1N0 disease (p = 0.1), although ypT0N0 responses were numerically more frequent in patients with irAEs+ PET/CT (47.5% vs 32%). Furthermore, irAE+ PET/CT events were associated with longer, not statistically significant, 24-mo PFS: 88.3% versus 76.5% (p = 0.5). Our results warrant further validation in larger datasets. We presented unique surrogate data of PET/CT that could help improve our understanding of nonclinically evident effects of ICI administration, especially in patients at the early disease stage. We evaluated the utility of PET/CT to visualize the occurrence of inflammatory changes after pembrolizumab in patients with localized bladder cancer without metastases. After immunotherapy, 39% of the patients developed 18[F] fluorodeoxyglucose uptake consistent of inflammatory changes. Overall, our data improve our knowledge on the effects induced by im