Initial Experience with 68Ga-FAP-2286 PET Imaging in Patients with Urothelial Cancer - Beyond the Abstract
For those with localized MIBC, involvement of regional lymph nodes is a major prognostic factor that portends inferior outcomes. Thus, timely and accurate nodal staging, as well as identification of any metastatic lesions, is critical to guide appropriate treatment. Currently accepted imaging for staging relies on size criteria or metabolic activity and includes contrast-enhanced CT scans of the chest, abdomen, and pelvis; contrast-enhanced MRI of the abdomen and pelvis; as well as 18F-fluorodeoxyglucose (FDG)-PET. However, conventional scans are estimated to have only approximately 50% sensitivity to accurately define nodal disease in MIBC. Thus, there is an urgent need for improved imaging modalities to accurately stage patients with MIBC.
Fibroblast Activation Protein (FAP) is a transmembrane serine protease that is overexpressed on cancer associated fibroblasts Cancer Associated Fibroblasts (CAFs) that are present in the tumor microenvironment of diverse tumor types, thus making it an attractive target for imaging various cancers. Several classes of FAP targeting molecules, including small molecule inhibitors (FAPI) and peptide binders, are being developed for this purpose. The FAPI family of compounds has been the most extensively studied and has identified lesions associated with diverse epithelial-based tumors, including lesions in small cohorts of patients with bladder cancer. The cyclic peptide binder FAP-2286 was recently developed to improve tumor residence time relative to FAPI. Therefore, in this study, we investigated the ability of 68Ga-FAP-2286 to stage patients diagnosed with MIBC.
Patients with histopathologically confirmed bladder cancer who either had localized disease at diagnosis (localized cohort, n=13) or known metastatic disease (metastatic cohort, n=8) were imaged with both 68Ga-FAP-2286-PET and with conventional scans as part of a clinical trial (NCT04621435). The maximum standardized uptake value (SUVmax) of 68Ga-FAP-2286- PET positive lesions and lesion size were documented. In cases where there was a discrepancy between imaging modalities on retrospective review, a biopsy of suspicious lesions was performed as a standard of care. In the metastatic and localized cohorts, 36 and 18 68Ga-FAP-2286-avid lesions, respectively, were identified across multiple anatomic locations, including lymph nodes (LNs), visceral metastases, and bones. Importantly, 14/36 lesions in the metastatic cohort and 14/18 lesions in the localized cohort were lymph nodes measuring <1cm which would have appeared as unremarkable lymph nodes on conventional imaging. Among the five patients who had a FDG-PET scan available for comparison, the average SUVmax for FAP-PET and FDG-PET avid lesions were 9.9±3.4 versus 4.2±1.9, respectively (n=16 lesions), which suggests improved tumor-to-background signal that is clinically relevant for challenging anatomic areas, such as the pelvis. Critically, for 3 patients in the localized cohort, 68Ga-FAP-2286-PET identified false positive findings on FDG-PET and false negative findings on conventional CT scans, which subsequently altered the clinical decision making and treatment course for these patients.
Overall, these findings suggest that 68Ga-FAP-2286 imaging is highly sensitive and effective in accurately staging patients with urothelial cancer, including identification of sub-centimeter lymph nodes which would not have raised suspicion on conventional scans. Our results more broadly add to the growing body of literature regarding the use of FAP-based imaging across various tumors and will hopefully improve the accuracy of cancer staging for tumors that are traditionally difficult to stage, including those of the pelvis. When faced with treatment options that include quality-of-life altering surgeries, such as cystectomy, patients deserve the highest quality data to guide whether they would truly benefit from intended treatment. In this context, our study highlights an exciting opportunity for 68Ga-FAP-2286 PET to identify this subset of patients with MIBC more accurately. The limitations of this study include a small cohort size and lack of blinded radiology review. Nonetheless, we hope that these results can be translated into larger, prospective studies designed to more definitively measure the sensitivity and specificity of 68Ga-FAP-2286-PET in patients with MIBC, with the long term goal of making this imaging modality available in the clinic.
Written by: Vipul Kumar, MD, PhD, Sima Porten, MD, MPH, Thomas Hope, MD, & Vadim Koshkin, MD
University of California San Francisco, San Franciso, CA
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