Introduction:

Bladder cancer is a common and aggressive malignancy that can be categorized as non-muscle invasive, muscle invasive (MIBC) or metastatic. Computed tomography (CT) and magnetic resonance imaging (MRI) and FDG PET scans are the most commonly used imaging modalities for disease staging across the clinical spectrum of bladder cancer but are limited in identifying patients with nodal or metastatic disease. There is significant clinical need for accurate imaging in these patients. Fibroblast activation protein (FAP) is a cell surface protein that is highly expressed on the surface of cancer-associated fibroblasts (CAFs) present in many epithelial cancers, including bladder cancer. Initial studies evaluating the use of ⁶⁸Ga-FAP-2286 PET (FAP-PET) imaging have shown promising results. Here, we present the results of a pilot study assessing the diagnostic performance of FAP-PET imaging in a cohort of patients with presumed clinically localized MIBC.

Methods:

Patients with histopathologically confirmed solid tumors were imaged at UCSF with FAP-PET as part of a clinical trial (NCT04621435), including 16 patients with urothelial carcinoma. We report on ten patients with clinically localized disease who were treated with curative intent at the time of imaging. Standard imaging with CT, MRI, FDG-PET, or bone scan was required within 8 weeks of the FAP-PET scan. The maximum standardized uptake value (SUVmax) of FAP-PET -positive lesions and the size (short axis for lymph nodes) were documented. In patients who had an available FDG-PET performed within 8 weeks of FAP-PET, uptake on the two scans was compared. Chart review was performed and clinical and demographic data was collected.

Results:

Most patients were men (90%) and Caucasian (80%) with age ranging from 28-90. 50% (5) were cT2 and 4 patients had <50% variant histology on transurethral resection. (Table 1). Two patients had FAP-PET imaging pre/post neoadjuvant chemotherapy: one with complete resolution of lymphadenopathy (pN0) and one with decrease in SUVmax but persistent uptake (pathology from pelvic lymph node dissection positive for urothelial carcinoma.) Of 12 evaluable FAP-PET studies, concordance was 33% (4/12) with standard imaging and 43% (3/7) with FDG-PET. Of 8 patients with definitive histopathology or imaging follow up, FAP-PET was concordant with disease presence/absence in 100% (standard imaging 25% concordance (2 of 8 patients) and FDG-PET CT 40% concordance (2 of 5 patients)). We highlight two example cases where FAP-PET altered treatment decision, one due to identifying distant metastases and one due to ruling out tumor spread to regional lymph nodes (Figure 1).

Conclusion:

FAP-PET imaging is a promising tool that may allow for more accurate staging in patients with bladder cancer. This has the potential to change treatment pathways and improve patient care by better identifying metastatic sites in patients who may have been previously identified as having localized disease, identifying falsely positive lymph nodes in clinically localized disease, and improving assessment of response to systemic therapy. These promising results are informing the design of a larger clinical trial investigating the role of ^FAP- PET imaging in staging patients with MIBC.

Funding: IIT, Clovis Oncology