Expression of Circulating Prostate-specific Membrane Antigen Extracellular Vesicles in Blood of Patients with Recurrent and Metastatic Salivary Gland Cancer

Purpose/Objective(s) Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein known to be overexpressed in prostate cancer and certain types of salivary gland cancer (SGC). Extracellular vesicles (EVs) are membrane-bound vesicles released from cells that are emerging as a promising blood biomarker for disease monitoring. The purpose of this exploratory analysis is to determine if circulating PSMA EVs can be detected in patients with recurrent or metastatic (R/M) SGC and to explore whether the direction of PSMA EV change correlates with tumor volume change. Materials/Methods Research blood samples were collected prospectively from patients with R/M SGC being treated on a clinical trial. Blood samples and controls were incubated with fluorescent antibody-matched isotypes or antibodies against PSMA and analyzed by nanoscale flow cytometry. Positive counts in the controls were subtracted from the counts observed in corresponding samples to correct for the level of non-specific binding. Total tumor volume was approximated using two-dimensional measurements on cross-sectional imaging and converted to volume using a validated formula. Results 19 individual patients had 27 blood samples available for analysis (57.9% male, median age 60 years, range 43-79) with the following histologies: 6 adenoid cystic, 5 acinic cell, 4 salivary duct, 1 high grade mucoepidermoid (MEC), 2 adenocarcinoma, 1 poorly differentiated carcinoma NOS. Number of prior lines of cancer therapy (1 missing value): 1 line in 12 patients (66.7%), 2 lines in 5 patients (27.8%), and 3+ lines in 1 patient (5.6%). 8 patients had paired samples at baseline (BL) and 3-month post-treatment. All patients had detectable circulating PSMA EVs across all histologies. The median concentration of PSMA EVs for all 27 samples was 1.73E+06 (historical comparison 1.64E+06 for oligometastatic hormone sensitive prostate cancer). Baseline PSMA EVs/mL, total EV particles/mL, and relative fluorescence intensity of PSMA by histology are listed in Table 1. In patients with paired samples, the direction of the change was concordant between volume change and EV change in 6 out of 8 patients (75%). Conclusion Circulating PSMA EVs appear to represent a possible novel biomarker of disease across salivary cancer histologies. Further prospective data collection is warranted.