Introduction: Extracellular vesicles (EV) released by prostate cancer cells are emerging liquid biomarkers for risk stratification, disease recurrence, and predicting treatment response. Our overarching goal is to determine whether prostate-derived extracellular vesicles (PEVs) can help identify patients with metastatic disease ab initio. For this study, our objectives are to 1) determine the levels of blood-derived PEVs in localized and metastatic prostate cancer and 2) analyze the kinetics of PEVs in patients undergoing radical prostatectomy for localized prostate cancer.
Methods: Levels of PEVs were measured by nanoscale flow cytometry using fluorescent antibodies against PSMA and STEAP1 as prostate markers. We analyzed plasma samples collected from localized prostate cancer patients pre-radical prostatectomy (RP) (N=43), localized prostate cancer patients within 4 months post-RP (N=24), oligometastatic CRPC (N=77), and metastatic CRPC (N=20).
Results: Median PEV concentrations were higher in omCRPC compared to localized PCa patients post-RP for both PSMA (Fold change: 3.1 p=0.0001) and STEAP1 (Fold change: 6.41, p<0.0001). mCRPC patients also had a higher median level of PSMA EV levels (Fold change: 1.64 p<0.05) and STEAP1 (fold change 4.51, p<0.0001) compared to omCRPC.
A cohort of 43 patients with localized prostate cancer underwent RP between 2020-2021. 24/43 patients provided blood prior to RP and within 4 months post-RP and 19/43 patients were lost during follow-up. 9/24 and 13/24 patients had detectable levels of PSMA and STEAP1-EVs pre-RP respectively. Following RP, mean PEV levels significantly decreased for both PSMA (Fold Change: 3.2-fold, p-value = 0.0078) and STEAP1 (Fold Change: 3.7-fold, p-value = 0.0002). All patients had undetectable PSA at 4 months post-RP. To this date, 1 patient with high pre-RP levels of PSMA- and STEAP1-EVs showed PEV persistence post-RP 1 year prior PSA biochemical recurrence and positive bone metastases.
Conclusions: Blood levels of prostate-specific EVs correlate with disease burden. Radical prostatectomy is associated with a reduction of PEVs. Further studies are warranted to evaluate the diagnostic accuracy of PEVs compared to PET imaging in patients with a high risk of developing recurrence.