Adv Lab Med. 2025 Jul 17;6(4):442-449. doi: 10.1515/almed-2025-0023. eCollection 2025 Dec.

ABSTRACT

OBJECTIVES: Prostate-specific antigen (PSA) circulates bound to extracelular vesicles (EVs). Levels of this PSA form (ev-PSA) are higher in prostate cancer (PCa) compared to benign pathologies and healthy controls, being the PSA extracellular vesicles/serum (ev/srm) ratio potentially useful as PCa diagnostic biomarker. We evaluated the utility of ev-PSA as a follow-up biomarker for detecting relapse or monitoring response to systemic treatments in advanced PCa.

METHODS: Samples were obtained sequentially (baseline, response and progression) from 10 patients with advanced PCa undergoing hormonal therapy or chemotherapy. EVs were isolated from serum by size exclusion chromatography. Total PSA (T-PSA) and free PSA (F-PSA) were quantified in serum and EVs in a c602 module of a Cobas 8000 (Roche Diagnostics) using Elecsys immunoassays, and PSA ev/srm ratio was calculated.

RESULTS: T-PSA in EVs (ev-T-PSA) was quantified in all samples and T-PSA ev/srm ratio median was 1.4 % (Q1-Q3: 1.1-1.9 %). At clinical response, there was not a significant decrease in ev-T-PSA (p=0.055) and neither an increase in T-PSA ev/srm ratio values (p=0.078). During progression, the T-PSA ev/srm ratio decreased significantly with respect to baseline (p=0.037) and clinical response values (p=0.008), although srm-T-PSA and ev-T-PSA concentrations did not change (p=0.625 and p=0.482, respectively). The greatest decrease in srm-T-PSA and ev-T-PSA concentrations was observed in patients undergoing hormonal therapy.

CONCLUSIONS: T-PSA ev/srm ratio could be useful for detecting tumor progression and relapses in advanced PCa. However, its utility as a follow-up biomarker for assessing clinical response to hormonal treatments and chemotherapy would be limited.

PMID:41466738 | PMC:PMC12744380 | DOI:10.1515/almed-2025-0023