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Randomized Controlled Trial
. 2025 Mar 17;31(6):1142-1149.
doi: 10.1158/1078-0432.CCR-24-3027.

PSMA+ Extracellular Vesicles Are a Biomarker for SABR in Oligorecurrent Prostate Cancer: Analysis from the STOMP-like and ORIOLE Trial Cohorts

Jack R Andrews  1 , Yohan Kim  2 , Edlira Horjeti  2 , Ali Arafa  3   4 , Heather Gunn  5 , Aurélie De Bruycker  6   7 , Ryan Phillips  8 , Daniel Song  9 , Daniel S Childs  10 , Oliver A Sartor  10 , Jacob J Orme  10 , Aadel A Chaudhuri  8 , Phuoc Tran #  11 , Ana Kiess #  9 , Philip Sutera #  9 , Carole Mercier #  12   13 , Piet Ost #  7   12 , Sean S Park #  8 , Fabrice Lucien #  2   14
Affiliations
Randomized Controlled Trial

PSMA+ Extracellular Vesicles Are a Biomarker for SABR in Oligorecurrent Prostate Cancer: Analysis from the STOMP-like and ORIOLE Trial Cohorts

Jack R Andrews et al. Clin Cancer Res. .

Abstract

Purpose: Two randomized clinical trials (STOMP and ORIOLE) demonstrated that stereotactic ablative radiotherapy (SABR) can prolong androgen-deprivation therapy-free survival or progression-free survival (PFS) in patients with metachronous oligometastatic castration-sensitive prostate cancer (omCSPC). Although most patients with omCSPC have a more modest delay in progression, a small subset achieves a durable response following SABR. We investigated the prognostic and predictive value of circulating prostate-specific membrane antigen-positive (PSMA+) extracellular vesicles (EV) and PSA in a biomarker correlative study using blood samples from three independent patient cohorts.

Experimental design: Plasma samples from 46 patients with omCSPC on the ORIOLE trial and 127 patients with omCSPC on the STOMP trial protocol treated with SABR were included in the study. Pre-SABR PSMA+EV levels (EV/mL) were measured by nanoscale flow cytometry. Kaplan-Meier curves and logistic regression models were used to determine the association of PSMA+EV and PSA levels with clinical outcomes.

Results: In the pooled cohorts, the median biochemical PFS were 26.1 and 15.0 months (P = 0.005), and the median radiographic PFS were 36.0 and 25.0 months (P = 0.003) for PSMA+EV-low and -high groups, respectively. The combination of pre-SABR low levels of both PSMA+EV and PSA was associated with a lower risk of radiographic progression (HR, 0.34, 95% confidence interval, 0.18-0.58; P = 0.0002). In the ORIOLE cohort, which included both an SABR arm and an observation arm, low PSMA+EV was predictive of benefit from SABR (P = 0.012).

Conclusions: PSMA+EV is a novel prognostic and predictive biomarker of radiographically occult tumor burden in omCSPC. PSMA+EV may inform clinical decisions about identifying patients who will achieve a durable benefit from consolidative SABR alone.

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Conflict of interest statement

J.R. Andrews reports personal fees from Bayer and Blue Earth Diagnostics outside the submitted work. R. Phillips reports nonfinancial support from Novartis AG and Veracyte, Inc outside the submitted work. D.S. Childs reports other support from Novartis, Janssen, and Abdera outside the submitted work. J.J. Orme reports grants from the Prostate Cancer Foundation, Department of Defense, and NCI during the conduct of the study. A.A. Chaudhuri reports nonfinancial support from Roche, personal fees and nonfinancial support from Illumina, personal fees from Myriad Genetics, Invitae, Daiichi Sankyo, AstraZeneca, Guardant Health, Caris, AlphaSights, DeciBio, Guidepoint, and Agilent; other support from Geneoscopy, Droplet Biosciences, and LiquidCell Dx; and grants and other support from Tempus outside the submitted work, as well as a patent for filings related to cancer biomarkers pending. P. Tran reports personal fees from Natsar Pharmaceuticals, RefleXion Medical, Bayer, Janssen, Regeneron, Lantheus, and Pfizer outside the submitted work, as well as a patent for “Compounds and methods of use in ablative radiotherapy; patent No. 9114158” licensed and with royalties paid from Natsar Pharmaceuticals. A. Kiess reports grants from Bayer during the conduct of the study, as well as grants from Novartis, Convergent, and Lantheus outside the submitted work. C. Mercier reports grants from RaySearch Laboratories outside the submitted work. P. Ost reports grants from Bayer and other support from Bayer, AstraZeneca, Novartis, and Janssen outside the submitted work. F. Lucien reports grants from NaNotics, personal fees from Mursla Bio, and grants and nonfinancial support from Early is Good outside the submitted work, as well as a patent for US 63-633200 issued. No disclosures were reported by the other authors.

Figures

Figure 1.
Figure 1.
PFS stratified by baseline PSMA+EV levels. Kaplan–Meier curves for bPFS (A) and rPFS (B) in the pooled cohorts.
Figure 2.
Figure 2.
PFS stratified by baseline PSA and PSMA+EV levels. Kaplan–Meier curves for bPFS (A) and rPFS (B) in the pooled cohorts. NR, not reached.
Figure 3.
Figure 3.
bPFS stratified by baseline PSMA+EV levels in the observation and SABR arms of the ORIOLE trial. Kaplan–Meier curves for bPFS in patients of the ORIOLE SABR and observation arms stratified by low (A) and high (B) baseline levels of PSMA+EV. NR, not reached.
See this image and copyright information in PMC

References

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