Pre-diagnosis urine exosomal RNA (ExoDx EPI score) is associated with post-prostatectomy pathology outcome

Alexander Kretschmer, Ronald Tutrone, Jason Alter, Elena Berg, Christian Fischer, Sonia Kumar, Phillipp Torkler, Vasisht Tadigotla, Michael Donovan, Grannum Sant, Johan Skog, Mikkel Noerholm, Alexander Kretschmer, Ronald Tutrone, Jason Alter, Elena Berg, Christian Fischer, Sonia Kumar, Phillipp Torkler, Vasisht Tadigotla, Michael Donovan, Grannum Sant, Johan Skog, Mikkel Noerholm

Abstract

Purpose: ExoDx Prostate IntelliScore (EPI) is a non-invasive urine exosome RNA-based test for risk assessment of high-grade prostate cancer. We evaluated the association of pre-biopsy test results with post-radical prostatectomy (RP) outcomes to understand the potential utility of EPI to inform invasive treatment vs active surveillance (AS) decisions.

Methods: Urine samples were collected from 2066 men scheduled for initial biopsy with PSA between 2 and 10 ng/mL, no history of prostate cancer, and ≥ 50 years across multiple clinical studies. 310 men proceeded to RP, of which 111 patients had Gleason group grade 1 (GG1) at biopsy and would have been potential candidates for AS. We compared pre-biopsy urine scores with ERSPC and PCPT multivariate risk calculator scores for men with GG1 at biopsy to post-RP pathology.

Results: Urine EPI scores were significantly lower in men with GG1 at biopsy than in men with > GG1 (p = 0.04), while there were no differences in multivariate risk scores used in standard clinical practice (p > 0.05). Further, EPI scores were significantly lower in men with GG1 at biopsy who remained GG1 post-RP compared to men upgraded to ≥ GG3 post-RP (p < 0.001). In contrast, none of the multiparametric risk calculators showed significant differences (p > 0.05). Men with GG1 at biopsy and EPI score < 15.6 had zero rate of upgrading to ≥ GG3 post-RP compared to 16.0% for EPI scores ≥ 15.6.

Conclusions: The EPI urine biomarker outperformed the multivariate risk calculators in a homogenous risk group of pre-biopsy men. The EPI score was associated with low-risk pathology post-RP, with potential implications on informing AS decisions.

Trial registration: NCT02702856, NCT03031418, NCT03235687, NCT04720599.

Keywords: Exosomes; PSA-gray-zone; Prostate cancer; Radical-prostatectomy; Upgrading; Urine-biomarker.

Conflict of interest statement

CF, SK, MN, PT, JS, JA are employees of Bio-Techne. AK, MD, GS are consultants for Bio-Techne. All other authors declare no conflict of interest.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
EPI/PSA/PCPT/ERSPC score vs RP upgrading. Distribution scores of different parameter for patients with GG1 at biopsy who (1) remained GG1 post- RP, (2) were upgraded to GG2 post-RP, and (3) were upgraded to > GG3 post-RP for A EPI, ExoDx™ Prostate (IntelliScore) (p values for group comparisons shown in the figure); B PSA levels (Kruskal–Wallis rank sum test, p = 0.95 for comparison of all three groups); C PCPT risk calculator (Kruskal–Wallis rank sum test, p = 0.29); and D ERSPC risk calculator (one-way ANOVA, p = 0.76)
Fig. 2
Fig. 2
Receiver operator curves (ROC) (A) and decision curve/net benefit analysis (B) of EPI vs PSA, PCPT and ERSPC for prediction of RP GG > 2 after Bx GG1
Fig. 3
Fig. 3
Pre-biopsy EPI score correlation with post-RP pathology by the previously established 15.6 EPI score cut point. No GG1 cases (0%) with an EPI score p < 0.001). Fifty-eight percent of GG1 cases with an EPI score < 15.6 (10/17) were upgraded to GG2 post-RP compared to 55% (52/94) when EPI scores were ≥ 15.6 cut-point (p = 0.95)

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Source: PubMed

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