Significant progress in treatment of metastatic castration resistant prostate cancer (mCRPC) has been made. Biomarkers to tailor therapy are scarce. To facilitate decision-making we evaluated dynamic changes of alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and prostate specific antigen (PSA) under therapy with Abiraterone. Men with bone mCRPC (bmCRPC) on Abiraterone 12/2009-01/2014 were analyzed. Dynamic ALP-, LDH- and PSA-changes were analyzed as predictors of best clinical benefit and overall survival (OS) with logistic-regression, Cox-regression and Kaplan-Meier-analysis. Thirty-nine pre- and 45 post-chemotherapy patients with a median follow up of 14.0 months were analyzed. ALP-Bouncing can be observed very early during therapy with Abiraterone. ALP-Bouncing is defined as rapidly rising ALP-levels independent of baseline ALP during the first 2–4 weeks of Abiraterone-therapy with subsequent equally marked decline to pretreatment levels or better within 8 weeks of therapy, preceding potentially delayed PSA-decline. In univariate analysis failure of PSA-reduction ≥50 % and failure of ALP-Bouncing were the strongest predictors of progressive disease (p = 0.003 and 0.021). Rising ALP at 12 weeks, no PSA-reduction ≥50 % and no ALP-Bouncing were strongest predictors of poor OS, (all p < 0.001). Kaplan-Meier-analysis showed worse OS for rising ALP at 12 weeks, no PSA-reduction ≥50 % and no ALP-Bouncing (p < 0.001). In subgroup-analysis of oligosymptomatic patients all parameters remained significant predictors of poor OS, with no PSA-reduction ≥50 % and rising ALP at 12 weeks being the strongest (p < 0.001). In multivariate analysis PSA-reduction ≥50 % remained an independent predictor of OS for the whole cohort and for the oligosymptomatic subgroup (both p = 0.014). No patient with ALP-Bouncing had PD for best clinical benefit. Patients with rising ALP at 12 weeks had no further benefit of Abiraterone. Dynamic changes of ALP, LDH and PSA during Abiraterone-therapy are associated with best clinical benefit and OS in bmCRPC. ALP-Bouncing occurring earlier than PSA-changes as well as prior to equivocal imaging results and rising ALP at 12 weeks under Abiraterone may help to decide whether to discontinue Abiraterone. An external validation of these findings on a prospective cohort is planned.

Background/Objectives: Early detection of prostate cancer (PCa) enables timely therapeutic intervention and improved clinical outcomes. Screening strategies are increasingly individualized and now incorporate multiparametric MRI findings, reported using the Prostate Imaging Reporting and Data System (PI-RADS), to refine biopsy decision-making. PROSTest is a novel machine learning (ML)-enhanced, 30-gene mRNA liquid biopsy assay developed to detect PCa from whole blood. In this prospective study (NCT06872619), we evaluated whether PROSTest could function as a pre-biopsy triage tool to inform biopsy decisions while preserving sensitivity for clinically significant prostate cancer (csPCa). Methods: Of 121 men evaluated, 111 (91.7%) completed the full diagnostic work-up—including PSA testing, PROSTest analysis, and PI-RADS assessment—and subsequently underwent image-guided biopsy. Peripheral blood samples for PROSTest were collected prior to biopsy. RNA-stabilized samples underwent RNA isolation followed by reverse transcription and quantitative PCR. Gene expression data were processed using a proprietary machine learning algorithm to generate a continuous range from 0 to 100. A clinically validated cut-off ≥ 50 was applied to produce a binary (positive/negative) result. The diagnostic accuracy of PROSTest was assessed against histology-confirmed prostate cancer. Results: The median age of participants was 69 years (47–83 years) and the median PSA was 7.5 ng/mL (IQR: 5.8–11.4 ng/mL); most patients (104 of 111; 93.7%) had a PI-RADS score of three to five. PCa was diagnosed in 97 men (87.4%) including eight in ISUP Grade Group (GG) 1, 46 in GG2, 33 in GG3, three in GG4 and seven in GG5. PROSTest was positive in 102/111 (91.9%). Among men with biopsy-confirmed PCa, diagnostic accuracy was 99% (93/94). Of the 17 men without histologic evidence of disease, eight (47%) were PROSTest-negative. The overall accuracy was 91% (84.1–95.6%) with an NPV of 89% (51.6–98.4%). Among the nine patients with positive PROSTest but negative biopsy, PI-RADS scores were 4 (n = 6), 3 (n = 1), and 2 (n = 2). Conclusions: PROSTest demonstrated an overall accuracy of 91% (95% CI: 84.1–95.6%) with an NPV of 89%. Among men without a detectable prostate cancer on biopsy, 47% (8/17) were PROSTest-negative. These results suggest that PROSTest may serve as a useful pre-biopsy triage assay.