Elucidating the need for prostate cancer risk calculators in conjunction with mpMRI in initial risk assessment before prostate biopsy at a tertiary prostate cancer center.

OBJECTIVE: Utilizing personalized risk assessment for clinically significant prostate cancer (csPCa) incorporating multiparametric magnetic resonance imaging (mpMRI) reduces biopsies and overdiagnosis. We validated both multi- and univariate risk models in biopsy-naïve men, with and without the inclusion of mpMRI data for csPCa detection. METHODS: N = 565 men underwent mpMRI-targeted prostate biopsy, and the diagnostic performance of risk calculators (RCs), mpMRI alone, and clinical measures were compared using receiver operating characteristic curve (ROC) analysis and decision curve analysis (DCA). Subgroups were stratified based on mpMRI findings and quality. RESULTS: csPCa was detected in 56.3%. PI-RADS score achieved the highest area under the curve (AUC) when comparing univariate risk models (AUC 0.82, p < 0.001). Multivariate RCs showed only marginal improvement in csPCa detection compared to PI-RADS score alone, with just one of four RCs showing significant superiority. In mpMRI-negative cases, the non-MRI-based RC performed best (AUC 0.80, p = 0.016), with the potential to spare biopsies for 23%. PSA-density and multivariate RCs demonstrated comparable performance for PI-RADS 3 constellation (AUC 0.65 vs. 0.60-0.65, p > 0.5; saved biopsies 16%). In men with suspicious mpMRI, both mpMRI-based RCs and the PI-RADS score predicted csPCa excellently (AUC 0.82-0.79 vs. 0.80, p > 0.05), highlighting superior performance compared to non-MRI-based models (all p < 0.002). Quality-assured imaging consistently improved csPCa risk stratification across all subgroups. CONCLUSION: In tertiary centers serving a high-risk population, high-quality mpMRI provides a simple yet effective way to assess the risk of csPCa. Using multivariate RCs reduces multiple biopsies, especially in mpMRI-negative and PI-RADS 3 constellation.

Identification of F-Box/SPRY Domain-Containing Protein 1 (FBXO45) as a Prognostic Biomarker for TMPRSS2-ERG-Positive Primary Prostate Cancers.

BACKGROUND: F-box/SPRY domain-containing protein 1 (FBXO45) plays a crucial role in the regulation of apoptosis via the ubiquitylation and degradation of specific targets. Recent studies indicate the prognostic potential of FBXO45 in several cancers. However, its specific role in prostate carcinoma remains unclear. METHODS: A systematic analysis of FBXO45 mRNA expression in PCA was performed using The Cancer Genome Atlas database and a publicly available Gene Expression Omnibus progression PCA cohort. Subsequently, FBXO45 protein expression was assessed via immunohistochemical analysis of a comprehensive tissue microarray cohort. The expression data were correlated with the clinicopathological parameters and biochemical-free survival. The immunohistochemical analyses were stratified according to the TMPRSS2-ERG rearrangement status. To assess the impact of FBXO45 knockdown on the tumour proliferation capacity of cells and metastatic potential, transfection with antisense-oligonucleotides was conducted within a cell culture model. RESULTS: FBXO45 mRNA expression was associated with adverse clinicopathological parameters in the TCGA cohort and was enhanced throughout progression to distant metastasis. FBXO45 was associated with shortened biochemical-free survival, which was pronounced for the TMPRSS2-ERG-positive tumours. In vitro, FBXO45 knockdown led to a significant reduction in migration capacity in the PC3, DU145 and LNCaP cell cultures. CONCLUSIONS: Comprehensive expression analysis and functional data suggest FBXO45 as a prognostic biomarker in PCA.

Downstream Neighbor of SON (DONSON) Expression Is Enhanced in Phenotypically Aggressive Prostate Cancers.

Downstream neighbor of Son (DONSON) plays a crucial role in cell cycle progression and in maintaining genomic stability, but its role in prostate cancer (PCa) development and progression is still underinvestigated. Methods: DONSON mRNA expression was analyzed with regard to clinical-pathological parameters and progression using The Cancer Genome Atlas (TCGA) and two publicly available Gene Expression Omnibus (GEO) datasets of PCa. Afterwards, DONSON protein expression was assessed via immunohistochemistry on a comprehensive tissue microarray (TMA). Subsequently, the influence of a DONSON-knockdown induced by the transfection of antisense-oligonucleotides on proliferative capacity and metastatic potential was investigated. DONSON was associated with an aggressive phenotype in the PCa TCGA cohort, two GEO PCa cohorts, and our PCa TMA cohort as DONSON expression was particularly strong in locally advanced, metastasized, and dedifferentiated carcinomas. Thus, DONSON expression was notably upregulated in distant and androgen-deprivation resistant metastases. In vitro, specific DONSON-knockdown significantly reduced the migration capacity in the PCa cell lines PC-3 and LNCaP, which further suggests a tumor-promoting role of DONSON in PCa. In conclusion, the results of our comprehensive expression analyses, as well as the functional data obtained after DONSON-depletion, lead us to the conclusion that DONSON is a promising prognostic biomarker with oncogenic properties in PCa.