Prostate cancer is the most common cancer among men in the western world. Clinical practice is continuously challenged by the pitfalls of the available diagnostic tools. microRNAs may represent promising biomarkers in many types of human cancers, including prostate cancer. The aim of this study was to investigate microRNA expression in tumour tissue and matched plasma in a cohort of patients with primary metastatic prostate cancer. The relative expression of 12 microRNAs was assessed in diagnostic needle biopsies from the prostate and matched plasma samples in two prospective cohorts (screening cohorts) comprising 21 patients with metastatic prostate cancer and 25 control patients. An independent validation cohort of plasma samples was collected prospectively from 149 newly diagnosed patients with local/locally advanced prostate cancer. Analyses were performed using real-time polymerase chain reaction. miRNA-93 showed a significant negative correlation between expression in tumour tissue and plasma in patients with metastatic prostate cancer. Furthermore, the plasma level of miRNA-93 significantly decreased after treatment in patients with local/locally advanced prostate cancer compared to baseline plasma level. The expression of six microRNAs (let-7b, miRNA-34a, -125b, -143, -145 and -221) was downregulated, and three microRNAs (miRNA-21, -25 and miRNA-93) were upregulated in tumour tissue compared to benign prostate tissue. In plasma, six microRNAs were upregulated (miRNA-21, -125b, -126, -141, -143 and -375), while let-7b was downregulated in patients with metastatic prostate cancer compared to the control cohort. In the metastatic prostate cancer cohort, the expression of four microRNAs (miRNA-125b, -126, -143 and -221), and miRNA-141 in tissue was associated with Gleason score and prostate-specific antigen, respectively. The expression of miRNA-93 in tumour tissue was correlated with matched plasma levels and showed a significant decrease in plasma level after intervention in local prostate cancer. Differential expression between tumour and benign prostate was detected for several microRNAs in both tissue and plasma.

Metastatic castration resistant prostate cancer (mCRPC) is associated with high mortality, where monitoring of disease activity is still a major clinical challenge. The role of microRNAs (miRs) has been widely investigated in prostate cancer with both diagnostic and prognostic potential. The aim of this study was to investigate the relationship between circulating miRs and treatment outcome in mCRPC patients. The relative expression of five miRs (miR-93-5p, -125b-1-5p, -141-3p, -221-3p, and miR-375-3p) was investigated in plasma samples from 84 mCRPC patients; 40 patients were treated with docetaxel (DOC cohort) and 44 patients with abiraterone (ABI cohort). Blood was sampled at baseline before treatment start and at radiological progression. The plasma levels of four miRs; miR-93-5p, -141-3p, -221-3p, and miR-375-3p decreased significantly after treatment initiation in patients receiving docetaxel, and for miR-141-3p and miR-375-3p the level increased again at the time of radiological progression. In the patients treated with abiraterone, the plasma level of miR-221-3p likewise decreased significantly after the first treatment cycle. High baseline levels of both miR-141-3p and miR-375-3p were significantly associated with a shorter time to radiological progression in both cohorts. Additionally, high baseline levels of miR-141-3p and miR-221-3p were significantly associated with a shorter overall survival (OS) in the ABI cohort, while high levels of miR-141-3p and miR-375-3p were significantly associated with shorter OS in the DOC cohort. Plasma levels of miR-141-3p and miR-375-3p may predict time to progression in mCRPC patients treated with docetaxel or abiraterone. The clinical impact of these findings is dependent on validation in larger cohorts.

Background Overtreatment is a well‐known clinical challenge in local prostate cancer (PCa). Although risk assessment models have contributed to a better stratification of patients with local PCa, a tailored management is still in its infancy. Over the last few decades, microRNAs (miRNAs) have shown promising results as biomarkers in PCa. The aim of this study was to investigate circulating miRNAs after management of local PCa. Methods The relative expression of four miRNAs (miRNA‐21, ‐93, ‐125b, and miRNA‐221) was assessed in plasma from 149 newly diagnosed patients with local or locally advanced PCa. Real‐time polymerase chain reaction was used for analysis. A baseline sample at time of diagnosis and a follow‐up sample after 6 months were assessed. The patients were grouped in an interventional cohort (radical prostatectomy, curative intent radiotherapy, or androgen‐deprivation therapy alone) and an observational cohort (watchful waiting or active surveillance). Results In the interventional cohort, levels of both miRNA‐93 and miRNA‐221 were significantly lower in the follow‐up samples compared to baseline z = −2.738, P = 0.006, and z = −4.498, P < 0.001, respectively. The same observation was recorded for miRNA‐125b in the observational cohort ( z = −2.656, P = 0.008). Both miRNA‐125b and miRNA‐221 were correlated with risk assessment r = 0.23, P = 0.015, and r = 0.203, P = 0.016 respectively, while miRNA‐93 showed tendency to significant correlation with the prostatectomy Gleason score ( r = 0.276, P = 0.0576). Conclusions The current results indicate a possible role of miRNA‐93 and miRNA‐221 in disease monitoring in localized and locally advanced PCa. Larger studies are warranted to assess the clinical impact of these biomarkers.

e16507 Background: Metastatic castration resistant prostate cancer (mCRPC) is associated with high mortality. Monitoring of disease activity at this stage, with lack of validated prognostic models, is still a major clinical challenge. The role of microRNAs (miRNAs) has been widely investigated in prostate cancer with both diagnostic and prognostic potential. The aim of this study was to investigate the relationship between circulating miRNAs and treatment outcome in mCRPC patients. Methods: The relative expression of four miRNAs was investigated in plasma samples from 84 mCRPC patients; 40 patients were treated with docetaxel and 44 patients with abiraterone. Real-time polymerase chain reaction was used for analysis. Blood was sampled at baseline, before the second treatment cycle, and at radiological progression (RP). Associations to prognoses were analyzed using the Cox Regression analyses. Results: The plasma levels of all four miRNAs decreased significantly after treatment initiation in patients receiving docetaxel, and for miRNA-141 and miRNA-375 the level increased again at the time of RP. High baseline levels of miRNA-141 were significantly associated with a shorter time to RP in patients receiving both abiraterone, hazard ratio (HR) 3.18 (95% confidence interval (CI) 1.31-7.32), p < 0.01, and docetaxel HR 2.56 (95% CI 1.45-4.50), p < 0.01, and a shorter overall survival (OS), HR 3.20 (95% CI 1.25-9.37), p = 0.02, and HR 1.77 (95% CI 1.07-2.83), p = 0.02, respectively. Likewise, high baseline levels of miRNA-375 were also significantly associated with a shorter time to RP in both cohorts and OS in patients receiving docetaxel. Conclusions: Plasma levels of miRNA-141 and miRNA-375 were of prognostic importance in patients with mCRPC receiving both abiraterone and docetaxel and may be used in treatment monitoring irrespective of treatment modality.