PSA screening has led to an over-diagnosis of prostate cancer (PCa) and unnecessary biopsies of benign conditions due to its low cancer specificity. Consequently, more accurate, preferentially non-invasive, tests are needed. We aim to evaluate the potential of semen sEV (small extracellular vesicles) tsRNAs (tRNA-derived small RNAs) as PCa indicators. Initially, following a literature review in the OncotRF database and high-throughput small RNA-sequencing studies in PCa tissue together with the sncRNA profile in semen sEVs, we selected four candidate 5′tRF tsRNAs for validation as PCa biomarkers. RT-qPCR analysis in semen sEVs from men with moderately elevated serum PSA levels successfully shows that the differential expression of the four tRFs between PCa and healthy control groups can be detected in a non-invasive manner. The combined model incorporating PSA and specific tRFs (5′-tRNA-Glu-TTC-9-1_L30 and 5′-tRNA-Val-CAC-3-1_L30) achieved high predictive accuracy in identifying samples with a Gleason score ≥ 7 and staging disease beyond IIA, supporting that the 5′tRF fingerprint in semen sEV can improve the PSA predictive value to discriminate between malignant and indolent prostate conditions. The in silico study allowed us to map target genes for the four 5′tRFs possibly involved in PCa. Our findings highlight the synergistic use of multiple biomarkers as an efficient approach to improve PCa screening and prognosis.

Background: Penile prosthesis implantation (PPI) is an established treatment for erectile dysfunction (ED). Nevertheless, the effectiveness of and satisfaction with PPI in mainly psychogenic ED compared to mainly organic ED patients remain underexplored. Aim: To evaluate patient satisfaction outcomes following PPI in individuals diagnosed as mainly psychogenic ED vs. mainly organic ED. Methods: Twenty-five patients with psychogenic ED who underwent PPI were included. Data were collected from medical records and a follow-up assessment was done using the Quality of Life and Sexuality with Penile Prosthesis (QolSPP) questionnaire. Additionally, the patients filled out an ad hoc questionnaire including self-reported satisfaction rated on a 1-to-10 scale, the Global Assessment Questionnaire-Questions 1 and 2 (GAQ-1, 2), and the Sexual Encounter Profile Questions 2 and 5 (SEP-2, 5). Results were compared with those of 36 patients with mainly organic ED (control) for comparative analysis. Results: In the psychogenic ED group, 96% reported improved erections, 92% felt more confident initiating sex, 92% achieved penetration and 95% had satisfactory sexual encounters. The overall satisfaction score was 8.71 on a 10-point scale. Comparative analysis using the QolSPP questionnaire revealed statistically significant differences favouring the psychogenic group in 8 of 16 questions, regarding prosthesis satisfaction and overall well-being. Surgical complications were noted in 16% of the psychogenic group, compared to a 2.8% complication rate in the organic ED control group. Conclusions: The findings indicate high levels of satisfaction with PPI among patients with psychogenic ED, comparable to those with organic ED. However, an increase in complications in the psychogenic cohort highlights the need for careful consideration of surgical risks in this population.

The need for prostate cancer (PCa)-specific biomarkers that enable more accurate detection of the disease and better prediction of tumor aggressiveness remains ongoing due to the low cancer specificity of PSA screening. Several potential mRNA markers for diagnosing PCa, in tissue and urine, have been reported in the literature. In this study, we aim to explore the potential of selected prostate-specific molecules and transcripts contained in small extracellular vesicles (sEVs) in semen to predict PCa risk reclassification for patients with moderately elevated PSA levels—a clinical scenario where identifying truly non-invasive biomarkers is especially critical. RT-qPCR analysis in semen sEVs successfully showed differential expression of KLK3 and PCA3 genes between PCa and healthy controls, whereas CREB3L4, CCNQ and DUSP23 levels were related to the severity or degree of PCa affectation. Our findings also present strong evidence that classifiers based on combined long transcript levels in semen sEVs serve as effective biomarkers. They can be used alone or in combination with blood PSA and/or semen citric acid levels to improve the diagnosis of PCa and assess its severity and disease progression with high accuracy. This strategy would allow a more comprehensive assessment, increase prognostic accuracy, and facilitate accurate clinical decision-making in the management of PCa.

PSA testing plays an important role in the diagnostic workup of prostate cancer; despite this, its cancer specificity is a well-recognised limitation. Consequently, more reliable, non-invasive diagnostic tools that are capable of improving specificity while maintaining sensitivity are needed, thereby enabling better risk stratification, personalised patient management, and reduction in unnecessary invasive procedures. In this study, we characterised the small RNA profile—including miRNAs and tsRNAs—in seminal small extracellular vesicles (sEVs) using high-throughput sequencing to expand biomarker discovery for distinguishing benign from malignant prostate conditions in patients with moderately elevated PSA levels, a setting where non-invasive biomarkers are critically needed. Our analysis confirms a small number of differentially represented sncRNA transcripts contained in seminal sEVs between benign and malignant prostate disease, most of which are of low abundance. This result suggests that shared underlying molecular mechanisms are likely to occur between both prostate disease conditions, especially in patients with moderate PSA levels. Subsequent RT-qPCR analysis revealed differences in expression in PCa compared with healthy controls but not when compared with benign prostatic disease. Given the complexity of the underlying pathophysiological process and the heterogeneity in clinical phenotypes, this limitation was addressed through the application of multivariate approaches (including isomiRs or tRFs), which are proposed as fluid-based biomarkers for prostate cancer, collectively offering improved accuracy and enhancing the negative predictive value of PSA used in clinical settings.