European urology focus最新文献

Intravesical instillation of gemcitabine is an effective treatment for non-muscle-invasive bladder cancer but is hampered by short indwelling times, which can limit tissue exposure and efficacy. Gemcitabine intravesical system (gem-iDRS; formerly TAR-200) is a novel intravesical drug-releasing system designed for prolonged local gemcitabine delivery within the bladder, offering the potential for sustained tissue penetration. We investigated the penetration, tissue distribution, and retention of gemcitabine and its active metabolites following gem-iDRS administration versus traditional intravesical instillation in a preclinical model. Five female minipigs received either a 2-h bolus gemcitabine hydrochloride (n = 3) intravesical instillation or insertion of gem-iDRS (n = 2) into the bladder. Bladder tissue regions and layers (dome, left and right lateral walls, and trigone) were collected at postinstillation time points and analyzed using liquid chromatography-tandem mass spectrometry. Following traditional intravesical gemcitabine instillation, active phosphorylated metabolites were detected across bladder layers at 2 h but were undetectable by 24 h. In contrast, gem-iDRS maintained measurable metabolite levels across bladder regions and layers for at least 96 h. This small sample size and the use of only healthy animals limit the generalizability of the findings to tumor-bearing bladder tissue. These findings demonstrate that gem-iDRS prolongs bladder tissue exposure compared with traditional intravesical instillation of gemcitabine. PATIENT SUMMARY: Our study compared two different ways of delivering gemcitabine (a chemotherapy drug) into the bladder of minipigs. We found that gem-iDRS (a new intravesical drug-releasing system) kept gemcitabine and active metabolites in the bladder tissue for a longer time than the traditional way of delivering gemcitabine.

In men presenting with lower urinary tract symptoms (LUTS), prostate-specific antigen (PSA) testing has limited clinical value and frequently leads to false positives and unnecessary investigations. LUTS are more often related to benign enlargement than cancer. Evaluation should focus on symptom assessment and functional causes rather than routine PSA-driven testing.

Background and objective: Although the effects of 5-α-reductase inhibitors (5-ARIs) on prostate-specific antigen (PSA) have been well-studied, the effects on other kallikrein markers have not been firmly established. Accordingly, a statistical model based on blood measurements of four kallikreins-known commercially as the "4Kscore"-cannot be used for men taking 5-ARIs. We investigated how finasteride affects kallikrein markers and whether suitably adjusted marker levels could be used in the four-kallikrein model to accurately predict the prostate biopsy results.

Methods: We analyzed 500 participants from the Prostate Cancer Prevention Trial (PCPT) with PSA ≤3 ng/ml before finasteride and who had marker measurements after 1 yr on finasteride. Conversion factors were generated from this cohort to estimate prefinasteride marker levels in a separate PCPT cohort of 459 men on finasteride biopsied for cause. Adjusted marker levels were entered into the prespecified 4K model and performance characteristics assessed for predicting high-grade prostate cancer on biopsy.

Key findings and limitations: Finasteride use halved total PSA (β 0.51, 95% confidence interval 0.49, 0.54). human kallikrein 2 was also halved (β 0.50); free PSA and intact PSA were slightly more than halved (β 0.44 for both). Predictions from the 4K model using adjusted markers improved discrimination over adjusted total PSA alone (AUC 0.734 vs 0.595; p < 0.001). While this cohort underwent only sextant biopsy, the ProtecT model, created on 10-12 core biopsies was still well-calibrated at clinically important thresholds. In decision-curve analysis, the 4K model had the highest net benefit for risk thresholds of ≥7%.

Conclusions and clinical implications: The 4K model can be used to inform prostate biopsy decision-making in men taking 5-ARIs for at least 3 mo by incorporating adjusted kallikrein levels into the scoring algorithm.

Continuous treatment with an androgen receptor pathway inhibitor (ARPI) plus androgen deprivation therapy (ADT) in low-volume metastatic castration-sensitive prostate cancer (mCSPC) may lead to overtreatment, resulting in increased toxicity and higher costs. Evidence to guide a shorter duration of ARPI therapy is currently lacking. The Apa/Enza-short trial evaluates whether a 12-mo course of apalutamide or enzalutamide is noninferior to continuous treatment in low-volume mCSPC. This randomized, open-label, noninferiority study enrolls 400 patients across Dutch hospitals. After 12 mo of ADT + ARPI, eligible patients are randomized to continue or discontinue ARPI treatment, with reinitiation permitted upon prostate-specific antigen (PSA) increase. The primary end point is clinical progression-free survival (cPFS). If noninferiority is demonstrated, this strategy could maintain efficacy while reducing treatment-related toxicity and health care costs.

The antimicrobial resistance of Mycoplasma genitalium is an escalating crisis that highlights a need for closer collaboration between clinical guideline panels and regulatory bodies. We propose a approach whereby the European Medicines Agency and European Association of Urology could work together for a bridge between regulatory oversight and proactive clinical leadership.

Background and objective: Prostate biopsies remain a key step in the diagnosis of prostate cancer and are performed either via a transrectal (TR) or a transperineal (TP) route. In general, the approaches are considered to provide similar diagnostic power. However, infectious complications appear to differ in favour of the TP approach. Furthermore, antibiotic prophylaxis is felt to have limited additional value in a TP biopsy, which aligns with antimicrobial stewardship principles. Urology association guidelines have provided conflicting recommendations on the best approach for a prostate biopsy. This systematic review aims to compare the infectious complications and antibiotic usage of the two approaches.

Methods: A systematic review and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines after registration with PROSPERO (CRD42024513309). MEDLINE, Embase, Scopus, and Web of Science were searched for articles published until April 1, 2025. Randomised controlled trials (RCTs) assessing infectious complications (fever, urinary tract infection, and hospitalisation with infectious complications) following a prostate biopsy were included. The risk of bias was assessed with the RoB 2 tool, and statistical analyses included visualisation through funnel and forest plots and assessing the publication bias via Egger's regression test.

Key findings and limitations: Ten RCTs were included in the analysis, encompassing 4188 prostate biopsies. Of seven studies reporting hospitalisation for infectious complications, the TP route showed significantly lower odds (odds ratio 0.23, 95% confidence interval [CI] 0.10-0.54; graphical abstract), reducing hospitalisation risk by 77% compared with the TR route. Postinterventional fever occurred less frequently, with an odds ratio of 0.68 (95% CI 0.52-0.89). There was no statistically significant difference in infectious complications after a TP biopsy with or without antibiotics. All TR route biopsies utilised antibiotic prophylaxis. The small number of eligible studies and the high risk of bias, as well as sparse data on bias in most studies, limit the power of our manuscript.

Conclusions and clinical implications: TP biopsy is associated with a lower admission risk due to postprocedural infection compared with TR biopsy. TP biopsy seems to be a safe procedure without antibiotics in patients without risk factors, advocating for enhanced antimicrobial stewardship in urology.