Background We identify and validate accurate diagnostic biomarkers for prostate cancer through a systematic evaluation of DNA methylation alterations. Materials and methods We assembled three early prostate cancer cohorts (total patients = 699) from which we collected and processed over 1300 prostatectomy tissue samples for DNA extraction. Using real‐time methylation‐specific PCR, we measured normalized methylation levels at 15 frequently methylated loci. After partitioning sample sets into independent training and validation cohorts, classifiers were developed using logistic regression, analyzed, and validated. Results In the training dataset, DNA methylation levels at 7 of 15 genomic loci (glutathione S‐transferase Pi 1 [GSTP1], CCDC181, hyaluronan, and proteoglycan link protein 3 [HAPLN3], GSTM2, growth arrest‐specific 6 [GAS6], RASSF1, and APC) showed large differences between cancer and benign samples. The best binary classifier was the GAS6/GSTP1/HAPLN3 logistic regression model, with an area under these curves of 0.97, which showed a sensitivity of 94%, and a specificity of 93% after external validation. Conclusion We created and validated a multigene model for the classification of benign and malignant prostate tissue. With false positive and negative rates below 7%, this three‐gene biomarker represents a promising basis for more accurate prostate cancer diagnosis.

S.M.N. and G.H. contributed equally towards the data analysis and article preparation. ObjectivesTo report the 3-year follow-up of a Phase I study of magnetic resonance imaging (MRI)-guided transurethral ultrasound ablation (TULSA) in 30 men with localised prostate cancer. Favourable 12-month safety and ablation precision were previously described. Patients and MethodsAs a mandated safety criterion, TULSA was delivered as near whole-gland ablation, applying 3-mm margins sparing 10% of peripheral prostate tissue in 30 men. After 12-month biopsy and MRI, biannual follow-up included prostate-specific antigen (PSA), adverse events (AEs), and functional quality-of-life assessment, with repeat systematic biopsy at 3 years. ResultsA 3-year follow-up was completed by 22 patients. Between 1 and 3 years, there were no new serious or severe AEs. Urinary and bowel function remained stable. Erectile function recovered by 1 year and was stable at 3 years. The PSA level decreased 95% to a median (interquartile range) nadir of 0.33 (0.1-0.4) ng/mL, stable to 0.8 (0.4-1.6) ng/mL at 3 years. Serial biopsies identified clinically significant disease in 10/29 men (34%) and any cancer in 17/29 (59%). By 3 years, seven men had recurrence (four histological, three biochemical) and had undergone salvage therapy without complications (including six prostatectomies). At 3 years, three of 22 men refused biopsy, and two of the 22 (9%) had clinically significant disease (one new, one persistent). Predictors of salvage therapy requirement included less extensive ablation coverage and higher PSA nadir. ConclusionWith 3-year Phase I follow-up, TULSA demonstrates safe and precise ablation for men with localised prostate cancer, providing predictable PSA and biopsy outcomes, without affecting functional abilities or precluding salvage therapy.

Introduction: This study aims to assess the longer-term functional, anatomical, and metabolic outcomes of patients who underwent Studer neobladder (SNB) urinary diversion. Methods: A retrospective review of patients who underwent SNB at a single center from 1995–2017 (n=116) was performed. Demographics, comorbidities, pathological data, and longer-term functional, anatomical, and metabolic outcomes were collected from hospital records. The primary outcome was voiding function of patients at most recent followup. Secondary outcomes included postoperative complications, renal function, nephrolithiasis, infections, and metabolic outcomes. Results: Excluding those with incomplete followup data, 72 patients with minimum followup of one year were included for analysis. Median followup was 70±11 months, with 52.8% of patients having ≥5 years of followup. Clean intermittent catheterization (CIC) was used by 22.2% of patient at most recent followup, which was mostly necessitated by bladder overdistension, deteriorating renal function, or recurrent urosepsis despite timed voiding. Patients experienced more daytime and nighttime urinary incontinence in the early postoperative setting that improved over time. Generally, renal function declined over time; poorer long-term renal function was predicted by hydronephrosis within one year (p=0.002). Conclusions: Longer-term followup of SNB reveals significant but manageable complications. Gradual decline in renal function was common. Strict adherence to bladder emptying protocols (e.g., timed voiding or CIC) may reduce incidence of renal deterioration, metabolic disorders, and urinary dysfunction. Early onset (<1 year) of hydronephrosis may indicate a need for intervention to preserve long-term renal function.

No abstract