Round up

ERDAFITINIB IN PATIENTS WITH HIGH- AND INTERMEDIATE-RISK NONMUSCLE-INVASIVE BLADDER CANCER: FINAL ANALYSIS OF THE THOR-2 STUDY The phase II THOR-2 study evaluated oral erdafitinib, a pan-fibroblast growth factor receptor (FGFR) inhibitor, in patients with FGFR3/2-altered nonmuscle-invasive bladder cancer (NMIBC), including those with Bacillus Calmette–Guérin (BCG)-treated high-risk papillary disease, BCG-unresponsive carcinoma in situ (CIS) ± papillary tumors, and intermediate-risk NMIBC.1 In the randomized high-risk cohort (n = 73), erdafitinib significantly improved recurrence-free survival compared with intravesical chemotherapy, with median recurrence-free survival not reached versus 11.6 months (hazard ratio HR: 0.28). Among patients with BCG-unresponsive CIS ± papillary disease (n = 16), complete response rates were 94% at 8 weeks and 81% at 32 weeks, with a median duration of response of 23.3 months. In patients with intermediate-risk NMIBC (n = 18), the complete response rate was 89%, with durable disease control observed in most responders. Treatment-related adverse events were manageable, with hyperphosphatemia (76%) representing the most common toxicity. Despite early study termination and the limited sample size, these findings support FGFR-targeted therapy as a promising bladder-preserving treatment strategy in selected patients with NMIBC. PRIMARY NONCONTRAST MAGNETIC RESONANCE IMAGING FOR PROSTATE CANCER SCREENING: A RANDOMIZED CLINICAL TRIAL (PROSA) The PROSA trial was a prospective randomized controlled study evaluating whether contrast-free biparametric magnetic resonance imaging (bpMRI) could improve prostate cancer screening compared with the conventional prostate-specific antigen (PSA)-based approach.2 A total of 759 asymptomatic men aged 49–69 years were randomized to either an MRI-first screening strategy (arm A) or a PSA-triggered MRI strategy (arm B). Clinically significant prostate cancer (csPCa; International Society of Urological Pathology grade group ≥2) was detected more frequently in the MRI-first arm (4.6% vs. 1.8%), representing a 2.5-fold increase in detection. Importantly, nearly half of the csPCa cases identified in the MRI-first group had normal PSA levels, highlighting the limitations of PSA-based screening. Although biopsy rates were higher with MRI-first screening, overdiagnosis of low-grade cancer was not increased. Benefit–harm metrics, biopsy efficiency, and biopsy avoidance favored the MRI-first strategy. Economic analysis demonstrated favorable cost-effectiveness, with an incremental cost-effectiveness ratio of €2201.75 per additional csPCa detected. The study concludes that bpMRI is a feasible, effective, and economically sustainable population-based screening strategy for prostate cancer. FLEXIBLE URETEROSCOPY WITH A FLEXIBLE AND NAVIGABLE SUCTION URETERAL ACCESS SHEATH VERSUS MINI-PERCUTANEOUS NEPHROLITHOTOMY FOR TREATMENT OF 2–3 CM RENAL STONES: AN INTERNATIONAL, MULTICENTER, RANDOMIZED, NONINFERIORITY TRIAL This international, multicenter, randomized noninferiority trial (conducted across 12 centers, n = 720) compared flexible ureteroscopy using a flexible and navigable suction ureteral access sheath (FANS f-URS) with mini-percutaneous nephrolithotomy (mPCNL) for the treatment of 2–3 cm renal stones.3 Patients were randomized 1:1, with immediate computed tomography (CT)-confirmed stone-free status (SFS) as the primary endpoint. FANS f-URS achieved noninferior immediate SFS compared with mPCNL (84% vs. 85%; risk difference, −1.4%), meeting the prespecified 8% noninferiority margin. Three-month SFS was also comparable between the groups (90% vs. 92%). However, FANS f-URS required a longer operative time (88 vs. 59 min) but demonstrated significant perioperative advantages, including lower hemoglobin drop, a reduced transfusion rate (0.28% vs. 2.5%), less postoperative pain, shorter hospitalization (1 vs. 4 days), and superior quality-of-life improvement. Infectious complications and auxiliary procedure rates were similar between the groups. Notably, 22% of mPCNL cases required multiple tracts, likely contributing to the higher bleeding-related morbidity. These data suggest that, in experienced hands, FANS f-URS is a viable first-line alternative to mPCNL for selected patients with 2–3 cm renal calculi, offering equivalent stone clearance with reduced morbidity and faster recovery. PERIOPERATIVE APALUTAMIDE IN HIGH-RISK LOCALIZED PROSTATE CANCER The PROTEUS trial is a phase 3, double-blind, placebo-controlled study in which patients with newly diagnosed high-risk localized or locally advanced prostate cancer (Grade Group 8, PSA >20 ng/mL, and/or >T3 disease) were randomly assigned in a 1:1 ratio to receive androgen deprivation therapy (ADT) plus apalutamide (240 mg per day) (n = 1057) or ADT plus placebo.4 Patients received six cycles (28 days each) of neoadjuvant treatment (ADT plus apalutamide or ADT plus placebo), with cessation of apalutamide or placebo during the period from 2 weeks before radical prostatectomy with pelvic lymph node dissection to 4 weeks after prostatectomy, followed by six cycles (28 days each) of adjuvant treatment (ADT plus apalutamide or ADT plus placebo) after prostatectomy. The median follow-up was 61.7 months. The percentage of patients with a pathological complete response (pCR; defined as a pathological stage of ypT2 or lower) or minimal residual disease (defined as a tumor size of ≤ 5 mm in the greatest dimension) was significantly higher in the apalutamide group than in the placebo group (8.9% vs. 1.0%; odds ratio, 10.17; 95% confidence interval CI, 5.27–19.64; P < 0.001). Similarly, metastasis-free survival was significantly improved in the apalutamide group (5-year metastasis-free survival probability, 78.2% vs. 73.5%; HR for distant metastasis or death, 0.80; 95% CI, 0.67–0.96; P = 0.02). Event-free survival, time to first subsequent treatment, and time to distant metastasis significantly favored ADT plus apalutamide (P < 0.001 for all between-group comparisons). Grade 3 or 4 adverse events occurred in 39.6% of patients in the apalutamide group and 31.0% of those in the placebo group. PERIOPERATIVE ENFORTUMAB VEDOTIN AND PEMBROLIZUMAB IN CISPLATIN-INELIGIBLE MUSCLE-INVASIVE BLADDER CANCER: RESULTS FROM THE PHASE III KEYNOTE-905/EV-303 TRIAL The phase III, open-label KEYNOTE-905/EV-303 trial evaluated perioperative enfortumab vedotin plus pembrolizumab (EV-P) versus radical cystectomy alone in 344 patients with muscle-invasive bladder cancer who were ineligible for or declined cisplatin chemotherapy.5 Participants with nonmetastatic muscle-invasive bladder cancer (stage T2–T4a with N0M0, or T1–T4a with N1M0) with predominantly (≥50%) urothelial histologic features received three neoadjuvant cycles of EV-P before surgery, followed by adjuvant EV (total of 9 cycles) and pembrolizumab (total of 17 cycles) after surgery. The median follow-up was 25.6 months. Surgery was performed in 87.6% of participants in the EV-P group and 89.7% in the control group. Two-year event-free survival was significantly improved with EV-P compared with surgery alone (74.7% vs. 39.4%; HR, 0.40; P < 0.001), while overall survival (OS) was also superior (79.7% vs. 63.1%; HR, 0.50; P < 0.001). pCR rates were markedly higher with EV-P (57.1% vs. 8.6%). Pathological downstaging occurred in 65.9% versus 12.6% of patients. Although adverse events were more frequent with EV-P (grade ≥3 adverse events: 71.3%), the safety profile was manageable and consistent with previous studies. The trial establishes perioperative EV-P as a highly effective treatment option for cisplatin-ineligible muscle-invasive bladder cancer. ROBOT-ASSISTED VERSUS OPEN BLADDER CUFF EXCISION AFTER RADICAL NEPHROURETERECTOMY The oncological safety of robotic bladder cuff excision (BCE), particularly regarding the risk of intravesical recurrence, remains a concern. This multicenter retrospective study compared robot-assisted BCE (RA-BCE) and open BCE (O-BCE) following radical nephroureterectomy for upper tract urothelial carcinoma.6 Among 487 patients from 8 French centers, 37% underwent RA-BCE and 63% underwent O-BCE, with a median follow-up of 30.1 months. Three-year intravesical recurrence-free survival (68.9% vs. 59.7%, P = 0.10), extravesical recurrence-free survival (69.2% vs. 63.8%, P = 0.20), cancer-specific survival (85.5% vs. 76.2%, P = 0.08), and OS (76.0% vs. 67.6%, P = 0.10) were comparable between the groups. Multivariable analysis confirmed that there was no significant association between RA-BCE and recurrence or mortality outcomes. However, RA-BCE was associated with lower overall complication rates (10.1% vs. 21.3%, P = 0.02), fewer major complications (4.7% vs. 7.1%, P = 0.02), and shorter hospital stay (5 vs. 7 days, P < 0.01). These findings support RA-BCE as a safe and effective minimally invasive alternative for localized upper tract urothelial carcinoma. VALIDATION AND TESTING OF AN IN VITRO MODEL TO STUDY MEDICAL TREATMENTS FOR ANTERIOR URETHRAL STRICTURE DISEASE: ASSESSING THE POTENTIAL EFFICACY OF PHOSPHODIESTERASE-4 INHIBITION AND TESTOSTERONE Anterior urethral stricture disease (aUSD) remains challenging to manage because of high recurrence rates following endoscopic treatment and concerns regarding paclitaxel-coated balloon therapy.7 This study validated a novel in vitro model of aUSD and evaluated phosphodiesterase-4 (PDE4) inhibition and testosterone as potential therapeutic strategies. PDE4 expression was assessed in five cadaveric male urethras, demonstrating uniform expression of PDE4-A, PDE4-B, and PDE4-D throughout the anterior urethra, while PDE4-C was absent. Fibroblasts and epithelial cells were successfully cultured from healthy urethras (n = 3) and idiopathic bulbar strictures (n = 3). Transforming growth factor-β1 stimulation induced dose-dependent changes in fibroblast proliferation and fibrosis-related gene expression. In stricture-derived fibroblasts, roflumilast and testosterone preserved cell viability and proliferation, unlike paclitaxel, which significantly reduced both. High-dose roflumilast reduced PDGFB expression (P = 0.03), while testosterone decreased PDE4D expression (P = 0.02–0.04). These findings establish a reproducible human cell-based model and suggest that PDE4 inhibitors and testosterone may represent promising noncytotoxic alternatives for the management of aUSD. TIME TOXICITY OF INTRAVESICAL BACILLUS CALMETTE–GUÉRIN VERSUS SEQUENTIAL INTRAVESICAL GEMCITABINE AND DOCETAXEL (GEM/DOCE) FOR NONMUSCLE-INVASIVE BLADDER CANCER Gem/Doce administration, compared with BCG, entails a significant treatment burden for patients and the healthcare system.8 Time toxicity has been proposed as a complementary endpoint to financial toxicity and quality of life in oncology, capturing the cumulative hours patients devote to clinic visits, procedures, hospitalizations, and recovery, all of which may influence treatment preference, satisfaction, and adherence. This retrospective single-center study evaluated the time toxicity of intravesical BCG versus sequential Gem/Doce in 133 patients with NMIBC treated between 2022 and 2025. Sixty-five percent of patients received BCG, while 35% received Gem/Doce. Although demographic and tumor characteristics were largely comparable, patients in the Gem/Doce group were more likely to have received prior BCG therapy. The median time per instillation was significantly longer with Gem/Doce (192 min) than with BCG (179 min), representing an additional 27 min per treatment. Across the standard 6-week induction course, Gem/Doce required 1188 min compared with 845 min for BCG, resulting in an additional 306 min (5.1 h) of healthcare-related time. However, transurethral resection of bladder tumor duration, office-visit times, hospitalization rates (23% vs. 30%), and treatment completion rates (91% vs. 96%) were similar between the groups. The authors concluded that although Gem/Doce imposes a greater time burden, this modest increase should be weighed against treatment efficacy, BCG availability, patient preferences, and tolerability when counseling patients with NMIBC. PREVENTION OF URINARY STONES WITH HYDRATION (PUSH TRIAL): A RANDOMISED CLINICAL TRIAL OF AN ADHERENCE INTERVENTION Increased fluid intake is universally recommended to decrease the risk of recurrent urinary stones; however, long-term adherence remains challenging. The Prevention of Urinary Stones With Hydration (PUSH) trial was a large-scale study involving 1,658 participants and aimed to determine whether multicomponent behavioral interventions – such as smart water bottles (Bluetooth-enabled devices that measured and recorded fluid intake), coaching, and incentives – could prevent kidney stone recurrence by improving hydration.9 Participants had a history of urinary stone disease and low 24-h urine volumes. All participants underwent low-dose noncontrast CT, while participants younger than 18 years underwent renal ultrasonography; all participants also completed a 24-h urine collection. Although participants using these interventions achieved greater increases in urine volume than those receiving standard care, this improvement did not translate into fewer clinical stone events. Over a 2-year period, stone recurrence occurred in 18.6% of the intervention group compared with 19.8% of the control group, a difference that was not statistically significant. The study demonstrated that although behavioral strategies are safe and effective in promoting increased fluid intake, they do not provide additional protection against new stone formation or stone growth when combined with existing medical guidelines. No episodes of hyponatremia requiring hospitalization (the predefined safety endpoint) were reported; however, asymptomatic hyponatremia occurred more frequently in the intervention group than in the control group (1.5% vs. 0.2%; P = 0.018). Ultimately, the findings suggest that while these high-technology interventions can successfully modify hydration behavior, they do not necessarily translate into improved long-term clinical outcomes in patients with a history of urinary stone disease. TRANSURETHRAL INJECTION OF AUTOLOGOUS MICRONIZED ADIPOSE TISSUE FOR REFRACTORY INTERSTITIAL CYSTITIS/BLADDER PAIN SYNDROME Regenerative medicine approaches using mesenchymal stromal cells (MSCs) derived from adipose tissue (AT) have gained attention because of their potential to protect against tissue injury in interstitial cystitis/bladder pain syndrome (IC/BPS) through multiple mechanisms.10 Molecular studies suggest that MSCs may migrate into the bladder, contribute to urothelial repair, modulate immune responses, and reduce inflammation.11,12 Several studies have focused on adipose-derived MSCs because of their abundance and ease of harvest, demonstrating promising results with minimal adverse events.13,14 This retrospective pilot study evaluated the feasibility, safety, and preliminary efficacy of transurethral injection of autologous micronized AT in 20 patients with refractory IC/BPS.10 AT was harvested by liposuction, mechanically processed using the Matrigen device, and injected into the bladder submucosa.10 At 6 months, 65% of patients achieved clinically meaningful improvement in pain and/or urgency symptoms. Significant improvements were observed in quality of life 36-Item Short Form Survey (SF-36), Interstitial Cystitis Problem Index scores, sexual function scores, urgency symptoms, bladder capacity (from 275 to 325 mL), and postvoid residual urine volume (from 80 to 40 mL). Cystoscopic evaluation demonstrated marked improvement in bladder mucosal appearance, including regression of some Hunner lesions. The procedure was generally well tolerated, with no serious adverse events or immunological complications reported. Although encouraging, the study was limited by its small sample size, retrospective design, lack of a control group, and short follow-up duration, necessitating larger randomized studies to validate these findings. Financial support and sponsorship: Nil. Conflicts of interest: There are no conflicts of interest.