Carbonic anhydrase IX (CAIX) is a cell surface protein expressed in over 90% of clear cell renal cell carcinoma (ccRCC), driven by hypoxia or Von-Hippel Lindau (VHL) loss. The phase 3 ZIRCON trial evaluated [Zr]girentuxi...Carbonic anhydrase IX (CAIX) is a cell surface protein expressed in over 90% of clear cell renal cell carcinoma (ccRCC), driven by hypoxia or Von-Hippel Lindau (VHL) loss. The phase 3 ZIRCON trial evaluated [Zr]girentuximab, a CAIX-targeted positron emission tomography (PET) radiotracer, and met its primary endpoint for the accurate detection of ccRCC in patients with renal masses. Many aggressive forms of non-ccRCC (nccRCC) can express CAIX, which is linked to a hypoxic state. A reanalysis of the trial was performed demonstrating the tracer also identified nccRCC, particularly in forms of papillary RCC (pRCC) with higher CAIX expression (H score) and PET avidity (SUVmax). The positive predictive value for any renal malignancy was 98%, with sensitivity/specificity of 82% and 87%, respectively. This suggests [Zr]girentuximab has applications beyond the detection of ccRCC in primary renal masses and may have implications to management of nccRCC. PATIENT SUMMARY: The ZIRCON phase 3 trial used an imaging agent ([Zr]girentuximab) with a primary focus to detect the most common kidney cancer, clear cell renal cell carcinoma. Other forms of kidney cancer can express the marker that the imaging agent can identify. The additional analysis showed that when positive, 98% of cases were correctly identified as any form of cancer.
BACKGROUND AND OBJECTIVE: Perioperative bleeding is common. Evidence for tranexamic acid (TXA) in urology remains limited and conflicting, and major urologic guidelines provide no recommendations. In an a priori planned...BACKGROUND AND OBJECTIVE: Perioperative bleeding is common. Evidence for tranexamic acid (TXA) in urology remains limited and conflicting, and major urologic guidelines provide no recommendations. In an a priori planned analysis, we evaluated TXA among patients undergoing urologic surgery in POISE-3. METHODS: POISE-3 was an international randomized trial of patients undergoing surgery with bleeding and cardiovascular risk factors. Participants received TXA (1 g intravenous bolus at surgery start and end) or placebo. The primary efficacy outcome was a 30-day bleeding composite (life-threatening/major/critical organ), and the primary safety outcome was a 30-day thrombosis composite (myocardial injury after noncardiac surgery [MINS], nonhemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism [VTE]). KEY FINDINGS AND LIMITATIONS: Among 1124 urologic participants (556 TXA and 568 placebo), 489 had laparoscopic/robotic, 360 open, 244 transurethral, and 31 percutaneous surgery. The composite bleeding outcome occurred in 45 (8.1%) with TXA and in 62 (10.9%) with placebo (hazard ratio [HR] = 0.73, 95% confidence interval [CI] = 0.50-1.07). Major bleeding occurred in 34 (6.1%) with TXA and in 54 (9.5%) with placebo (HR = 0.63, 95% CI = 0.41-0.97). The composite safety outcome occurred in 67 (12.1%) with TXA and in 62 (10.9%) with placebo (HR = 1.12, 95% CI = 0.79-1.58; MINS: 62 vs 58; strokes: 2 vs 2; VTEs: 3 vs 3). We identified no interactions by surgical approach, cancer status, or recent antithrombotic usage. Patient-important thrombotic events were few, limiting precision for stroke and VTE estimates. CONCLUSIONS AND CLINICAL IMPLICATIONS: TXA reduced major bleeding and supports perioperative use in urologic surgery, especially when the bleeding risk is high.
Baboudjian M, Creta M, Pyrgidis N
… +14 more, Moris L, Duran MB, de Nunzio C, Elterman D, Hashim H, Herrmann TRW, Karavitakis M, Malde S, Netsch C, Rieken M, Sakalis V, Tutolo M, Schouten N, Cornu JN
CONTEXT: The European Association of Urology (EAU) male lower urinary tract symptoms (MLUTS) Guideline Panel has updated its evidence-based guidelines and recommendations 2026 for the management of MLUTS. OBJECTIVES: To...CONTEXT: The European Association of Urology (EAU) male lower urinary tract symptoms (MLUTS) Guideline Panel has updated its evidence-based guidelines and recommendations 2026 for the management of MLUTS. OBJECTIVES: To present a summary of the 2026 MLUTS guideline updated with standardised methodology to provide reproducible evidence for the management of MLUTS. EVIDENCE ACQUISITION: For the 2026 EAU Guidelines on non-neurogenic male LUTS, evidence was identified through a structured review across Medline, EMBASE, and the Cochrane Library, prioritising systematic reviews with meta-analysis, randomised controlled trials and prospective comparative studies. Literature search was conducted from 1 May 2023 to 1 May 2025. A detailed search strategy is available at https://uroweb.org/guidelines/management-of-non-neurogenic-male-luts/publications-appendices. EVIDENCE SYNTHESIS: Clinical practice recommendations were updated across all chapters of the male LUTS guideline based on a structured literature search. Included studies consisted predominantly of systematic reviews, randomised controlled trials, and prospective comparative studies. Updates addressed diagnostic evaluation, conservative and surgical management of benign prostatic obstruction, and for the first time, a dedicated section on voiding dysfunction in young men. CONCLUSIONS: The 2026 MLUTS Guidelines have been updated by the multidisciplinary Panel of experts employing methodological standards to provide a contemporary evidence base for the management of MLUTS. PATIENT SUMMARY: The European Association of Urology Male Lower Urinary Tract Symptoms Guidelines Panel has reviewed the available scientific evidence on non-neurogenic male lower urinary tract symptoms to develop international recommendations for the diagnosis and management of men with LUTS.
Local and androgen-deprivation therapies are guideline recommendations in localized and metastatic prostate cancer, respectively. However, in select patients the alternative use of radiopharmaceutical therapies may be co...Local and androgen-deprivation therapies are guideline recommendations in localized and metastatic prostate cancer, respectively. However, in select patients the alternative use of radiopharmaceutical therapies may be considered to delay or avoid quality-of-life decline associated with other systemic treatments.
Emmett L, Papa N, Sartor O
… +30 more, Morris MJ, Subramaniam S, Crumbaker M, Ayati N, Chen J, Herrmann K, Gafita A, Swiha M, Joshua AM, Weickhardt A, Lee ST, Ng S, Francis RJ, Goh JC, Pattison DA, Ho B, Khan S, Tan TH, Bills M, Nguyen A, Thein T, Sidhom G, Wong K, Martin AJ, Hofman MS, Sandhu S, Thomas H, Stockler MR, Davis ID, ENZA-p Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP)
BACKGROUND AND OBJECTIVE: Interim [Ga]Ga-prostate-specific membrane-antigen positron emission tomography/computed tomography (PSMA-PET/CT) has prognostic potential for overall survival (OS) in metastatic castrate-resista...BACKGROUND AND OBJECTIVE: Interim [Ga]Ga-prostate-specific membrane-antigen positron emission tomography/computed tomography (PSMA-PET/CT) has prognostic potential for overall survival (OS) in metastatic castrate-resistant prostate cancer (mCRPC), although evidence is limited. This ENZA-p sub-study evaluated 3-mo PSMA-total-tumor-volume (PSMA-TTV) as a prognostic biomarker for OS with enzalutamide ± [Lu]Lu-PSMA-617. DESIGN, SETTING AND PARTICIPANTS: ENZA-p is a randomized, phase 2 trial. Participants with mCRPC and risk factors for early treatment failure with enzalutamide were randomized (1:1) to enzalutamide or enzalutamide + [Lu]Lu-PSMA-617. Participants underwent baseline and 3-mo [Ga]Ga-PSMA-11-PET/CT, quantified to derive PSMA-TTV. We evaluated the prognostic value of PSMA-TTV change, and residual PSMA-TTV at 3-mo for OS (NCT04419402). RESULTS AND LIMITATIONS: This sub-study included 152/162 (94%) randomized participants with a 3-mo PSMA-PET. Median OS was 27 mo (95% confidence interval [CI] 23-30). Baseline median PSMA-TTV 230 ml (interquartile range [IQR] 75-635) and 3-mo PSMA-TTV 103 ml (IQR 24-457). The median change in PSMA-TTV from baseline was -34% (IQR -76% to 16%) with 50/152 (33%) participants with increase in PSMA-TTV. Any increase versus decrease in PSMA-TTV at 3-mo was associated with shorter OS (HR 2.52, 95% CI 1.65-3.85) and decreased 2-yr survival 30% (95% CI 17-43) versus 67% (95% CI 56-75) (log-rank p < 0.0001). Residual 3-mo PSMA-TTV higher versus lower than the median (103 ml) was associated with shorter OS (HR 3.76, 95% CI 2.39-5.92) and lower 2-yr survival 34% (95% CI 23-45) versus 76% (95% CI 64-84) (log-rank p < 0.0001). This association was independent of treatment arm and prostate-specific antigen (PSA) response. CONCLUSIONS: PSMA-TTV at 3 mos was prognostic for OS independent of study treatment and PSA response in ENZA-p, warranting further prospective validation of interim PSMA-PET response criteria.
BACKGROUND AND OBJECTIVE: Trimodality therapy (TMT) is an accepted bladder-preserving option for selected patients with muscle-invasive bladder cancer (MIBC). Pembrolizumab has demonstrated activity in MIBC and may enhan...BACKGROUND AND OBJECTIVE: Trimodality therapy (TMT) is an accepted bladder-preserving option for selected patients with muscle-invasive bladder cancer (MIBC). Pembrolizumab has demonstrated activity in MIBC and may enhance the effects of chemotherapy and radiation. We evaluated the safety and efficacy of adding pembrolizumab to TMT. METHODS: In this multicenter phase 2 trial, patients with MIBC received one dose of pembrolizumab followed by maximal transurethral resection, then definitive bladder radiation with concurrent low-dose gemcitabine and pembrolizumab every 3 wk for three doses. The primary end point was 2-yr bladder-intact disease-free survival (BIDFS). Secondary end points included safety, metastasis-free survival (MFS), and overall survival (OS). KEY FINDINGS AND LIMITATIONS: Fifty-four patients were enrolled, including 48 in the efficacy cohort; 67% had clinical stage T2 disease. The 2-yr BIDFS was 60% (95% confidence interval [CI], 45-73). Two-yr MFS and OS were 81% (95% CI, 66-92) and 83% (95% CI, 69-91), respectively. Grade ≥3 treatment-related adverse events occurred in 25% of patients. Limitations include the single-arm design and modest sample size. CONCLUSIONS AND CLINICAL IMPLICATIONS: Pembrolizumab combined with gemcitabine-based chemoradiation was feasible and showed efficacy comparable to standard TMT. Ongoing phase 3 trials will further define its role in bladder preservation.
Testicular germ cell tumor (GCT) has survival rates exceeding 90% and thus contemporary research has focused on reducing morbidity. While chemotherapy is efficacious, long-term effects are significant. Primary retroperit...Testicular germ cell tumor (GCT) has survival rates exceeding 90% and thus contemporary research has focused on reducing morbidity. While chemotherapy is efficacious, long-term effects are significant. Primary retroperitoneal lymphadenectomy (P-RPLND) has been offered, and postchemotherapy lymphadenectomy (PC-RPLND) is considered, based on residual node size, to reduce overtreatment. A significant number of patients have necrosis in the retroperitoneum and are thus overtreated. Circulating tumor DNA (ctDNA) may be used to determine which patients would benefit from RPLND. This retrospective analysis sought to determine the performance of ctDNA to detect retroperitoneal GCT only, teratoma only, and GCT/teratoma. All patients had a ctDNA obtained preoperatively and at 3, 6, and 12 months postoperatively. Ninety-two patients underwent P or PC-RPLND. The sensitivity, specificity, and positive predictive values (PPVs) and negative predictive values (NPVs) for detecting active GCT/teratoma in the entire cohort were 60%, 87%, 96%, and 30%, respectively. For GCT only these were 85%, 75%, 73%, and 86%. For teratoma only, these were 31%, 34%, 23%, and 43%. These findings indicate that patients with a positive ctDNA likely harbor active GCT and/or teratoma, as suggested by a PPV of 96%. Future studies may use whole-genome ctDNA assays to improve detection of teratoma and incorporate ctDNA into surveillance protocols.
The International Society of Urological Pathology Florence Multidisciplinary Consensus Conference establishes a contemporary framework for the definition and standardized reporting of genitourinary cancer precursor lesio...The International Society of Urological Pathology Florence Multidisciplinary Consensus Conference establishes a contemporary framework for the definition and standardized reporting of genitourinary cancer precursor lesions. These consensus recommendations provide evidence-based guidance for diagnostic practice, inform clinical management, and define priorities for future research in genitourinary premalignancy.
Kidney injury molecule 1 (KIM-1) is a promising biomarker in adjuvant clear cell renal cell carcinoma (ccRCC), but its relevance in advanced ccRCC or papillary RCC (pRCC) remains unclear. CALYPSO (NCT02819596) was a pros...Kidney injury molecule 1 (KIM-1) is a promising biomarker in adjuvant clear cell renal cell carcinoma (ccRCC), but its relevance in advanced ccRCC or papillary RCC (pRCC) remains unclear. CALYPSO (NCT02819596) was a prospective, multi-arm trial that evaluated durvalumab alone or in combination with tremelimumab or savolitinib in metastatic ccRCC and pRCC. Circulating KIM-1 levels were measured at baseline and on-treatment. The primary endpoint was to explore if KIM-1 levels were raised in pRCC. Analyses were exploratory and p values were nominal. KIM-1 was measured in 123 patients with ccRCC and 31 patients with pRCC. Higher median concentrations occurred in pRCC compared to ccRCC (7835 vs 5470 pg/ml, p = 0.05). Reductions in KIM-1 levels occurred with systemic therapy in both ccRCC and pRCC (-59.2% and -32% respectively). In pRCC, radiological responders had significantly lower baseline KIM-1 levels (p = 0.025). In ccRCC, high baseline KIM-1 levels were associated with significantly shorter overall survival (OS) (hazard ratio [HR] 1.77; 95% CI, 1.15-2.72; p = 0.01). Also, an increase in KIM-1 during therapy was linked to worse progression-free survival (HR 1.7; 95% CI, 1.13-2.58; p = 0.01) and OS (HR 1.95; 95% CI, 1.23-3.08; p = 0.004) in ccRCC. This exploratory analysis supports the utility of KIM-1 in advanced ccRCC and pRCC.