GPNMB is considered a relatively specific marker for MiTF-associated renal cell carcinoma (RCC) and renal neoplasms with mTOR pathway alteration. However, more recent studies have broadened this view, demonstrating that its specificity is lower than previously thought due to expression in other renal tumour subtypes. In this study, we evaluated GPNMB expression in a cohort of clear cell papillary renal cell tumours (CCPRCT) and compared to a cohort of renal epithelial neoplasms with clear cell morphology. A total of 35 CCPRCTs were analysed, along with a control cohort of 50 renal tumours, comprising clear cell RCC (CCRCC; n = 32), multilocular cystic renal neoplasm of low malignant potential (MCRNLMP; n = 6), and RCC with fibromyomatous stroma (RCC FMS; n = 12). All CCPRCTs had typical morphologic features with strong and diffuse CK7 positivity. The majority of CCPRCTs (89%) showed GPNMB reactivity (diffuse weak/moderate in 20, and focal weak/moderate in 11 tumours). In the CCRCC and MCRNLMP group, 92% (35/38) did not show any GPNMB expression (29/32 CCRCCs and 6/6 MCRNLMPs). Among 12 RCC FMS, three tumours harbouring TSC1/2 alterations demonstrated diffuse strong GPNMB staining. In contrast, among 9 MTOR-mutated RCC FMS, diffuse moderate staining was observed in only 2 tumours; 6 tumours exhibited focal weak to moderate reactivity, and one showed diffuse weak staining. Weak to moderate GPNMB expression is frequently observed in CCPRCT. The GPNMB staining pattern identified in a substantial proportion of MTOR-mutated RCC FMS overlapped with that seen in CCPRCT. This finding underscores the limited specificity of GPNMB as a diagnostic marker.

Current World Health Organization (WHO) Classification of Urinary and Male Genital Tumours (2022) has introduced minor updates in the classification of renal cell carcinomas (RCC). Among the most notable changes is the recognition of a new category: molecularly defined RCC. This group comprises several distinct tumour entities characterized by specific genetic alterations. The inclusion of this category reflects the growing importance of molecular testing in the diagnosis, prognosis and treatment planning of renal malignancies. This review summarizes the basic information, clinical data, and treatment options of these rare RCCs. Due to the low prevalence of molecularly defined RCCs, the clinical management remains challenging, and standardized, evidence-based treatment guidelines are still lacking, particularly for the systemic therapy of advanced RCCs. As part of the review, a clinical case of a female patient with metastatic TFE3-translocated RCC is also presented, illustrating the diagnostic and therapeutic challenges.

Introduction: Doppler ultrasonography (DUSG) enables intraoperative assessment of renal perfusion during partial nephrectomy. This study evaluated the feasibility of DUSG and compared its outcomes with indocyanine green (ICG) fluorescence imaging and a control group (CG) without intraoperative perfusion imaging. Methods: We retrospectively analyzed 426 patients undergoing minimally invasive partial nephrectomy between 2018 and July 2025. Ischemia verification was performed using DUSG in 174 patients (41%) and ICG in 29 patients (7%). The CG included 223 patients (52%). Selection of imaging modality depended on the surgeon’s preference and intraoperative findings. Perioperative, oncological, and functional outcomes were analyzed using one-way analysis of variance and chi-square tests. Results: No significant differences were observed in tumor size, BMI, warm ischemia time, blood loss, RENAL score, or complication severity assessed by the Clavien-Dindo classification. Selective clamping and clamp adjustment were significantly more frequent in the DUSG and ICG groups compared with controls (both p < 0.001). Positive surgical margin rates were low and comparable between groups. Conclusion: Both DUSG and ICG represent safe and effective methods for ischemia verification; however, DUSG offers the advantages of lower cost, wider availability, and no risk of contrast-related adverse reactions, making it a practical option for routine clinical use.

Metastatic renal cell carcinoma (mRCC) is a serious malignancy often treated with tyrosine kinase inhibitors (TKIs). However, approximately half of mRCC patients do not benefit from TKIs. To identify a molecular marker for these non-responders, we performed a retrospective proteomic study on a training (n=53) and validation (n=22) cohorts of TKIs-treated mRCC tumors. To evaluate the identified protein as a potential therapeutic target, we knocked out its expression using CRISPR/Cas9 and analyzed its effects on migration and invasion capacities, and cell proliferation of RCC-derived cells. Of 6,183 protein groups (FDR 0.01) quantified using proteomics, transmembrane glycoprotein B (GPNMB) had higher abundance in TKIs non-responding tumors, was associated with progression-free survival, and the trend of increased GPNMB levels was visible using immunohistochemistry (n=40). Comparison of parental, GPNMB-/- cells and cells with GPNMB overexpression showed that GPNMB promotes the migration and invasion capacity of 786-0 cells as well as the proliferation of RCC-MF cells. Our data show that GPNMB has the potential to serve as a predictive biomarker of poor TKIs response and potentially as a therapeutic target in mRCC.

Xanthogranulomatous ureteritis (XGU) has been described as a rare, mass-forming, locally destructive ureteral inflammatory lesion, most often associated with enteric Gram-negative bacilli. The current case report documents that XGU may be associated with the urinary tract congenital anomalies including a complete duplex kidney, ureter duplex, and ureterocele. An overlap with the definition of malakoplakia is discussed.

Lymph node-positive renal cell carcinoma is a heterogeneous condition. Patients with bulky or multiple nodal metastases often behave like those with metastatic disease and may benefit more from upfront systemic therapy than from surgery alone.

Adenoid cystic/basal cell carcinoma (ACBCC) of the prostate is a rare tumor, with only about 100 tumors reported in the literature. We present a 66-year-old man with incidental finding of prostatic cancer duplicity-ACBCC of the prostate and prostatic acinar adenocarcinoma in radical prostatectomy specimen. Prostatic acinar adenocarcinoma was of Gleason score 6 (3 + 3), focally present at surgical margin, exhibited perineural invasion but no extraprostatic extension. Concurrently, ACBCC was detected, the tumor exhibited adenoid cystic-like morphology, with multifocal involvement of the resection margins and extraprostatic extension. This coincidence presented a unique opportunity to comprehensively examine the molecular characteristics of both tumors. SETD2 mutation was identified in ACBCC, while it was absent in acinar adenocarcinoma. No significant differences were detected by other genetic analyses, and both tumors clustered together within "Prostatic adenocarcinoma" control group and separated from adenoid cystic carcinoma of other locations using methylation profiling.

Background/Aim: New generation androgen receptor-targeting agents (ARTA) have been in the spotlight for their efficacy in metastatic castration-resistant prostate cancer (mCRPC). Prostate-specific antigen (PSA) represents one of the most commonly used serum cancer biomarkers worldwide. The present retrospective study focused on the prognostic role of serum PSA isoforms and their early dynamics in mCRPC patients treated with abiraterone acetate (ABI) or enzalutamide (ENZ). Patients and Methods: The association between outcomes of 334 mCRPC patients treated with ABI or ENZ and the levels of serum total PSA (tPSA), free PSA (fPSA), [-2]proPSA and the Prostate Health Index (PHI) at baseline and one month after treatment initiation was analyzed retrospectively. Results: In the multivariable Cox proportional hazards models, baseline tPSA>50 mu g/l (p<0.001), and [-2]proPSA>300 ng/l (p=0.017) remained independent significant factors associated with inferior OS, while baseline fPSA>1.75 mu g/l (p=0.050) and Delta [-2]proPSA >-50% approached statistical significance (p=0.062). The results of ROC analyses assessing the ability of baseline tPSA, fPSA, and [-2]proPSA to predict mortality within two years showed area under the curve (AUC) values of 0.709, 0.685, and 0.740, respectively. Among the subgroup with baseline tPSA <= 20.0 mu g/l, the results of ROC analyses for baseline tPSA, fPSA and [-2]proPSA showed AUC values of 0.441, 0.682, and 0.688, respectively. Conclusion: Our results suggest a significant correlation between pretreatment serum levels of tPSA and [-2]proPSA with OS in mCRPC patients receiving ARTA.

The influence of surgical volume on partial nephrectomy (PN) outcomes is a subject of debate. The European Association of Urology (EAU) renal cell carcinoma (RCC) guideline panel performed a protocol-driven systematic review of the association between hospital volume (HV) and oncological, functional, and complication outcomes following PN for RCC. The intervention was PN performed in a higher-volume hospital (defined according to the number of procedures per unit time) and the comparator was PN performed in a lower-volume hospital. Ten studies involving a total of 106 569 patients were included in the review. Higher HV was associated with lower complication rates, shorter length of stay, lower positive surgical margin rates, and lower transfusion rates. For six studies, multivariable analyses showed that low HV was an independent risk factor for inpatient complications, PSM presence, longer LOS, and failure to achieve a trifecta of no complications, warm ischemia time <25 min, and negative surgical margins. Most studies were judged to have high risk of bias. The available evidence suggests a potential association between higher HV and better PN outcomes in RCC. The EAU RCC guidelines panel encourages the development and rigorous evaluation of indicators of surgery quality in RCC to better inform the designation of high-quality centers within models of centralized care.

BACKGROUND AND OBJECTIVE:The European Association of Urology (EAU) renal cell carcinoma (RCC) guideline panel has updated their evidence-based guidelines and recommendations for the management of RCC. Here we present a summary of the 2025 RCC guidelines updated with standardised methodology to provide reproducible evidence for the management of RCC. METHODS:For the 2025 update, a literature search was performed covering the period from May 1, 2023 to May 1, 2024 using the Medline, EMBASE, and Cochrane Libraries. The data search focused on meta-analyses, systematic reviews, randomised controlled trials (RCTs), and retrospective or controlled comparator-arm studies. Evidence was synthesised as outlined for all EAU guidelines. KEY FINDINGS AND LIMITATIONS:Clinical practise recommendations were updated in all chapters of the RCC guidelines on the basis of a structured literature search. The studies included were predominantly retrospective with matched or unmatched cohorts based on single- or multi-institutional data. Several prospective studies and RCTs provided data that resulted in recommendations based on higher levels of evidence. Specifically, updates include new recommendations on stereotactic body radiotherapy for localised RCC, adjuvant therapy, systemic therapy for clear-cell RCC in later lines, other subtypes, and a new chapter on hereditary RCC. CONCLUSIONS AND CLINICAL IMPLICATIONS:The 2025 RCC guidelines have been updated by a multidisciplinary panel of experts using methodological standards to provide a contemporary evidence base for the management of RCC.

Carbonic anhydrase IX (CA IX) is traditionally considered to be an immunomarker of clear cell renal cell carcinoma (RCC). However, CA IX expression has also been documented in other RCCs subtypes. Discrimination between clear cell RCC and non-clear cell RCC is crucial for further patient management. The aim of this study was to assess CA IX immunoreactivity across the spectrum of RCC with sarcomatoid differentiation. The expression of CA IX was evaluated in 32 cases of RCCs with sarcomatoid differentiation (12 clear cell RCC, 7 papillary RCC and 13 chromophobe RCC). Seven urothelial carcinomas (UC) with sarcomatoid differentiation (originally from renal pelvis) and 23 soft tissue tumors were also included as a control cohort. The sensitivity for CA IX in sarcomatoid component of clear cell RCC was 91.7 % (moderate/strong CA IX staining in >60 % of sarcomatoid component). However, the CA IX specificity was rather low (45 %), as a significant proportion of sarcomatoid components in different renal cell carcinoma subtypes also stained with CA IX (2/7 papillary RCC, 9/14 chromophobe RCC). When urothelial carcinoma and soft tissue tumors were included in the evaluation, the specificity of CA IX staining for sarcomatoid clear cell RCC reached 60 %. In conclusion, CA IX shows decent sensitivity for sarcomatoid clear cell RCC, but with low specificity, hence limiting its diagnostic utility as a reliable marker of in tumors with predominant sarcomatoid component.

The KEYNOTE-564 trial showed that adjuvant immune checkpoint inhibitor (ICI) therapy with pembrolizumab, a PD-1 antibody, significantly improved disease-free survival (DFS) and overall (OS) survival in localised clear-cell renal cell carcinoma (RCC) with a high risk of relapse. The TiNivo and CONTACT-03 trials have reported results for subsequent therapy after progression on ICI therapy in the metastatic setting. The European Association of Urology (EAU) RCC guidelines panel reassessed the new trial results to update recommendations for adjuvant therapy and post-adjuvant therapy. Adjuvant pembrolizumab significantly improved OS (hazard ratio 0.62, 95% confidence interval 0.44-0.87; p = 0.005). Recent trials of subsequent ICI after recurrence on ICI in the metastatic setting do not support ICI monotherapy or combination therapy in patients with recurrence on or after adjuvant ICI therapy. There are no prospective trial results for treatment after adjuvant pembrolizumab failure. On the basis of the recent results, the EAU RCC guidelines panel has updated the recommendation for adjuvant therapy and now issues a strong recommendation for adjuvant pembrolizumab. ICI monotherapy or combination therapy is not recommended in patients with recurrence during or shortly after adjuvant pembrolizumab. PATIENT SUMMARY: Treatment with an immunotherapy drug called pembrolizumab after surgery in patients with intermediate-risk or high-risk kidney cancer delays the time to recurrence of cancer and prolongs survival. Therefore, pembrolizumab after surgery is strongly recommended for these patients. However, a significant proportion of patients have life-changing or serious side effects and these must be discussed.