Intraepithelial penile lesions encompass non-neoplastic and preneoplastic lesions. Non-neoplastic lesions comprise condyloma acuminatum, including giant condyloma acuminatum, also known as Buschke-Löwenstein tumor. It is usually the low-risk human papillomavirus (HPV) types 6 and 11 that are most prevalent in penile condylomas. However, high-risk HPV types can be detected along with low-risk types in a subset of patients. Penile intraepithelial neoplasia (PeIN) is a preneoplastic lesion that is either HPV-associated or HPV-independent. HPV-associated PeIN represents the majority of PeIN in regions where the incidence of penile cancer is lower, as in North America and Europe. HPV-associated PeIN is subdivided into basaloid, warty, and mixed subtypes and, less commonly, into pagetoid, clear-cell, and spindle-cell subtypes based on morphologic characteristics. HPV-associated PeIN is positive for immunohistochemical stain p16 and high-risk HPV in situ hybridization (ISH). Immunohistochemical stain p53 usually exhibits a wild-type staining pattern. HPV-independent PeIN/differentiated PeIN is more frequent in countries with a high incidence of penile cancer and an uncircumcised population. It is usually associated with predisposing factors like lichen sclerosus and chronic inflammatory conditions such as lichen planus, lichen simplex chronicus, and phimosis. The degree of atypia in differentiated PeIN ranges from subtle to full-thickness proliferation of markedly atypical pleomorphic cells. Many cases are associated with TP53 mutations and other alterations involving PIK3CA and HRAS. Recently, it has been proposed to further subclassify differentiated PeIN. Extramammary Paget disease (EMPD) can involve the skin of the penis and glans mucosa in elderly men. It is either primary or secondary, and when secondary, it can be associated with prostate or urothelial carcinoma. Lastly, rare case reports of primary penile melanoma in situ have been reported. The lesions can involve either the skin or mucosa, with the glans penis being the most commonly reported site.

Training and external validation of machine learning supervised prognostic models of upper tract urothelial cancer (UTUC) after nephroureterectomy.

To characterize the incidence, clinicopathologic features, treatment patterns, and both oncologic and graft-related outcomes of de novo urothelial carcinoma (UC) in kidney transplant recipients (KTRs) at a large German transplant center. Retrospective single-center cohort of KTRs (2005-2024). 19 patients with post-transplant UC were identified among 4,012 KTRs. We extracted demographics, transplant and tumor characteristics, treatments, graft outcomes, and survival. The standardized incidence ratio (SIR) was calculated using population-based incidence rates, and Kaplan-Meier estimates were used for overall survival (OS), metastasis-free survival (MFS), and graft survival (GS). UC occurred in 0.47% of KTRs, yielding an SIR of 2.21 (95% confidence interval [CI] 1.33-3.44) compared with the general population. Most tumors were bladder-based (63.2%), but there was a high proportion of upper-tract urothelial carcinoma (UTUC; 31.6%), including graft-involving tumors. Radical surgery was performed in 47.4% of patients, 15.8% received systemic chemotherapy, and intra-vesical therapy was rarely used. Median OS after UC diagnosis was 55months, with estimated 3- and 5-year OS rates of 70% and 51%, respectively, and 3- and 5-year MFS rates of 73%. Graft failure occurred in 47.4% of patients, and in 21.1% of the total cohort it was directly attributed to UC. Post-transplant UC in KTRs is associated with a more than twofold increased incidence compared with the general population and a disproportionate burden of upper tract and graft-involving tumors. Management must carefully balance oncologic control against preservation of transplant function in a setting where standard intra-vesical and systemic therapies are constrained by immunosuppression. These findings support risk-adapted lifelong urologic surveillance and highlight the need for dedicated treatment strategies tailored to immunosuppressed patients.

In the phase 3 EV-302 study, enfortumab vedotin-pembrolizumab (EV + P) significantly prolonged overall survival (OS) and progression-free survival (PFS) versus chemotherapy in patients with untreated locally advanced/metastatic urothelial carcinoma (la/mUC). We present a posthoc analysis in a pan-Asian population. Patients from China, Japan, Singapore, South Korea, Taiwan, and Thailand received 3-week cycles of EV (1.25mg/kg; intravenously; Days 1 and 8) plus P (200mg; intravenously; Day 1) or chemotherapy (gemcitabine [Days 1 and 8] plus cisplatin/carboplatin [Day 1]). Primary endpoints were PFS and OS. Secondary endpoints included objective response rate (ORR) and safety. Overall, 176 patients were included (EV + P, n = 94; chemotherapy, n = 82). Median follow-up was 28.9months for EV + P recipients and 26.6months for chemotherapy recipients. EV + P prolonged PFS and OS versus chemotherapy, reducing the risk of disease progression or death by 63% (hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.24-0.57) and death by 67% (HR, 0.33; [95% CI, 0.20-0.54]), respectively. Confirmed ORR was 72.2% versus 35.0%. Grade ≥ 3 treatment-related adverse events occurred in 66.0% of EV + P recipients and 68.4% of chemotherapy recipients. Most commonly maculopapular rash (11.7%) and hyperglycemia (10.6%) for EV + P and neutropenia (25.0%), anemia (19.7%), and neutrophil count decreased (18.4%) for chemotherapy. EV + P demonstrated a clinically meaningful survival benefit in Asian patients with untreated la/mUC, with no new safety signals observed, consistent with the global EV-302 study. Results support guideline recommendations for EV + P as preferred first-line therapy in la/mUC. NCT04223856 (registered January 8, 2020).

Immune checkpoint inhibitors (ICIs) have significantly changed cancer therapy, yet their response rates remain relatively low. Identifying methods for robust prediction is crucial. This study evaluates the efficacy of gene-based methods for deriving predictive tumor-microenvironment scores in cancer patients, focusing on their performances in predicting survival outcomes and response to ICI therapy across various cancer types. The TIP Hot method demonstrated robustness as a predictive method for ICI response, particularly in Non-Small Cell Lung Cancer, Head and Neck Squamous Cell Carcinoma, and Urothelial Cancer. However, no score is robustly applicable to all cancer types. Therefore, significant challenges remain due to the variability of tumor biology and host immune responses, and universally applicable method should be further explored. Future research should aim to refine these predictive scoring methods through larger and more diverse datasets, and integrate advanced computational techniques to enhance predictive accuracy and utility in personalized cancer treatment.

This study introduces a novel “tunnel method” for single-position laparoscopic nephroureterectomy in women with upper urinary tract urothelial carcinoma (UTUC), enabling complete resection of the kidney and entire ureter while preserving the uterine round ligament during dissection of the intramural ureter and bladder cuff excision. By creating a tunnel-like space beneath the round ligament via precise dissection of the uterine broad ligament, this technique avoids round ligament transection, thereby maintaining pelvic anatomical integrity, reducing risks of pelvic organ prolapse, minimizing postoperative adhesions, and preserving reproductive and pelvic function-particularly critical for women of childbearing age or those at risk of prolapse. This innovative approach ensures effective oncological resection while prioritizing female-specific anatomical and functional considerations, providing a more comprehensive and patient-centered treatment option for UTUC.

The Paris System for Reporting Urinary Cytology (TPS) provides a non-invasive screening tool for high-grade urinary bladder carcinomas. In resource-poor settings, urinary cytology continues to be performed on conventional sediment smears (CSS) only. Cell blocks (CBs), though an essential part of cytology, are not part of routine protocol for urinary cytology. The present study was undertaken to compare CSS and liquid-based cytology (LBC) in urinary cytology, and to assess the utility of CB preparation in decreasing the indeterminate/grey zone diagnosis (Non-diagnostic/Atypical Urothelial Cells/Suspicious for High-Grade Urothelial Carcinoma). This prospective study evaluated 1051 urine samples from 417 patients. All these samples were processed using CSS and LBC. Diagnostic parameters (sensitivity/specificity/positive predictive value [PPV]/negative predictive value [NPV]/diagnostic accuracy) were analyzed for each preparation with their individual and combined comparisons. CBs were also prepared for each sample. For all urine samples in terms of percentage reduction of indeterminate diagnosis, results of CSS alone (29.88% of indeterminate diagnosis) versus LBC alone (30.83% of indeterminate diagnosis) showed no statistically significant difference (p-value 0.468). When the findings were combined for CSS with LBC, the percentage of indeterminate diagnosis was reduced to 27.12%. When the combined results were compared with the findings of CSS alone, the results were statistically significant (p-value < 0.001), and when the combined results were compared with the findings of LBC alone, the results were statistically insignificant (p-value 0.68). Follow-up histopathological diagnosis and/or relevant radiology and/or positive CBs were considered the gold standard, which was available for 620 cases. Diagnostic parameters, along with the Risk of High-Grade Malignancy (ROHM) for these 620 cases, were calculated. Evaluation of the CB reduced the grey zone diagnosis in four cases and helped to reach a definitive diagnosis. However, it was statistically insignificant (p-value 0.125). CSSs give as good and comparable cytological results as LBC. Though LBC provides a more determinate diagnosis (Negative for High-Grade Urothelial Carcinoma or High-Grade Urothelial Carcinoma) when compared to CSS, this difference is not statistically significant. A combination of LBC with CSS provides superior results than CSS or LBC alone. This study highlights the promising results CSSs provide, which is relevant in resource-poor settings where LBC facilities are not readily available. CBs are useful in reducing indeterminate diagnoses on cytology; however, the results are not statistically significant.

Abstract Malakoplakia (MP) is a rare granulomatous inflammation that primarily affects the urinary system and has a characteristic histological appearance. We report a case of ureteral and bladder MP associated with renal failure that clinically mimicked urothelial carcinoma. A 60-year-old woman presented to our clinic with a one-year history of left flank pain. Computed tomography urography (CTU) and magnetic resonance (MR) imaging revealed asymmetric thickening of the left ureteral and bladder walls, along with polypoid, contrast-enhancing intraluminal masses. The diagnosis was confirmed by histopathological evaluation, which demonstrated the pathognomonic Michaelis-Gutmann bodies.

The renin-angiotensin system (RAS) plays a central role in regulating blood pressure and has recently been implicated in cancer biology. Although angiotensin II (AngII) receptor blockers (ARBs) have shown clinical benefit in bladder cancer, their mechanisms of action remain unclear. Here, we investigated the contribution of AngII type 1 receptor (AGTR1) to bladder cancer progression and assessed the therapeutic potential of the ARB losartan (LOS). In patients with primary non-muscle-invasive bladder cancer, intravesical recurrence following transurethral tumor resection correlated with AGTR1 expression levels. Public database analysis revealed that the expression of AGTR1 and its downstream kinases, extracellular signal-regulated kinase (ERK) 1 and ERK2, was associated with overall survival in bladder urothelial carcinoma. In AGTR1-overexpressing T24 bladder cancer cells, AngII promoted invasion and migration and upregulated neuronal nitric oxide synthase, without affecting proliferation. These effects were accompanied by rapid ERK phosphorylation alongside Akt dephosphorylation. RNA sequencing revealed that AGTR1 expression and AngII stimulation activated NF-κB, mTOR, and epithelial-mesenchymal transition (EMT) pathways. LOS suppressed these AngII-mediated responses, whereas the AngII-independent upregulation of EMT-related proteins and the enhancement of mitochondrial energy metabolism by AngII in AGTR1-overexpressing cells remained unaffected. In vivo, AGTR1 facilitated early tumor engraftment and promoted tumor progression, accompanied by reduced E-cadherin and elevated N-cadherin expression, with most of these changes suppressed by LOS treatment. In conclusion, our findings highlight the crucial role of AGTR1 in bladder cancer and support the repositioning of ARBs, such as LOS, as therapeutics for AGTR1-upregulated bladder cancer, while underscoring the importance of AGTR1 stratification for future clinical evaluation.

POU2F3 defines tuft cell-like carcinomas, yet POU2F3-driven neuroendocrine neoplasia in the urinary bladder remains incompletely characterized and can morphologically mimic basaloid carcinomas. We report a case of an octogenarian woman with a diverticular bladder tumor composed of conventional high-grade urothelial carcinoma juxtaposed with a sharply demarcated basaloid component. Although the basaloid component lacked classical small-cell morphology and showed scant conventional neuroendocrine marker expression, it was diffusely POU2F3-positive, underscoring a potential diagnostic pitfall with human papillomavirus (HPV)-associated basaloid squamous cell carcinoma. Both components showed concordant aberrant tumor-suppressor immunoprofiles (p53 overexpression and Rb loss), and high-risk HPV RNA in situ hybridization (RNAscope) was negative. This case expands the recognized morphologic spectrum of bladder neuroendocrine carcinoma to include POU2F3-defined non-small cell neuroendocrine carcinoma with basaloid architecture, supporting the practical value of incorporating POU2F3 into immunohistochemical panels for poorly differentiated basaloid bladder tumors.

Treatment paradigms for advanced urothelial carcinoma have evolved rapidly with the introduction of antibody-drug conjugates and novel immunotherapy combinations. Enfortumab vedotin plus pembrolizumab has redefined first-line therapy, demonstrating unprecedented survival benefits compared with platinum-based chemotherapy. However, high cost and limited availability remain major barriers to its global implementation. Accordingly, gemcitabine-cisplatin with nivolumab and platinum-based chemotherapy followed by maintenance avelumab remain validated evidence-based alternatives, particularly for cisplatin-eligible patients or in regions where enfortumab vedotin plus pembrolizumab is not readily accessible. These advances have created new challenges in treatment sequencing, particularly for patients who progress after enfortumab vedotin plus pembrolizumab, where prospective evidence remains limited. Enfortumab vedotin monotherapy retains activity post-platinum and immune checkpoint inhibition, erdafitinib provides a targeted benefit in fibroblast growth factor receptor 3-altered tumors, and trastuzumab deruxtecan has emerged as a later-line option for HER2-positive disease. In parallel, circulating tumor DNA is an emerging biomarker with potential to individualize sequencing strategies, although its clinical application remains investigational. This review synthesizes current evidence and highlights practical considerations, emphasizing the need to balance therapeutic innovation with cost effectiveness, equitable access, and global applicability, while identifying critical research priorities in the post-enfortumab vedotin plus pembrolizumab era.

Background:Enfortumab vedotin (EV), an antibody-drug conjugate targeting Nectin-4, has demonstrated efficacy in advanced urothelial carcinoma (UC) following platinum-based chemotherapy and immune checkpoint inhibitor (ICI) therapy. However, real-world evidence on its effectiveness and safety remains limited.Methods:We conducted a multicenter retrospective study across Italian oncology centers to evaluate EV in patients with metastatic UC (mUC) who had progressed after prior platinum-based chemotherapy and ICI. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. We also assessed prognostic factors, including a composite index (HERO score) based on baseline hemoglobin and neutrophil-to-lymphocyte ratio (NLR).Results:Fifty-three patients were included (median age 72 years; 41.5% ⩾75 years). The ORR was 34.0% (all partial responses), with a DCR of 58.5%. Median PFS and OS were 6.1 and 9.7 months, respectively. Multivariate analysis identified NLR ⩾ 4 and lung metastases as independent predictors of inferior PFS, while NLR ⩾ 4 remained independently associated with worse OS. Dose reductions and peripheral neuropathy were associated with improved outcomes. The HERO score significantly stratified patients by PFS and OS (p = 0.017 and p < 0.001, respectively). EV was generally well tolerated, with most adverse events being low-grade.Conclusion:In this real-world cohort, EV confirmed its efficacy and manageable safety profile in mUC. The HERO score may provide a simple tool for risk stratification in clinical practice, though prospective validation is needed.

Mesenteric panniculitis is a rare benign entity that affects the mesentery, often detected incidentally in an imaging examination. Its association with cancer is a controversial topic. The objective of the study was to determine the frequency of this condition in a known oncological population and compare it with that of a control population. Cross-sectional, retrospective study, comparative with a control group. Patients referred for PET/CT (Positron Emission Tomography/Computed Tomography) staging for recently diagnosed cancer, who had not been treated and had no history of other previous cancer, were selected. This oncological group was separated according to type of cancer. The control group included patients referred for multiple traumatic injuries to undergo computed tomography that included the abdomen and pelvis. Control patients with a history of cancer were excluded. In both cases, the images were reviewed in search of mesenteric panniculitis. Of the oncological group (1911 patients), 5.2% presented mesenteric panniculitis. The types of cancer with the highest frequency of mesenteric panniculitis were non-Hodgkin lymphoma (16.1%) and prostate cancer (12.8%), followed by multiple myeloma (6.9%), urothelial carcinoma (6.2%), cancer of the head and neck (5.3%) and pancreatic cancer (5.2%). Hodgkin lymphoma and cancers exclusive to women (breast, cervix, uterus, ovary) presented a low frequency of mesenteric panniculitis, similar to the control population. The frequency of mesenteric panniculitis in the control population (1056 individual) was 0.6%. The Odds Ratio of the oncological population vs. control for mesenteric panniculitis exposure was 9.6 (95% CI4.2249 to 22.1015, p < 0,0001). The frequency of mesenteric panniculitis depends on the type of cancer, and it is high in non-Hodgkin lymphoma and prostate cancer, but low and similar to that of the control population in other neoplasms.

Purpose Upper urinary tract urothelial carcinoma (UTUC) is an uncommon malignancy of the urogenital tract with a wide range of clinical outcomes. While prognostic factors for bladder-based UC are established, less is known about tumors in other locations and the impact of socioeconomic disparities. This study uses a large national database to identify key demographic, clinical, and socioeconomic predictors of overall survival in UC patients, focusing on the primary tumor site. Methods We conducted a retrospective analysis of 12,300 patients diagnosed with UC of the kidney and renal pelvis between 2004 and 2020 from the National Cancer Database (NCDB). Multivariable Cox proportional hazards regression was used to analyze the association between overall survival and factors including patient demographics, tumor characteristics, primary tumor site, and socioeconomic status. Results The cohort was predominantly male (59%) and White (91%), with a mean age of 71 at diagnosis. Multivariable analysis identified several factors significantly associated with survival. Renal pelvis tumors, the most common primary site (84.9%), were associated with significantly improved survival (HR = 0.84; 95% CI: 0.8–0.9; p&amp;lt;0.001). Compared to males, females exhibited a 15% lower hazard of death (HR = 0.85; 95% CI: 0.81-0.90; p&amp;lt;0.001). Factors associated with worse survival included a higher Charlson-Deyo comorbidity score (HR = 1.51; 95% CI: 1.39-1.65; p&amp;lt;0.001) and advanced NCDB tumor stage. Socioeconomically, patients with higher income (HR = 0.82; 95% CI: 0.75-0.90; p&amp;lt;0.001) and private insurance or Medicare (HR = 0.70; 95% CI: 0.57-0.87; p&amp;lt;0.001) had improved survival. Adjuvant chemotherapy was associated with a lower hazard of death (HR = 0.84; 95% CI: 0.75-0.95; p=0.007), whereas primary radiation therapy was associated with a higher hazard of death (HR = 1.69; 95% CI: 1.54-1.86; p&amp;lt;0.001). Conclusion This large-scale analysis identifies the primary tumor site as a key prognostic factor in UC, with renal pelvis tumors demonstrating more favorable survival. The study also confirms the significant influence of comorbidity and tumor stage while uniquely highlighting that socioeconomic factors, such as income and insurance, are powerful predictors of outcome. These findings underscore the need for optimized, site-specific treatment strategies and concerted efforts to address healthcare inequities in the management of upper tract UC.

Background: Urine cytology remains widely used for surveillance of non-muscle-invasive bladder cancer despite well-known limitations in sensitivity, especially for low-grade tumors. Uromonitor®, a molecular assay detecting TERT promoter, FGFR3, and KRAS mutations in voided urine, has emerged as a promising adjunct. To evaluate its suitability for routine use, a consolidated assessment of diagnostic performance and a direct comparison with urine cytology are needed. Methods: We conducted a prospectively registered systematic review (PROSPERO CRD420251173244), synthesizing all available studies that evaluated Uromonitor® for the detection of urothelial carcinoma of the bladder (UCB). Methodological quality was assessed using the QUADAS-2 framework, and certainty of evidence was evaluated following GRADE for diagnostic tests. Sensitivity was prespecified as the primary endpoint. Comparative datasets were identified, and random-effects meta-analyses were performed for sensitivity, specificity, accuracy, and predictive values (PVs). Results: Across eight cohorts evaluating Uromonitor®, 832 of 3196 patients (26.0%) had histologically confirmed UCB. Aggregated sensitivity was 0.55 (95% CI 0.52–0.58). Specificity was 0.95 (0.94–0.96). Accuracy was 0.85 (0.83–0.86). PPV was 0.79 (0.76–0.82), and NPV was 0.86 (0.84–0.87). Across seven paired datasets, urine cytology demonstrated a sensitivity of 0.42, a specificity of 0.91, an accuracy of 0.78, a PPV of 0.64, and an NPV of 0.81. Pooled odds ratio for sensitivity was 3.16 (0.73–13.76), while diagnostic accuracy yielded 1.71 (1.01–2.90). Differences in specificity and NPV were not statistically significant, whereas the PPV favored Uromonitor®, reaching statistical significance in pooled analyses. Conclusions: Uromonitor® demonstrates higher sensitivity and improved accuracy compared with urine cytology, although current performance remains insufficient for stand-alone surveillance. The sensitivity estimate showed very low certainty due to pronounced heterogeneity, underscoring the need for careful interpretation. With advancing DNA recovery methods, incorporation of droplet digital PCR, and rigorous evaluations in prospective multicenter studies, Uromonitor® may become an integral element of risk-adapted follow-up strategies.

First-line treatment options for cisplatin-ineligible patients with metastatic urothelial cancer (mUC) are limited. We conducted a phase II study of erdafitinib, alone or with cetrelimab, in FGFR-altered mUC. Adults with mUC and select FGFR alterations who are ineligible for cisplatin were randomly assigned 1:1 in a noncomparative design to once-daily erdafitinib 8 mg (with pharmacodynamically guided uptitration to 9 mg) or erdafitinib 8 mg plus intravenous cetrelimab 240 mg once every 2 weeks at cycles 1-4 and 480 mg once every 4 weeks thereafter. Primary end points were investigator-assessed confirmed overall response rate (ORR) and safety; secondary end points included duration of response (DOR), progression-free survival, and overall survival (OS). No statistical hypotheses were tested. At data cutoff, 87 patients were randomly assigned and treated (erdafitinib, n = 43; erdafitinib plus cetrelimab, n = 44). Of 64 patients with PD-L1 expression data, 56 (87.5%) had low levels of PD-L1 expression (combined positive score <10). Median survival follow-up was 14.2 months. Investigator-assessed confirmed ORR for erdafitinib was 44.2% (95% CI, 29.1 to 60.1) with one complete response (CR); median DOR and median OS were 9.7 months (95% CI, 4.6 to not estimable [NE]) and 16.2 months (95% CI, 8.3 to NE), respectively. Investigator-assessed confirmed ORR for erdafitinib plus cetrelimab was 54.5% (95% CI, 38.8 to 69.6), with six (13.6%) CRs; median DOR and median OS were 11.1 months (95% CI, 8.8 to NE) and 20.8 months (95% CI, 12.0 to NE), respectively. The most frequent treatment-related adverse events (TRAEs) were hyperphosphatemia (83.7% and 68.2% in erdafitinib and erdafitinib plus cetrelimab groups, respectively), stomatitis (69.8% and 56.8%), and dry mouth (37.2% and 56.8%). Grade ≥3 TRAEs occurred in 46.5% and 45.5% of patients receiving erdafitinib and erdafitinib plus cetrelimab, respectively. First-line erdafitinib monotherapy and erdafitinib plus cetrelimab demonstrated antitumor activity and a manageable safety profile in cisplatin-ineligible patients with mUC.

Clinical utility of cell-free urine miR-93-5p, miR-191-5p, miR-31-5p for invasive urothelial carcinoma detection and immune signature-based subtyping

Objective: To evaluate treatment patterns, predictors of treatment selection, and overall survival (OS) in patients with noninvasive (Ta–Tis) urothelial carcinoma of the urethra (UUC). Patients and Methods: We conducted a retrospective cohort study of adults diagnosed with noninvasive UUC (stage Ta or Tis, N0, M0) between 2018 and 2021 using the National Cancer Database. Patients were categorized into prostatic and non-prostatic urethral cohorts. Treatment groups included endoluminal ablation alone, ablation combined with topical intraluminal therapy, urethrectomy, and no subsequent treatment. Multinomial logistic regression was used to identify predictors of treatment selection. The OS was assessed using Kaplan–Meier and multivariable Cox regression, with separate models for each anatomical cohort. Results: A total of 436 patients were included (185 non-prostatic, 251 prostatic); 91.9% (n = 401) were male. Ablation alone was the most common treatment in both cohorts (non-prostatic: 57.3%; prostatic: 62.6%), followed by urethrectomy (non-prostatic: 21.1%) and ablation plus topical therapy (prostatic: 20.3%). In the non-prostatic cohort, high-grade histology (OR 15.15; 95% CI, 3.82–60.04) and Tis stage (OR 3.27; 95% CI, 1.10–9.69) were associated with increased odds of urethrectomy. In the prostatic cohort, high-grade histology was associated with increased use of urethrectomy (OR 59.29; 95% CI, 4.61–763.17) and ablation plus topical therapy (OR 3.09; 95% CI, 1.21–7.90). Tis stage was also associated with ablation plus topical therapy (OR 2.53; 95% CI, 1.14–5.62). This treatment approach was associated with improved OS compared with ablation alone (HR 0.18; 95% CI, 0.05–0.60; p = 0.005). Conclusions: Treatment selection differed substantially by tumor location, stage, and grade, reflecting both treatment selection in noninvasive UUC varied by tumor location, grade, and stage. In prostatic tumors, ablation plus topical therapy was associated with improved survival, supporting its role as a risk-adapted, organ-sparing strategy in selected patients.

Although immune checkpoint inhibitor therapies have revolutionized oncology, many cancers are unresponsive or develop resistance that involves transforming growth factor-β1 (TGFβ1). This multicenter, open-label, phase 1 study (DRAGON trial, SRK-181-001) evaluated safety, pharmacokinetics, pharmacodynamics, predictive biomarkers and efficacy of linavonkibart, a first-in-class fully human selective anti-latent TGFβ1 antibody with anti-programmed cell death protein 1 (PD-1) therapy. The DRAGON trial was divided into three treatment parts: part A1 (dose-escalation cohorts with single-agent linavonkibart), part A2 (dose-escalation cohorts with the combination treatment of linavonkibart and pembrolizumab) and part B (dose-expansion cohorts with the combination treatment). The primary objective of the study was to determine the safety and tolerability of linavonkibart alone and in combination with pembrolizumab. Secondary objectives included evaluation of linavonkibart pharmacokinetics for each treatment paradigm, assessment of anti-linavonkibart antibody development (parts A and B) and measurement of antitumor activity (part B) after treatment. All primary and secondary objectives were met in the study. Overall, linavonkibart had a manageable safety profile, and combined therapy with pembrolizumab was generally consistent with that of pembrolizumab monotherapy. Dermatological reactions were the only additional risk identified. Neither cytokine release syndrome nor infusion interruption was observed in any patient enrolled in DRAGON. In part A (n = 34), no dose-limiting toxicities or grade 4 or 5 treatment-related adverse events occurred (linavonkibart; ≤3,000 mg once every 3 weeks (Q3W) and 2,000 mg once every 2 weeks (Q2W)). In part B (n = 78), patients progressing on prior anti-PD-1 therapy received linavonkibart (1,500 mg Q3W/1,000 mg Q2W) with pembrolizumab (200 mg Q3W). This combination demonstrated confirmed objective response rates of 20.0%, 18.2%, 9.1% and 9.1% in anti-PD-1-resistant patients with clear cell renal cell cancer (ccRCC), melanoma, head and neck squamous cell cancer and urothelial cancer, respectively. Biomarker data provide proof of mechanism and a potential ccRCC patient selection strategy. ClinicalTrials.gov identifier: NCT04291079 .

While monopolar and bipolar energy modalities are commonly used, their comparative impact on oncologic and functional outcomes remains uncertain regarding transurethral resection (TUR) of bladder tumors involving the ureteral orifice. A total of 112 patients undergoing TUR for orifice-involved bladder tumors were retrospectively analyzed, with 46 treated with monopolar (Group 1) and 66 with bipolar energy (Group 2). Primary outcomes included upper tract urothelial carcinoma (UTUC) development and functional complications such as new-onset hydronephrosis (HN). The mean tumor size was significantly larger in group 2 (67.8 mm vs. 45 mm, p = 0.014). UTUC developed in 5 patients in group 1 and 1 patient in group 2 (p = 0.066). Although the mean UTUC-free survival time was longer in group 1 than in group 2 (39.4 ± 23.3 months vs. 5 months), there was no significant difference between the groups (p = 0.578). Postoperative HN occurred in 11 patients in group 1 and 17 patients in group 2 (p = 0.603), and the bipolar group exhibited more spontaneous resolution. Fewer HN and a trend toward lower UTUC incidence suggest a potential advantage of bipolar systems in preserving ureteral integrity. Prospective randomized trials are warranted to validate these findings and establish evidence-based strategies.