Urinary Tract Cytopathology: Current and Future Impact on Patient Care.

Urine cytology is a non-invasive, cost-efficient, and sensitive test to detect high-grade urothelial carcinoma. The Paris System (TPS) for Reporting Urinary Cytology is an evidence-based system that uses the risk of malignancy to guide patient management. Since its inception, TPS has standardized urine cytology reports, facilitating communication among pathologists and between pathologists and clinicians. It is imperative to correlate the urine cytology findings with the concurrent tissue sample to avoid false-negative and false-positive results when possible. Several ancillary tests and artificial intelligence algorithms are being developed to increase the accuracy of urine cytology interpretation.

Three-dimensional imaging of upper tract urothelial carcinoma improves diagnostic yield and accuracy.

Upper tract urothelial carcinoma (UTUC) is a rare form of urothelial cancer with a high incidence of recurrence and a low survival rate. Almost two-thirds of UTUCs are invasive at the time of diagnosis; therefore, improving diagnostic methods is key to increasing survival rates. Histopathological analysis of UTUC is essential for diagnosis and typically requires endoscopy biopsy, tissue sectioning, and labeling. However, endoscopy biopsies are minute, and it is challenging to cut into thin sections for conventional histopathology; this complicates diagnosis. Here, we used volumetric 3-dimensional (3D) imaging to explore the inner landscape of clinical UTUC biopsies, without sectioning, revealing that 3D analysis of phosphorylated ribosomal protein S6 (pS6) could predict tumor grade and prognosis with improved accuracy. By visualizing the tumor vasculature, we discovered that pS6+ cells were localized near blood vessels at significantly higher levels in high-grade tumors than in low-grade tumors. Furthermore, the clustering of pS6+ cells was associated with shorter relapse-free survival. Our results demonstrate that 3D volume imaging of the structural niches of pS6 cells deep inside the UTUC samples improved diagnostic yield, grading, and prognosis prediction.

Sacituzumab Govitecan Demonstrates Efficacy across Tumor Trop-2 Expression Levels in Patients with Advanced Urothelial Cancer.

PURPOSE: Human trophoblast cell surface antigen 2 (Trop-2) is a protein highly expressed in urothelial cancer (UC). Sacituzumab govitecan (SG) is a Trop-2-directed antibody drug conjugate with a hydrolysable linker and a potent SN-38 payload. This study explored Trop-2 expression in tumors treated with SG in cohorts 1 to 3 (C1-3) from the TROPHY-U-01 study and evaluated whether efficacy was associated with Trop-2 expression. PATIENTS AND METHODS: TROPHY-U-01 (NCT03547973) is an open-label phase II study that assessed the efficacy and safety of SG (alone or in combinations) in patients with unresectable locally advanced or metastatic UC (mUC). Archival tumor samples collected at enrollment for C1-3 were analyzed for Trop-2 membrane expression by considering histological scores (H-scores; scale 0-300) and the percentage of membrane positive tumor cells at low magnification (4×). The association of Trop-2 with clinical endpoints [objective response rate (ORR), progression-free survival (PFS), and overall survival (OS)] was evaluated. RESULTS: In C1-3, tissue was collected from 158 (82%) of 192 treated patients, and 146 (76%) had evaluable Trop-2 data. Trop-2 was highly expressed in tumor samples. The median [interquartile range (IQR)] Trop-2 H-score was 215 (180-246), and the median (IQR) percentage of membrane positive tumor cells was 91% (80-98). Trop-2 expression at any level was observed in 98% of patients. Furthermore, ORR, PFS, and OS benefits were observed across all Trop-2 expression levels. CONCLUSIONS: Trop-2 protein is highly expressed in UC, as confirmed by examining tumors from patients enrolled in the TROPHY-U-01 trial. The results indicate that SG demonstrates efficacy in mUC across Trop-2 expression levels.

Impact of LAG-3/FGL1 pathway on immune evasive contexture and clinical outcomes in advanced urothelial carcinoma.

BACKGROUND: Anti-programmed death-1 (PD-1)/anti-PD-ligand-1 (PD-L1) pathway inhibition is a standard regimen for advanced urothelial carcinoma (UC); however, its limited efficacy has been reflected in reported medium response rates. This study explored the role of next-generation coinhibitory receptors (IRs; lymphocyte activation gene 3 (LAG-3), T-cell immunoglobulin and mucin domain 3 (TIM-3), and T-cell immunoreceptor with Ig and ITIM domains (TIGIT)) and their ligands (LGs) in the response to PD-(L)1 blockade therapy and the oncological outcomes in patients with UC. METHODS: We investigated metastatic UC cases who underwent PD-(L)1 therapy (cohort 1: n=348, cohort 2: n=89, and cohort 4: n=29) or advanced UC cases involving surgery (cohort 3: n=293 and cohort 5: n=90). We assessed the mRNA expression profiles and corresponding clinical information regarding IRs and LGs using cohorts 1, 2, and 3. Additionally, we elucidated the spatial features of these targeted markers using multiplex immunohistochemistry (mIHC) on formalin-fixed paraffin-embedded samples from cohorts 4 and 5. Survival, differential expressed gene, and Gene Set Enrichment analyses were performed. For mIHC, quantitative analyses were also performed to correlate immune and tumor cell densities with patient survival. RESULTS: LAG-3 expression was strongly associated with the responsiveness of PD-(L)1 blockade compared with the expression of TIM-3 and TIGIT. In tumors with high LAG-3 levels, the increased expression of fibrinogen-like protein 1 (FGL1) had a significantly negative effect on the response to PD-(L)1 blockade and overall survival. Moreover, high FGL1 levels were associated with elevated CD4+ regulatory T-cell gene signatures and the upregulation of CD39 and neuropilin-1, with both indicating CD8+ T-cell exhaustion. mIHC analyses revealed that patients with stromal CD8+LAG-3+cellshigh-tumor FGL1+cellshigh exhibited a significant negative correlation with survival rates compared with those with stromal CD8+LAG-3+cellshigh-tumor FGL1+cellslow. CONCLUSIONS: LAG-3 expression and high FGL1 coexpression are important predictive factors of adverse oncological outcomes related to the presence of immunosuppressive contextures. These findings are hypothesis-generating, warranting further mechanistic and clinical studies aimed to evaluate LAG-3/FGL1 blockade in UC.

De Novo Urological Malignancies After Renal Transplantation: An Asian 30-Year Experience.

BACKGROUND: As the incidence of urological malignancies after renal transplantation (RT) is observed to be greater than in the general population, a better understanding of them is important. We present our experience with urological tumors in RT recipients at our transplant center, and analyze their incidence, management and outcomes. MATERIALS AND METHODS: A retrospective analysis of 2177 RT recipients on follow-up at our center between 1990 and 2022 was conducted for de novo genitourinary malignancy. Patients diagnosed with malignancy before transplantation were excluded. Clinicopathological data at diagnosis and follow-up were collected and analyzed. Kaplan-Meier estimates were used to evaluate overall survival (OS) and cancer-specific survival (CSS). Statistical analysis was performed using IBM SPSS v.24 (IBM Corp., Armonk, NY, USA). RESULTS: The overall incidence of Urological malignancies was 3.9%, with 89 cancers diagnosed in 85 patients. Renal cell carcinoma was most common (n = 61, 68.5%), followed by prostate cancer (n = 10, 11.2%), urothelial carcinoma (n = 10, 11.2%), squamous cell carcinoma of the penis/scrotum (n = 7, 7.9%), and testicular cancer (n = 1, 1.1%). Mean duration between transplantation and diagnosis of malignancy was 9.9 (0.4-20.7) years. At a median follow-up of 4.6 (018.2) years, 27 deaths were seen; 7(25.9%) were due to urological malignancy. CSS rates were 86% and 78% at five and ten years, respectively, after diagnosis. CONCLUSION: We present one of the largest series of de novo urological malignancies observed over an extended 30-year follow-up of RT recipients, demonstrating an elevated risk in line with other studies. Regular surveillance for malignancies is advised, in order to ensure early diagnosis and management.

Impact of baseline body composition on prognostic outcomes in urological malignancies treated with immunotherapy: a pooled analysis of 10 retrospective studies.

OBJECTIVE: Numerous epidemiological investigations have explored the impact of body composition on the effectiveness of immune checkpoint inhibitors (ICIs) in urological malignancies (UM) patients, yielding conflicting findings. As a result, our study aims to elucidate the influence of baseline body composition on the long-term prognosis of UM patients treated with ICIs. METHODS: We employed a rigorous systematic search across various databases, including PubMed, Embase, the Cochrane Library, and Google Scholar, to identify studies meeting our inclusion criteria. Our primary endpoints of interest encompassed overall survival (OS) and progression-free survival (PFS). RESULTS: This analysis included a total of 10 articles with a combined patient cohort of 707 individuals. Our findings revealed a noteworthy association between several body composition parameters and unfavorable OS outcomes, including low psoas muscle index (PMI; HR: 3.88, p < 0.001), low skeletal muscle index (SMI; HR: 1.63, p < 0.001), sarcopenia (HR: 1.88, p < 0.001), low visceral adipose index (VAI; HR: 1.38, p = 0.018) and low subcutaneous adipose index (SAI; HR: 1.37, p = 0.018). Furthermore, our analysis demonstrated that low PMI (HR: 2.05, p = 0.006), low SMI (HR: 1.89, p = 0.002), sarcopenia (HR: 1.80, p < 0.001), and low VAI (HR:1.59, p = 0.005) were significantly correlated with inferior PFS. Conversely, SAI did not manifest a pronounced association with PFS in UM patients treated with ICIs. CONCLUSION: Collectively, our study findings underscore a substantial relationship between baseline body composition and reduced clinical efficacy in UM patients undergoing ICI therapy.

Epacadostat plus pembrolizumab versus placebo plus pembrolizumab for advanced urothelial carcinoma: results from the randomized phase III ECHO-303/KEYNOTE-698 study.

BACKGROUND: Indoleamine 2,3-dioxygenase 1 (IDO1) levels correlate with poor outcomes in urothelial carcinoma (UC). IDO1 and programmed death-ligand 1 (PD-L1) are often co-expressed. Epacadostat is a potent and highly selective inhibitor of IDO1. In a subgroup analysis of patients with advanced UC participating in a phase I/II study, epacadostat-pembrolizumab treatment produced an objective response rate (ORR) of 35%. METHODS: ECHO-303/KEYNOTE-698 was a double-blinded, randomized phase III study of adults with metastatic or unresectable locally advanced UC with recurrence or progression following first-line platinum-based chemotherapy. Participants were randomized to epacadostat 100 mg twice daily (BID) plus pembrolizumab or placebo plus pembrolizumab until completion of 35 pembrolizumab infusions, disease progression, or unacceptable toxicity. The primary endpoint was investigator-assessed ORR per Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: Target enrollment was 648 patients; enrollment was halted early based on efficacy results from the phase III ECHO-301/KEYNOTE-252 study in metastatic melanoma. Forty-two patients were randomized to each treatment arm. Median duration of follow-up was 62 days in each arm. The investigator-assessed ORR (unconfirmed) was 26.2% (95% CI 16.35-48.11) for epacadostat plus pembrolizumab and 11.9% (95% CI 4.67-29.50) for placebo plus pembrolizumab. Two complete responses were reported, both in the placebo-plus-pembrolizumab arm. Circulating kynurenine levels increased from C1D1 to C2D1 in the placebo-plus-pembrolizumab arm and numerically decreased in the epacadostat-plus-pembrolizumab arm. The safety profile of epacadostat plus pembrolizumab was similar to that of pembrolizumab monotherapy, although a numerically greater proportion of patients in the combination vs. control arm experienced treatment-related grade ≥ 3 adverse events (16.7% vs. 7.3%). One patient in each arm died due to cardiovascular events, which were not deemed drug-related. No new safety concerns were identified for either agent. CONCLUSIONS: Epacadostat plus pembrolizumab demonstrated anti-tumor activity and was generally tolerable as second-line treatment of patients with unresectable locally advanced or recurrent/progressive metastatic UC. Epacadostat 100 mg BID, when administered with pembrolizumab, did not normalize circulating kynurenine in most patients. Further study of combined IDO1/PD-L1 inhibition in this patient population, particularly with epacadostat doses that result in durable normalization of circulating kynurenine, may be warranted. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03374488. Registered 12/15/2017.

Pembrolizumab plus either epacadostat or placebo for cisplatin-ineligible urothelial carcinoma: results from the ECHO-307/KEYNOTE-672 study.

BACKGROUND: Indoleamine 2,3- dioxygenase 1 (IDO1) is an immunosuppressive enzyme that has been correlated with shorter disease-specific survival in patients with urothelial carcinoma (UC). IDO1 may counteract the antitumor effects of immune checkpoint inhibitors. Epacadostat is a potent and highly selective inhibitor of IDO1. In the phase I/II ECHO-202/KEYNOTE-037 study, epacadostat plus pembrolizumab resulted in a preliminary objective response rate (ORR) of 35% in a cohort of patients with advanced UC. METHODS: ECHO-307/KEYNOTE-672 was a double-blinded, randomized, phase III study. Eligible adults had confirmed locally advanced/unresectable or metastatic UC of the urinary tract and were ineligible to receive cisplatin-based chemotherapy. Participants were randomly assigned (1:1) to receive epacadostat (100 mg twice daily) plus pembrolizumab (200 mg every 3 weeks) or placebo plus pembrolizumab for up to 35 pembrolizumab infusions. The primary endpoint was investigator-assessed ORR per Response Evaluation Criteria in Solid Tumors (version 1.1). RESULTS: A total of 93 patients were randomized (epacadostat plus pembrolizumab, n = 44; placebo plus pembrolizumab, n = 49). Enrollment was stopped early due to emerging data from the phase III ECHO-301/KEYNOTE-252 study. The median duration of follow-up was 64 days in both arms. Based on all available data at cutoff, ORR (unconfirmed) was 31.8% (95% CI, 22.46-55.24%) for epacadostat plus pembrolizumab and 24.5% (95% CI, 15.33-43.67%) for placebo plus pembrolizumab. Circulating kynurenine levels numerically increased from C1D1 to C2D1 in the placebo-plus-pembrolizumab arm and decreased in the epacadostat-plus-pembrolizumab arm. Epacadostat-plus-pembrolizumab combination treatment was well tolerated with a safety profile similar to the placebo arm. Treatment discontinuations due to treatment-related adverse events were more frequent with epacadostat (11.6% vs. 4.1%). CONCLUSIONS: Treatment with epacadostat plus pembrolizumab resulted in a similar ORR and safety profile as placebo plus pembrolizumab in cisplatin-ineligible patients with previously untreated locally advanced/unresectable or metastatic UC. At a dose of 100 mg twice daily, epacadostat did not appear to completely normalize circulating kynurenine levels when administered with pembrolizumab. Larger studies with longer follow-up and possibly testing higher doses of epacadostat, potentially in different therapy settings, may be warranted. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03361865, retrospectively registered December 5, 2017.

Enfortumab Vedotin for Elderly Advanced Urothelial Carcinoma Patients or Those With a Poor Performance Status.

BACKGROUND/AIM: The efficacy, safety, and liver toxicity of enfortumab vedotin (EV) for elderly advanced urothelial carcinoma (UC) patients and patients with a poor performance status (PS) are unclear. PATIENTS AND METHODS: We retrospectively analyzed the efficacy, safety, and liver toxicity of EV in elderly patients and patients with a poor PS between December 2021 and August 2023. RESULTS: Sixty-two patients (≥75 years old, n=22; PS≥2, n=10) were enrolled. Patients with PS≥2 had significantly lower albumin levels than those with PS<2 (p=0.023). The objective response and disease control rates did not differ significantly between patients <75 and ≥75 years old (p=0.598 and p=0.769, respectively) or between those with PS<2 and PS≥2 (p>0.99 and p=0.178, respectively). Progression-free survival (PFS) and overall survival (OS) were not significantly different in patients <75 years and ≥75 years (p=0984, 0.368). A significant difference in PFS (p=0.047) but not OS (p=0.086) was observed between the PS<2 and PS≥2 groups. The rates of any-grade and severe (grade ≥3) adverse events did not differ significantly between patients <75 and ≥75 years (p=0.471, p=0.136) or between PS<2 and PS≥2 groups (p>0.99, 0.99). Aspartate aminotransferase (AST) levels significantly increased, but alanine aminotransferase levels did not, following EV treatment (p<0.001). Multivariate analyses revealed that the albumin level was an independent prognostic factor (hazard ratio=0.159; p<0.001). CONCLUSION: EV demonstrated similar efficacy and safety in elderly and younger patients with advanced UC. In patients with a poor PS, although the safety was similar, survival was significantly worse in terms of PFS, while the AST levels were significantly elevated.

Clinical Outcomes of Enfortumab Vedotin in Advanced Urothelial Carcinoma With Prior Avelumab Versus Pembrolizumab Therapy.

BACKGROUND/AIM: This study retrospectively evaluated whether enfortumab vedotin (EV) monotherapy is effective as a late-line treatment according to prior treatment type in patients with advanced urothelial carcinoma (UC). PATIENTS AND METHODS: We assessed consecutive patients from the Uro-Oncology Group in the Kyushu study population with lower and upper urinary tract cancer treated with EV monotherapy after platinum-based chemotherapy and immune checkpoint inhibitor therapy failure between December 2021 and March 2024. In particular, patients receiving avelumab maintenance or pembrolizumab therapy before EV for advanced UC were analyzed and compared according to the response rate, progression-free survival (PFS), and overall survival (OS). RESULTS: Of the 80 enrolled patients, 31 and 49 received avelumab and pembrolizumab before EV therapy, respectively. The avelumab and pembrolizumab groups had comparable objective response rates (48.4% vs. 44.9%, p=0.820) and disease control rates (77.4% vs. 67.3%, p=0.448). These two groups showed no significant difference in PFS from the initiation of EV (median: 6.4 months vs. 4.2 months, p=0.184); meanwhile, the avelumab group had better OS from the initiation of EV than the pembrolizumab group (median: 16.0 months vs. 10.2 months, p=0.019). Moreover, the median OS after first-line chemotherapy initiation was longer in the avelumab group than in the pembrolizumab group (40.3 months vs. 24.7 months, p=0.054). On multivariate analysis, avelumab maintenance therapy before EV reduced the mortality risk by 47% (95% confidence interval=0.27-1.03; p=0.059). CONCLUSION: EV monotherapy after avelumab maintenance therapy provides favorable survival outcomes in patients with advanced UC.

Same Organ, Two Cancers: Complete Analysis of Renal Cell Carcinomas and Upper Tract Urothelial Carcinomas.

Background and Objectives: Renal cell carcinomas and upper tract urothelial carcinomas are types of malignancies that originate in the kidneys. Each of these examples shows an increasing trend in the frequency and the mortality rate. This study aims to comprehensively define carcinomas by analyzing clinical, paraclinical, and histological aspects to predict aggressiveness and mortality. Materials and Methods: We conducted a retrospective investigation on a group of patients suspected of kidney cancers. Results: We identified 188 cases. We observed a higher mortality rate and older age in individuals with urothelial carcinomas. Anemia, acute kidney injury, hematuria, and perineural invasion were the main risk factors that predicted their mortality. Tumor size in renal cell carcinomas correlates with the presence of necrosis and sarcomatoid areas. Factors that indicate a higher rate of death are older age, exceeding the renal capsule, a lesion that includes the entire kidney, lymphovascular invasion, acute kidney injury, and anemia. Conclusions: Even if they originate at the renal level, and the clinical-paraclinical picture is similar, the histopathological characteristics make the difference. In addition, to these are added the previously mentioned common parameters that can represent important prognostic factors. In conclusion, the characteristics commonly identified in one type of cancer may act as risk factors for the other tumor. The detected data include threshold values and risk factors, making a significant contribution to the existing literature.

Trends and Disparities in Next-Generation Sequencing in Metastatic Prostate and Urothelial Cancers.

Importance: Targeted therapies based on underlying tumor genomic susceptible alterations have been approved for patients with metastatic prostate cancer (mPC) and advanced urothelial carcinoma (aUC). Objective: To assess trends and disparities in next-generation sequencing (NGS) testing among patients with mPC and aUC. Design, Setting, and Participants: This retrospective cohort study used an electronic health record-derived database to extract deidentified data of patients receiving care from US physician practices, hospital-affiliated clinics, and academic practices. Patients diagnosed with mPC or aUC between March 1, 2015, and December 31, 2022, were included. Exposures: Social determinants of health evaluated by race and ethnicity, socioeconomic status (SES), region, insurance type, and sex (for aUC). Main Outcomes and Measures: The primary outcomes were (1) NGS testing rate by year of mPC and aUC diagnosis using Clopper-Pearson 2-sided 95% CIs and (2) time to NGS testing, which considered death as a competing risk. Cumulative incidence functions were estimated for time to NGS testing. Disparities in subdistributional incidence of NGS testing were assessed by race and ethnicity, SES, region, insurance type, and sex (for aUC) using the Fine-Gray modified Cox proportional hazards model, assuming different subdistribution baseline hazards by year of mPC and aUC diagnosis. Results: A total of 11 927 male patients with mPC (167 Asian [1.6%], 1236 Black [11.6%], 687 Hispanic or Latino [6.4%], 7037 White [66.0%], and 1535 other [14.4%] among 10 662 with known race and ethnicity) and 6490 patients with aUC (4765 male [73.4%]; 80 Asian [1.4%], 283 Black [4.8%], 257 Hispanic or Latino [4.4%], 4376 White [74.9%], and 845 other [14.5%] among 5841 with known race and ethnicity) were eligible and included. Both cohorts had a median age of 73 years (IQR, 66-80 years), and most underwent NGS testing before first-line treatment in the mPC cohort (1502 [43.0%]) and before second-line treatment in the aUC cohort (1067 [51.3%]). In the mPC cohort, the rates of NGS testing increased from 19.0% in 2015 to 27.1% in 2022, but Black patients (hazard ratio [HR], 0.75; 95% CI, 0.67-0.84) and Hispanic or Latino patients (HR, 0.70; 95% CI, 0.60-0.82) were less likely to undergo NGS testing. Patients with mPC who had low SES (quintile 1: HR, 0.74 [95% CI, 0.66-0.83]; quintile 2: HR, 0.89 [95% CI, 0.80-0.99]), had Medicaid (HR, 0.53; 95% CI, 0.38-0.74) or Medicare or other government insurance (HR, 0.89; 95% CI, 0.82-0.98), or lived in the West (HR, 0.81; 95% CI, 0.70-0.94) also were less likely to undergo testing. In the aUC cohort, the NGS rate increased from 14.1% in 2015 to 46.6% in 2022, but Black patients (HR, 0.76; 95% CI, 0.61-0.96) and those with low SES (quintile 1: HR 0.77 [95% CI, 0.66-0.89]; quintile 2: HR, 0.87 [95% CI, 0.76-1.00]) or Medicaid (HR, 0.72; 95% CI, 0.53-0.97) or Medicare or other government insurance (HR, 0.88; 95% CI, 0.78-0.99) were less likely to undergo NGS testing. Patients with aUC living in the South were more likely to undergo testing (HR, 1.29; 95% CI, 1.12-1.49). Conclusions and Relevance: These findings suggest that although NGS tumor testing rates improved over time, the majority of patients still did not undergo testing. These data may help with understanding current disparities associated with NGS testing and improving access to standard-of-care health care services.

Prolonged Response to Osimertinib in EGFR-Mutated Metastatic Urothelial Carcinoma, a Case Report.

A 48-year-old woman without obvious environmental risk factors was diagnosed with metastatic urothelial carcinoma harboring a mutation in EGFR typical of driver mutations for non-small cell lung cancer. Within a year, her cancer progressed on four standard therapies for urothelial cancer, including cancer in lungs, liver, bone, and brain. As fifth-line therapy, she received osimertinib, leading to a complete response in the brain and improvement elsewhere, and the cancer remained controlled for six months. Targeted therapy for rare driver mutations can be effective in urothelial cancer and should be considered prior to exhausting standard therapies.

[A real-world study of the clinical application of the Paris system for reporting urinary cytology in cancer hospital].

Objectives: To evaluate the clinical value of the Paris system for reporting urinary cytology (TPS) in the diagnosis of urothelial carcinoma (UC). Methods: A total of 1 744 cytological diagnostic records (from 751 cases) were collected retrospectively. All specimens were voided urines and histopathology as the gold standard. The sensitivity and specificity of urinary cytological diagnosis of UC and risk of high grade malignant (ROHM) in each diagnostic category were compared. Results: There were 360 cases with histopathology. The percentage of negative for high-grade urothelial carcinoma (NHGUC) was 30.1% (226/751), atypical urothelial cells (AUC) was 29.8% (224/751), suspicious for high-grade urothelial carcinoma (SHGUC) was 16.8% (126/751), high grade urothelial carcinoma (HGUC) was 21.2% (159/751), and non-urothelial malignancy (NUM) was 2.1% (16/751). The histpathologic ROHM corresponding to each cytological diagnosis category were 27.3% for NHGUC, 32.7% for AUC, 74.7% for SHGUC, 96.6% for HGUC and 100.0% for NUM, respectively. ROHM of SHGUC was significantly higher than that of AUC group, and the difference between the two groups was statistically significant (P＜0.001). ROHM of HGUC group was significantly higher than that of SHGUC group, and the difference was statistically significant (P＜0.001). With SHGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 76.7% (165/215) and 85.7% (18/21), and with HGUC as the cut-off value, the sensitivity and specificity of cytological diagnosis of HGUC were 53.0% (114/215) and 100.0% (21/21), respectively. Conclusions: Urine cytology has high sensitivity and specificity in the diagnosis of HGUC. The malignant risk of TPS varies with different diagnosis category. The high malignant risk population in cancer hospital leads to the relatively high malignant proportion and ROHM in each diagnosis category. Urinary cytology TPS reporting system is helpful to clinical management and has good clinical application value.

Frontline immune checkpoint inhibitors in patients ≥ 90 years with advanced urothelial cancer: a single center experience.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) are approved for advanced urothelial cancer alone and as first-line in combination with enfortumab vedotin. Platinum based chemotherapy which is another frontline choice is often not a treatment option for older patients due to comorbidities that increase with age. Despite ICIs being better tolerated compared to traditional chemotherapy little is known about their efficacy and toxicity in patients ≥ 90 years due to the rarity of this population in clinical trials. Our objective was to analyze the efficacy and toxicity of immune checkpoint inhibitors in patients ≥ 90 years. MATERIALS AND METHODS: We conducted a single center retrospective review of patients ≥ 90 years treated between July 2019 and September 2023 with standard of care ICIs for advanced urothelial cancer. RESULTS: Six patients treated with pembrolizumab were identified. Four (66.7%) were male and mean age was 93.5 years at the time of treatment initiation. Response rate was 66.7% (4 patients) with 3 complete responses, which were durable off therapy. Median follow up was 18.2 months. Median progression free survival (PFS) was 10.2 months [95%confidence interval (95%CI): 1.77, not reached (NR)] and median overall survival (OS) was 18.2 months (95%CI: 12.1, NR). Side effects presented in 4 (66.7%) patients and included hypothyroidism, diarrhea, anemia, thrombocytopenia, rash, and bullous dermatitis. One patient developed grade 3 anemia and no patients experienced grade 4 events or required hospitalization due to treatment side effects. CONCLUSIONS: Our experience in a small cohort of patients ≥ 90 years indicate that ICIs are well tolerated and effective for the treatment of advanced urothelial carcinoma in this patient population.

[Urinary cytology for the detection of urothelial lesions]. / Rôle de la cytologie urinaire dans le dépistage des lésions urothéliales.

Urine cytology is a long-used technique for the detection of high grade neoplastic urothelial lesions. Since 2016, «The Paris System¼ classification has revolutionized this field by introducing a standardized terminology widely adopted by cytopathologists and urologists. In this article, we explain this classification and discuss its impact on the clinical management of patients with urothelial lesions, as well as its role in the secondary prevention of these lesions.

La cytologie urinaire est une technique utilisée depuis longtemps dans la détection des lésions urothéliales tumorales de haut grade. Depuis 2016, la classification «The Paris System¼ a révolutionné ce domaine en introduisant une terminologie standardisée largement adoptée par les cytopathologistes et les urologues. Dans cet article, nous expliquons cette classification et discutons de son impact sur la prise en charge clinique des lésions urothéliales, ainsi que son rôle dans la prévention secondaire de ces lésions.

Implications of c-Myc in the pathogenesis and treatment efficacy of urological cancers.

Urological cancers, including prostate, bladder, and renal cancers, are significant causes of death and negatively impact the quality of life for patients. The development and progression of these cancers are linked to the dysregulation of molecular pathways. c-Myc, recognized as an oncogene, exhibits abnormal levels in various types of tumors, and current evidence supports the therapeutic targeting of c-Myc in cancer treatment. This review aims to elucidate the role of c-Myc in driving the progression of urological cancers. c-Myc functions to enhance tumorigenesis and has been documented to increase growth and metastasis in prostate, bladder, and renal cancers. Furthermore, the dysregulation of c-Myc can result in a diminished response to therapy in these cancers. Non-coding RNAs, ß-catenin, and XIAP are among the regulators of c-Myc in urological cancers. Targeting and suppressing c-Myc therapeutically for the treatment of these cancers has been explored. Additionally, the expression level of c-Myc may serve as a prognostic factor in clinical settings.