Introduction: Staging inaccuracies in muscle-invasive bladder cancer (MIBC) can lead to undertreatment or overtreatment. We evaluated clinical and pathological predictors of pathologic upstaging (pUS) stratifying by neoadjuvant chemotherapy (NAC) receipt among patients undergoing robot-assisted radical cystectomy (RARC). Methods: We included patients with MIBC (≥cT2N0M0) who underwent RARC from February 2004 through October 2020. Patients were grouped as (1) pUS with NAC, (2) pUS without NAC, and (3) no pUS (reference). Baseline characteristics were summarized using descriptive statistics. Logistic regression assessed the association between baseline characteristics and odds for upstaging. Kaplan–Meier method estimated overall survival (OS) and recurrence-free survival (RFS), and log-rank test compared the survival distribution between groups. Univariable and multivariable Cox regression models identified variables associated with OS and RFS. Results: Among 277 patients, 38.6% (n = 107) were upstaged with NAC (n = 37) or without NAC (n = 70). Most were male (79%), white (72%), and had cT2 stage (85%). Median age at surgery was 72 yrs. Preoperative hydronephrosis showed higher odds of upstaging [OR 2.24 (95% CI, 1.31–3.81), p = 0.003]. pUS with NAC [HR 1.99 (95% CI, 1.23–3.22), p = 0.005] and without NAC [HR 3.18 (95% CI, 2.21–4.55), p < 0.001] predicted worse OS (33.5 vs. 18.8 mos) compared to patients without pUS (135.3 mos). pUS with NAC [HR 2.49 (95% CI, 1.58–3.94) p < 0.001] and without NAC [HR 3.02 (95% CI 2.11–4.31), p < 0.001] predicted worse RFS. Conclusions: Preoperative hydronephrosis was the strongest predictor for pUS, independent of other baseline covariates. This highlights the need for better pre-operative risk stratification strategies for patients with MIBC undergoing RARC.

PURPOSE: Clinical trials for cancer tend to be less available in regions of the United States corresponding to high socioeconomic vulnerability; however, specific patterns for renal cell carcinoma (RCC) have yet to be reported. The aim of this study was to evaluate the current county-level distribution of RCC trials in the United States and identify factors contributing to disparities of access. METHODS: We performed a cross-sectional analysis of all interventional trials on ClinicalTrials.gov enrolling adult patients with RCC between June 1, 2019, and June 1, 2025. After mapping each US study site to its corresponding county, we used a zero-inflated negative binomial (ZINB) model to evaluate the relationship between county-level trial availability and corresponding Social Vulnerability Index (SVI) designations, renal cancer incidence rates, and renal cancer mortality rates. Trial characteristics were extracted and summarized descriptively. Incidence rate ratios were estimated to quantify the relationship between trial availability and county-level characteristics. RESULTS: In total, 289 trials met the inclusion criteria, corresponding to a total of 5,028 unique trial sites. Only 672 (21.4%) of all US counties had at least 1 trial site; no state had a trial in every county. Compared with high-SVI counties, counties with low, low-medium, and medium-high SVIs had 3.1-fold, 2.0-fold, and 1.8-fold higher trial incidence rates (all P < .001). Higher renal cancer incidence and mortality rates were not significantly associated with county-level trial prevalence ( P = .55 and P = .40, respectively). CONCLUSION: Most US counties lacked RCC clinical trial representation. Counties with higher social vulnerability had fewer trials, highlighting key structural disparities in access to new RCC interventions within the United States and emphasizing the importance of accounting for regional social vulnerability in the trial design and site selection process.

PURPOSE: Clinical trial availability often varies between countries, independent of the local burden of disease. We aimed to evaluate the current global availability of prostate cancer clinical trials and the factors affecting it. METHODS: We searched for clinical trials involving prostate cancer between June 2019 and June 2024 through Clinicaltrials.gov. Noninterventional trials were excluded. Countries were classified according to the World Bank Ranking (WBR) as high-, upper-middle–, lower-middle–, and low-income countries (HICs, UMICs, LMICs, and LICs). Multivariable negative binomial regression was used to evaluate the association between the number of trials and country's characteristics. Multivariable logistic regression was used to evaluate the association between trial availability and country's characteristics. In addition, we collected data on sponsorship, funding, intervention, intervention intent, end point selection, trial phase, and cancer stage. RESULTS: Of the 1,531 trials identified, 1,413 met the eligibility criteria. Most trials were conducted exclusively in HICs (80.4%), included patients with metastatic disease (55.4%), and were sponsored by academia (68.8%). Pharma-funded trials had a higher number of participating countries (mean 2.7 v 1.0, P < .001) and were more likely to include metastatic disease (72.0% v 32.3%, P < .001) and to investigate systemic therapy (76.3% v 29.4%, P < .001). In the multivariable analysis, WBR, gross national income (GNI), and annual health expenditure were all associated with the presence of at least one trial ( P < .001). Only GNI was independently associated with the number of trials within a country ( P < .001). CONCLUSION: Prostate cancer trials are disproportionately concentrated in HICs despite a lower burden of disease. Intentional efforts are needed to ensure global representation and long-term benefits for populations historically excluded from research.

Background: Bladder cancer disproportionately affects non-high-income countries, yet clinical trials underrepresent global diversity. We assessed global availability of bladder cancer trials, their alignment with disease burden, and barriers to equitable care. Methods: We queried ClinicalTrials.gov for adult bladder cancer trials from June 2019 to June 2024, excluding observational and non-oncologic trials. Trial characteristics were summarized descriptively, and country data came from the Global Cancer Observatory. Countries were classified per World Bank Ranking (WBR) into high-income (HICs), upper middle-income (UMICs), lower middle-income (LMICs), and low-income countries (LICs). Trials were categorized as HIC-only, non-HIC, or mixed-income trials. Fisher’s exact and Kruskal–Wallis tests compared groups. Multivariable logistic regression assessed associations between trial availability and WBR, national health expenditure, and gross national income (GNI). Univariable linear regression and ANOVA assessed the association between the mortality-to-incident ratio and WBR. Results: Of 611 trials, 75.1% were HIC-only, 16.9% non-HIC, and 8.0% mixed-income trials. Non-HIC trials were mainly academic-sponsored (80.6%), while all mixed-income trials had pharmaceutical sponsorship (p < 0.001). Non-HIC trials had lower enrollment, less pharmaceutical funding, fewer multinational collaborations, and fewer basket, multi-arm, early-phase designs (all p < 0.001). Mixed-income trials were larger, led by HICs, had broader eligibility criteria, more novel therapies, and more frequent use of overall survival endpoints. Trial availability was lower in UMICs (p = 0.011), LMICs (p = 0.024), and absent in LICs, and positively associated with higher national health expenditure (p = 0.007) and GNI (p = 0.001). Conclusions: Bladder cancer trials remain concentrated in HICs. Mixed-income trials expand access in non-high-income countries, but are exclusively led by HICs and require balanced sponsorship, early-phase research, and lasting local benefits.

Background: Sarcomatoid carcinoma of the upper urinary tract (SCUT) is a rare and aggressive malignancy. Due to its rarity, the molecular landscape and the prevalence of potentially targetable alterations are poorly characterized. We aimed to compare the clinical, pathological, and genomic profiles of SCUT and upper tract urothelial carcinoma (UTUC). Methods: We leveraged the Tempus Lens clinically annotated genomic dataset to extract clinicopathologic and somatic genomic alteration data from patients with UTUC and SCUT. Patients with any-stage disease who underwent either blood- or tissue-based next-generation sequencing were included. Baseline clinical and demographic characteristics were summarized using descriptive statistics. Comparisons between groups were performed using Wilcoxon rank-sum test for continuous variables and the Chi-square test/Fisher’s exact test for categorical variables. Mutational frequencies and pairwise comparisons were performed to assess significant differences between groups. Results: In total, 1721 patients were included, of which 1600 (93%) had UTUC and 121 (7%) had SCUT. Patients with SCUT were younger at diagnosis, 61 years (interquartile range (IQR) 54, 70), compared to UTUC, 71 years (IQR 64, 77) (p < 0.001), and were more likely to have node-positive disease at presentation (all p < 0.001). SCUT patients were more likely to show visceral metastases to the lung (44% vs. 21%), bone (31% vs. 17%), and brain (7% vs. 1%), compared to UTUC (all p < 0.05). Among SCUT patients, the most common genomic alterations were TERT (30%), TP53 (29%), NF2 (19%), PTEN (13%), SETD2 (12%), PBRM1 (12%), and BAP1 (8%). Among UTUC patients, the most common were TERT (52%), TP53 (52%), KMT2D (30%), FGFR3 (25%), ARID1A (20%), and KDM6A (18%). Compared to UTUC, SCUT was significantly enriched with NF2, SETD2, PBRM1, PTEN, and BAP1 (all p < 0.05). SCUT was depleted in FGFR3 (0% vs. 25%) and FGF4 (0% vs. 8%) mutations compared to UTUC (both p < 0.05). Targetable alterations were observed in SCUT, including NF2, SETD2, and PTEN. Conclusion: Compared with UTUC, SCUT exhibits a more aggressive clinical and genomic phenotype, characterized by enrichment in NF2, SETD2, PBRM1, and PTEN. These findings underscore the divergent molecular landscape of SCUT and highlight potentially targetable genomic alterations.