George Zhang

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.

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.