Alexander Chehrazi-Raffle

Background: Availability of clinical trials for prostate cancer in the US varies greatly by region. County-level analyses are vital to characterize healthcare access, disease burden, and population-level disparities. Methods: Utilizing the ClinicalTrials.gov trial database, we collated all interventional prostate cancer trials between June 1, 2019, and June 1, 2025. We compiled data on county characteristics along with Social Vulnerability Index (SVI) designations derived from the CDC, NCI, and the Agency for Toxic Substances and Disease Registry data. A zero-inflated negative binomial regression model was used to evaluate trial availability. Trial characteristics were summarized using descriptive analysis. Results: We found 884 eligible trials. Among 3,145 counties, only 631 had at least one clinical trial over the study period. Most trials (51%) included patients with metastatic disease. Sixteen percent of trials investigated curative treatments, while 65% examined palliative interventions. The majority of studies (52.5%) had funding from pharmaceutical companies. There was no significant relationship between trial availability and incidence or mortality rates. Among counties with at least one trial, those with a low SVI had twice as many trials per household when compared to those with high SVI (IRR 2.05, 95% CI 1.54 - 2.74, p<0.001). Counties with no trials were more rural (72.3% vs 22.0%) and had fewer specialist physicians (17.1% vs 69.1%). Conclusion: Prostate cancer trials are disproportionately concentrated in the US, with lower representation in vulnerable areas. Expanding trial access to underserved areas is a crucial step in promoting equitable access to care.

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.

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.

Demographic and clinical characteristics of the study cohort (N = 30).

Immunohistochemical expression for 21 cell surface markers across testicular germ cell tumor subtypes and histologic components.

Immunohistochemical staining of selected cell surface markers across testicular GCT subtypes. A, CLDN6 (membranous staining) in seminoma, (B) CLDN6 (membranous staining) in yolk sac tumor, (C) EGFR (membranous staining) in seminoma, (D) EGFR (membranous staining) in teratoma, (E) TAG72 (membranous and cytoplasmic staining) in seminoma, (F) TAG72 (membranous and cytoplasmic staining) in choriocarcinoma, (G) TROP2 (membranous staining) in seminoma, (H) TROP2 (membranous staining) in teratoma, (I) Nectin-4 (membranous and cytoplasmic staining) in seminoma, (J) Nectin-4 (membranous and cytoplasmic staining) in teratoma, (K) GPNMB (membranous and cytoplasmic staining) in seminoma, (L) GPNMB (membranous and cytoplasmic staining) in embryonal carcinoma, (M) c-MET (nuclear staining) in seminoma, (N) c-MET (nuclear staining) in embryonal carcinoma, (O) HER2 (membranous staining) in teratoma, and (P) c-MET (membranous and cytoplasmic staining) in choriocarcinoma.

Antibodies used for immunohistochemistry, including clone, catalog number, and vendor.

To characterize clinically actionable cell surface proteins in testicular germ cell tumors (GCT), we retrospectively analyzed archival formalin-fixed, paraffin-embedded orchiectomy specimens from 30 patients, including 11 with pure seminoma and 19 with mixed GCTs. Immunohistochemistry was performed for 21 surface antigens using an automated platform. Staining intensity (0 to 3+) and the percentage of positive tumor cells were used to derive H-scores (0–300). Expression was summarized by patient classification and histologic component; high expression was defined as H-score ≥100. Claudin-6 (CLDN6) was diffusely and strongly expressed, with H-score ≥100 in 100% of pure seminomas and 89.5% of mixed GCTs. At the component level, 100% of seminoma and 92.9% of embryonal carcinoma samples reached this threshold. Epidermal growth factor receptor (EGFR) showed high expression in 68.4% of mixed GCTs and 45.5% of pure seminomas, with most enrichment in teratoma components (73.3%, ≥100; mean H-score, 212). TROP2 was markedly upregulated in mixed GCTs (78.9%, ≥100; mean, 194.7), particularly in teratoma components (86.7%, ≥100). Nectin-4 and glycoprotein nonmetastatic melanoma B (GPNMB) were expressed in smaller but notable subsets, including teratoma and seminoma, whereas most remaining antigens, including CD19, DLL3, FOLR1, and BCMA, showed minimal or no expression. These findings demonstrate a distinct surface antigen landscape in testicular GCTs, with CLDN6, EGFR, and TROP2 emerging as leading candidates for further translational evaluation. The enrichment of these targets highlights antigenic heterogeneity within GCTs and supports further validation in appropriate disease settings, including metastatic, posttreatment, and relapsed or refractory disease.Significance:Relapsed or refractory testicular GCT remains a clinical challenge with limited treatment options. We evaluated cell surface antigens of primary GCTs and identified CLDN6, EGFR, and TROP2 as candidate targets for antigen-directed approaches. These findings provide a rationale for future validation in metastatic and posttreatment disease settings.

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.