Urology San Antonio

32 Background: PET-based radiopharmaceuticals targeting prostate-specific membrane antigen (PSMA) have become the mainstay of prostate cancer imaging; however, high urinary radioactivity from these primarily renally cleared compounds may obscure tumors in the prostate and peri-ureteric regions. We conducted the first intra-patient comparator study to assess the urinary radioactivity of two 18 F-labelled PSMA-PET radiopharmaceuticals, 18 F-piflufolastat and 18 F-flotufolastat. Methods: This multicenter, prospective, intra-patient comparator study (NCT06604442) enrolled men ≥ 18 years with low PSA (≤ 0.5 ng/mL) biochemical recurrence of prostate cancer ≥ 6 months after radical prostatectomy with undetectable PSA post-surgery, scheduled for a standard-of-care (SoC) 18 F-piflufolastat PET. Patients had a SoC PET/CT after IV 18 F-piflufolastat (target dose 333 MBq), and a second PET/CT 1–10 days later after IV 18 F-flotufolastat (target dose 296 MBq), both scans started approximately 60 min after administration and used the same scanner. The primary endpoint was the difference in urinary bladder radioactivity (mean standardized uptake value [SUV mean ]) between 18 F-piflufolastat PET and 18 F-flotufolastat PET. Secondary endpoints included patient and region-level detection rates (DR) for each radiopharmaceutical. Images were interpreted by two blinded central readers, with a third to resolve disagreements, allowing majority read results. Results: Between Oct 2024 and Jun 2025, 55 patients (mean PSA, 0.28 [range 0.09–0.50] ng/mL) were included in the primary efficacy analysis. Median bladder SUV mean was significantly higher with 18 F-piflufolastat (29.0; interquartile range [IQR], 18.9–40.8) than 18 F-flotufolastat (10.9; IQR, 6.0–18.5) with a median difference of 15.1 (IQR, 8.5–27.0; p<0.001 [Wilcoxon signed-rank test]). The patient-level DR was 27.3% (15/55) for 18 F-piflufolastat and 45.5% (25/55) for 18 F-flotufolastat (majority read). Among the 21 patients with very low PSA levels (≤ 0.2 ng/mL), 38.1% had a positive 18 F-piflufolastat scan compared with 52.4% for 18 F-flotufolastat scans (majority read). Regional and sub-regional DRs are shown in the table. Conclusions: In this intra-patient study, 18 F-flotufolastat showed significantly lower urinary radioactivity, and a higher overall DR than 18 F-piflufolastat indicating it may offer improved image assessment in regions close to the bladder. Clinical trial information: NCT06604442 . Region 18 F-Piflufolastat DR* n (%)N=55 18 F-Flotufolastat DR*n (%)N=55 Prostate bed 6 (10.9) 10 (18.2) Vesicourethral anastomosis 1 (1.8) 4 (7.3) Retrovesical 2 (3.6) 2 (3.6) Remnant seminal vesicles/ lateral surgical margin 2 (3.6) 4 (7.3) Pelvic lymph nodes 8 (14.5) 9 (16.4) Majority read. *≥ 1 PET positive lesion.

Abstract R-loops, transcription-induced three-stranded nucleic acid structures, play essential roles in gene regulation but jeopardize genomic integrity when unresolved. BRCA2, a key tumor suppressor required for homologous recombination (HR) repair of DNA double-strand breaks (DSBs), also maintains R-loop homeostasis, though its mechanisms remain incompletely understood. To identify BRCA2-interacting factors involved in R-loop resolution during DNA repair, we employed biotin-based proximity labeling and mass spectrometry (BioID-MS), uncovering HELZ—a previously uncharacterized RNA-specific helicase—as a direct BRCA2 binding partner. BRCA2 enhances HELZ’s catalytic activity in vitro and promotes its recruitment to transcription-associated R-loops in vivo, particularly at DSB sites. Functionally, HELZ resolves co-transcriptional R-loops, facilitates DNA end resection, and promotes efficient HR. HELZ depletion results in R-loop accumulation, impaired HR capacity, and heightened sensitivity to genotoxic stress. Notably, HELZ activity is context-dependent and proves indispensable in hormone-driven malignancies such as estrogen receptor-positive (ER+) breast cancers, which exhibit transcriptional dysregulation and elevated R-loop burden. These findings establish HELZ as a critical mediator of BRCA2-dependent genome integrity in R-loop-rich chromatin environments. HELZ expression or function may serve as a biomarker for therapeutic response, and HELZ helicase activity offers a promising target to restore HR proficiency in transcriptionally dysregulated breast tumors. By integrating proximity proteomics with functional assays, our study identifies HELZ as a novel and therapeutically actionable regulator of R-loop resolution and BRCA2-mediated repair in breast cancer. Citation Format: W. Li, B. Wu, B. Gao, E. M. Irvin:, A. Arijit Ghosh, L. Eliaz, Y. Huang, Y. Kwon, C. M. Stiefel, T. T. Nguyen, D. Zhao, H. J. Suarez, T. Ni, S. Alejo, O. Fitzgerald, X. Song, E. V. Wasmuth, S. Zheng, J. Leung, X. Xue, H. Wang, J. Ji, L. Lan, W. Zhao. Helz-mediated r-loop resolution orchestrates brca2-dependent dna repair in hormone-driven breast cancers [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-12-29.

Abstract Background: Latin American (LA) women are more likely to be diagnosed with aggressive early-stage breast cancer (EBC) compared to Non-Hispanic White (NHW) women, yet population-specific tumor biology remains underexplored. Previously, we reported elevated immune gene expression in BluePrint® (BP) Luminal B tumors in LA patients (pts) with EBC and obesity compared to Black and NHW cohorts. Here, we present updated clinical comparisons between LA, NHW and Black pts with EBC and whole transcriptome analysis (WTA) between BP Luminal B and Basal BC in pts with obesity. Methods: Clinical and WT data were analyzed from 15,577 EBC pts self-identified as LA, Black, or NHW enrolled in FLEX (NCT03053193), a prospective observational study with MammaPrint® risk of recurrence and BP molecular subtyping assays, and WT profiles. ImPrint, 53-gene immune signature, results (+/-) were generated for pts with hormone receptor positive (HR+) EBC. Chi-square and t-tests were conducted on clinical groups using arsenal R package. For WT comparisons, 215 obese LA pts with BP Luminal B and 77 with BP Basal EBC were matched to corresponding NHW and Black pts by age, T and N status. Differentially expressed genes (DEGs) were evaluated using limma, and pathway enrichment was performed using gene set enrichment analysis with Hallmark gene sets. Significant results were reported with adjusted p < 0.05. Results: Compared to Black and NHW pts, LA pts were younger and more often premenopausal (Table). Both LA and Black pts had statistically significantly higher rates of obesity compared to NHW pts. Significantly higher rates of MP High Risk 2, BP Basal and ImPrint+ tumors were observed in LA and Black pts vs NHW. WT comparisons among the obese subpopulations revealed that metabolic pathways, including adipogenesis, angiogenesis, epithelial-mesenchymal transition, and oxidative phosphorylation were significantly downregulated in EBC in LA pts vs NHW and Black cohorts. Conversely, immune-related pathways such as allograft rejection and interferon gamma response were enriched among LA pts with Basal cancers compared to NHW and Black groups. These coordinated pathway alterations suggest unique metabolic and immune profiles in LA EBC subtypes with a median absolute fold change of 1.3 among DEGs. Conclusion: The data suggest that signals from metabolic pathway alterations from modest immune-related gene upregulation may contribute to more aggressive tumor behavior in obese LA pts with EBC. Clinical and transcriptomic analyses demonstrated differences in Luminal B and Basal EBC biology among self-identified LA pts compared to NHW and Black cohorts, consistent with prior research. With further research, these findings may offer treatment targets which may enhance outcomes and reflect the importance of including racially and ethnically diverse pts in clinical trials to characterize population-specific differences in EBC outcomes. Citation Format: M. Mazo Canola, A. Santillan, J. Alberty-Oller, E. Dias, V. Kaklamani, A. Elkhanany, K. Hoskins, M. Habibi, R. Hampton, J. L. Barone, N. M. Johnson, N. Gordon, N. Sookhan, T. Bah, P. John, E. Aponte, S. Diab, V. Klimberg, N. Stivers, C. Page, S. Uygun, W. Audeh, J. O'Shaughnessy. Distinct Immune and Metabolic profiles in Latin American breast cancer patients with obesity enrolled in FLEX [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-09-09.

Abstract Background Endocrine therapy (ET) in combination with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) is a preferred first-line (1L) treatment for patients (pts) with HR+/HER2− mBC. However, ET resistance frequently emerges after 1L treatment, with many pts receiving subsequent chemotherapy or other targeted regimens. This study aimed to assess treatment patterns and clinical outcomes in pts with HR+/HER2− mBC that progressed on 1L ET + CDK4/6i in real-world (rw) practice settings. Methods This was a noninterventional, retrospective, observational cohort study using the US-based Flatiron Health Enhanced Datamart. Adult pts with HR+/HER2− mBC (with no other actionable genomic alterations [ESR1, PIK3CA, AKT1, PTEN, or gBRCA]) that progressed on 1L ET + CDK4/6i were included if they initiated a second-line (2L) therapy between Jan 2017 and Sep 2024 with ≥90 d of potential follow-up. Pt demographics, clinical characteristics, and treatment utilization were assessed descriptively. Treatment data were recorded as documented by physicians and may reflect off-label use. The primary (rw progression-free survival [rwPFS]) and secondary (rw overall survival [rwOS], rw time to discontinuation or death [rwTTD/D], and rw time to next treatment or death [rwTTNT/D]) endpoints were assessed using Kaplan-Meier methods. Analyses were performed in all pts, by 2L regimen, and by time to progression on 1L treatment. Results 1415 pts with HR+/HER2− mBC were included (median age, 65 y; 66.2% were White). Of these, 57.3% (n=811) had disease progression on ET + CDK4/6i within 12 mo of 1L initiation (early progression; 33.3% in ≤6 mo); 25.5% had disease progression in 12 to 24 mo and 17.2% within >24 mo. In the 2L, 63.6% of pts received an ET-based regimen, 27.1% received chemotherapy (CT; monotherapy, 23.8%; multiagent, 3.3%), and 9.3% received other regimens (including AKTi, PARPi, and the ADC sacituzumab govitecan or trastuzumab deruxtecan). Pts with early vs later times to disease progression on 1L ET + CDK4/6i used 2L CT more frequently (40.6% [≤6 mo] vs 14.0% [>24 mo]); the opposite was true for 2L ET (52.2% [≤6 mo] vs 75.3% [>24 mo]). With a median follow-up of 14.6 mo, the 2L median rwPFS ranged from 4 to 8 mo and median rwOS ranged from 14 to 32 mo; the shortest estimates were among pts on 2L CT and with early disease progression on 1L ET + CDK4/6i (Table). Conclusions In this study of pts with HR+/HER2− mBC that progressed on 1L ET + CDK4/6i, over half had 1L disease progression within 12 mo and about one-third received CT in a subsequent line. The median rwPFS on 2L treatments was shorter among those who were using CT in 2L or had early progression (<12 months) on 1L ET + CDK4/6i, highlighting the emergence of ET resistance and a need for more effective therapeutic alternatives to improve pt outcomes. Citation Format: V. Kaklamani, S. Valliant, S. Hunter, O. Tymejczyk, A. Yu, P. Earla, S. Mehta, E. Pang. Treatment patterns and clinical outcomes following progression on first-line ET + CDK4/6i among patients with HR+/HER2− metastatic breast cancer (mBC) in the US [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-02-20.

D-dimer, a fibrin degradation product, is crucial for diagnosing thrombotic and fibrinolytic conditions. Despite its expanding utility, D-dimer testing faces challenges due to varying assay methodologies and non-standardized reporting. To understand D-dimer reporting practices, the College of American Pathologists (CAP) Hemostasis and Thrombosis Committee (HaTC) analyzed proficiency testing data from D-dimer surveys conducted between 2020 and 2023 across multiple laboratories. The data demonstrate that laboratories commonly report units that differ from the assay package insert when reporting their proficiency testing results. We sought to quantify the proportion of laboratories reporting units that may be considered incorrect. To accomplish this, we harmonized all D-dimer results to ng/mL fibrinogen equivalent units (FEU) for all results from one distributed sample and assessed distinct populations of entries per instrument/reagent combination. Notable trends emerged from this analysis. Data from laboratories using the same instrument/reagent combinations clustered around different means, suggesting issues with unit reporting and/or conversion. Entries reported in mg/L or ug/mL DDU commonly exhibited significant deviations from the dominant population. For one instrument/reagent combination, most reported values differed by approximately twice the COA value. This analysis highlights potential issues with D-dimer reporting in proficiency testing. Whether these issues translate into issues with clinical D-dimer reporting requires further study.

Sembrando Amor was a collaborative effort between Community Experts, public health professionals, and university-based action researchers, each of whom made explicit decisions to work outside of their normal roles for the good of the broader community and of our shared Community-Based Participatory Action Research (CBPAR) project. The project, which included a Photovoice and cartoon zining process, centers community experiences and voices with the intent to honor their role as experts in frontline matters that impact them as an institutionally marginalized community. Our main outcome is a community-driven vision for what a holistic breastfeeding support system looks like—a system that engages the expertise present in community breastfeeding experiences and wisdom, creates solidarity and builds on family support, critically engages the social determinants of health, and recasts the helpers to enable community-centered care. By sharing their stories of resilience, we hope to encourage others in the community to breastfeed and encourage institutions to learn from their stories and experiences to change policy and attitudes to more effectively support breastfeeding in ways that are meaningful, practical, and culturally and linguistically sensitive and supportive for their needs and goals.

Competency-based obesity medicine education is critically needed in undergraduate medical training, as emphasized by the Association of American Medical Colleges. Using a competency-based framework, we identified key gaps in obesity education across ten diverse U.S. medical schools. Each institution formed a working group to conduct a gap analysis of the curriculum based on 32 obesity medicine competencies recognized by the obesity medicine fellowship council. The least-addressed domains were Practice-Based Learning and Improvement and Systems-Based Practice, accounting for nine of the ten least-covered competencies. Additional gaps were noted in clinical skills and bias awareness. Most schools were relying on passive teaching methods and limited assessment. Findings highlight opportunities to develop shared, scalable resources to strengthen and standardize obesity medicine education nationwide.