Purpose Social support, specifically marital status, has been shown as a significant prognostic factor for survival of multiple malignancies, including prostate cancer. However, this has not been investigated in an equal access Veterans Affairs (VA) cohort where other support systems exist that may minimize the potential benefit of social support from a partner. Methods We retrospectively reviewed data from 9,931 patients undergoing primary radical prostatectomy (RP) in the VA from 1988-2020 across 9 VA centers. Univariable and multivariable Cox proportional hazards models were used to test the association between marital status and biochemical recurrence (BCR), metastasis, castration-resistant PC (CRPC) and prostate cancer specific mortality (PCSM). Results 8,285 patients met the inclusion criteria: 54% were married, 30% were divorced/separated, 9% were single/never married, and 6% were widowed at the time of RP. Single/never married men were younger (median 61 vs 62-65 years), had surgery more recently (median 2009 vs 2003-2008), had higher PSA (median 6.9 ng/mL vs 6.4-6.8 ng/mL), and had lower BMI (median 27 vs 28) compared to other groups (all p < 0.05). The median time to BCR was significantly shorter for divorced/separated men (188.2 months) and single/never married men (154.8 months) compared to married men (243.0 months). Consistent with this finding, compared to married men, divorced/separated men had higher risk of BCR (HR = 1.12; 95% CI 1.03-1.21), as did single/never married men (HR = 1.13; 95% CI 1.00-1.28). However, these associations were insignificant in multivariable analyses (all p > 0.05). Conclusion Among men with localized prostate cancer undergoing RP within the VA, we found no association between marital status-defined as a demographic indicator of self-reported relationship category-and oncologic outcomes. Whether marital satisfaction or perceived partner support, which were not assessed in this study, influence post-RP outcomes remains to be investigated.

Food swamps (FS) –areas with a high density of ultra-processed food outlets relative to grocery stores and supermarkets –have emerged as contextual determinants of cancer risk and survival. We hypothesized that greater FS exposure would be associated with higher prostate cancer-specific mortality (PCSM) and that this association would differ by race in Georgia, a state marked by persistent prostate cancer (PCa) disparities. We conducted a retrospective analysis of men diagnosed with PCa in Georgia (2000–2022) using Georgia Cancer Registry data. Census tract–level Federal Information Processing Series (FIPS) codes linked neighborhood-level food data from the National Neighborhood Data Archive (NaNDA; 1990–2021) and the Modified Retail Food Environment Index (RFEI) with patient-level cancer registry data. The RFEI, defined as the ratio of ultra-processed food outlets to grocery stores, farmers markets, and supermarkets, was categorized into low, moderate, and high FS exposure. Chi-square tests and ANOVA assessed group differences, and Cox proportional hazards models estimated associations between FS exposure and PCSM, stratified by race. Fully adjusted models controlled for age, race, insurance status, Gleason grade, PSA, stage at diagnosis, and primary treatment. Among 154,480 men (95,517 non-Hispanic [NH] White; 55,288 NH Black), 70% (N=108,146) lived in moderate/high FS tracts. Men in high FS areas (N = 33,330) were more likely to have public insurance, localized disease, and undergo surgery (p<0.05). Median follow up time was 8 years (IQR 4-13). There were 14,656 (9.5%) PCa-deaths. After age adjustment, each 1-unit increase in FS score corresponded to a 1% higher risk of PCSM (aHR 1.01 [95% CI 1.00–1.02], p = 0.005). The FS score ranged from 0-17 (median 1.16, mean 1.77; IQR 0.50–2.33). The association was attenuated after full adjustment (aHR 1.01 [95% CI 0.99-1.03], p=0.23). NHB men in moderate (aHR 1.14 [95% CI 1.01 – 1.28], p=0.04) or high (aHR 1.18 [95% CI 1.01 – 1.37], p=0.04) FS tracts had a higher risk of PCSM versus NHW men in low FS census tracts. No difference was observed among NHW men in high (aHR 1.09 [95% CI 0.96 – 1.24], p=0.20) FS census tracts. The neighborhood food environment represents a potentially modifiable, contextual determinant of cancer outcomes and potential target for intervention. The higher mortality risk among NHB men across FS levels underscores the enduring effects of systemic inequities on PCa outcomes. None Divya Lagisetti, Samuel Kennedy, Katherine J. Kim, R. Seth. Rozelle, Phillipe Gaillard, Avirup Guha, Zachary Klaassen, Martha K. Terris, Justin X. Moore, Malcolm S. Bevel, Ashanda R. Esdaille. Association of Neighborhood-Level Food Environment with Prostate Cancer-Specific Mortality Among Men in Georgia [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research and Treatment; 2026 Jan 20-22; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(2_Suppl):Abstract nr B034.

5091 Background: Prior studies suggest statin use may improve PC outcomes, including PC specific mortality (PCSM) and disease progression in patients receiving ADT. However, prior studies compared patients taking vs not taking statins at the time of ADT, ignoring that many statin non-users initiate statins later on. We evaluated the association between statin use and PC outcomes using both baseline (yes/no) and time-dependent exposure definitions in patients initiating ADT after RP. Methods: We conducted a retrospective cohort study of 9,931 patients with PC treated with RP between 1988 and 2020 at 9 VA hospitals from SEARCH Database. Patients who received ADT for biochemical recurrence after 2000 were included. Those with known metastasis prior to ADT or missing covariates of interest were excluded. Characteristics at ADT were stratified by statin use at time of ADT and compared with rank-sum for continuous variables and chi-square for categorical. Univariable and multivariable Cox models tested associations between statin use at ADT and time to metastasis, castration-resistant PC (CRPC), PCSM and all-cause mortality (ACM), adjusted for clinicopathological variables. As ~50% of non-statin users initiated statins after ADT, additional models treated statin use as time-dependent covariate. Results: Among 1,274 patients treated with ADT, 784 (62%) used statins at time of ADT. Users were older (median 67 vs 65), initiated ADT in more recent years (median 2013 vs 2010), had longer time from RP to ADT (median 39 vs 21 months), and had higher obesity rates (38% vs 25%). PC characteristics were similar between groups, except users had lower rates of positive nodes (11% vs 17%) and seminal vesicle invasion (28% vs 33%). Statin use at ADT was not significantly associated with time to metastasis, CRPC, PCSM or ACM, though HRs indicated lower risk for statin users (all HRs 0.89-0.98, all p>0.2; see table). On time-dependent multivariable analysis, statin use was significantly associated with lower risk of CRPC (p=0.019), PCSM (p=0.020) and ACM (p<0.001). Similar results were seen for metastases, though this did not reach significance (p=0.058) (see table). Conclusions: Statin use at ADT was not associated with PC outcomes after RP. However, accounting for statin initiation during ADT, statin use was associated with notably lower rates of CRPC, PCSM and ACM, with a trend towards reduced metastasis. These findings support the potential role of statins in slowing PC progression and highlight the need for prospective randomized trials of statins in patients initiating ADT. Outcome Statin at ADT, HR (95% CI) p Time-varying statin, HR (95% CI) p Metastasis 0.92 (0.71, 1.20) 0.541 0.74 (0.55, 1.01) 0.058 CRPC 0.95 (0.73, 1.24) 0.702 0.69 (0.51, 0.94) 0.019 PCSM 0.98 (0.70, 1.39) 0.920 0.62 (0.42, 0.93) 0.020 ACM 0.89 (0.73, 1.08) 0.229 0.51 (0.40, 0.64) <0.001

246 Background: ADT is standard for advanced prostate cancer (PC) but increases cardiometabolic risk. The proteomic mechanisms, and whether they differ by age, remain poorly defined. We profiled longitudinal plasma proteomes around ADT initiation to test for age-modified effects. Methods: Men with PC starting ADT (n = 14; baseline, 1, 3 months) underwent Olink Explore profiling (2,874 proteins). Standardized NPX changes were modeled with linear mixed-effects (random intercepts; fixed effects for visit and age <70 vs ≥70) and FDR control. Age×time interactions, baseline traits, and pathway enrichments were analyzed. Results: Median age 65.5 years (IQR 64–72.8); 43% African American; BMI 30.4; 50% diabetes; 79% hypertension; 50% metastatic; median Gleason 8.5. Nine proteins changed over 3 months (FDR q<0.05): Upregulated: ITIH4 (acute-phase/complement), MDGA1. Downregulated: KLK3/PSA (on-target), INSL3 (Leydig), EDDM3B, galanin, PI3 (elafin), SPINT3, ENDOU. Most trajectories were consistent across ages except PI3, which declined only in <70 (β −0.71, FDR <10⁻⁴) and was unchanged in ≥70 (β −0.003, FDR 0.99; interaction q = 0.025). Galanin and ENDOU were significant only in younger men. ITIH4, INSL3, KLK3, EDDM3B, SPINT3, and MDGA1 changed in both (≥70 q ≤ 0.05). Baseline clustering revealed two proteomic phenotypes without differential response. Two deaths occurred (non-significant). Conclusions: ADT induces rapid, multisystem proteomic remodeling with suppression of androgen-linked and activation of innate immune/complement–ECM pathways. Age modifies anti-inflammatory protease regulation (PI3), suggesting divergent inflammatory and matrix-remodeling responses after ADT in younger vs older men. These findings link ADT to early complement–ECM biology underlying cardiometabolic risk and highlight age and select proteins as candidates for biomarker-guided monitoring. Larger, outcome-linked cohorts are needed for validation. Age stratified 3 month effects (standardized NPX β) and FDR q-values. Protein (biology) Direction β (<70y) q (<70y) β (≥70y) q (≥70y) Age×time q ITIH4 (acute-phase/complement-linked) Up +0.42 0.0016 +0.56 0.0218 0.65 MDGA1 (neuronal glycoprotein) Up +0.41 0.0009 +0.56 0.0501 0.65 KLK3/PSA (on-target) Down −4.20 2.9×10⁻⁵ −5.10 0.0167 0.53 INSL3 (Leydig function) Down −5.89 7×10⁻⁶ −5.09 0.0115 0.65 EDDM3B (reproductive) Down −1.55 7×10⁻⁶ −1.87 0.0167 0.65 Galanin (neuroendocrine) Down −1.35 0.00029 −0.76 0.168 0.65 PI3 / Elafin (anti-inflammatory) Down −0.71 9×10⁻⁶ −0.003 0.987 0.025 SPINT3 (serine protease inhibitor) Down −4.48 2.9×10⁻⁵ −4.65 0.0115 0.65 ENDOU (RNA processing) Down −0.72 0.00029 −0.48 0.123 0.65 β = standardized effect (baseline→3 mo); FDR = Benjamini–Hochberg; interaction q from mixed-effects age×time term.

Genomic analysis has revealed that approximately 40

Abstract Cardiovascular disease (CVD) is a leading cause of mortality in men with prostate cancer (PC), with non‐Hispanic Black (NHB) men experiencing disproportionately higher CVD‐related mortality compared to non‐Hispanic White (NHW) men. Vascular endothelial dysfunction precedes overt CVD; however, the mechanisms underlying racial disparities in CVD among men with PC remain unclear. This study tested the hypothesis that NHB men with PC would exhibit impaired vascular health compared to NHW men. Thirty‐four men (12 NHW and 22 NHB) with a clinical diagnosis of PC underwent comprehensive vascular assessment, including arterial stiffness (pulse wave velocity [PWV] and augmentation index at 75 bpm [AIx75]), conduit‐vessel endothelial function (flow‐mediated dilation [FMD]), and microvascular function (post‐occlusive reactive hyperemia [PORH], local thermal heating [LTH], and acetylcholine iontophoresis). Clinical laboratory values, senescence‐associated secretory phenotype (SASP), and allostatic load were also evaluated. NHW men were older (p = 0.050), with no differences in body mass index (BMI), laboratory values, allostatic load, or SASP (all p > 0.05). NHB men demonstrated significantly lower PORH, LTH, and acetylcholine responses (all p < 0.001), while PWV, AIx75, and FMD were similar between groups. Despite comparable conduit‐vessel and arterial stiffness measures, NHB men exhibited impaired microvascular function, suggesting racial differences in vascular bed‐specific dysfunction following PC diagnosis.

Cigarette smoke promotes bladder tumor growth by enhancing cancer cell survival and proliferation through smoke mediated carcinogens. FASN, a key enzyme in fatty acid synthesis, is dysregulated in many cancers and correlates with aggressive phenotypes. In this study, we demonstrate elevated fatty acid levels and FASN specifically in smokers with bladder cancer. Elevated FASN under smoke exposure imparted epigenetic alterations, particularly histone acetylation, impacts DNA repair and DNA-binding transcription factors which regulate metabolic pathways. Under cigarette smoke, bladder cancer cells undergo a metabolic shift, utilizing glutamine as a major carbon source through reductive carboxylation to fuel fatty acid biosynthesis via FASN. Genetic and pharmacological inhibition of FASN significantly reduced tumor growth in a Chicken embryo Chorio-allantoic Membrane model exposed to smoke. FASN inhibitors such as TVB-2640, currently in clinical trials, may represent an effective therapeutic strategy for smokers with bladder cancer exhibiting high FASN levels.

PURPOSE With the growing interest in urology, it is increasingly important and useful to understand the factors that attract urology residency applicants to programs. We sought to investigate the impact of social media and other program-related characteristics on the application rates of urology residency programs. Materials and METHODS Match cycle data for 2019–2022 was collected for 140 accredited urology residency programs in the United States. The associations between the number of applicants, program social media presence and activity, Doximity rankings, program size, city population, and city quality of life were assessed. Multivariate analyses were conducted. RESULTS Programs with Twitter/X, Facebook, and YouTube had significantly more applicants than those without ( p < 0.05). There was a significant positive correlation between application rates and activity metrics on Twitter/X but not on other platforms ( p < 0.05). Programs with more residents and higher reputation rankings received more applications from 2019 to 2022, including in the multivariate model ( p < 0.05). Programs in cities with larger populations, but not better city quality of life rankings, received significantly more applicants from 2019 to 2022 ( p < 0.0001). CONCLUSIONS Programs should prioritize the use of Twitter/X to enhance their visibility, showcase their strengths, and connect with applicants. Reputation rankings and program size have the greatest effect on application rates, while city population and overall social media presence also play important roles. Residency programs can leverage these insights to enhance their appeal to potential applicants who might be the best “fit”.

Supplementary Table 1. Demographic and disease characteristics of patients with and without biopsy grade groups

Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1, such as pembrolizumab, are widely used for the treatment of various malignancies. These therapies, while typically less toxic than traditional chemotherapy, are associated with immune related adverse events which may affect the gastrointestinal tract, lungs, skin, liver, and less commonly the nervous system. Neurologic irAE are rare but carry high mortality rates. We present a case of seronegative myasthenia gravis in a patient treated with pembrolizumab for refractory bladder cancer. This case highlights the importance of early recognition of neurologic manifestations of irAE in patients receiving therapy with ICIs.

Background:Transrectal ultrasound (TRUS)-guided transperineal (TP) and transrectal (TR) approaches have been used for systematic prostate biopsy. A meta-analysis was conducted to compare the cancer detection rates (CDRs) and associated complications between TP and TR prostate biopsies. Methods:PubMed, Web of Science, Embase, Cochrane Library, China Wanfang data, and China National Knowledge Infrastructure (CNKI) were searched for literature on TP and TR biopsies of the prostate from inception to September 2024. Results:A total of 20 studies were included in the meta-analysis of 2,979 and 2,610 patients undergoing TP and TR biopsies, respectively. The pooled analysis indicated no significant difference in the CDR between the TP and TR biopsies [relative risk (RR) =0.98; 95% confidence interval (CI): 0.92-1.04; P=0.46]. Compared to the TR approach, the TP approach was associated with a lower risk of rectal bleeding (RR =0.05; 95% CI: 0.02-0.13; P<0.001), urinary retention (RR =0.70; 95% CI: 0.49-0.99; P=0.046), and fever (RR =0.24, 95% CI: 0.15-0.39; P<0.001). However, the risk of pain after the procedure was higher in the TP group (RR =2.04; 95% CI: 1.47-2.82; P<0.001). No significant difference was found in the risk of hematuria between the two groups (RR =1.05; 95% CI: 0.91-1.22; P=0.52). Conclusions:TP and TR biopsies of the prostate have similar CDRs. Remarkably, compared to TR biopsy, TP biopsy involves a lower risk of rectal bleeding, urinary retention, and fever, but a higher risk of pain.

315 Background: Socioeconomic position (SEP) is a key social determinant of health (SDOH) associated with disparities in cancer care and cardiovascular (CV) outcomes in patients with prostate cancer (PC). Understanding the impact of SEP on cardiovascular health is critical for addressing inequities in PC CV outcomes. Methods: We conducted a retrospective cohort study on the SEER-Medicare database. Multiple CV outcomes were assessed in patients ≥65 years of age with no prior CV disease and with localized or advanced PC. SEP was defined using the census-tract level Yost index where those living in first and second quintiles were considered as living in low SEP areas. A competing risk analysis using univariable and multivariable Fine-Gray Models was used for CV events (CVE), CV mortality (CVm) and PC specific mortality (PCsm). CVEs included myocardial infarction, heart failure, atrial fibrillation, ischemic stroke, and peripheral artery disease. All-cause mortality was assessed using Cox proportional hazard (PH) models. All models were adjusted for age, race, marital status, education level, PC grade, PC TNM stage, diabetes, hypertension, hyperlipidemia, chronic kidney disease, and receiving chemotherapy. A sub-group analysis was further conducted in patients who self-identified as non-Hispanic Black (NHB). Results: We included 150,647 patients of whom 102,271 had high SEP and 48,376 had low SEP. Patients with low SEP have shown higher associated risks of CVm (subdistribution hazard ratio [sHR] 1.25, 95% CI 1.19-1.32, p<0.001), PCsm (sHR: 1.20, 95% CI 1.14-1.26, p<0.001), CVE (sHR 1.07, 95% CI 1.04-1.09, p<0.001), and all-cause mortality (adjusted HR 1.17, 95% CI 1.14-1.20, p<0.001) when compared to patients with high SEP. Similarly, in the NHB subgroup analysis, patients with low SEP showed an increase of 11% in CVE, 37% in CVm, and 21% in PCsm and 20% all-cause mortality (Table). Conclusions: Adverse SEP, as a proxy for SDOH, plays an important role in patients with localized or metastatic PC by increasing associated risks for adverse cardiovascular and survival outcomes by up to 25% in the overall population and 37% in NHB individuals. Survival analysis using Fine-Gray analysis (competing risk models) and Cox PH regression for the various cardiovascular outcomes using the fully adjusted model. Overall (n=150,647) NHB (n=15,474) CVE (Competing risk = All-cause mortality)sHR (95% CI, p-value) 1.07 (1.04-1.09, p<0.001) 1.11 (1.03-1.20, p=0.007) CVm (Competing risk = All-cause mortality except CVD mortality)sHR (95% CI, p-value) 1.25 (1.19-1.32, p<0.001) 1.37 (1.15-1.64, p<0.001) PCsm (Competing risk = All-cause mortality except PCsm)sHR (95% CI, p-value) 1.20 (1.14-1.26, p<0.001) 1.21 (1.04-1.41, p=0.016) All-cause mortality (Cox)aHR (95% CI, p-value) 1.17 (1.14-1.20, p<0.001) 1.20 (1.08-1.35, p=0.001)