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Abstract Introduction 0.05% Chlorhexidine Gluconate (CHG) has gained popularity as an irrigant and dip for inflatable penile prosthesis (IPP) surgery. Prior in vitro data is conflicting on the impact of CHG use with hydrophilic coated devices. Objective We sought to identify possible associations between CHG use and hydrophilic IPP infection rate. Methods We conducted a retrospective cohort study of 2,933 patients undergoing IPP implantation across 14 referral centers. Data collection spanned from January 1, 2017 to March 1, 2024. Each surgeon contributed patients who underwent IPP implantation with CHG used as an irrigant and/or dip as well as an equal number of consecutive control patients without CHG use. The primary outcome was IPP explant for postoperative infection. Univariable analysis was used to compare patient demographics, and logistic regression analysis was performed to assess factors associated with infection. Results Hydrophilic devices were implanted in 2,150 patients. Median follow-up for non-CHG patients was 13 months (IQR 18) and four months (IQR 9) for CHG patients. The incidence of infection with intraoperative CHG use was significantly higher compared to those without CHG use (4.6%, 46/1,001 vs. 2.1%, 24/1,148, p<0.001). On multivariable logistic regression analysis, intraoperative CHG use was associated with infection (OR 2.07, 95% CI 1.24-3.47, p=0.01). Additional variables associated with infection included immunosuppression, prior IPP infection, prior priapism, and revision surgery (p<0.01, Table). On subgroup analyses, the increased infection risk of CHG was most clear when CHG was used as both irrigation and dip (OR 2.03, 95% CI 1.19-3.46, p=0.01) and when CHG was used during revision surgery (OR 3.36, 95% CI 1.15-9.82, p=0.03). Conclusions In a large multi-institutional cohort, intraoperative CHG use was associated with an elevated incidence of hydrophilic IPP infection. Providers may take these findings into consideration when performing IPP surgery with hydrophilic devices, especially during revision surgery. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Intuitive Surgical, Fidelis, Urofill, Boston Scientific, Coloplast, Cynosure, Antares Pharma, Clarus Pharmaceuticals, Acerus Pharma; Endo Pharma

BACKGROUND: Although the prognostic utility of positron emission tomography (PET) myocardial flow reserve (MFR) is well established, emerging data suggest that reduced subendocardial flows also predict adverse outcomes. However, the incremental value of subendocardial MFR (MFR SE ) beyond transmural MFR (MFR TM ) remains unclear. METHODS: We studied patients in a multicenter PET registry with normal perfusion on stress/rest Rb-82 PET, excluding those with a previous history of coronary artery bypass surgery, heart transplantation, or left ventricular ejection fraction <40%. The optimal MFR SE cutoff for predicting major adverse cardiovascular events (MACEs; death, myocardial infarction [MI], revascularization, or heart failure [HF] hospitalization) was determined using Youden’s index. Patients were stratified into 3 groups: concordant-normal (MFR TM ≥2.0; MFR SE ≥2.1), discordant (low-MFR SE , normal MFR TM ), and abnormal MFR TM . Clinical outcomes were compared by MFR groups. RESULTS: Among 6603 patients (normal N=4103; discordant N=885; abnormal N=1615) the mean age was 66.3±12.4 years, and 54% were women. Compared with the concordant-normal group, patients with discordant low-MFR SE were older and more likely to have hypertension, diabetes, peripheral artery disease, and previous percutaneous coronary intervention. The median MFR TM for normal, discordant, and abnormal groups were 2.86, 2.15, and 1.72, respectively. Over a median follow-up of 4.9 years, 1661 MACE events occurred. Discordant low-MFR SE patients had a higher risk of MACE (hazard ratio [HR], 1.41; 95% CI, 1.22–1.64) and all-cause mortality (HR, 1.36; 95% CI, 1.14–1.61) compared with concordant-normal patients. The discordant group had an intermediate absolute risk of MACE, with an adjusted annualized event rate of 5.79% (95% CI, 5.10–6.49) compared with 3.99% (95% CI, 3.67–4.30; P <0.001) in the concordant-normal group and 8.35% (95% CI, 7.71–9.00; P <0.001) in the abnormal MFR TM group. CONCLUSIONS: Subendocardial MFR reveals clinically meaningful risk heterogeneity among patients with preserved transmural flow reserve, helping refine risk stratification beyond traditional PET metrics.

Abstract Background Distal (ileal) metabolic bariatric surgeries (DMBS) have gained increasing adoption due to their enhanced metabolic effects. However, the absence of standardized definitions, classification, and clinical indications limits their consistent application. This consensus aimed to establish an international consensus on the definition, classification, indications, and postoperative management of DMBS. Methods A three-round modified Delphi study was conducted including international expert surgeons from 16 countries. A total of 98 statements were developed across three domains: procedural characteristics, patient selection, and postoperative follow-up. Consensus was defined as ≥75% agreement. Statements not reaching consensus were revised and resubmitted. Results Consensus was achieved on 81 statements. DMBS were defined as procedures involving gastro-ileal or duodeno-ileal bypass, emphasizing ileal stimulation as a key metabolic mechanism. Procedures with a common channel ≤350 cm, including single-anastomosis duodenal-ileal with SG (SADI-S), single anastomosis sleeve-ileal transit bipartition (SASI), sleeve gastrectomy with Roux-en-Y transit bipartition (SG+TB), and biliopancreatic diversion with duodenal switch (BPD-DS), as well as one-anastomosis gastric bypass (OAGB) with biliopancreatic limb > 50% of total small bowel length were classified as DMBS. Routine measurement of total small bowel length was strongly recommended. DMBS were considered appropriate as primary procedures in patients with BMI ≥40 kg/m² with comorbidities, a BMI ≥50–60 kg/m², irrespective of the presence of comorbidities, and as revisional options for suboptimal clinical response (SoCR), recurrent weight gain (RWG), or persistent metabolic disease. Comprehensive preoperative and multidisciplinary evaluation was deemed mandatory, and liver cirrhosis, heart failure, end-stage kidney disease, and inflammatory bowel disease were considered contraindications. Postoperative care requires lifelong multidisciplinary follow-up, with increased attention to nutritional deficiencies and supplementation. Conclusions This consensus provides a standardized framework for DMBS, supporting harmonization of practice and improved patient safety.

e19536 Background: Chronic kidney disease (CKD) may impair physiologic resilience during chimeric antigen receptor (CAR) T-cell therapy for multiple myeloma (MM). While cytokine response syndrome (CRS) and immune cell-associated neurotoxicity syndromes (ICANS) have been described in MM CAR-T recipients with CKD, the broader cardiopulmonary, infectious, renal, and economic implications of CKD remain insufficiently defined. We examined the national impact of CKD on mortality, immune cell effector toxicities, organ dysfunction, infections and resource utilization. Methods: Adult MM hospitalizations receiving CAR T-cell therapy were identified from the National Inpatient Sample (2018–2022) using ICD-10-PCS codes. Patients with ESRD were excluded. CKD was categorized as CKD3a+ (eGFR <60 mL/min) versus no CKD/CKD1–2. Outcomes included in-hospital mortality, CRS (2021–2022), ICANS (2022), cardiac arrhythmias, acute kidney injury (AKI), renal replacement therapy, respiratory failure, infections and total hospitalization cost (calculated using TOTCHG variable and adjusted cost to charge ratio). Comparative analysis was done using chi-square testing. Multivariate analysis adjusted for demographics, comorbidities, and hospital characteristics. Results: Among 2,045 weighted MM CAR-T hospitalizations, 7.6% had CKD3a+. Overall CRS rates were similar (66.7% vs 64.9%; p=0.839) between CKD3a+ vs no/CKD1-2. Overall ICANS rates were also comparable (16.7% vs 17.3%; p=0.941). Differences in CRS/ICANS grades were not significant. CKD3a+ patients experienced sharply higher AKI (58.1% vs 13.0%; p<0.001; adjusted odds ratio [OR] 9.2, p<0.001). Renal replacement therapy was more frequent in CKD3a+ but non-significant (3.2% vs 0.8%; p=0.196). Acute respiratory failure was more frequent (9.7% vs 2.9%; p=0.045) in patients with CKD. Cardiac arrhythmias were numerically higher but non-significant (25.8% vs 20.6%; p=0.527; adjusted OR 1.3, 95% CI 0.4–4.9; p=0.673). Infections were amplified, including gram-negative bacteremia (3.2% vs 0.3%; p=0.026), sepsis (9.7% vs 2.6%; p=0.040), and septic shock (3.2% vs 0.3%; p=0.027) in patients with CKD. Inpatient mortality was numerically higher (6.5% vs 1.9%; p=0.101), though nonsignificant after adjustment (OR 6.9; p=0.319). Hospital costs were substantially higher in CKD3a+ (USD 346,769 vs 239,175; p=0.006), though not significant in adjusted models (OR 1.3; p=0.120). Conclusions: CKD3a+ is associated with markedly increased AKI, higher respiratory failure and infections, with a trend towards higher hospitalization costs. Inpatient mortality, CRS and ICANS rates were similar. CKD3a+ represents a significant vulnerability that amplifies downstream complications in MM CAR-T recipients, warranting enhanced pre-treatment risk stratification, infection surveillance and renal-preserving strategies.

e19046 Background: While outcomes in pts with R/R FL have improved with current SOC treatments (Tx), there remains a need for safe, efficacious, and convenient Tx options. GOLCA is a potential, first-in-class, oral CELMoD designed for Tx of lymphoma, with preferential distribution to lymphoid organs and enhanced activity in lymphoma cell lines. GOLCA induces rapid and deep degradation of Ikaros and Aiolos, leading to direct cell killing and immunomodulatory activity. GOLCA + R was well tolerated and effective in heavily pretreated pts in the two-part Ph 1/2 study, CC-99282-NHL-001. Here, we provide longer f/u in pts with R/R FL from Part B of the study. Methods: Pts with R/R FL with ≥2 prior lines of Tx (≥1 if prior anti-CD20 Tx) received GOLCA orally, once daily at 0.2 mg (n=22) or 0.4 mg (n=38) ± R for up to 2 y or until progressive disease (PD)/unacceptable toxicity. Primary endpoints included safety and RP2D determination; secondary endpoints are preliminary efficacy and PK. Results: As of September 15, 2025, 60 pts were enrolled. In 0.2 and 0.4 mg groups, median prior Tx lines were 3 and 3, 32% and 32% had prior lenalidomide (LEN), 27% and 29% had prior T-cell–redirecting Tx (CAR T and/or bispecific antibody) and 32% and 32% were refractory to last regimen. Tx is ongoing in 6 (27%) and 17 (45%) pts at 0.2 and 0.4 mg, respectively; discontinuations (d/c) were mostly due to PD. Neutropenia, an on-target side effect of GOLCA, was the most common grade 3/4 Tx-emergent adverse event (TEAE) occurring in 59% and 68% of pts at 0.2 and 0.4 mg, followed by anemia (9% and 16%) and febrile neutropenia (9% and 8%). Median time to resolution of neutropenia was 8 days. Dose reductions occurred in 14% and 37% of pts at 0.2 and 0.4 mg, most commonly due to neutropenia (5% and 21%) and febrile neutropenia (5% and 5%). No d/c or deaths were from GOLCA-related TEAEs. Non-hematologic TEAEs were infrequent and mostly low grade. In efficacy-evaluable pts (GOLCA 0.2 and 0.4 mg + R, n=22 and n=36), median f/u was 14.03 months (mo), overall response rate (ORR) was 77% (complete response rate [CRR], 41%) at 0.2 mg, and 97% (CRR, 78%) at 0.4 mg. In the 0.4 mg group, responses were consistent in high-risk subsets including pts with prior LEN (ORR, 100%; CRR, 75%) and/or T-cell–redirecting Tx (ORR, 91%; CRR, 64%). GOLCA 0.4 mg + R demonstrated durable responses (median DOR, 9.17 mo; 91% of pts who achieved a CR remained in CR at cutoff). Conclusions: With longer f/u, GOLCA + R demonstrated promising efficacy with durable responses and no new safety signals. The 0.4 mg group had higher ORR and CRR than 0.2 mg, including in pts with prior LEN-based and/or T-cell–redirecting Tx, with a manageable safety profile at both doses. The results support the development of GOLCA + R as a fixed-duration, chemotherapy-free outpatient Tx in the Ph 3 GOLSEEK-4 study in 2L+ FL (NCT06911502). Clinical trial information: NCT03930953 .

e17134 Background: Despite being the most prevalent malignancy among men, prostate cancer (PC) lacks FDA-approved primary prevention therapies. Current options, such as 5-alpha reductase inhibitors (5-ARIs), offer only modest risk reduction—approximately 23–25%—as shown in the PCPT and REDUCE trials. Emerging preclinical data indicate that GLP-1 receptor agonists (GLP-1RAs) may offer a novel alternative by inhibiting oncogenic pathways and inducing apoptosis in PC cell lines. To investigate this potential, we conducted the first real-world comparative analysis of PC incidence among high-risk men receiving GLP-1RAs versus 5-ARIs. Methods: Using the TriNetX global collaborative network (150M patients), we identified men with elevated PC risk (genetic risk, family history, or high-risk demographics/comorbidities). GLP-1RA users (cohort A) were propensity-score-matched 1:1 with 5-ARI users (cohort B) on demographics, metabolic comorbidities, baseline PSA, BMI and HbA1c. A minimum of 2 month’s prescription was required. The primary endpoint was incident PC. The secondary endpoint was adverse events related to GLP-1RA and 5-ARI. Patients with outcomes before the study inclusion were excluded. Sensitivity and subgroup analyses were performed, adjusting for screening frequency and baseline BMI. Kaplan–Meier curves assessed cumulative incidence, Cox models estimated hazard ratios (HRs, 95% CI), and logistic regression analyzed binary outcomes. Results: After matching, 118,904 high-risk men were identified (59,452 patients per cohort). Cohorts had comparable demographics with a mean age of 48 years, 77% White, 9% Black, and 2% Asian. GLP-1RA users had higher mean A1C (6.3% vs 5.7%) and BMI (38 vs 31), while 5-ARI users had higher mean PSA (3.1 vs 1.3). Median follow-up was 7 years for both cohorts. PC incidence was 2.10% (1,245/59,189) in GLP-1RAs users versus 2.85% (1,689/59,164) in 5-ARI users (NNT 133). GLP-1RAs were associated with a 20% reduction in PC risk (HR: 0.803; CI: 0.746–0.864). Safety outcomes showed that GLP-1RAs were associated with an increased risk of erectile dysfunction and nausea/vomiting. In contrast, GLP-1RAs were associated with lower risks of abdominal pain and constipation. No significant associations were observed for gynecomastia or diarrhea. Conclusions: In this large-scale, head-to-head comparison, GLP-1RAs demonstrated superior efficacy over 5-ARIs, providing a 20% relative risk reduction in PC incidence among high-risk men. Given the global surge in GLP-1RA utilization, these findings suggest a profound public health opportunity: the ability to achieve systemic oncologic protection through existing metabolic therapies. If validated by prospective trials, GLP-1RAs could transition from metabolic blockbusters to a cornerstone of precision oncology and primary cancer prevention.

e16510 Background: Early-onset RCC may reflect distinct biology and hereditary predisposition, yet data on stage-specific clinical features and outcomes remain limited. We comprehensively evaluated age-stratified, stage-specific clinical features and survival outcomes using the National Cancer Database. Methods: Adults with histologically confirmed RCC diagnosed between 2004 and 2022 were analyzed. Patients were categorized into three groups by age at diagnosis: early-onset ( < 40 years), middle-aged (40–50 years), and late-onset ( > = 50 years). The sociodemographic and clinical characteristics, comorbidities, histology, and treatment patterns were compared using descriptive statistics. Overall survival (OS) was evaluated using Cox proportional hazards models, adjusting for the aforementioned variables. Stage-specific analyses were conducted, including a metastatic disease cohort. Results: Among 742,114 patients, 4.3% were classified as early-onset, 10.9% as middle-aged, and 84.8% as late-onset. Overall, 12.6% presented with metastatic disease. Compared with late-onset, early-onset patients were more likely to be from racial minority populations (non-White: 16.9 % vs. 20.2 % in late-onset), uninsured, and had fewer comorbidities (Charlson–Deyo score 0: 85.2% vs. 65.2%). Early-onset RCC was characterized by a lower proportion of papillary RCC (8.9% vs. 12.5%) and higher proportions of clear cell (54.9% vs. 50.8%) and chromophobe RCC (9.3% vs. 4.5%) than late-onset RCC and more likely to undergo partial nephrectomy (50.4% vs. 30.2%). They also presented with earlier-stage disease, with lower rates of stage III (7.4% vs. 10.2% vs. 13.4%) and stage IV disease (5.4% vs. 8.9% vs. 13.5%) compared with middle-aged and late-onset groups. Among patients with metastatic disease, early-onset RCC demonstrated higher minority representation (30.8% vs. 14.1%) and a higher prevalence of non-clear cell histology (70.6% vs. 58.1%). In multivariable analysis, compared with early-onset RCC, middle-aged (HR 1.44, 95% CI 1.39–1.50; P < 0.001) and late-onset patients (HR 2.83, 95% CI 2.74–2.93; P < 0.001) experienced significantly worse OS. However, among metastatic disease, this survival advantage was attenuated. Early-onset patients had similar OS to middle-aged patients (HR 0.99, 95% CI 0.93–1.05, p = 0.69) and late-onset patients only had a modestly worse OS than the early-onset group (HR 1.09, 95% CI 1.03–1.15 p = 0.003). Conclusions: Early-onset RCC was associated with more favorable baseline characteristics, earlier stage at diagnosis, and higher utilization of nephron-sparing nephrectomy, corresponding to improved OS. However, this survival advantage diminishes in metastatic disease despite better baseline health, highlighting stage-dependent differences in outcomes and suggesting distinct histologic patterns in advanced early-onset RCC.

e16488 Background: Small bowel adenocarcinoma (SBA) and ampullary adenocarcinoma (ampullary AC) are rare gastrointestinal (GI) malignancies. Treatment strategies are largely extrapolated from colorectal cancer, where oxaliplatin-based regimens are the most common first-line therapy in advanced disease. Although bevacizumab is considered safe in metastatic SBA, its efficacy remains unproven, and evidence is limited to small retrospective studies. We assessed the association of adding bevacizumab to FOLFOX with survival and toxicity in a large real-world cohort. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network (January 2000-December 2025), including data from 105 healthcare organizations. Adults (≥18 years) with SBA or ampullary AC treated with FOLFOX with or without bevacizumab were identified. Cohorts were propensity score-matched on age, sex, race, comorbidities, and metastatic sites. Outcomes included overall mortality, GI perforation, bleeding, venous thromboembolism (VTE), hospital admission, and emergency department (ED) visits. Kaplan-Meier and Cox proportional hazards models were used for time-to-event analyses. Results: After matching, 818 patients were included in each cohort. In the FOLFOX + bevacizumab cohort, mean age was 66.1 ± 12.0 years and 53.8% were male; 63.7% were White, 13.8% Black, 5.6% Asian, 12.0% Unknown/Other, and 4.4% Hispanic/Latino. Over a median follow-up of 13 months, FOLFOX + bevacizumab was associated with higher overall mortality compared with FOLFOX alone (55.3% vs 45.2%; HR 1.24 [95% CI 1.1-1.4]; p = 0.002) and shorter median OS (15.1 vs 19.5 months). Rates of GI perforation (15.5% vs 16.7%; HR 0.90 [95% CI 0.71-1.15]; p = 0.39), GI bleeding (13.1% vs 13.6%; HR 0.96 [95% CI 0.73-1.25]; p = 0.74), and VTE (19.1% vs 21.4%; HR 0.88 [95% CI 0.71-1.09]; p = 0.23) were similar between groups. Hospital admissions were higher in the FOLFOX + bevacizumab cohort (2.8% vs 1.3%; HR 2.1 [95% CI 1.0-4.3]; p = 0.04). Findings were consistent at 5-year follow-up. Conclusions: In this real-world cohort, the addition of bevacizumab to FOLFOX was not associated with improved survival and was associated with higher healthcare utilization. Prospective, disease-specific studies are needed to define its role in this population. Outcomes at median 13-month follow-up after propensity matching (FOLFOX + bevacizumab vs FOLFOX). Outcome % vs % HR p Overall mortality 55.3 vs 45.2 1.24 0.002 Hospital admission 2.8 vs 1.3 2.1 0.04 ED visit 45.2 vs 42.4 1.02 0.75 GI perforation 15.5 vs 16.7 0.90 0.39 GI bleeding 13.1 vs 13.6 0.96 0.74 VTE 19.1 vs 21.4 0.88 0.23

e16449 Background: Pancreatic cancer (PC) carries a dismal 5-year survival of < 12%, and no FDA-approved agents exist for primary prevention. PC risk is strongly linked to obesity, diabetes, and chronic inflammation. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) directly target obesity-driven inflammatory pathways, reduce metabolic stress, and modulate signaling pathways (PI3K/AKT/mTOR) that drive cancer apoptosis. Based on this biological rationale, we conducted the first large-scale real-world study to evaluate the safety and efficacy of GLP-1RA for primary prevention of PC in high-risk patients. Methods: Leveraging a large real-world database (TriNetX), we identified patients aged 18-90 years with ≥1 PC risk factor (tobacco use, obesity, type 2 diabetes, alcohol use disorder, chronic pancreatitis, first-degree relative with PC, genetic susceptibility to PC) based on ICD-10 codes. Patients were stratified by GLP-1RA exposure into two cohorts: Cohort A (GLP-1RA users with ≥ 2 months of prescriptions) and Cohort B (controls). The primary endpoint was incident PC, and the secondary endpoints were adverse events related to GLP-1RAs. Patients with outcomes before the study window were excluded. Propensity score matching adjusted for confounders. Multivariate logistic regression was used to estimate odds ratios for categorical outcomes, and the Cox proportional hazards model was used to estimate hazard ratios for time-to-event outcomes. Subgroup and sensitivity analyses were employed to validate the strength of our results. Results: Median follow-up was 3,397 days for GLP-1RA users and 2,531 days for controls. Demographics were balanced between cohorts (mean age 42 years; 74% White, 15% Black; 72% female). Among 572,330 high-risk patients (286,165 per cohort), PC incidence was significantly lower among GLP-1RA users (0.05%; 134/286,165) than among non-users (0.13%; 362/286,097), with a 2.6-fold reduction in the absolute incidence of PC among high-risk patients (NNT of 1,255). GLP-1RA use was associated with a 71% reduction in PC incidence (HR 0.289; 95% CI 0.237–0.352). GLP-1RA use was associated with an increased risk of gastrointestinal adverse events, including nausea/vomiting (HR 1.108; 95% CI 1.096–1.121), abdominal pain (HR 1.081; 95% CI 1.066–1.097), diarrhea (HR 1.199; 95% CI 1.182–1.217), and constipation (HR 1.159; 95% CI 1.143–1.176). Conclusions: GLP-1RA use significantly reduced PC incidence by 71% in high-risk patients, the strongest real-world signal yet for a pharmacologic prevention of this lethal malignancy. Although the absolute incidence remained low, the magnitude of the risk reduction underscores the transformative potential of GLP-1RA in preventive oncology. These findings address a critical unmet need in pancreatic oncology. Prospective mechanistic and randomized studies are warranted to validate these associations.