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Racial and ethnic disparities in urinary continence recovery post-prostatectomy.

376 Background: Urinary incontinence is a common complication following prostatectomy, with continence recovery rates varying widely across the literature. While 12-month continence rates are consistently above 90%, disparities in short- and intermediate-term recovery rates exist. This study investigates the differences in overall urinary continence outcomes among Black, non-Black Hispanic, and non-Black non-Hispanic men within 12 months post-surgery. Methods: Data were collected from two sources: (1) men recruited in clinic from the Northwestern University Department of Urology as part of the URO-QOL study, an observational study of Quality Of Life (QOL), and (2) cross-sectional, retrospective data from an online health panel maintained by OP4G (Opinions 4 Good, http://op4g.com/). Eligible participants had clinically localized prostate cancer, were 18 years or older, and were able to read and speak English. Urinary continence outcomes were assessed within 12 months post-surgery using the American Urological Association Symptom Score (AUASS), Expanded Prostate Cancer Index Composite-26 (EPIC-26), and Functional Assessment of Cancer Therapy-Bladder (FACT-Bl). One-way ANOVA, as well as Chi-squared tests, were performed to assess differences in functional outcomes across racial and ethnic groups. Results: There were 417 patients total, with 57 (14%) Black men, 87 (21%) non-Black Hispanic men, and 273 (65%) non-Black non-Hispanic men.One-way ANOVA demonstrated significant differences in overall AUA Symptom Score (p=0.0166) and EPIC-26 Urinary Symptom Score (p=0.00276), but not FACT-Bl Scores (p=0.253), between Black, non-Black Hispanic, and non-Black non-Hispanic men, with Black men demonstrating highest symptom burden across all three surveys (Table). Conclusions: Racial and ethnic disparities in urinary continence recovery following radical prostatectomy are evident, with Black men in particular experiencing worse outcomes compared to Hispanic and non-Black non-Hispanic men. While overall functional recovery improves within 12 months post-surgery, these disparities suggest a need for further investigation into underlying factors influencing these outcomes. Ultimately, targeted pre- and post-operative interventions such as pelvic floor muscle training may help mitigate the racial and ethnic disparities highlighted in this study. Univariate ANOVA analysis of summed scores of post-treatment urinary symptoms surveys. Overall Black Non-Black Hispanic Non-Black Non-Hispanic P-value AUASS Sum (mean) 21.40 23.32 22.95 20.48 0.0166* Category (mean) 2.556 2.737 2.628 2.494 0.0137* EPIC-26 Sum Urinary Symptom Responses (mean) 19.96 22.78 20.92 19.07 0.00179* Overall Urinary Symptom Score^ (mean) 50.584 42.644 48.109 53.053 0.00276* FACT- Bl Sum (mean) 8.856 9.302 9.076 8.678 0.253 *p<0.05 denotes statistical significance. ^Lower EPIC-26 score represents higher symptom burden.

Impact of belzutifan on anemia and hypoxia in sporadic and <i>VHL</i> -syndrome-associated renal cell carcinoma.

522 Background: Inactivation of the tumor suppressor von Hippel-Lindau ( VHL ) gene is associated with VHL -syndrome-associated renal cell carcinoma ( VHL- RCC) and sporadic renal cell carcinoma (spRCC). The inactivation of the VHL results in the accumulation of HIF-2a, promoting the expression of genes involved in angiogenesis and cycle-cell progression. Belzutifan, a HIF2α inhibitor, is approved for the treatment of VHL -RCC and spRCC patients (pts). Understanding the safety differences of belzutifan in these two populations can inform clinical management. Methods: This is a single-center, retrospective analysis of pts with spRCC and advanced VHL- RCC treated with belzutifan monotherapy between November 2018 and August 2024. The study population was separated into groups based on RCC type: spRCC and VHL- RCC. Demographic and clinical data were collected from medical records. The primary endpoints were the incidence of anemia and hypoxia. Continuous variables were reported as median with interquartile ranges (IQR) and compared using Wilcoxon rank-sum test. Categorical variables were presented as frequencies and percentage, with group comparisons performed using the Pearson Chi-Square test. Results: Pts with spRCC were older than those with VHL -RCC pts, with a median age of 67 y vs 41 y (p&lt; 0.001), and were predominantly male, (68% vs 36%, p = 0.035). Reduced glomerular filtration rate (defined as &lt; 50ml/min), was more prevalent in spRCC pts (36.5% vs 4.5%, p = 0.009). Baseline hemoglobin levels were similar between groups 13 g/dL (IQR: 10 – 14) vs.13 g/dL (IQR: 12.8 – 14.8). VHL- RCC pts received belzutifan for longer duration than spRCC pts (30.9 m vs 3.4 m, p &lt; 0.001). In terms of safety, any-grade and Grade 3 anemia were similar between groups, 82% vs 91% (ns) and 54% vs 36% (ns), respectively. However, anemia developed more rapidly in spRCC pts, 29 d vs. 82 d (p &lt;0.01) for any-grade, and 46 d vs. 104 d (p = 0.018) for grade 3 anemia. The need for blood transfusion was more frequent in spRCC patients (18% vs 0%, p &lt; 0.05) as was the use of erythropoietin-stimulating agents 2% vs 4.5%, p = 0.08). Any-grade hypoxia was more frequent in spRCC pts (59% vs 18%, p 0.005), and there was a trend towards more grade 3 hypoxia (54.5% vs 9%, p = 0.052). Grade 3 hypoxia developed faster in spRCC pts (29 d vs 225 d, p = 0.039), the need for oxygen was more frequent in this population (52.5% vs 9.5%, p =0.003). Treatment discontinuations were more frequent in spRCC pts than in the VHL -RCC pts, 36.4% vs 4.5% (p = 0.009), 75% of discontinuations in spRCC were due to toxicity. Conclusions: Our cohort demonstrates differences in the safety profile of belzutifan between spRCC and VHL -RCC patients. These findings underscore the importance for personalized monitoring and management for each patient population.

Bivariate multilevel modeling of antenatal care contacts and place of delivery among reproductive-aged women in Ethiopia

Background Antenatal care (ANC) contacts, along with enhanced health facilities for delivery, are essential components of maternal and child healthcare, as these significantly contribute to both mothers and their newborn child’s health. Antennal care contacts primarily help women maintain normal pregnancies by detecting pre-existing conditions and preventing complications that may arise during childbirth. This study intended to determine possible factors that affect both ANC contact and place of delivery among women in Ethiopia. Methods The 2019 Ethiopian Mini Demographic and Health Survey data were used for this study. A total weighted sample of 3,926 women nested within 68 zones was used. The bivariate multilevel logistic regression model was utilized to assess the association between antenatal care contact and place of delivery and determinant factors among reproductive-aged women in Ethiopia. Results In this study, 57% and 47.5% of women had no ANC contacts and home delivery respectively. Similarly, about 36.73% of women delivered at home and didn’t utilize the recommended ANC contacts. Only 32.99% of women have both health facility delivery and at least four ANC contacts during their pregnancy. Women who reside in rural areas were 0.612 and 0.352 times less likely to have ANC and health facility delivery compared to women who reside in urban areas. Whereas, the estimated odds of women with higher education levels were 3.803 and 8.406 times the estimated odds of women with no education. Conclusion A high proportion of women are still delivering their new child at home and still don’t have at least four ANC contacts during their pregnancy. Women’s age, women education level, marital status, wealth status, sex of household head, place of residence, and region were significant predictors of antenatal care visits and place of delivery simultaneously in Ethiopia. Although the country tried to maximize these services, it still requires expansion of health facilities media campaigns, and women’s literacy to reduce maternal and newborn child mortality in Ethiopia.

Minimizing makespan for mixed batch scheduling with identical machines and unequal ready times

Treatment patterns in prostate cancer patients who received darolutamide in the ARAMIS trial in Spain: PARASEC study.

142 Background: Darolutamide, enzalutamide or apalutamide have demonstrated to prolong overall survival in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). Despite their effectiveness, almost all patients progress to mCRPC. In the last few years, several new options for treatment of advanced prostate cancer have shown survival benefit. Darolutamide showed significantly prolonged metastasis-free survival compared with placebo in patients with nmCRPC in ARAMIS phase III trial. There is a lack of data about treatment patterns of patients that progress after receiving darolutamide in nmCRPC in the real-world setting in this new scenario with so many treatments available. Methods: This is a retrospective, observational, multicenter, longitudinal follow-up study to describe the treatment patterns received by the Spanish patients who received darolutamide in the ARAMIS study, according to standard clinical practice in Spain. This study involved at Urology and Oncology Departments of 18 selected hospitals. Results: Eighty-five patients were included in the study; median age was 76 years; 49 patients (58%) progressed to mCRPC and, of these, 35 (71%) received treatment for mCRPC; median number of lines post-progression was 2 (range 1-5). Abiraterone (22/35 [63%]) and docetaxel (10/35 [29%]) were the most commonly used drugs in the first line, docetaxel (12/21 [57%]) and cabacitaxel (12/21 [19%]) in the second line and cabacitaxel (4/12 [33%]) and docetaxel (3/12/21 [25%]) in the third line. Eleven patients received palliative radiotherapy (11/35 [31%]) and 7 (7/35 [20%]) osteoclast targeted therapy (5 zoledronate and 2 denosumab) after darolutamide. Conclusions: The results show that 29% of patients who progressed to mCRPC do not receive treatment after darolutamide and of those receiving treatment, 63% receive abiraterone, which appears not to be in line with current European guidelines. Only one-fifth of patients receive osteoclast targeted therapy, which is clearly insufficient. The variability in the duration of treatments and sequences suggests a lack of consensus in Spanish clinical practice. It is critical to explore more standardized strategies to maximize treatment effectiveness in these patients.

Exploring social vulnerability in prostate cancer management: Insights into utilization of watchful waiting and active surveillance from 1998 to 2017.

322 Background: Active surveillance (AS) and watchful waiting (WW) represent different conservative management strategies for prostate cancer (PCa), with AS being the preferred strategy. The Social Vulnerability Index (SVI) is enhancing our understanding of healthcare treatment disparities and social risk factors in the cancer care, but its impact in prostate cancer care remains unclear. We examine how social vulnerability influences the choice of WW vs AS in managing men with low and intermediate risk prostate cancer. Methods: The Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database was used to identify men diagnosed with localized, low, and intermediate-risk prostate cancer (i.e., those potentially eligible for active surveillance) from 1998 to 2017. Participants' data were geocoded and de-identified, then combined with Social Vulnerability Index (SVI) data, which is based on four themes: socioeconomic status, household composition, minority status, and housing &amp; transportation. We used multinomial logistic regression to examine the association between SVI and conservative management strategies of WW and AS. Results: Among 681 low-risk and intermediate-risk prostate cancer patients diagnosed from 1998 to 2017, 135 were assigned to watchful waiting (WW) and 546 to active surveillance (AS), reflecting a trend toward AS. The mean Social Vulnerability Index (SVI) was higher in the WW group (0.30) than in the AS group (0.21). Significant differences were noted by Socioeconomic Status (0.33 vs 0.15, p = 0.02). Conclusions: For patients with low and intermediate risk localized prostate cancer higher SVI, particularly in communities with greater socioeconomic challenges and higher proportion of racial while the overall proportion of AS increased over time. Our findings underscore how patients with higher SVI may experience considerable undertreatment, even with the concomitant increase in AS utilization over time. Identifying these communities remains a crucial step in addressing local drivers of treatment disparities in PCa care.

Cabozantinib as subsequent therapy to an immune checkpoint-based therapy in renal cell carcinoma, phase 2 interventional study (AT ASIA, KCSG GU21-02).

547 Background: Immune checkpoint inhibitors (ICIs) have significantly advanced the treatment of advanced renal cell carcinoma (aRCC). However, many patients develop disease progression, underscoring the need for effective second-line therapies. The optimal sequencing after ICI-based treatment remains under investigation. This phase II study evaluates the efficacy and safety of cabozantinib in patients with aRCC who progressed on first-line ICI combination therapies. Methods: This multicenter, prospective, phase II trial enrolled patients with advanced RCC who had progressed after receiving either nivolumab plus ipilimumab (Cohort 1) or a PD-1/PD-L1 inhibitor in combination with a VEGFR-TKI (e.g., pembrolizumab plus axitinib or pembrolizumab plus lenvatinib; Cohort 2). Non-clear cell histology was allowed in Cohort 2. Eligible patients were treated with cabozantinib at standard dosing. The primary endpoint was objective response rate (ORR) per RECIST 1.1 criteria. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Results: From September 2021 to August 2024, 88 patients (Cohort 1, n=49; Cohort 2, n=39) were enrolled across 13 institutions. The baseline International Metastatic RCC Database Consortium (IMDC) risk categories were as follows: favorable (15.9%), intermediate (71.6%), and poor (12.5%). Prior nephrectomy was reported in 42.0% of patients, and non-clear cell histology accounted for 20.5% of Cohort 2. After a median follow-up of 18.3 months (95% CI, 11.3–25.3), the ORR was 47.7%. Partial responses were observed in 51.0% (95% CI, 40.1–61.5) of patients in Cohort 1 (ICI-ICI) and 43.6% (95% CI, 30.5–56.8) in Cohort 2 (ICI-VEGFR-TKI). Stable disease was achieved in 43.2% of patients overall. The median PFS was 7.9 months, with a PFS of 9.2 months (95% CI, 6.6–11.8) in Cohort 1 and 7.1 months (95% CI, 6.7–7.6) in Cohort 2. No significant difference in OS was observed between the cohorts, with a 12-month OS rate of 65.2%. Safety analysis revealed no novel adverse events beyond the known cabozantinib toxicity profile, with grade 3/4 hypertension, hand-foot syndrome, and fatigue being the most commonly reported events. Conclusions: Cabozantinib demonstrated substantial efficacy as a second-line treatment for advanced RCC following progression on ICI-based therapies, with a tolerable safety profile. These findings reinforce cabozantinib as an important treatment option for patients progressing after ICI regimens. Clinical trial information: NCT04714697 .

S2,3PSA% as a predictor of reclassification of 1st protocol biopsy on active surveillance for early-stage prostate cancer patients: From the PRIAS-JAPAN study.

358 Background: Recently, α2,3-sialylated prostate-specific antigen (S2,3PSA)% has been developed as a new serum biomarker for Prostate cancer (PCa). So, we aimed to investigate S2,3 PSA% to predict reclassification of the first repeat protocol biopsy (1st re-PBx) on Active surveillance (AS) for PCa patients. Methods: Patients who participated in PRIAS-JAPAN and its ancillary studies from August 2013 to January 2022 and met the following criteria were included: clinical stage: T1c/T2, PSA: &lt;10ng/ml, PSA density: &lt;0.2ng/ml/cc, number of positive cores: &lt;2, Gleason score: &lt;6. All participants were required to receive a blood sampling test on a protocol visit at inclusion and at the 1st re-PBx. Significant predictors of reclassification in 1st re-PBx were investigated in univariate and multivariate analyses by logistic regression analysis. Then, to assess the predictive power and thresholds for reclassification, we plotted Receiver Operating Characteristic (ROC) curves. Further, a decision curve analysis (DCA) was conducted to identify net benefits. Results: A total of 188 patients were analyzed. Reclassification was shown in 61 patients (32.4%). Both univariate and multivariate analysis by logistic regression analysis showed that S2,3PSA% at diagnosis and before 1st re-biopsy were both significant predictors of reclassification. In ROC analysis, S2,3 PSA% at diagnosis and before 1st re-biopsy had comparable predictive power. The AUC for S2,3PSA% before 1st re-biopsy was 0.63, with a sensitivity of 0.41 and specificity of 0.87. Analysis of the net benefit of PSA doubling time (PSADT) and S2,3PSA% with DCA using PSA, prostate volume, and age as the base model showed that S2,3PSA% had a higher net benefit than PSADT. Conclusions: S2,3PSA% before 1st re-PBx has a high net benefit for reclassification and is a useful tool for clinical decision making. Result of ROC curve analysis and decision curve analysis about S2,3PSA% for reclassification at 1st repeat biopsy. ROC curves about reclassification for differences in S2,3PSA% between baseline and before the 1st repeat PBx Variable AUC Standard Error p value (for AUC) 95% CI Optimal cut off point Sensitivity Specificity p value (vs baseline) S2,3PSA%(baseline) 0.65 0.05 &lt;0.001 0.56 - 0.74 44.3 54.1% 75.6% - S2,3PSA%(before 1yr PBx) 0.63 0.05 0.0065 0.54 - 0.72 1.64 41.0% 87.4% 0.33 Decision curve analysis for reclassification at 1st repeat biopsy High Risk Threshold 0 0.1 0.2 0.3 0.4 0.5 Baseline model* 1 0.769 0.488 0.222 0.044 -0.016 Baseline model+PSADT** 1 0.77 0.492 0.29 0.011 -0.016 Baseline model+S2, 3PSA%** 1 0.769 0.504 0.215 0.186 0.131 *Baseline model is composed of age, prostate volume and PSA before 1yr PBx. **The value of PSADT and S2,3PSA% are calculated by the data before 1yr PBx.

Research on the construction of a sustainable scientific research capability evaluation model for university teachers based on the T-S fuzzy neural network

Introduction This study aims to enhance educational quality and academic standards by proposing a model based on critical research ability indicators to objectively evaluate the sustainable scientific research capabilities of university teachers. Methods Using T-S fuzzy neural network technology, we developed an evaluation model to measure the sustainability of university teachers’ research capabilities. We collected data from 126 university teachers, using 90 samples for training and 36 for testing, to ascertain the model’s applicability and accuracy. Results The T-S fuzzy neural network showcased exceptional learning efficiency and achieved a 98.15% accuracy rate in assessing the sustainable scientific research capabilities of university teachers, outperforming both Naive Bayes and BP neural networks in effectiveness. Conclusion The research successfully constructs a T-S fuzzy neural network-based evaluation model for assessing the sustainable scientific research capabilities of university teachers. With high accuracy and broad applicability, this model is an effective tool for objectively evaluating university teachers’ research capabilities, clearly achieving the study’s objective.

Phenotypic and genotypic characterization of Candida parapsilosis complex isolates from a Lebanese hospital

Efficacy outcomes with belzutifan versus everolimus by baseline disease characteristics and burden subgroups in the phase 3 LITESPARK-005 study.

538 Background: At first interim analysis of the randomized, multicenter, open-label, phase 3 LITESPARK-005 study (NCT04195750), belzutifan was associated with a significant and clinically meaningful improvement in progression-free survival (PFS) and objective response rate (ORR) vs everolimus in participants (pts) with advanced clear cell renal cell carcinoma (ccRCC) after both anti–PD-(L)1 and VEGF-targeted therapy. PFS and ORR results remained consistent at final analysis (FA); significant improvement in overall survival (OS) in this heavily pretreated population was not observed. Efficacy outcomes by baseline disease characteristics and tumor burden at FA are presented here. Methods: Pts were aged ≥18 years, had advanced ccRCC, and 1–3 prior systemic regimens (including ≥1 prior PD-[L]1 inhibitor and VEGFR-TKI in combination or in sequence). Belzutifan 120 mg QD or everolimus 10 mg QD were administered to randomized (1:1) pts until disease progression or unacceptable toxicity. An exploratory analysis of PFS and ORR per RECIST 1.1 by central review and OS was conducted in subgroups by bone metastasis (present at baseline, yes vs no), liver metastasis (present at baseline, yes vs no), and baseline tumor burden (sum of diameters of target lesions, &lt; median vs ≥ median). No formal statistical testing was performed. Results: A total of 374 pts were randomized to belzutifan, and 372 to everolimus. At FA (data cutoff: April 15, 2024), median follow-up was 35.8 mo (range 26.9–49.2) for the total population. PFS and ORR benefits with belzutifan vs everolimus were generally consistent with the total population across all analyzed subgroups (Table). In line with the total population at FA, improvement in OS was not observed across most subgroups. Conclusions: Belzutifan is a novel treatment option for patients with advanced ccRCC after prior anti–PD-(L)1 and VEGF-targeted therapies. Exploratory analysis suggests that PFS and ORR benefits with belzutifan vs everolimus are generally consistent across subgroups by baseline disease characteristics and tumor burden. Clinical trial information: NCT04195750 . Bone mets, yes Bone mets, no Liver mets, yes Liver mets, no Sum target lesion diameters,&lt; median Sum target lesion diameters,≥ median Bel Eve Bel Eve Bel Eve Bel Eve Bel Eve Bel Eve N 187 181 187 191 89 103 285 269 174 193 198 171 PFS, median, mo 3.7 4.3 7.0 6.3 4.6 3.7 5.6 5.8 7.3 5.7 4.2 4.8 PFS HR(95% CI) 0.88(0.69–1.11) 0.65(0.51–0.82) 0.55(0.39–0.77) 0.84(0.69–1.02) 0.67(0.52–0.86) 0.80(0.63–1.01) OS, median, mo 15.0 15.1 26.5 23.7 19.1 12.9 21.7 21.8 26.4 26.5 17.3 12.3 OS HR(95% CI) 0.95(0.75–1.20) 0.89(0.69–1.15) 0.63(0.45–0.88) 1.06(0.86–1.30) 0.95(0.73–1.24) 0.76(0.61–0.96) ORR, % 17.6 2.8 27.8 4.2 24.7 3.9 22.1 3.3 28.7 4.1 17.7 2.9 Bel=belzutifan; eve=everolimus; mets=metastasis.

Age-related efficacy and safety of darolutamide plus androgen-deprivation therapy (ADT) and docetaxel in patients with metastatic hormone-sensitive prostate cancer (mHSPC): A subgroup analysis of ARASENS.

143 Background: In ARASENS, darolutamide (DARO) + ADT + docetaxel (DOC) significantly reduced the risk of death by 32.5% (HR 0.68; 95% CI 0.57–0.80; P &lt;0.0001) vs placebo (PBO) + ADT + DOC with similar incidence of treatment-emergent adverse events (TEAEs) between groups in patients (pts) with mHSPC. DARO + ADT + DOC has become one of the standards of care in mHSPC. We report post-hoc efficacy and safety in pts by age subgroups (&lt;75 y, ≥75 y) in ARASENS. Methods: Pts were randomized to receive DARO 600 mg orally twice daily or PBO, with ADT + DOC. Age subgroups were analyzed for baseline characteristics including ongoing comorbidities, treatment duration, completion of DOC therapy, use of first subsequent therapy, key efficacy outcomes, and safety. Results: Of 1305 pts analyzed in ARASENS, ages ranged from 41–89 y, with 1086 pts &lt;75 y (83%; DARO n=546; PBO, n=540) and 219 pts ≥75 y (17%; DARO n=105; PBO n=114). Baseline characteristics were generally similar in the DARO and PBO groups by age subgroup. The most common comorbidities by system organ class in pts &lt;75 y and ≥75 y were vascular (55%, 67%), musculoskeletal/connective tissue (42%, 42%), and metabolism/nutrition (35%, 43%) disorders. Treatment duration was consistently longer with DARO vs PBO (&lt;75 y: 41.2 vs 16.8 mo; ≥75 y: 38.5 vs 15.0 mo). Most patients completed 6 cycles of DOC (&lt;75 y: 89%, 88%; ≥75 y: 80%, 76%). Among pts who entered follow-up, fewer DARO vs PBO pts initiated subsequent therapy independent of age (&lt;75 y: 57% vs 76%; ≥75 y: 54% vs 73%). The overall survival (OS) benefit of DARO vs PBO was consistent across age subgroups (&lt;75 y: HR 0.70, 95% CI 0.58–0.84; ≥75 y: HR 0.61, 95% CI 0.41–0.91). Time to metastatic castration-resistant prostate cancer (mCRPC) was longer with DARO vs PBO across age subgroups (&lt;75 y: HR 0.35, 95% CI 0.30–0.43; ≥75 y: HR 0.42, 95% CI 0.28–0.64) as was time to initiation of subsequent therapy (&lt;75 y: HR 0.40, 95% CI 0.34–0.48; ≥75 y: HR 0.35, 95% CI 0.22–0.54). TEAEs were generally similar between DARO and PBO, with slightly higher incidence rates in older pts. Few patients discontinued DARO or PBO due to TEAEs in both age subgroups (&lt;75 y: 13.2%, 9.1%; ≥75 y: 15.1%, 17.7%). The most common grade 3/4 TEAEs were generally similar between DARO and PBO across age subgroups and occurred most frequently during overlapping DOC treatment. TEAEs commonly associated with androgen receptor pathway inhibitors occurred at similar incidences between treatment groups in both age subgroups. Conclusions: Pts with mHSPC benefited from DARO + ADT + DOC irrespective of age (&lt;75 y and ≥75 y), with consistent improvements in OS, time to mCRPC, and time to initiation of subsequent therapy. DARO was well tolerated in both age subgroups, with similar incidences of TEAEs vs PBO. Clinical trial information: NCT02799602 .

Changes in circulating tumor cells (CTCs) and HER2 expression in evaluating the efficacy of neoadjuvant disitamab vedotin plus toripalimab treatment in patients with muscle-invasive bladder cancer (MIBC).

837 Background: Disitamab vedotin (DV) combined with toripalimab has shown promising efficacy as neoadjuvant therapy for MIBC, with a pathological CR (pCR) rate of 62.1% in the previous report (2024 ASCO). In real-world practice, many patients who achieved clinical complete response (cCR) after neoadjuvant therapy, confirmed by re-TURBT, imaging, and urine cytology, opted for bladder-preserving treatment (BPT). However, biomarkers to confirm the absence of residual tumors in cCR pts are lacking. This study aims to evaluate the correlation between changes in CTCs and HER2+ CTCs during neoadjuvant therapy with clinical efficacy outcomes in MIBC. Methods: 18 pts were retrospectively included from July 2023 to July 2024. The primary endpoint was to assess the correlation between changes in CTCs and HER2+ CTCs before and after neoadjuvant therapy, and clinical efficacy (cCR or non-cCR). Eligible pts had previously untreated MIBC (cT2-T3N0-1M0) with HER2 expression of IHC ≥ 2+. Pts received DV (2 mg/kg) plus toripalimab (3 mg/kg) every two weeks for six cycles, followed by radical surgery or BPT for cCR pts (choice made after communication between the physician and the pts). cCR criteria included no residual tumor confirmed by re-TURBT, no evidence of tumor on imaging, and negative urine cytology. Peripheral blood samples were collected to measure CTC counts and HER2 phenotype by HER2-iFISH. Results: Among 18 pts, 15 (83.3%) achieved cCR, while 3 pts (16.7%) were in the non-cCR group, including 2 pts with cPR confirmed as pT2N0 postoperatively, and 1 pt with clinical progression (cPD). All 15 cCR pts underwent BPT. There were no significant differences in the total CTCs and HER2+ CTCs between the cCR and non-cCR groups before treatment (P = 0.426, P = 0.654, respectively). After neoadjuvant therapy, CTC and HER2+ CTC counts were significant lower in the cCR group compared to the non-cCR group (P = 0.039, P = 0.005, respectively). Only 1 (6.7%) cCR pt had detectable HER2+ CTCs post-treatment, while all 3 non-cCR pts had measurable HER2+ CTCs. Conclusions: Changes in CTCs and HER2+ CTCs correlated with clinical efficacy outcomes of DV plus toripalimab neoadjuvant therapy, particularly in HER2+ CTCs. CTCs and CTC HER2 expression may serve as potential biomarkers for evaluating clinical efficacy and guiding treatment strategies in MIBC. The clinicopathological characteristics of the 18 MIBC patients. Characteristic All patients (n=18) cCR (n=15) non-cCR (n=3) P value Clinical T stage, n (%) 1.00 cT2 10 (55.6) 8 (53.3) 2 (67) cT3 8 (44.4) 7 (46.7) 1 (33) Clinical N stage, n (%) 1.00 cN0 15 (83.3) 12 (80.0) 3 (100) cN1 3 (16.7) 3 (20.0) 0 (0) HER-2 expression, n (%) 0.44 2+ 15 (83.3) 13 (86.7) 2 (66.7) 3+ 3 (16.7) 2 (13.3) 1 (33.3)

Treatment patterns and survival in men with metastatic castration-resistant prostate cancer (mCRPC): A systematic literature review of 35 real-world observational studies.

101 Background: Treatment landscapes have changed dramatically in prostate cancer in the past decade. Therapies like androgen receptor pathways inhibitors (ARPIs), which were initially approved for mCRPC are now approved in the earlier disease spectrum, including biochemical recurrence (BCR), non-metastatic castration-resistant prostate cancer (nmCRPC), and hormone-sensitive metastatic prostate cancer (mHSPC). Further, several other life-prolonging therapies, including radiopharmaceuticals, immunotherapies, and poly-ADP ribose polymerase inhibitors (PARPi), have been approved for mCRPC in the last decade. Given these changes, this systematic literature review (SLR) aimed to summarize treatment patterns and survival in patients with mCRPC. Methods: Electronic databases (PubMed, Embase) and key conferences (2022-2024) were searched systemically for real-world (RW) observational studies published between Jan 2015 and March 2024 that examined treatment patterns and survival in patients with mCRPC. A GenAI-powered literature review platform assisted in study selection alongside human validation, and independent reviewers extracted and assessed the data for narrative synthesis of key findings. Results: From 4,565 retrieved citations, 35 studies with a total of 86,131 patients with mCRPC met inclusion criteria. In most studies, patient median age ranged from 65 to 75. Studies predominantly utilized electronic medical records (EMR)/chart review (n=24), followed by a registry/-linked claims (n=10). Most studies were from North America (n=21; 18 United States; 3 Canada), followed by Europe (n=6), Asia (n=3), Oceania (n=3), and others (n=2). Bone and visceral metastases were present in ≥ 70% of mCRPC and ≤30% in most studies, respectively. ARPI was the most frequently utilized first line of therapy(1L) for mCRPC in all studies (≥50% in most studies), followed by chemotherapy, albeit with varying magnitude by geographic regions. Chemotherapy for 1L mCRPC was more common in Europe and Oceania than in the US. The use of radiopharmaceuticals, PARPIs, and immunotherapy was low in most studies (&lt;10%) as 1L mCRPC. Most studies found ARPI to ARPI was the most common 1L to 2L mCRPC sequence, though in few studies, ARPI-chemotherapy was the common 1L to 2L mCRPC sequence. In most studies, median real-world overall survival ranged from 18 to 27 months and varied by genetic mutation status. Conclusions: Findings highlight that ARPI remained the most utilized 1L/2L in men with mCRPC, and back-to-back ARPI was also a common practice even after the availability of the other life-prolonging therapies. This SLR highlights the need to optimize treatment beyond systemic hormone therapy.

Gains vs losses in pay-for-performance: Stated preference evidence from a U.S. survey

Background Pay-for-performance (P4P) incentives can be paid as a bonus (gain) or a penalty (loss). Diminishing marginal utility of wealth suggests that, starting from the same initial wealth, individuals dislike losses more than they like equivalent gains. Objective This study reports the minimum financial gain or loss required to motivate primary care providers and clinical staff to try to increase their human papillomavirus (HPV) vaccination rates. Data In 2022, we conducted a national U.S. survey through WebMD’s Medscape Network of clinical staff working in primary care clinics that provided HPV vaccination to children ages 9 through 12 years (N = 2,527; response rate = 57%). Methods We randomized respondents to one of two hypothetical HPV vaccine incentive designs: a bonus for reaching an unspecified target HPV vaccination rate and a penalty for failing to reach the unspecified target. The primary outcome is the self-reported smallest incentive amount (U.S. dollars) that would motivate participants to try and increase their HPV vaccination rates. We tested for differences across P4P designs using unadjusted responses and linear regressions adjusting for clinic and respondent characteristics. We also tested for heterogeneous responses by experience with incentizves, training, and rurality. Results The mean amount required to motivate effort was $2,155 in the gain P4P design and $1,185 in the loss P4P design (unadjusted difference =  $970 [p &lt; 0.001], adjusted difference =  $967 [p &lt; 0.001]). There were no heterogeneous effects by rurality or experience with incentives. Physicians reported the highest differences (in dollars) between gain and loss P4P designs. Conclusions Stated preference data from primary care clinical staff suggests that effective P4P incentives could be half as large if designed as losses rather than gains.

Unraveling a novel therapeutic facet of Etravirine to confront Hepatocellular Carcinoma via disruption of cell cycle

Abstract Hepatocellular Carcinoma (HCC) is a malignancy with high mortality rates and limited treatment options. This study aimed to unearth the repurposable potential of FDA-approved drugs against specific genetic targets governing the HCC pathological pathways. The transcriptomics microarray datasets were explored to retrieve the HCC specific differentially expressed genes, and the significant genes were fed in Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database to capture the protein-protein interactions, which were visualized in Cytoscape. This revealed CCNA2, a cell cycle regulator, as a potential target, which mediates its action by interacting with CDK1 and CDK2. Further, with the intention of identifying inhibitors for CDK1 and CDK2, a drug library was created, and the drugs were virtually screened against their respective targets via molecular docking and dynamics studies. This captured the binding affinity of Steviolbioside towards CDK1 and Etravirine and Fludarabine towards CDK2. In vitro, validation confirmed the cytotoxic potential of Etravirine and Fludarabine in Huh-7 cell lines. Further, enzymatic assays, gene expression analysis, and cell cycle analysis signified the anti-proliferative potential of Etravirine in Huh-7 cells via inhibition of CDK2. In this drug repurposing venture, Etravirine, a non-nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV, emerged as a promising candidate for HCC treatment. The findings warrant further preclinical and clinical investigations to ascertain the repurposable potential of Etravirine against HCC, particularly in patients with viral infections.

Long-term results of a phase 2 study of neoadjuvant chemotherapy combined with tislelizumab followed by radiotherapy for bladder-preserving treatment in selected high-risk/locally advanced muscle invasive urothelial bladder cancer (HOPE-02).

786 Background: The “bladder-sparing” trimodal therapy (TMT) has gained popularity among selected patients with muscle-invasive bladder cancer (MIBC) who are either unfit for or decline radical cystectomy (RC). This Phase 2 study aimed to evaluate the bladder-sparing efficacy of neoadjuvant chemotherapy combined with tislelizumab, followed by radiotherapy for high-risk, locally advanced MIBC, who were considered as non-ideal candidates for bladder-sparing treatment (Trial registration number: ChiCTR2100045213). Methods: Patients diagnosed with cT2-4bN0-3M0-1a MIBC will be included in the study if they demonstrate non-progression of disease (PD) after two cycles of neoadjuvant chemotherapy (gemcitabine and cisplatin or carboplatin) combined with tislelizumab. Radiotherapy will be administered to patients after one or two additional cycles of neoadjuvant therapy, and tislelizumab will continue for up to one year. The primary endpoint is the complete response rate (CR, including T0/Ta/Tis) after radiotherapy, while the secondary endpoints include progression-free survival (PFS), bladder-intact disease-free survival (BI-DFS), overall survival (OS), and toxicity. Results: Preliminary results of safety were presented at the ASCO-GU meeting in 2023, and we are now reporting the long-term outcomes. A total of 45 patients were enrolled. The median follow-up time was 36.10 ± 2.92 months. All participants completed 3 to 4 cycles of neoadjuvant therapy, resulting in a CR rate of 51.11%. Among the patients, 36 completed radiotherapy and underwent efficacy evaluations through imaging and cystoscopic biopsy. However, nine patients withdrew from the study due to personal requests for surgery, traditional Chinese medicine, or changes in systemic therapy. Of the 36 patients, 2 were Tis, and 31 were T0 after radiotherapy, indicating a primary CR rate of 100%. The 2 Tis patients received intravesical BCG vaccine therapy and achieved T0 by the time of the second therapeutic evaluation. No patient underwent radical cystectomy. 3-year PFS rate and 3-year BI-DFS were 76.0%, and 3-year OS was 81.0%. One patient experienced bladder recurrence with T1, while 3 patients developed distant metastases. Four patients died, with 2 deaths attributed to other reasons. Conclusions: Neoadjuvant chemotherapy combined with tislelizumab provides an opportunity for suboptimal candidates to become suitable for bladder-sparing approaches, and radiotherapy-based bladder-preserving treatment demonstrated excellent long-term efficacy and acceptable toxicity, making it a potentially optimal strategy for high-risk, locally advanced MIBC patients who wish to preserve their bladder. Clinical trial information: ChiCTR2100045213.

Phase 3 OMAHA-004 study of CYP11A1 inhibitor opevesostat versus next-generation hormonal agent (NHA) switch in patients with metastatic castration-resistant prostate cancer (mCRPC) after 1 prior NHA.

TPS301 Background: Androgen receptor (AR) somatic mutation activation is a resistance mechanism to AR-directed therapies (ADT) in mCRPC. Upstream targeting of androgen biosynthesis may provide a therapeutic advantage over available AR-directed therapies in patients with mCRPC. Opevesostat (MK-5684; ODM-208) is an oral, nonsteroidal inhibitor of cytochrome P450 11A1 (CYP11A1), a catalyst of the first and rate-limiting step of steroid biosynthesis. By blocking the first step of the enzymatic pathway, opevesostat has the potential to inhibit all steroid hormones involved in AR signaling activation. In the phase 1/2 CYPIDES study, opevesostat had antitumor activity in patients with heavily pretreated mCRPC, especially in those with AR ligand binding domain (AR-LBD) mutations (1). The randomized, open-label, phase 3 OMAHA-004 trial (NCT06136650) will evaluate the efficacy and safety of opevesostat versus abiraterone or enzalutamide in patients with molecularly unselected mCRPC previously treated with 1 prior NHA. Methods: Eligible patients have mCRPC that progressed during ADT ≤6 months before screening and during/after 1 NHA for hormone-sensitive prostate cancer or non-mCRPC. Approximately 1500 patients (375 with, 1125 without AR-LBD mutations) will be randomly assigned 1:1 to receive opevesostat 5 mg PO BID (+ dexamethasone 1.5 mg and fludrocortisone 0.1 mg PO QD) or abiraterone acetate 1000 mg PO QD (if prior enzalutamide/darolutamide/apalutamide) or enzalutamide 160 mg PO QD (if prior abiraterone). Primary endpoints are radiographic progression-free survival per Prostate Cancer Working Group 3 (PCWG3)-modified RECIST v1.1 by blinded independent central review (BICR) and overall survival in AR-LBD mutation–positive and –negative disease, separately. Secondary endpoints include time to initiation of first subsequent anticancer therapy or death; objective response rate and duration of response per PCWG3-modified RECIST v1.1 by BICR; and safety. Recruitment is ongoing. 1. Fizazi et al. NEJM Evid. 2024. Clinical trial information: NCT06136650 .

PSA response and survival based on metastatic site in patients with metastatic castration resistant prostate cancer (mCRPC) treated with lutetium-177-PSMA-vipivotide tetraxetan (Lu177-PVT).

107 Background: Patients (pts) with mCRPC can have different metastatic sites with variable outcomes. Lu177-PVT is a novel treatment for mCRPC but response and outcomes in the real world are still being defined. We hypothesized that pts with lung and liver metastases (mets) would have worse outcomes (lower PSA response and shorter survival) with Lu177-PVT than those without as advanced of disease spread. Methods: This retrospective cohort study analyzed pts with mCRPC who were treated with at least one dose of Lu177-PVT. PSA50, PSA90, and overall survival were assessed for three comparisons of pts: bone only vs. other mets (including other site ± bone), lung-involved vs. lung-absent, and liver-involved vs. liver-absent. PSA50 and PSA90 were defined as achieving any reduction in PSA below 50% and 90% of baseline prior to Lu177-PVT therapy, respectively. Comparisons between groups were made using univariable logistic regression for PSA50 and PSA90 and Cox regression for OS. Results: We included 100 pts for OS analyses and 97 pts for PSA50 and PSA90 analyses treated between 03/2019 and 09/2024. Three pts were excluded from PSA analyses due to absence of baseline PSA prior to Lu177-PVT. Median age at Lu177-PVT start was 66 years, 67% white race, 45% ever smoker, median BMI was 26 kg/m 2 , 5 median previous lines of treatment, 77% received prior chemotherapy, and 4 median number of Lu-177-PVT treatments received. At time of initial Lu177-PVT, 94% had at least bone mets, 12% had LN mets, 14% had lung mets, 15% had liver mets, and 9% had other mets. Table shows results of all comparisons. Pts with only bone mets (vs those with other site ± bone) had numerically (not significant) longer OS (Table; median [m]OS 19 vs. 13 months, HR 0.88, p-value 0.70) and similar PSA50 and PSA90 rates. Pts with liver-involved (vs liver-absent) had a numerically shorter OS (mOS 15 vs. 18 months, HR 1.45 p-value 0.38) and lower (not significant) PSA90. Pts with lung-involved (vs lung-absent) had numerically shorter OS (15 vs. 18 months, HR 1.28, p-value 0.58) and lower PSA90. Conclusions: Pts with mCRPC responded to Lu177-PVT regardless of metastatic sites in our study, though liver mets had numerically lower OS. Study limited by small power and retrospective study design. Future work is needed to further dissect the interplay between Lu177-PVT response and metastatic disease sites. Results. N Median Lu177-PVT cycles received Median Overall Survival, months (95% CI) HR for OS, (95% CI) PSA50%, (95% CI) OR for PSA50, (95%CI) PSA90%, (95% CI) OR for PSA90, (95%CI) Bone only 56 5 19 (1-40) 0.88 (0.45-1.71) 58 (43-70) 1.04 (0.46-2.36) 33 (20-46) 1.56 (0.64-3.96) Lung-involved 15 4 15 (3-34) 1.28 (0.53-3.01) 57 (27-79) 0.97 (0.31-3.19) 14 (2-40) 0.37 (0.05-1.47) Liver-involved 15 3 15 (3-35) 1.45 (0.63-3.32) 67 (38-88) 1.57 (0.51-5.40) 13 (2-40) 0.33 (0.05-1.32)

A phase II single arm prospective study of high dose testosterone in combination with carboplatin chemotherapy in late line metastatic castrate-resistant prostate cancer (HIGH-TeCH study).

218 Background: Bipolar androgen therapy (BAT) is a safe and well-tolerated treatment paradigm in metastatic castrate resistant prostate cancer (mCRPC) but response rates and duration are modest. Preclinical data suggests supraphysiologic androgens interrupt DNA relicensing and increase double-stranded DNA breaks, suggesting a potential synergy with the addition of carboplatin chemotherapy. We assessed the safety and efficacy of this treatment combination in Arm B of the HIGH-TeCH trial. Methods: Men with refractory mCRPC after at least one line of taxane based chemotherapy and androgen signaling inhibitor received four weekly testosterone enanthate (500mg IM) with Carboplatin (AUC 5) and androgen deprivation therapy. Five (24%) PSA50 responses were achieved at planned interim analysis of the first 21 patients, meeting threshold for study expansion to a total of 40 participants. Results: Currently, 37 of a target total 40 patients have been recruited. Median follow up was 14.8 months as of 1st October 2024. Median age 72. Median prior lines of treatment 3; 51% of patients had prior 177-Lutetium. 27 patients discontinued treatment for disease progression (PSA, radiological, clinical), 1 discontinued due to a serious adverse event (CVA) and 9 patients remain on trial. Median of 5 cycles of BAT with Carboplatin were administered. Seven (19%) patients had a PSA response ≥ 50%. Fourteen (38%) patients had clinical benefit (&gt; 6 months duration on study). Median progression-free survival was 6.6 months (95% CI, 5.5 – 9.9). Median overall survival was 20.4 months (95% CI, 15.5 – not reached). Thirty-one (84%) patients experienced a treatment–related adverse event (TRAE); of which, 94% were grade 1 – 2. Highest rates of TRAEs were fatigue (52%), nausea (39%), musculoskeletal pain (23%), constipation (23%). There was no grade 4 TRAEs or deaths. Conclusions: BAT with carboplatin has an acceptable safety profile and demonstrated clinical benefit in heavily pre-treated mCRPC patients. Accrual will be completed imminently with final analysis to be presented. Translational studies to identify predictive biomarkers and quality of life analyses are underway. Clinical trial information: NCT00309985 .