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Aggressive-variant prostate cancer features and therapeutic outcomes in patients with de-novo metastatic hormone-sensitive prostate cancer.
264 Background: Aggressive variant prostate cancer (AVPC) was considered a combination of aggressive phenotypes in metastatic castration-resistant prostate cancer showing poor response to androgen depriving therapy (ADT). However, whether these phenotypes remain predictive and prognostic role in metastatic hormone-sensitive prostate cancer (mHSPC) remained unclear. This study aims to explore the prognostic role of AVPC in de-novo mHSPC. Methods: We retrospectively included 1,167 patients with de-novo metastatic hormone-sensitive prostate cancer (mHSPC) between 2016 and 2025. Patients meeting the clinical criteria of anaplastic prostate cancer at diagnosis or those with AVPC molecular signature (AVPC-MS) (≥2 mutations in TP53, PTEN, and RB1) were identified as AVPC. The main outcomes were castration-resistant free survival (CFS) and overall survival (OS). Univariate and multivariate Cox regression analyses were applied to assess the prognostic role of AVPC in the mHSPC. Results: A total of 208 AVPC were identified. AVPC was associated with poor CFS (median 14.6 vs. 26.8 months, p<0.001) and OS (median 53.7 vs. 76.4 months, p < 0.001) and showed deleterious role in predicting the efficacy of maximal androgen blocking, novel hormone therapy, but not docetaxel plus ADT. Additionally, we found intraductal carcinoma of the prostate, another aggressive pathological variant of prostate cancer not included in the AVPC criteria, was able to stratify patient’ prognosis in patients with AVPC (IDC-P+ vs. IDC-P-: median 11.3 vs. 16.8 months, p=0.0037; OS: 51.5 vs. 54.3 months, p=0.13) and without AVPC (CFS: 20.1 vs. 31.1 months, p<0.001; OS: 60.1 vs. 85.1 months, p<0.001). Multivariate Cox regression analysis confirmed that AVPC and IDC-P independently predicted worse CFS and OS. Conclusions: AVPC predicted worse efficacy of MAB and NHT in de-novo mHSPC. IDC-P could stratify patients with worse prognosis in those with AVPC.
Outcomes of cabazitaxel following 177Lu-PSMA-617 (LuPSMA) in patients with metastatic castration-resistant prostate cancer (mCRPC).
84 Background: LuPSMA and cabazitaxel are both standard of care options for men with PSMA-positive mCRPC post docetaxel. The phase 2 TheraP study demonstrated comparable overall survival (OS), although LuPSMA was associated with a more favorable toxicity profile and higher ≥50% PSA decline (PSA 50 ) rates. Consequently, LuPSMA is often preferred when available. Therefore, we retrospectively evaluated men who received cabazitaxel after LuPSMA to better define prognosis and inform treatment sequencing for this high-risk population. Methods: We identified consecutive men with mCRPC previously treated with ARPI and docetaxel who received ≥1 cycle of LuPSMA followed by cabazitaxel. Secondary endpoints included PSA progression-free survival (PSA-PFS) and OS, measured from the first cycle of cabazitaxel, and hematologic toxicity. Efficacy endpoints were stratified by PSA 50 response to LuPSMA and compared using log-rank test. PSA progression followed PCWG3 criteria. Results: Of 237 patients treated with LuPSMA (June 2022–January 2025), 28 (11.8%) subsequently received cabazitaxel. Among these 28 patients, 23 (82.1%) received ≥2 lines of ARPI therapy, and 1 (3.6%) received PARP inhibitor. Median age was 72.5 (range 65–88); median LuPSMA and cabazitaxel cycles were 3.5 (1–6) and 4 (1–11), respectively. PSA 50 was achieved in 35.7%. Median PSA-PFS was 2.1 months (95% CI 1.6–5.3) and OS 5.5 months (3.0–13.4). Nine patients (32%) achieved PSA 50 with LuPSMA; of these, 5 (56%) again achieved PSA 50 with cabazitaxel. Median PSA-PFS was 1.8 months (1.5–4.8) in LuPSMA non-responders vs 6.4 (1.3–NR) in responders (p = 0.11). OS was 5.0 months (3.8–14.1) vs 11.8 (4.0–NR) in non-responders vs responders (p = 0.07). Grade ≥3 thrombocytopenia and neutropenia occurred in 9 and 4 patients, respectively. Conclusions: Cabazitaxel demonstrates modest activity following LuPSMA. While PSA 50 were comparable to historical data, the poor survival outcomes suggest reduced taxane sensitivity. Patients who responded to LuPSMA trended to also have better responses with cabazitaxel. Prospective studies are warranted to define optimal sequencing and patient selection criteria.
Identifying and predicting non-cancer mortality risk in mHSPC following doublet therapy in the STAMPEDE trial.
134 Background: Body composition features derived from baseline computed tomography (CT) imaging can reveal clinical phenotypes which inform non-cancer mortality (NCM) risk in M1 HSPC. We measured the prognostic and predictive value of body composition phenotypes for NCM within the STAMPEDE Docetaxel (DOC) and Abiraterone (AAP) comparisons. Methods: A fully automated image analysis programme quantified body composition features from baseline CT scans in M1 patients recruited to STAMPEDE’s DOC and AAP comparisons. Random Forest feature importance identified six key imaging biomarkers: abdominal aortic calcium, bone mineral density, visceral adipose tissue, visceral adipose tissue: subcutaneous adipose tissue ratio, skeletal muscle area, and intramuscular adipose tissue. Unsupervised Gaussian mixture modelling defined three distinct phenotypic clusters. Fine-Gray competing-risk models, adjusted for age, WHO performance status, treatment, NSAID use, PSA, and Gleason grade group, evaluated the prognostic utility of cluster phenotypes for NCM. Predictive models incorporated cluster × treatment interaction terms to assess effect modification by therapy. Flexible parametric models generated 10-year cumulative incidence. Results: Among 937 men (docetaxel comparison: n=534; abiraterone comparison: n=553; n=150 contemporaneously recruited), median follow-up of 7.6 years, three distinct body composition phenotypes were identified: cardiovascular (high calcification, sarcopenia; n=163), reference (preserved muscle and bone; n=543), and metabolic (myosteatosis, visceral adiposity; n=231) phenotypes. Both adverse phenotypes predicted higher NCM versus the reference phenotype after adjustment for treatment and clinical factors: CV phenotype SDHR=2.08 (95% CI 1.23-3.52; p=0.006) and metabolic phenotype SDHR=1.75 (1.07-2.87; p=0.026). Age predicted NCM independently (SDHR=1.07 per year; p<0.001). A significant phenotype×AAP interaction revealed excess NCM risk in the metabolic phenotype (SDHR=3.78, 1.25-11.4; p=0.019). Ten-year NCM exceeded 20% in high-risk phenotypes versus <10% in the reference phenotype. Conclusions: CT body composition phenotypes from routine staging scans independently predict NCM following combination therapies in mHSPC identifying patients with metabolic phenotypes who experience excess mortality risk with AAP intensification. These findings support the role of imaging biomarkers in guiding personalised risk stratification and treatment selection.
Crystallographic Facet Engineering of LiF for Ultrastable and Superfast Charging Sodium Metal Batteries From –40°C to 60°C
ABSTRACT Sodium metal batteries (SMBs) are promising next‐generation energy storage devices but are plagued by dendritic growth and poor low‐temperature performance, rooted in uncontrolled nucleation and sluggish ion transport. Moving beyond conventional interfacial modifications, we report a crystallographic engineering strategy that precisely controls exposed crystal facets to dictate atomic‐scale electrochemical behavior. Through density functional theory (DFT) screening, we identify the (220) crystal facet of LiF as superior, exhibiting an optimal Na + adsorption energy (–1.48 eV) and an ultralow diffusion barrier (0.0978 eV), which promotes epitaxial sodium deposition along the (110) plane and significantly reduces nucleation overpotential. Experimentally, we synthesize LiF nanofibers with dominantly exposed (220) facets and construct a composite LiF@Na anode. This design induces a NaF‐rich interphase, markedly enhances desolvation kinetics at the interface, and ensures exceptional interfacial stability. The resulting full cells achieve ultra‐long cycling over 9000 cycles at 50 C with 70% capacity retention and outstanding performance from –40°C to 60°C. This study establishes crystal facet control as a fundamental materials design principle for regulating metal nucleation and interphase chemistry, providing a universal pathway toward high‐energy, durable, and all‐climate metal batteries.
<i>Aequorea Victoria</i> ‐Inspired Covalent Anchoring Enables Water‐Resistant and Scalable Room‐Temperature Phosphorescence in Cellulose
ABSTRACT Developing organic room‐temperature phosphorescence (RTP) materials stable in aqueous environments remains highly challenging due to the facile quenching of triplet excitons. Inspired by the protective β‐barrel architecture of the green fluorescent protein ( Aequorea victoria ), the study presented a covalent anchoring strategy based on an amphiphilic cellulose derivative (cellulose acetate) to construct water‐resistant and scalable RTP materials. Covalent immobilization of chromophores within the rigid framework yields dynamic photoactivated afterglow, extending the lifetime from 2.1 to 946.4 ms. The resulting films retain bright RTP even under water while exhibiting water‐mediated tunable mechanical properties. Furthermore, Förster resonance energy transfer with Rhodamine B enables full‐color RTP spanning blue to orange. Benefiting from the inherent thermoplasticity and hydroplasticity of cellulose acetate, the RTP cellulose derivatives are readily processed into diverse 1D/2D/3D architectures and applied in multilevel information encryption. This covalent anchoring strategy offers a sustainable and commercially viable pathway to robust polysaccharide‐based RTP, opening new opportunities for optoelectronics, security, and eco‐friendly photonic technologies.
The impact of the 2025 NCCN update in defining very high-risk prostate cancer on surgical outcomes after robot-assisted radical prostatectomy: A retrospective cohort analysis.
340 Background: Under the pre-2025 National Comprehensive Cancer Network (NCCN) definition, very high-risk (VHR) prostate cancer (PCa) included any of the following: clinical stage cT3b–T4, primary Gleason pattern 5, more than four biopsy cores with Grade Group (GG) 4–5, or multiple NCCN high-risk features. In 2025, the NCCN revised the VHR definition to include patients meeting at least two of the following: clinical stage ≥cT3, prostate-specific antigen (PSA) ≥40 ng/mL, and GG ≥4. This change, largely derived from radiotherapy trials evaluating the addition of abiraterone to androgen deprivation therapy with radiotherapy, substantially alters the composition of the VHR group. Importantly, this revised definition has not been validated in surgically treated cohorts, raising questions about its applicability to patients undergoing robot-assisted radical prostatectomy (RARP). We aimed to compare oncological and pathological outcomes under the pre-2025 and 2025 NCCN definitions among individuals treated with RARP without perioperative systemic therapy. Methods: We retrospectively reviewed 1,879 patients who underwent RARP at two institutions between July 2012 and November 2022. Of these, 641 patients classified as high risk or above were analyzed: historical high risk (Group 1: n = 379), reclassified from VHR to high risk under the 2025 definition (Group 2: n = 117), and VHR per 2025 criteria (Group 3: n = 145). Results: The median follow-up was 59.8 months. In terms of postoperative pathology, Group 2 exhibited significantly more adverse features, including higher pathological stage, Gleason grade, positive surgical margins, and lymph node involvement compared with Group 1, whereas no significant differences were observed between Groups 2 and 3. Five-year biochemical recurrence–free survival rates were 71.1%, 44.7%, and 29.8%; metastasis-free survival rates were 99.6%, 94.1%, and 88.9% for Groups 1, 2, and 3, respectively. Group 2 showed significantly worse outcomes than Group 1.Exploratory analyses within Group 3 revealed that patients with more than four biopsy cores containing GG 4–5 had markedly worse recurrence outcomes, whereas those without this factor demonstrated results closer to Group 2. Conclusions: The 2025 NCCN redefinition of high-risk prostate cancer, primarily based on radiation therapy data, substantially restructured patient classification while highlighting diversity within the surgical treatment group. Further validation in RARP cohorts is needed, and more precise risk stratification could guide individualized perioperative and multidisciplinary treatment strategies.
First results from CORE-008 cohort A: Phase 2 study of intravesical cretostimogene grenadenorepvec in patients with high-risk BCG-naïve non-muscle invasive bladder cancer.
756 Background: Standard of care treatment for HR NIMBC includes TURBT followed by intravesical BCG. However, high recurrence rates and BCG shortages highlight the need for effective, well-tolerated, and readily available treatment options. Cretostimogene grenadenorepvec is an oncolytic immunotherapy with dual mechanisms of action. It replicates in and lyses cancer cells with Retinoblastoma (Rb)-E2F pathway alterations, while simultaneously amplifying anti-tumor immune response, further mediated by the GM-CSF transgene. CORE-008 (NCT06567743) is a Phase 2, multi-arm, multi-cohort trial evaluating the efficacy and safety of intravesical cretostimogene in patients with HR NMIBC. Methods: Cohort A includes patients age ≥18 years, ECOG PS of 0-2, with pathologically confirmed HR NMIBC with CIS and who are BCG-naïve (no prior BCG, BCG administered > 24 months ago, or receipt of only 1-2 BCG doses within the past 24 months). Patients receive intravesical cretostimogene for six weekly doses during the induction phase, followed by three weekly maintenance cycles quarterly through Month 12, then every six months through Month 36. Re-induction is permitted at Month 3, if persistent HG Ta and/or CIS is noted at biopsy. Response assessments included urine cytology, serial cystoscopy with directed biopsy, and axial imaging (as indicated). The primary endpoint is Complete Response (CR) at any time. Enrollment is complete. Results: As of the September 1, 2025 data cut off, 54 patients in Cohort A received treatment with intravesical cretostimogene. 88.8% of participants were 65 years of age or older, 9.3% are female, and 18.5% have an ECOG PS of 1. Baseline disease characteristics demonstrate CIS alone in 44.4%, CIS + HGTa in 31.5%, and CIS + T1 in 24.1%. 53 (98.1%) patients completed induction with 49 assessed for efficacy. Median exposure of the cohort is 15.3 weeks (range 1.1, 41.0 weeks). The CR rate at any time in evaluable patients is 83.7% (41/49) (95% CI 70.3-92.7%). No patients progressed to MIBC or metastatic disease. The safety and tolerability profile of cretostimogene is consistent with prior clinical trials with this agent. The most common adverse events are low grade and localized to the bladder. There are no related Serious Adverse Events, Grade 3+ adverse events or treatment related discontinuations. To date, only 3.7% (2/54) of patients required a dosing delay due to a related adverse event; however, none of these delays resulted in missed doses. Further, updated data will be presented. Conclusions: Cretostimogene has promising clinical efficacy and safety in patients with high-risk, BCG-naïve NMIBC. These findings support the further development of cretostimogene in other early, HR NMIBC disease states. Currently, additional treatment arms are planned for patients with BCG-naïve NMIBC. Clinical trial information: NCT06567743 .
Real-world comparison of prostate-specific antigen (PSA) response in metastatic castration-sensitive prostate cancer (mCSPC) patients treated with apalutamide (APA) without docetaxel vs darolutamide (DARO) without docetaxel.
106 Background: APA and DARO are androgen receptor pathway inhibitors (ARPIs) approved for the treatment of mCSPC in combination with androgen deprivation therapy (ADT), with DARO also approved in combination with ADT and docetaxel. Deep PSA response, evaluated as ≥90% decline in PSA (PSA90), is an important indicator of treatment prognosis after ARPI initiation, with rapid response associated with longer survival. This study compared PSA90 response in a sample of ARPI-naïve patients with mCSPC initiated on APA without docetaxel versus DARO without docetaxel. Methods: Linked US healthcare databases (PPS Analytics and Komodo Research Database; 1/1/2016-4/30/2025) were used in this longitudinal, retrospective cohort analysis. Patients with mCSPC were grouped into two cohorts based on the first APA or DARO dispensation or pharmacy claim on or after 8/5/2022 (index date) and followed until the earliest of index ARPI discontinuation or switch, docetaxel or radiopharmaceutical initiation, end of clinical activity or end of data availability (4/30/2025). PSA90 was defined as the earliest ≥90% decline in PSA relative to the most recent detectable pre-index PSA. Baseline patient characteristics were balanced between cohorts using inverse-probability of treatment weighting. Weighted Kaplan-Meier and Cox proportional hazards models were used to compare time-to-PSA90 and proportion achieving PSA90 response between APA vs DARO. Results: Baseline characteristics were well balanced between APA (N=714) and DARO (N=145) cohorts after weighting (Table). Mild-to-moderate diabetes (APA: 34.6%, DARO: 40.7%) and peripheral vascular disease (APA: 33.4%, DARO: 33.2%) were the most common comorbidities. Most patients had bone (APA: 52.2%, DARO: 50.5%) or nodal metastasis (APA: 51.0%, DARO: 49.2%). By 6 months, APA patients had a statistically significant 49% increase in PSA90 response rates as compared to DARO (hazard ratio [HR]: 1.49 [95% CI: 1.07, 2.07]; p=0.017; Table). Median time-to-PSA90 response was 2.8 months for APA and 3.3 months for DARO. Conclusions: This real-world study of patients with mCSPC demonstrated a significant increase in the likelihood of achieving deep PSA response for patients initiated on APA without docetaxel relative to those treated with DARO without docetaxel. Even without treatment intensification with docetaxel, APA remains an effective treatment option for achieving early deep PSA response. Weighted cohorts. Baseline APAN=714 DARON=145 Standardized difference (%) Median age, years 75 74 4.9 White / Black (%) 59.6 / 21.2 58.8 / 21.6 1.7 / 0.9 PSA level (%), ng/mL >0.2 to ≤2 34.1 31.7 5.1 >2 to ≤10 32.5 35.2 5.8 >10 to <20 9.8 9.6 0.7 ≥20 23.6 23.5 0.4 Follow-up PSA90 response (%) HR (95% CI),p-value By 6 months 74.6 56.1 1.49 (1.07, 2.07), 0.017
Redox Cascade‐Driven Structural Degradation Under Reverse Bias in All‐Perovskite Tandem Solar Cells
ABSTRACT Reverse bias, originating from current mismatch or shading, has emerged as a hidden yet fatal instability in all‐perovskite tandem solar cells. Here we reveal that sustained reverse bias triggers a redox‐coupled lattice collapse within the narrow‐bandgap subcells. Under electrical stress, hole injection oxidizes iodide ions into neutral iodine species, which subsequently oxidize tin cations and drive field‐directed ion migration. This redox cascade propagates vertically through the lattice, coupling ionic transport with structural reconstruction and interfacial corrosion, ultimately leading to irreversible performance loss. These findings expose all‐perovskite tandems as chemomechanical systems in which electrical stress is converted into internal electrochemical damage. To suppress this feedback loop, we introduce a “multideck‐fence” interfacial design that integrates a nanometric oxide diffusion barrier with a chemically stable dual‐metal electrode. This strategy halts the redox‐driven degradation, yielding a power conversion efficiency of 29.03% and more than 30‐fold enhancement in reverse‐bias endurance. Our results redefine reverse bias as a chemomechanically driven failure mode and establish a mechanistic framework for bias‐resilient perovskite architectures.
Alleviating the Misalignment of Fe Single Sites Relative to Triple‐Phase Interfaces to Achieve High Performance Fuel Cell
ABSTRACT Single‐atom catalysts (SACs), represented by Fe─N─C, are promising alternatives to Pt in proton exchange membrane fuel cells (PEMFCs). However, the molecular‐scale misalignment of the SACs at the triple‐phase interfaces (TPIs) has led to extremely low atomic efficiency, making it difficult to translate the high activity of SACs into the actual cell performance. Therefore, the design of the catalyst layer structure to increase the density of reactant‐accessible single sites is crucial for the application of SACs in PEMFCs. Here, we report tailored catalyst layer structure induced by hierarchical porous Fe─N─C pot catalysts with tuned surface hydrophilicity. Coarse‐grained molecular dynamic (MD) reveals macropores and tuned surface hydrophilicity act as molecular‐level “on‐switches” that pull Nafion/water domains deep inside, collapsing the classic transport bottlenecks for both O 2 and H 3 O + . Combinatory spectroscopic evidence confirms the superiority of the structure in forming continuous mass transfer channels, thereby increasing site utilization of Fe by 80%. Exceptional P max at 1581 mW cm −2 is achieved, and capable of sustaining 60k AST with 63% performance retained. This study establishes the first design rule that links pore hierarchy and surface chemistry to TPI activation.
Clinical characteristics and molecular evolution of treatment-emergent small-cell/neuroendocrine prostate cancer in the era of doublet and triplet systemic therapy.
240 Background: Transformation to treatment-emergent small-cell/neuroendocrine prostate cancer (teSC/NEPC) represents one mechanism of progression in prostate adenocarcinoma. Other rare treatment-associated histologies, including adenocarcinoma with neuroendocrine features and squamous carcinoma, have been described. We present 52 cases with clinical, pathologic, and molecular features of transformed prostate cancer, including comparative genomic analyses with available paired specimens. Methods: Records of 52 patients from four Cancer Centers were reviewed under IRB approval to identify prostate adenocarcinoma that transformed to teSC/NEPC or other variant histologies (pathologically confirmed). Demographic, clinical, and molecular data were abstracted using a standardized template. When available, paired next-generation sequencing (NGS) results were analyzed from baseline and transformation biopsies. The primary outcome was 1-year overall survival (OS) after transformation. Results: 42 patients with teSC/NEPC (Cohort 1) and 10 with other transformed variants (Cohort 2) met inclusion criteria. Median age at diagnosis was 64 (IQR 13.8) years. Median time from metastatic adenocarcinoma diagnosis to transformation was 27.0 (IQR 40.0) and 32.5 months (IQR 24.5) in Cohort 1 and 2 respectively. All patients received androgen-deprivation therapy; 34 (65.4%) received AR-signaling inhibitors, and 26 (50%) chemotherapy. PSA at transformation was frequently discordant with disease progression (median 0.08 and 2.15 ng/mL in Cohort 1 vs 2). 1-year OS from transformation was 45.8% for teSC/NEPC and 50.0% for other variants. Paired NGS was available for 16 cases. 15 (93.8%) exhibited shared genomic alterations (alt) between biopsies, indicating clonal continuity. Baseline TP53 alt was common (69%) and stable through transformation (75%). Marked enrichment of alt in other tumor suppressor genes (TSG) was apparent. Notably, the prevalence of RB1 alt increased from 12.5% (baseline) to 81.3% (transformation), while PTEN inactivation increased from 37.5% to 62.5%. The prevalence of HRR gene alt increased from 35.7% to 57.1%, mainly involving BRCA2 (31.3%), ATM (12.5%), BRCA1 and CHEK2 (6.3% each). Triple TSG alt was found in 31.3% of baseline vs 100% of transformed biopsies. MYC amplification emerged in 25% of cases. Conclusions: Transformation from adenocarcinoma to other variant histologies is an area of active investigation. Comparative genomic profiling permitted analysis of clonal evolution. RB1 loss emerged as the most frequent acquired event, underscoring its central role in lineage reprogramming. Treatment-associated transformation after doublet or triplet therapy confers poor survival, emphasizing the need to investigate mechanisms of transformation and develop precision-directed interventions.
Real-world treatment outcomes of advanced prostate cancer among Black compared to White men in the Medstar Health Network.
97 Background: Health disparities in prostate cancer (PC) have been well-documented, with Black men historically experiencing 60% higher incidence and twice higher mortality compared to White men. While these differences have been attributed to a combination of biological, socioeconomic, and healthcare-related factors, the extent to which treatment and access to care influence outcomes remains unclear. This study examines whether racial disparities persist in disease progression among men with advanced PC who receive comparable treatment. Methods: This is a real-world retrospective cohort study of men diagnosed with advanced PC (defined as unfavorable intermediate-risk, high-risk, very high-risk, metastatic hormone-sensitive and castration-resistant PC) in the MedStar Health Network from 2016-2024 who received treatment with surgery, radiation plus or minus androgen deprivation therapy (ADT), or systemic (chemotherapy-hormonal) therapy. Prostate Specific Antigen (PSA) failure was the measured outcome with PSA failure defined as an absolute increase of 2ng/mL or greater over the nadir within 1 and 2 years of treatment. Chi-square test was performed to assess the association between PSA failure and race across different treatment modalities and time. Results: A cohort of 4129 men (44.2% Black, 40.4% White, and 15.4% Other) treated with systemic therapy (41.6%), surgery (33.0%) or radiation (25.4%) were included. The association between PSA failure and race was not statistically significant between Black, White or Other men treated with surgery (1 year (p= 0.435); 2 year (p= 0.547)) nor radiation (1 year (p= 0.227); 2 year (p=0.483)). Association between PSA failure and race was significant in men treated with systemic therapy at both 1 year (p= 0.047) and 2 year (p= 0.024) intervals. Pairwise chi-square analysis found no significant difference in PSA failure between Black and White men (1 year (p= 0.225); 2 year (p= 0.103)) or Black and Other men (1 year (p= 0.090); 2 year (p= 0.113)), but a statistically significant difference was observed between White and Other men (1 year (p= 0.014); 2 year (p= 0.008)). Conclusions: There was no statistical difference in disease progression at 1 and 2 year follow-up between Black men and White men treated with systemic therapy, radiation therapy or surgery for advanced PC. These results highlight that disparities in PC outcomes are largely attributable to differences in access to care rather than intrinsic racial differences in disease biology. Our findings are consistent with prior studies which demonstrated that racial disparities in PC outcomes are minimized or absent within equal-access health systems that provide uniform access to diagnostic and treatment services across populations. This study adds rationale to promote interventions that improve screening and access to care for disadvantaged populations to reduce mortality gaps.
Evaluation of the safety and efficacy of daily oral <i>Angelica gigas</i> Nakai (AGN)-INM176 in prostate cancer patients with rising plasma PSA (phase I/II trial).
TPS413 Background: There are currently no FDA approved modalities for intercepting biochemically recurrent prostate cancer after radical prostatectomy (RP) surgery and radiation therapies (RT) to delay or prevent the need for androgen deprivation therapy. Preclinical modeling suggests Angelica gigas Nakai (AGN) root through its signature pyranocoumarins decursin D and decursinol angelate DA and their hepatic metabolite decursinol DOH may meet this unmet clinical need. In a single ascending dose PK study in prostate cancer patients (NCT05375539), we have evaluated the acute safety and shown the exposure PK metrics (C max and AUC) exhibited a linear dose response to AGN (INM176) supplement in the range of 800 to 2000 mg. The progress strengthens the design and launch of an open label Phase I/II trial to assess the long-term safety and preliminary efficacy of AGN INM176 in intercepting prostate cancer-specific PSA levels with refined inclusion and exclusion criteria. Methods: The ongoing NCT06600698 trial uses a classical Phase I 3+3 dose escalation design to establish the recommended Phase II dose (RP2D). Cohorts of 3 are evaluated for safety of INM176 (800, 1200 and 1600 mg) during a 4-week cycle for dose-limiting toxicities (DLTs). Major inclusion criteria include patients with a history of prostate cancer or those under active surveillance for low-risk disease. Phase II will evaluate the safety and efficacy of INM176 at the RP2D in stabilizing or reducing plasma PSA levels after six cycles of treatment. A special Phase II inclusion criterion is post-RP and post-RT patients experiencing a rise in PSA. In both phases, any patient with warfarin anti-coagulation is excluded due to an adverse herbal-drug interaction raising bleeding risk uncovered in our PK-dose trial. At time of abstract submission, Phase I cohort 1 of three subjects have completed the 800 mg dosing. Enrollment to cohort 2 (1200 mg) began in October 2025. To our knowledge, this is the first known human trial to assess the long-term safety of INM176 at higher than dietary supplement dosage and its interception efficacy for recurrent prostate cancer. The data will inform additional trials in the oncology space and beyond. Grant: MPI R01CA260901 (Lu, Joshi). Clinical trial information: NCT06600698 .
Lipophilic Self‐Wetting Ionogel Electrodes for Long‐Term High‐Fidelity Electroencephalogram Recording
ABSTRACT Establishing a long‐term stable electrode‐scalp interface to ensure high‐quality electroencephalogram (EEG) signal acquisition is crucial for advancing the practical application of brain‐computer interfaces (BCIs). However, most non‐invasive electrodes face issues such as dehydration or mechanical mismatch, making them difficult to maintain stable and efficient contact with the hairy scalp during prolonged recordings. Inspired by the natural perspiration mechanism of the skin, this study develops a body temperature‐responsive self‐wetting ionogel electrode (SWIGE) to overcome these limitations. Through microphase separation, SWIGE continuously releases electrolyte, improving interfacial contact by filling microgaps. Concurrently, the choline geranate (CAGE) in electrolyte swells the stratum corneum, significantly improving the ionic conductivity across the skin‐electrode interface and thus strengthening bioelectrical signal transmission. Synergistically combined with the inherent fatigue resistance and low mechanical hysteresis of the ionogel matrix, this strategy establishes a highly reliable biointerface with an impedance of 10.3 ± 0.6 kΩ at 7.8 Hz. The SWIGE enables sustained, high‐fidelity EEG monitoring and demonstrates robust capabilities in capturing and classifying evoked potentials. Crucially, SWIGE maintains performance parity with daily‐replaced commercial conductive pastes during the 50‐day reuse, validating its exceptional durability for brainprint authentication systems.
Optimizing <i>f</i> ‐ <i>d</i> Hybridization Descriptor in Rare‐Earth Oxides for Efficient Sulfur Catalysis in all Solid‐State Lithium–Sulfur Batteries
ABSTRACT All‐solid‐state lithium–sulfur batteries (ASSLSBs) offer high theoretical energy density and intrinsic safety, yet their development is hindered by sluggish sulfur redox kinetics at the solid–solid interfaces due to the weak orbital overlap and discontinuous electronic coupling at these regions. Here, we propose rare‐earth oxide catalysts that accelerate the sulfur reduction reaction (SRR) in ASSLSBs by strengthening the f‐d‐p hybridization at catalyst‐sulfur‐electrolyte interfaces. We first define a hybridization‐strength factor, I f‐d , derived from the electron densities of occupied 4 f and unoccupied 5 d states, which quantifies interfacial hybridization and directly correlates with the metal‐sulfur coupling strength. Catalysts with higher I f‐d exhibit lower activation energy ( E a ) and the overpotential ( η ) during SRR, validating its role as a structure‐activity descriptor for catalyst screening and design. Guided by this descriptor, the screened Lu 2 O 3 catalyst minimizes kinetic barriers (0.088 eV), and thus enabling stable cycling for over 20 000 cycles at 5 C, and an ultra‐high areal capacity of 14.48 mAh cm −2 at room temperature, among the highest performances reported for ASSLSBs. This work fills the mechanistic gap between interfacial orbital interactions and battery performance and paves the way toward catalyst design for high‐energy, long‐life ASSLSBs.
Clinical outcomes among patients with metastatic hormone-sensitive prostate cancer in contemporary real-world US clinical practice: A prostate cancer disease observation (PRECISION) data platform analysis.
77 Background: The incidence of metastatic hormone-sensitive prostate cancer (mHSPC) is increasing in the US, likely due to a decrease in screening practices. There has also been a rapid increase in recent years in the number of treatment options that can improve progression-free and overall survival (OS) for these patients. The objective of the current study was to evaluate the clinical outcomes among patients with mHSPC treated in contemporary US clinical practice (2020 to 2025). Methods: This retrospective, observational cohort study used data from PRECISION, a harmonized dataset on advanced prostate cancer in patients in the US treated in a range of clinical settings. Patients aged ≥18 years who were diagnosed with mHSPC during 01/01/2020–01/01/2024 and who initiated ≥1 therapy (index date = first-line [1L] treatment initiation) were included. The study period was from 01/01/2010 to 06/30/2025. Patient characteristics at mHSPC diagnosis and treatment utilization were evaluated descriptively. Castration resistance-free survival (CRFS; defined as the time to castration-resistant prostate cancer or death) and OS were evaluated from index using Kaplan–Meier analysis. Results: A total of 27,708 patients were included (median age, 72 years); 20,015 (72%) were treated in community urology, 4994 (18%) in community oncology, and 2669 (10%) in academic oncology centers at index. Almost half of patients (47%) initiated 1L treatment with androgen-deprivation therapy (ADT) monotherapy, 44% initiated a 1L doublet regimen (36% ADT + androgen receptor pathway inhibitor [ARPI], 5% 1L ADT + radiotherapy, 2% 1L ADT + docetaxel), and 5% a 1L triplet regimen (ADT + radiotherapy + ARPI or docetaxel); the remaining patients received other regimens. The 5-year CRFS rate was 41%; this was significantly higher in patients with a 1L doublet (45%) or triplet (58%) regimen compared with patients with 1L ADT monotherapy (31%; p<0.001). Similarly, the 5-year OS rate was 59% overall and was significantly higher in patients with a 1L doublet (61%) or triplet (59%) regimen compared with patients with 1L ADT monotherapy (55%; p<0.001) (Table). Conclusions: Though both CRFS and OS rates appear to be increasing among real-world patients with mHSPC, >40% of patients in this study died within 5 years of initiating 1L treatment. Patients who received guideline-recommended combined systemic treatment regimens experienced improved CRFS and OS, confirming the importance of implementing therapies in practice that prolong survival. CRFS and OS rates from start of 1L therapy, by therapy type. CRFS rate (%) OS rate (%) 1 y 2 y 3 y 4 y 5 y 1 y 2 y 3 y 4 y 5 y Overall 68 58 51 46 41 93 84 76 67 59 ADT monotherapy 59 49 41 36 31 92 83 74 65 55 Doublet therapy 72 62 55 49 45 94 85 76 68 61 Triplet therapy 85 77 70 68 58 94 89 82 74 59
Transcriptomic characterization of prostate cancer in patients with HIV infection.
396 Background: Prostate cancer is the most commonly diagnosed malignancy in the aging population of men living with HIV. Despite an increasing burden of prostate cancer, limited data exist to determine whether HIV infection is associated with differences in tumor biology and clinical outcomes in prostate cancer. We leveraged a large real-world data linkage to evaluate transcriptional profiles in incident prostate cancers among persons living with HIV (PWH) versus people without HIV (PWoH). Methods: We used a secure, anonymous linkage between prostate biopsy or radical prostatectomy whole transcriptome profiling data from a 22-feature Decipher prostate genomic classifier (GC) and real-world data from insurance claims, pharmacy records, and electronic health records (Veracyte, San Diego, CA). HIV status was identified using claims-based algorithms combining diagnosis codes and antiretroviral pharmacy records. Propensity scores for HIV status were used to match PWH to PWoH (1:5) based on clinical risk group, Gleason score, and test type. We compared transcriptomic signatures and subtypes using Chi-squared and Wilcoxon rank sum descriptive statistics. Results: We identified 1,170 eligible PWH with genomic data who met inclusion criteria based on diagnosis and treatment codes, as well as 5,850 matched PWoH comparators. Transcriptomic profiling indicated that prostate tumors in PWH had a more activated tumor immune microenvironment with higher T cell inflamed, activated CD4, CD8, cytotoxic T cell, B cell activity, ESTIMATE immune bulk infiltration and a higher prevalence of the basal immune subtype (46% vs 38%, p<0.001) in PWH as compared with comparators. In addition, PWH demonstrated higher PORTOS radiation response and slightly higher Decipher scores (median 0.51 vs 0.48, p<0.01) were found as compared to PWoH. Lower androgen receptor activity, pTEN inactive and higher neuroendocrine-like, p53 mutation and pRb loss signature scores were observed in PWH. Conclusions: Using a large national linkage of prostate tumor profiling and clinical data, we found that primary tumors of PWH exhibited distinct prostate cancer transcriptomic profiles compared to PWoH counterparts, including a higher prevalence of an activated tumor immune microenvironment and basal immune subtype. These findings suggest potential biologic differences in prostate cancer linked to HIV that underscore a need for further inquiry to understand whether there is a need to tailor management in this population.
Phase 3 study of <sup>68</sup> Ga-PSMA-11 PET combined with MRI for the detection of prostate cancer (BIPASS).
TPS406 Background: Prostate cancer (PC) is diagnosed through directed & template/anatomical biopsy based on clinical and radiographic suspicion. In patients with high risk of PC, directed biopsies are performed to identify occult disease, which can lead to anxiety, complications, financial burden, & logistical challenges. PSMA PET combined with MRI for targeted biopsy may improve the detection of clinically significant PC (csPC) & treatment management, minimize cost and procedural risk, de-escalate the number of biopsies, & potentially eliminate the need for biopsies in select populations. In a study of 56 patients with PI-RADS 3 lesions, csPC was detected in only 8 patients (14.3%) by biopsy. When a PRIMARY score of ≥4 was used to make a biopsy decision in men with PI-RADS 3 lesions, 40/48 (83.3%) patients could have avoided unnecessary biopsies. Biopsy of the Prostate Avoidance Stratification Study (BIPASS) is evaluating the diagnostic performance of combining 68 Ga-PSMA-11 PET & MRI targeted biopsy for detection of PC, using histopathological confirmation as standard of truth (SOT). Methods: This Phase 3, single-arm, multicenter, prospective, open-label, longitudinal study (NCT07052214) will enroll 204 patients ≥18 years with clinical suspicion of PC are prostate biopsy naïve & scheduled to undergo template biopsy based on initial MRI within 3 months before enrollment (PI-RADS 1-4). Key exclusion criteria include prior treatment of PC, diagnosis of PC, or obvious metastatic disease on prior conventional imaging. Patients will undergo 68 Ga-PSMA-11 & MRI scans, followed by standard template biopsy. PSMA & MRI scans will be independently interpreted by 3 blinded readers. MRI- & PSMA-targeted biopsies will be performed with 2 cores per lesion. If PC is histopathologically identified, lesion linking with imaging will be performed with no further follow-up required. Follow-up data will be collected for up to 6m for patients with no baseline imaging or histopathological evidence of PC. Additional imaging & biopsies may be performed during the follow-up period at discretion of the investigator. Any additional biopsy, imaging, clinical, histological, genetic, & intervention data will contribute to the determination of SOT. Follow-up will provide longitudinal surveillance to ensure that patients initially evaluated as negative for PC on both imaging & histopathology are reliably negative. The co-primary endpoints are sensitivity & specificity of combining PSMA PET- and MRI- targeted biopsy for the detection of PC, calculated by comparing diagnostic findings to histopathological or composite SOT. Key secondary endpoints include detection performance (sensitivity, specificity, PPV, NPV, accuracy, & misclassification rate) of PSMA PET- & MRI- targeted biopsy for detection of PC and interobserver variability of PSMA PET interpretation. This study is open for enrollment & is sponsored by Telix Pharmaceuticals. Clinical trial information: NCT07052214 .
Tetraphenylsilane‐Engineered MR‐TADF Emitters for Pure‐Green OLEDs with High‐Efficiency, Long Lifetime, and Gamut Close to BT.2020 Standard
ABSTRACT Achieving the concurrent combination of superior color purity, high efficiency, and long operational durability remains a formidable challenge for organic light‐emitting diodes (OLEDs), which are indispensable for realizing ultra‐high‐definition (UHD) displays. Herein, we propose a rational molecular design strategy that peripherally functionalizes the multi‐resonance thermally activated delayed fluorescence (MR‐TADF) skeleton with tetraphenylsilane (TPS) and deuterated TPS groups to address these challenges. The resulting emitters, p ‐DBFSi, m ‐DBFSi, and m ‐DBFSi‐d, exhibit sharp green emission (515–517 nm) with ultra‐narrow full‐widths at half‐maximum (FWHMs) below 0.070 eV, ranking among the narrowest green MR‐TADF materials reported. OLEDs employing m ‐DBFSi and m ‐DBFSi‐d as emitters deliver the purest green electroluminescence (CIE y = 0.76), extraordinary maximum external quantum efficiencies (EQE max ) of 40.1% and 41.9%, and maximum power efficiency (PE max ) approaching 200 lm W −1 , without employing an additional sensitizer, positioning them among the state‐of‐the‐art narrowband pure‐green OLEDs. Furthermore, the m ‐DBFSi‐d‐based device exhibits remarkably enhanced operational stability with operational lifetime (LT 80 ) of 2491 h at initial luminance of 1000 cd m −2 . Collectively, this work establishes a TPS‐ and deuteration‐engineered MR‐TADF strategy that enables OLEDs to combine ultra‐narrowband emission, outstanding efficiency, and exceptional durability, paving the way for next‐generation UHD displays.
A Self‐Adaptive Periodontal Ecosystem Engineered With Molybdenum‐Based Nanozyme‐Embedded Composite Hydrogel for Microenvironment‐Responsive Precision Therapy
ABSTRACT Periodontitis, the sixth most significant global pandemic driven by bacterial biofilms, is characterized by cytotoxic reactive oxygen species (ROS) and histolytic matrix metalloproteinases (MMPs) accumulation, resulting in progressive periodontal destruction. Current therapies are limited by diagnostic inaccuracy, incomplete biofilm elimination, and inadequate tissue regeneration. To address these challenges, an injectable theranostic Ce6@PEG‐MoO x ‐loaded hydrogel through facile construction is proposed, encompassing an intelligent closed‐loop for comprehensive periodontitis management. After being injected into periodontal pockets, the hydrogel adheres to tissues and responds to microenvironmental MMPs, realizing on‐demand therapeutic release. By integrating photoacoustic imaging, the hydrogel facilitates noninvasive, precise and reproducible measurement of porcine periodontal pocket depths, enabling periodontitis diagnosis and monitoring. Subsequently, released oxygen‐vacancy‐rich MoO x nanozyme mitigates cellular oxidative stress, generates O 2 to enhance Ce6‐mediated photodynamic eradication of deep‐seated biofilms, and scavenges residual ROS after bactericidal process. Notably, this system avoids off‐target ROS generation and photothermal damage, preserving surrounding tissues including dental pulp, thus exhibiting exceptional light‐controlled ROS‐modulation. Furthermore, released Mo activates the PI3K/AKT pathway to upregulate angiogenic factors, reprograms M2 macrophages polarization, and stimulates osteogenesis of periodontal stem cells. Altogether, this self‐adaptive ecosystem integrates diagnosis, monitoring, biofilm debridement, and tissue regeneration, establishing a closed‐loop precision therapy for periodontitis with significant clinical potential.