Browse Articles

Prognostic utility of tumor mutational burden in older adults (≥75 years) with bladder cancer: A TCGA geriatric oncology analysis.

834 Background: Older adults represent nearly half of bladder cancer diagnoses but are underrepresented in biomarker studies. Tumor mutational burden (TMB) is an established predictive biomarker for immunotherapy response, yet its prognostic utility in elderly populations independent of treatment exposure remains unclear. We evaluated the prognostic significance of TMB in patients aged ≥75 years within the treatment naive TCGA BLCA cohort. Methods: Clinical and mutational data from TCGA-BLCA Pan-CanAtlas 2018 were accessed via cBioPortal. The geriatric subgroup was defined as age ≥75 years. TMB was calculated as nonsynonymous mutations per megabase and dichotomized using the standard clinical threshold (≥10 mut/Mb) and a cohort-specific median (5.8 mut/Mb). Cox proportional hazards models were adjusted for age and sex. Because TCGA patients were treatment naive, results reflect TMB as a pure prognostic biomarker. Kaplan-Meier curves were generated for visualization. Results: Of 408 eligible patients, 133 (32.5%) were ≥75 years, with 66 deaths observed. In this subgroup, high TMB defined by median cutoff was significantly associated with improved overall survival (HR 0.44, 95% CI 0.27–0.73; p = 0.002). The ≥10 mut/Mb cutoff showed a favorable but nonsignificant trend (HR 0.61, p = 0.186). TP53 mutation status was not prognostic (p > 0.2). Each additional year of age above 75 remained associated with increased mortality risk (HR 1.08, p = 0.024). Sex was not associated with survival. Conclusions: In patients aged ≥75 years with bladder cancer, elevated TMB remains independently associated with improved overall survival, even in the absence of immunotherapy. These findings suggest that age-related immune senescence does not eliminate the prognostic relevance of TMB and support further study of TMB driven risk stratification and tumor immunogenicity in geriatric urothelial carcinoma.

A retrospective evaluation of treatment patterns following cabozantinib treatment for advanced renal cancer: The CABONEXT study.

451 Background: Cabozantinib with nivolumab is considered as a standard of care in first-line treatment for metastatic renal cell carcinoma (mRCC). Cabozantinib, a TKI targeting anti-VEGFR, MET and AXL, showed efficacy as a monotherapy or combined with checkpoint inhibitors (CPI). However, little is known about subsequent systemic therapy. This study aimed to report clinical outcomes from subsequent lines following a 1 st or 2 nd line cabozantinib-based therapy in mRCC pts. Methods: We performed a multicentric retrospective study in 19 centers in Europe. From February 2024 to September 2025, all included pts received at least one treatment after 1st or 2nd line based on cabozantinib for mRCC. Patients were divided in 2 groups: Group A with patients that received 1st line cabozantinib-nivolumab and Group B for patients treated by CPI-based therapy followed by 2nd line monotherapy cabozantinib. Primary endpoint was time to treatment failure (TTF). Potential prognostic factors for TTF were assessed in Group B. Secondary endpoints included objective response rate (ORR), disease control rate (DCR) and safety. Results: 88 pts were included, 78% males with a median age of 62 years. 24 pts (27%) received cabozantinib with nivolumab as 1st-line therapy (group A), and 73% in 2nd line pretreated with dual CPI in 30% and CPI with TKI in 43% (group B). In group A, patients received axitinib (71%), 1st generation TKI (25%) and lenvatinib monotherapy (1pt). Median TTF was 7.5 months with an ORR of 25% and a DCR of 66.7%. 12 pts (50%) had a subsequent line, 8 pts were still on treatment and 4 died before starting a new line. In group B, pts receivred axitinib (25%),everolimus monotherapy (27%), lenvatinib-based therapy (25%), CPI (7.8%) including 2 in combination with tivozanib and 1 with belzutifan. Median TTF was 3.0 months with an ORR of 9.3% and a DCR of 39%. 6 pts (9.3%) were still on treatment, 31 pt (48%) had a subsequent line, 26 (41%) died before (Table 1.). Based on multivariable analysis, 2nd generation TKI seemed to be the best option in the Group B compared to other treatment (HR = 3.91, 95%CI [1.81;8.43], p=0.0005). Previous dose reduction of cabozantinib was associated with prolonged TTF (HR = 2.20, p=0.02). Complete data are expected until December 2025. Conclusions: This analysis confirms antitumoral efficacy of 2nd-generation TKI, mostly axitinib and lenvatinib, after 1st or 2nd-line cabozantinib. These benefits remain modest and the need for innovative therapies targeting resistance mechanisms and optimal treatment sequences is still pending. Treatment characteristics following cabozantinib-based therapy in group A and group B. Group A Group B Number of pt 24 64 Axitinib 17 (70.8) 16 (25) Lenvatinib based therapy 1 (4.1) 16 (25) Everolimus alone 0 17 (26.6) CPI 0 3 (4.7) Tivozanib 0 4 (6.3) Other 6 (25) 7 (10.9) Median TTF (months) 7.5 3 ORR 25.0% 9.3% DCR 66.7% 39.1%

Microplastics and prostate cancer.

379 Background: Plastics are ubiquitous in our environment. Tiny plastic particles called microplastics and nanoplastics (MNPs) have been found in many human tissues. A recent study of patients undergoing carotid endarterectomy found that patients with MNPs in their plaques were 4.5 times more likely to experience myocardial infarction, stroke or death. Preclinical data also suggests a potential link of MNPs with cancer; however, direct evidence of a link to human prostate cancer (PCa) is limited. The objective of our study was to determine whether MNPs are found in human PCa, and to compare levels of MNPs between tumor tissue versus benign tissue. Methods: We recruited 10 patients with PCa undergoing radical prostatectomy. The prostatectomy specimen was transported in a metal container, and underwent plastic-free pathological evaluation by an expert uro-pathologist. Separate samples of tumor tissue and benign tissue from elsewhere in the prostate were then transferred to the lab where we used 2 different techniques for MNP evaluation: (1) visual inspection in tandem with Raman microscopy to assess MNP particle abundance, size, and other characteristics, and (2) pyrolysis-Gas Chromatography/Mass Spectrometry (py-GC/MS) to identify and quantify MNPs on a mass basis. Descriptive statistics were used to tally the type and concentration of MNPs identified. Results: Microplastic particles were detected in 60% of patient samples using Raman, with individual particles ranging from 1.2 µm to 40.3 µm in diameter. Tumor tissue had a greater number of particles per sample than benign tissue. Using Py-GC/MS, we found MNPs in 90% of patients (90% of tumor and 70% of adjacent benign tissue). Tumor tissue concentrations of microplastics tended to be higher than para-tumor tissue concentrations. The mean concentration of MNP was 39.8 (µg/g) (median 16.3) in tumor tissue, compared to a mean of 15.5 (µg/g) (median 7.0) in adjacent benign tissue. With respect to particle types, nylon-6 and polystyrene were found above the method detection limit in the largest number of samples using py-GC/MS, while polyethylene and polyethylene copolymers were also identified on Raman. Conclusions: Microplastics were found in tissue samples from 9 out of 10 patients with prostate cancer using either method, with greater concentration in tumor tissue compared to benign tissue. Additional research is in progress to study the link between MNPs with prostate carcinogenesis. Supported by the Department of Defense HT9425-25-1-0145.

Antibody–lectin chimeras: new checkpoint inhibitors in the toolbox

Synergistic Coupling of Host and Electrolyte Achieving 1270 Wh L ⁻¹ in Anode‐Free Lithium Metal Batteries (Adv. Mater. 14/2026)

Real-world endpoints as surrogates for overall survival in metastatic bladder cancer.

693 Background: Overall survival (OS) remains the gold-standard endpoint in solid tumors, including metastatic bladder cancer (mBC), but requires extensive follow-up and resources. Real-world endpoints (RWE) such as real-world progression-free survival (rwPFS), time to next therapy (TTNT), time to end of first-line therapy (TTEFL), second-line rwPFS (rwPFS2), and treatment-free survival (TFS) may accelerate evidence generation if validated as OS surrogates. Methods: We analyzed 5,296 patients with mBC from who received first-line chemotherapy (n = 3,831) or single-agent immune checkpoint inhibitors (ICI, n = 1,465) using the Flatiron Health database. Patient-level surrogacy was assessed using Kendall’s tau. For group-level surrogacy, patients were stratified into 20 risk-based sub-cohorts via Cox regression–derived risk scores. The R² from linear regression quantified the association between 12-month OS rates and 3-month event-free rates for rwPFS, TTNT, and TTEFL across sub-cohorts. TFS was evaluated as the restricted mean survival time between TTEFL and TTNT over 12 months. Sensitivity analyses tested alternative timepoints and cohort sizes. Results: Median OS was 14.5 months (18-month OS, 43%) for chemotherapy and 8.9 months (18-month OS, 34%) for ICI. At patient level, rwPFS (τ = 0.67 chemotherapy; 0.71 ICI), TTNT (0.58; 0.78), and rwPFS2 (0.94; 0.96) showed robust correlations with OS, whereas TTEFL was weaker (0.30, 0.59). At group level, 3-month rwPFS (R² = 0.88) and TTNT (0.85) were strongly correlated with 12-month OS in chemotherapy, while in ICI, TTEFL (0.80) and TTNT (0.78) outperformed rwPFS (0.59) at 3 months. Extending rwPFS to 6 months against 18-month OS improved its correlation in ICI (0.70), reflecting delayed immunotherapy benefit. TFS paralleled OS in chemotherapy (R² = 0.85) but was less informative for ICI (0.03). Sensitivity analyses confirmed robustness across varied time horizons and cohort sizes. Conclusions: This study suggests RWEs as potential surrogates for OS in mBC, with optimal endpoints varying by treatment type. For chemotherapy, rwPFS and TTNT serve as reliable proxies. In ICI-treated patients, TTNT and TTEFL provide robust early signals, with rwPFS gaining predictive strength over longer follow-ups. These insights pave the way for faster, more effective evaluations of treatment outcomes in mBC, ultimately enhancing clinical and regulatory decision-making.

Prevalence of major adverse cardiac events in men with prostate cancer receiving androgen deprivation therapy in real-world clinical practice.

107 Background: Androgen deprivation therapy (ADT) is the backbone treatment for advanced prostate cancer (PC), but it has been associated with an increased risk of major adverse cardiac events (MACE), especially in men with pre-existing cardiovascular (CV) disease. The oral gonadotropin-releasing hormone (GnRH) receptor antagonist, relugolix, was approved in December 2020 based on the HERO trial. After 48 weeks of treatment, there was a 54% lower risk of MACE with relugolix compared with leuprolide. However, the prevalence of MACE in real-world clinical practice is unknown. This observational study evaluated the real-world prevalence of MACE among men receiving ADT in the United States. Methods: Men with PC who newly initiated ADT between January 2018 and May 2024 were identified in the Merative MarketScan Commercial and Medicare Databases. The first ADT claim was the index date, and men were followed for a 12-month pre-index and ≥60-day post-index period, defined by duration of ADT. Primary outcomes included the rate of 2- and 3-point MACE (non-fatal myocardial infarction or stroke [2- and 3-point], or all-cause death [3-point]). Demographics and baseline characteristics were also assessed. Reporting was carried out for the entire group, men who initiated GnRH agonists (eg, leuprolide) or antagonists (eg, degarelix, relugolix), and men who started ADT before or after relugolix approval (January 2021). Patients who initiated degarelix but switched to an agonist within 60 days were classified as agonist users. Results: Of 17,336 men newly initiating ADT, 90.4% (15,666) received a GnRH agonist, and 9.6% (1670) received a GnRH antagonist; 624 (3.6% of all patients) received relugolix. The overall median age was 69 years. Men treated with GnRH antagonists vs agonists were younger (65.5 vs 69.0 years), more likely to be commercially insured (48.3% vs 40.6%), and had a shorter follow-up (126 vs 189 days). Prevalence of 2- and 3-point MACE over the study period was 3.5 and 4.0 per 100 person-years, respectively. Antagonist vs agonist users had a 36% and 37% lower prevalence of 2-point (2.3 vs 3.6) and 3-point (2.6 vs 4.1) MACE, respectively. Prevalence of 2- and 3-point MACE decreased over the study period from 3.7 and 4.2 per 100 person-years in 9254 men (53.4%) who initiated ADT before January 1, 2021, to 3.3 and 3.7 per 100 person-years in 8082 men (46.6%) who initiated ADT after January 1, 2021. An increase in GnRH antagonist use was seen from 6.6% before January 1, 2021, to 13.2% after. Conclusions: In practice, MACE prevalence remained low after initiating ADT. Although differences in baseline characteristics remain, MACE rates were numerically lower in men receiving GnRH antagonists. Use of GnRH antagonists increased following relugolix approval and coincided with a greater awareness of CV risk factors, potentially leading to a decline in MACE rates.

Ascending dose escalation of belzutifan plus palbociclib for previously treated advanced clear cell renal cell carcinoma (ccRCC): Phase 1/2 LITESPARK-024 study part 1.

423 Background: Novel MoAs remain an unmet need for patients with advanced ccRCC with PD after multiple therapies. Combination of HIF-2α and CDK4/6 inhibitors showed synthetic lethality in preclinical ccRCC models (Nicholson, Sci Signal 2019). The phase 1/2 LITESPARK-024 study (NCT05468697) evaluates safety and efficacy of belzutifan (bel) + palbociclib (palbo) in pts with advanced ccRCC with PD after ≥2 systemic regimens, including both anti-PD-(L)1 and VEGFR-TKI therapy, and no prior HIF-2α and CDK4/6 inhibitors. Methods: Eligible adults had unresectable stage IV ccRCC, radiographic PD on/after most recent treatment, and ≥2 prior systemic regimens (including both anti–PD-[L]1 and VEGFR-TKI). Part 1 aimed to determine the recommended phase 2 dose (RP2D) by evaluating DLTs (based on a list of prespecified terms if treatment-related and occurring ≤28 days after first dose) and safety (evaluated in all pts who received ≥1 dose study drug). Pts received bel 120 mg QD + palbo 75 mg, 100 mg, or 125 mg QD for 21 days followed by 7 days off until PD, unacceptable AEs, pt withdrawal, or bel discontinuation. Exploratory efficacy (ORR, disease control rate [DCR], and PFS by investigator per RECIST 1.1) in all enrolled pts is also reported. Results: 59 pts were enrolled; 58 pts received ≥1 dose study drug (n = 20 in 75 mg palbo group, n = 19 each in 100 mg and 125 mg groups). 1 pt in the 100 mg group was enrolled but not treated. Data cutoff date was 28 July 2025. Median follow-up was 8.7 mo (range, 3.0–35.0). Total median (range) duration of therapy was 4.4 mo (0.2–23.4) for bel and 3.5 mo (0.2–23.4) for palbo. 2 DLTs occurred: 1 gr 3 anemia, and 1 gr 3 hypoxia (both in 125 mg group). Safety summary is shown in the Table. Most common grade ≥3 TRAE was anemia (50.0% in 75 mg group, 52.6% in 100 mg group, 57.9% in 125 mg group). ORR and DCR (95% CI) were 15.0% (3.2–37.9) and 70.0% (45.7–88.1) in 75 mg group, 0.0% (0.0–17.6) and 57.9% (33.5–79.7) in 100 mg group, and 21.1% (6.1–45.6) and 73.7% (48.8–90.9) in 125 mg group. Median PFS (95% CI) was 7.2 mo (1.9–NR), 5.4 mo (1.8–NR), and 9.1 mo (3.7–NR); estimated 12-mo PFS rates were 29.2%, 30.7%, and 44.4%. Conclusions: Bel + palbo had a manageable safety profile. Gr ≥3 TRAEs were frequent. No new safety signals occurred. In a population with heavily pretreated biomarker-unselected RCC, clear differentiation in efficacy outcomes with bel + palbo compared with historical bel monotherapy data was not observed. Interpretation of these results is limited by the sample size and the single-arm design. Clinical trial information: NCT05468697 . Pts with ≥1 event, % Bel +75 mg palbo Bel +100 mg palbo Bel +125 mg palbo Any AE 100.0 94.7 100.0 Gr ≥3 AE 85.0 84.2 100.0 Serious AE 60.0 47.4 36.8 AE led to discontinuation 15.0 26.3 10.5 AE led to death 0 0 5.3* Any TRAE 95.0 94.7 100.0 Gr ≥3 TRAE 65.0 78.9 78.9 Serious TRAE 15.0 15.8 10.5 TRAE led to discontinuation 15.0 26.3 5.3 TRAE led to death 0 0 0 *Cerebral hemorrhage.

Two-step screen for CARD9 inhibitors

Quasi‐Chimney Electrode Boosts Hydrogen Evolution Reaction via Polarized Laplace Pressure

ABSTRACT The effect of mass transfer on hydrogen evolution reaction (HER) is significantly underestimated under high‐current‐density conditions. Here, we designed a quasi‐chimney electrode by integrating 3D superaerophilic microchannels with superaerophobic Pt catalysts to elucidate the influence of mass transfer on HER. Upon encountering superaerophilic channels, hydrogen (H 2 ) bubbles generated on Pt catalysts experience Laplace pressure polarization at the bubble/channel interface, which drives both surface and internal bubbles from the superaerophobic catalytic sites into the superaerophilic network, functioning as a micro‐chimney for efficient bubble transport. In addition, the superaerophilic channels shorten the diffusion path of dissolved H 2 to the air/water interface, thereby reducing the dissolved H 2 concentration. This mass‐transfer enhancement yields an exceptional HER performance (a record‐low overpotential of about −30 mV at −100 mA cm −2 , and a high current density of −2.93 A cm −2 at −0.3 V vs RHE in H 2 SO 4 (0.5 M) along with remarkable durability, confirmed by <5% activity decay at −1000 and −2000 mA cm −2 for 160 h. The proposed quasi‐chimney design, which is also applicable to various catalysts, results in an 8‐ and 14‐times increase in current density for Cu–Co and Cu–Mo catalysts, at an overpotential of −500 mV compared with their superaerophobic electrode structures.

Theory‐Guided Design of Ru–NiFe Cathode Catalysts for Anion Exchange Membrane Water Electrolysis at Large Electrode Scale

ABSTRACT A significant gap persists between advanced catalyst synthesis in laboratories and the industrial requirements for water electrolysis. The key challenge lies in simultaneously achieving electrode scalability, high catalytic activity, and long‐term stability. Through theoretical simulation screening, we synthesized a free‐standing cathode catalyst composed of Ru clusters anchored on a Ni x Fe y OOH substrate via Ru─O─Ni/Fe bridges. Advanced characterizations and theoretical calculations reveal that the Ru–NiFe catalyst achieves efficient catalytic activity due to Ru─O─Ni/Fe bridges, fine‐tuning the electronic structure and enhancing catalytic energetics, while Ru cluster introduction increases the number of active sites and modulates hydrogen intermediate adsorption/desorption strength. The as‐prepared Ru–NiFe electrocatalyst for the hydrogen evolution reaction delivers ultralow overpotentials of 5 mV at 10 mA cm − 2 and maintains stable operation at 500 mA cm − 2 for over 1000 h. A large‐scale (19 × 19 cm 2 ) anion‐exchange‐membrane water electrolyzer (AEM–WE) based on Ru–NiFe shows a low cell voltage of 2.98 V at 10 A and stable operation for 2800 h. This study provides valuable insights into designing large‐area electrodes with high activity, long‐term stability, and scalable production for industrial AEM–WE applications.

Touch‐Driven Bi‐Chiral Superstructures for Nested Encryption of Multiplexed Optical Information

Abstract With the growing demand for data security, optical encryption has emerged as a promising solution due to its high‐speed, parallel and low‐power‐consumption characteristics. However, most optical encryption methods rely on static structures involved with only few optical degrees of freedom (DOFs), resulting in simple encryption methods susceptible to attacks. Herein, a dynamic nested optical encryption scheme is proposed using a touch‐driven bi‐chiral cholesteric liquid crystal (CLC) superstructure, where relief‐structured polymerized CLCs are combined with temperature‐sensitive opposite‐handed CLCs. Through delicate photopatterning and Bragg reflection engineering, independent geometric phases can be induced to the reflected light with orthogonal circular polarization and multiple wavelengths. Thus, various optical DOFs (wavelength, amplitude, and polarization) and environmental factors (temperature or human‐device interaction) are encoded as different encryption dimensions. Based on the developed four‐step encryption algorithm, the four‐level nested encryption is demonstrated by multiplexing the plaintext and multilevel ciphertexts in structural colors, multicolored vectorial holography and their temperature‐driven variations. The plaintext can be derived only through a specific order, with the final step completed by a human touch. This work advances the on‐demand construction of chiral nanostructures, and offers a new paradigm for high‐security and high‐capacity optical informatics.

Treatment patterns and survival outcomes among lutetium 177–experienced patients with metastatic castration-resistant prostate cancer.

69 Background: Survival expectations for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) receiving late-line therapies have historically been defined by trials conducted prior to the approval of lutetium-177 vipivotide tetraxetan (Lu177). With Lu177 now established as a standard of care following Phase 3 VISION trial, treatment (tx) sequencing and survival outcomes in the post–Lu177 setting remain poorly characterized. This real-world study evaluates outcomes of mCRPC pts who required subsequent tx after Lu177. Methods: This retrospective cohort study included pts with mCRPC who initiated subsequent tx after Lu177 from 01/01/2018 to 07/31/2024 in the U.S. based EHR-derived de-identified Flatiron Health Research Database. The data cut-off date was 07/31/2025. Overall survival was measured from initiation of post-Lu177 tx (index date) until death and was calculated by the Kaplan-Meier method. Predictors of survival were identified by multivariate Cox models. Subgroups were defined by prior exposure to taxane chemotherapy. Pre/post taxane subgroups required ≥1 androgen receptor pathway inhibitor (ARPI) before index date. Post-taxane was defined as prior receipt of docetaxel or cabazitaxel in mCRPC. Results: Among 743 pts treated with Lu177, 161 (22%) initiated subsequent therapy. Of these, 65% (n=105) were post-taxane. More than 40 distinct tx regimens were identified following Lu177. The most common regimens were cabazitaxel monotherapy (19%), cabazitaxel and carboplatin (12%), and enzalutamide monotherapy (9%). Overall, 50% of pts received a chemotherapy-based regimen. The median duration of post-177Lu tx was 2.4 months. Median overall survival (mOS) was 8.0 months overall, 13.5 months in pre-taxane subgroup, and 6.8 months in post-taxane subgroup. ECOG≥2 [Hazard Ratio (HR) (95% CI)=2.6(1.4 - 4.9)] and Lu177 duration <180 days [HR=1.7(1.1 - 2.8)] were predictors of shorter survival. Conclusions: Among the mCRPC pts receiving subsequent therapy after Lu177, tx selection was heterogeneous and primarily chemotherapy-based. The short tx duration and limited survival highlights more effective therapies after Lu177 tx are needed to improve outcomes in mCRPC. Baseline disease characteristics at initiation of post-Lu177 tx and survival. Overalln=161 Pre-Taxane n=37 Post-Taxane n=105 Median Age, years 73 70 73 Metastasis SitesBoneLymph NodeLiver 149 (93%)83 (52%)30 (19%) 35 (95%)18 (49%)4 (11%) 99 (94%)59 (56%)24 (23%) ECOG ≥2 30 (19%) 5 (14%) 23 (22%) Prior mCRPC Lines of Therapy <3 3 4 >4 32 (19%)38 (24%)35 (22%)56 (35%) 19 (51%)7 (19%)6 (16%)5 (14%) 6 (6%)25 (24%)24 (23%)51 (48%) Duration of Lu177, days <180 ≥180 80 (50%)81 (50%) 21 (57%)16 (43%) 49 (47%)56 (53%) mOS (95% CI), months 8.0 (6.8 -11.5) 13.5 (6.9- NR) 6.8 (5. 5- 9.3) Prior ARPI was not required in overall cohort. Prior ARPI was required for pre/post taxane subgroups.

Pelvic lymph node risk stratification in prostate cancer: A machine learning approach toward a predictive nomogram.

349 Background: Pelvic lymph node involvement (PLNI) is a critical prognostic factor in PCa, guiding decisions regarding extended lymphadenectomy during radical prostatectomy (RP). Existing nomograms, such as Briganti and MSKCC, are widely used but face challenges, including limited specificity and variable accuracy depending on patient selection and practice heterogeneity. Machine learning (ML) approaches may enhance predictive accuracy and identify key features for future nomogram development. We aimed to develop a ML model for predicting the presence of PLNI in patients who underwent RP with pelvic lymphadenectomy (PL) at our institution. Methods: This was an observational retrospective study conducted at our institution’s PCa Clinical Care Center. We included patients who underwent RP with PL between 2015 and 2024. The primary endpoint was the presence of PLNI. Random Forest (RF) and Logistic Regression (LR) models were developed to predict PLNI. Model performance was evaluated through cross-validation using accuracy, precision, recall, F1-score, and area under the curve (AUC). Accuracy reflects overall correctness, precision indicates the proportion of true positives, recall measures sensitivity to positive cases, and the F1-score balances both metrics. The AUC summarizes overall discriminative ability across different classification thresholds. Feature importance was assessed using SHAP (SHapley Additive exPlanations) values, which quantify each variable’s contribution to model predictions. Results: After data curation, 982 patients and 19 preoperative clinical, biopsy, and imaging variables were included. The initial RF model achieved an accuracy of 0.85 but showed limited sensitivity for PLNI (recall 0.28), potentially translating into a high proportion of false negative cases. Removing less relevant D’Amico Risk Classification, recall improved to 0.62 with accuracy 0.80, F1-score 0.82 and AUC 74%. A final LR model using only PIRADS, PSA density, MRI lesion characteristics, and D’Amico total score achieved the best balance (accuracy 0.83, recall 0.67, F1-score 0.85 and AUC 80%). Feature importance consistently identified PIRADS, PSA density, Gleason biopsy, and number of positive cores as key predictors. Conclusions: This represents the first Latin American study to internally develop predictive models for PLNI in PCa. ML models demonstrated promising performance, with LR providing the most balanced combination of accuracy and sensitivity. Key predictive features identified may serve as the foundation for developing a clinically useful nomogram and online risk calculator. These findings demonstrate the feasibility of locally trained ML models to complement global nomograms and enhance personalized surgical decision-making in PCa. External validation and prospective evaluation are needed.

Perioperative enfortumab vedotin plus pembrolizumab versus neoadjuvant pembrolizumab in cisplatin-ineligible patients with muscle-invasive bladder cancer (MIBC): An IPD-based comparative analysis of KEYNOTE-905/EV-303 and PURE-01.

779 Background: Cisplatin-based chemotherapy is the standard neoadjuvant therapy for patients (pts) with MIBC. However, a significant proportion of pts are ineligible for/refuse chemotherapy, requiring alternative perioperative strategies. PURE-01 tested neoadjuvant pembrolizumab (Pembro) monotherapy before radical cystectomy (RC) in pts with cT2–T4N0M0 MIBC, without an adjuvant period. KEYNOTE-905/EV-303 is a randomized, phase III study testing perioperative enfortumab vedotin (EV) plus Pembro (EVP), followed by RC and adjuvant EVP for 6 cycles, then Pembro alone for additional 6 cycles, versus RC alone. EV-303 included a third arm of Pembro monotherapy, which was stopped in 2022. The contribution of both therapeutic components in the EVP regimen and the neoadjuvant vs adjuvant part remains uncertain. Methods: An indirect comparison of trials was performed using IPD reconstructed from Kaplan–Meier curves. The endpoints were event-free survival (EFS) and overall survival (OS) since initiation of treatment. Individual pt-level data (IPD) were retrieved using a graphical reconstructive algorithm and merged into a single dataset including two treatment groups. EFS was estimated with Kaplan–Meier curves and compared with the log-rank test and the Cox proportional hazards model. Landmark estimates at 12- and 24 months and median values were calculated. Analyses were conducted in RStudio (v.2025.05.1+513). Results: A total of 170 pts from KEYNOTE-905/EV-303 (EVP arm) and 155 from PURE-01 were included. Baseline staging was cT2 in 17.6% of patients in the EVP group and 48.4% in the Pembro group; cT3/T4 in 78.2% and 51.6%, respectively; 4.1% and 0%, respectively, had a clinical N1 stage. Pathologic complete response (pCR) was higher in the EVP group than in the pembrolizumab group (57.1% with 95% CI, 49.3–64.6 and 39.5%, respectively). The IPD-based Cox analysis showed no significant difference in EFS (HR 0.75, 95% CI 0.49–1.14; p = 0.181). Conclusions: An indirect IPD-based comparison between EVP and Pembro did not result in statistically significant differences in EFS. These results emphasize the importance of conducting clinical trials aimed at discriminating the contribution of components that remain uncertain, representing a critical need. Limitations include the retrospective design, indirect comparison, patient, and geographical heterogeneity. Endpoint Time (months) EVP (%) [95% CI] Pembro (%) [95% CI] EFS 6 90.7 (86.4-95.3) 87.1 (82–92.5) 12 77.6 (71.3–84.4) 84.5 (78.5–90.9) 24 74.1 (67.2–81.6) 71.7 (62.7–82.0) Median NR (37.2-NR) NR (NR-NR)

Lipid flippase inhibitor tackles drug-resistant fungi

Liquid Transport‐Enhanced Bioinspired Heterogeneous Aerogel Fibers for Flexible Wearable and Outdoor Energy Harvesting System

ABSTRACT Flexible and wearable energy harvesting systems are of great significance for achieving lightweight and comfortable portable electronics. Among them, aerogel fibers, featuring ultralight weight and abundant nanoporous structures, are ideal building blocks for constructing liquid‐directed energy harvesting platforms. Herein, inspired by the efficient water transport behavior of plant vascular bundles, we report a liquid transport‐enhanced heterogeneous aerogel fiber (HAF) fabricated via microfluidic spinning. The fiber consists of a twisted, surface‐charge‐enhanced cotton core for rapid liquid transport, sheathed with a regenerated cellulose/carbon black layer that reinforces mechanical strength and enhances hydrovoltaic energy conversion. Optimizing the core twist level increased the liquid transport rate by 1.87‐fold, strengthening solid‐liquid interfacial interactions and enabling a single 5 cm fiber to stably output an open‐circuit voltage of 0.55 V for over 160 h. Furthermore, matrix‐type series‐parallel integration of multiple aerogel fiber units allows the system to harvest energy from wearable sweat or outdoor rainwater to power GPS devices, outdoor tent lighting, and carbon nanotube‐based electrothermal blankets. This work establishes a bioinspired liquid transport‐enhanced design strategy for flexible, lightweight, and sustainable aerogel fiber‐based self‐powered systems.

Dynamic Upconversion Manipulation via Cross‐Relaxation Engineering for Optical Encryption

ABSTRACT Lanthanide ions (Ln 3+ ) doped upconversion originates from their diverse 4 f electron transitions. However, the direct manipulation of excited‐state electron populations for dynamic emission modulation remains challenging. In this study, a cross‐relaxation control paradigm, enabled by dual‐wavelength cooperative excitation, is developed for dynamic upconversion engineering. The Er 3+ ‐Ln 3+ (Ln 3+ = Tm 3+ , Ho 3+ , Yb 3+ ) doped NaYS 2 platform precisely populates the dual‐target energy levels via cross‐relaxation pathways under cooperative excitation. This approach enables dynamic green‐to‐red luminescence switching while amplifying the red emission (∼20‐fold) by accelerating the cross‐relaxation kinetics; Er 3+ acts as the photon harvester, and Ln 3+ serves as the cross‐relaxation mediator to redirect population fluxes. The experimental and theoretical results demonstrate that this phenomenon originates from the unique properties of the low phonon energy, unique layered structure with a large interionic spacing, and high refractive index of the NaYS 2 host. Finally, programmable upconversion logic gate arrays are implemented to develop a dynamic‐ random‐visual encryption system for optical information security. This study establishes a novel paradigm for upconversion manipulation with unprecedented capabilities for advanced information technologies.

Dose optimisation and PSMA receptor intensification with ¹⁷⁷ Lu-PSMA-597 in metastatic castration-resistant prostate cancer (mCRPC): The randomised phase II OPTIMAL-PSMA trial.

TPS293 Background: [ 177 Lu]Lu-PSMA is a targeted radionuclide beta therapy in metastatic prostate cancer that affords excellent quality of life compared to chemotherapy in men who have few available options. However, its impact in improving overall survival (OS) has been limited using current dosing regimens, with an OS improvement of 4 months compared to a standard-of-care (SoC) that excluded chemotherapy. A phase 1 dose escalation study previously found 22Gbq dose of 177 LuPSMA-617 over 15 days to be safe and tolerable, but randomised data compared to conventional dosing are lacking. The objective of OPTIMAL-PSMA is to directly compare a dose intensification regimen to a SoC comparator using a novel PSMA peptide [ 177 Lu]Lu-PSMA-597, evaluating dosimetry, safety and efficacy. Methods: This open label, single centre, phase 2 trial randomises 120 participants 2:1 to either dose-intensified 177 LuPSMA-597 or SoC 177 Lu-PSMA-597 every 6 weeks for a total of 6 doses. Treatment continues until the pt is no longer clinically benefitting. The primary endpoint is PSA90% response rate(PSA90). The sample size provides 80% power to detect a 24.5% increase in PSA90 with an assumed 20% of participants achieving the primary endpoint in the SoC arm with a sample size of 120 participants (80:40) recruited over 18 months. Secondary endpoints include safety, dosimetry, rPFS, overall survival, and PSMA-PET response at 8 weeks. The target population is progressive mCRPC post androgen receptor pathway inhibition therapy. In the experimental arm 7.5GBq (8.5Gbq after patient 40) is administered on days 1, 3 and 15, then weeks 10, 20 and 30. In the SoC arm 7.5Gbq is administered at baseline and weeks 6, 12, 18, 24 and 30. Translational bloods for circulating tumour DNA genomic and epigenomic analysis are undertaken on both arms at each treatment timepoint. A PSMA-PET is undertaken at baseline and week 8 in both arms. Safety assessments including bloods are undertaken 3-weekly with diagnostic CT and bone scan every 12-weeks. As of October 2025, 33 participants have been randomised. An independent data safety monitoring assessment of the first 10 experimental patients identified no safety concerns and recommended a planned increased dose to 8.5Gbq in the experimental arm. 177 Lu-SPECT and PSMA PET quantitation will be used to assess both treatment response and compare biologic effective dose delivered with a dose intensified versus SoC 177 LuPSMA administration. Clinical trial information: ACTRN12625000971437 .

POSTER: Evaluating the impact of virtual peer-led support groups on prostate cancer survivorship—The AnCan experience.

265 Background: Comprehensive prostate cancer (PCa) survivorship requires more than just clinical care, including education, psychosocial support, self-advocacy, and lifestyle guidance—needs often unmet by traditional oncology visits. Virtual peer-led support groups, such as those offered by the AnCan Foundation, offer accessible, real-time platforms for patients to share experiences, receive guidance, and foster community, regardless of geography. This study evaluates the impact of AnCan participation on factors known to be associated with a better quality of life (QOL) among PCa survivors. Methods: A web-based survey was administered in 2024 to PCa survivors who attended or expressed interest in AnCan meetings. Respondents (N=294) provided demographic information and rated AnCan’s impact on QOL, peer support, self-advocacy, and satisfaction. Data were analyzed to assess the subjective influence of AnCan’s virtual support model on survivorship. Results: (2021 results are in brackets for comparison.) Most respondents were in their 60s–70s (75%), highly educated (82%), and 55% had incomes over $100,000. Eighty-three percent had someone in their lives they could rely on and with whom they maintained regular contact. Nearly all (97%) found AnCan meetings helpful for disease understanding, learning options, and well-being. Sixty-six percent reported improved QOL; 83% [50%] noted reduced stress; 62% [38%] improved nutrition; and 56% [58%] increased exercise. Satisfaction was high, with 99% recommending AnCan. AnCan involvement enhanced self-advocacy (88%), improved patient-provider communication, and improved decision-making. Seventy percent brought information from AnCan to their providers, 49% added new providers, and 40% changed their lead provider. Over half (54%) reported AnCan influenced their treatment path. Socially, 55% [43%] connected with peers outside meetings and 47% made new friendships. Conclusions: Survey responses indicate that the AnCan virtual peer-led model, to be described in the poster, meaningfully increases patient knowledge, empowers self-advocacy, reduces stress, and fosters healthy behaviors, improving quality of life for PCa survivors. We advocate for integrating such peer support into NCCN, AUA, and ASCO survivorship guidelines.