Browse Articles

Drug-releasing intravesical floating technology (DRIFT) for administration of sequential gemcitabine and docetaxel in non-muscle-invasive bladder cancer.

784 Background: Sequential intravesical gemcitabine and docetaxel (Gem/Doce) is a well-tolerated, efficacious option in a variety of settings for non-muscle invasive bladder cancer (NMIBC). This is widely utilized but nevertheless limited by logistics. We developed the Drug-Releasing Intravesical Floating Technology (DRIFT) to optimize Gem/Doce administration, enabling patient mobility and self-removal. Methods: The DRIFT device comprises a 3D-printed tube encased in a latex balloon, capped with a dissolvable polyvinyl acetate/polyvinylpyrrolidone endcap coated in Fluoropel, and a silicone endcap with a suture for patient removal. Device fabrication involved 3D printing, latex molding, and polymer coating. The procedure involves instilling intravesical gemcitabine through a 14-French catheter, followed by insertion of the deflated DRIFT device, which is then inflated with docetaxel and air to ensure buoyancy. After catheter removal, gemcitabine dwells temporarily and is subsequently voided, while the DRIFT device remains in the bladder, releasing docetaxel in a controlled, delayed fashion. Device performance was assessed in Merino sheep, dissolution kinetics were evaluated using methylene blue, and docetaxel tissue penetration was analyzed in rabbit bladder tissue using HPLC. Results: The DRIFT device enabled controlled, timed release of drug surrogate, with dissolution time of endcaps significantly prolonged by additional Fluoropel coatings as seen from 0 to 3 coatings (p < 0.0001). The device’s drug-release kinetics were evaluated by varying the inserted volume of methylene blue dye solution, used here as a drug analog. The time required for full dye release after cap dissolution significantly decreased when increasing the inserted volume from 1.5 mL to 2.0 mL (p = 0.03) and further to 3.0 mL (p = 0.003), indicating rapid dispersion and release capability at higher volumes. Volumes between 2.0 and 3.0 mL showed no significant differences, suggesting a plateau in release kinetics. In vivo, the device demonstrated reliable timed release and complete bladder dispersion of the surrogate in sheep, with retention until evacuation. Escalating gemcitabine pre-treatment concentrations enhanced subsequent docetaxel tissue penetration, with peak concentrations reaching 0.45 mg/mL versus 0.08 mg/mL with no pre-treatment. Extended gemcitabine pre-treatment dwell time further improved subsequent docetaxel delivery, achieving significant enhancement in deep tissue penetration (p = 0.0002). Conclusions: DRIFT enables controlled sequential delivery of Gem/Doce, reliably maintaining docetaxel containment for up to 120 minutes during gemcitabine pre-treatment. Future in vivo validation will establish safety and therapeutic potential.

Treatment of recurrent non-muscle invasive bladder cancer with UGN-301 (zalifrelimab) alone and in combination: A phase 1 dose escalation study.

752 Background: High-grade (HG) and intermediate-risk (IR) non-muscle invasive bladder cancer (NMIBC) often recurs/progresses. UGN-301 is an intravesical anti–cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody, zalifrelimab, in reverse thermal hydrogel (RTgel). This phase 1 study (NCT05375903) assessed safety, pharmacokinetics, and recommended phase 2 dose (RP2D) of UGN-301 alone or combined with either a fixed dose of intravesical UGN-201 (imiquimod; toll-like receptor 7 agonist) or gemcitabine (gem) for recurrent NMIBC. Methods: Adults with recurrent NMIBC (IR low-grade Ta/T1 [Arm A] or HG Ta/T1 and/or carcinoma in situ [CIS] ± Ta/T1) were eligible if they underwent tumor resection/fulguration pre-study treatment. Patients had 6 once-weekly intravesical instillations, with optional maintenance doses at 6, 9, and 12 months for recurrence-free (RF) Ta/T1 patients and CIS patients with complete response (CR). Treatment arms were UGN-301 monotherapy (Arm A), UGN-201 (200 mg)/UGN-301 (Arm B), or gem (1000 mg)/UGN-301, with assessments every 3 months post-initiation. Adaptive Bayesian logistic regression modeling guided dose escalation/selection of RP2D. Data cut: 9/5/25. Results: 20 patients received UGN-301 monotherapy (100 mg [n = 3], 300 mg [n = 6], 500 mg [n = 8], and 700 mg [n = 3]; Arm A), 11 received UGN-201/UGN-301 (300 mg [n = 3], 500 mg [n = 8]; Arm B), and 10 received gem/UGN-301 (300 mg [n = 3], 500 mg [n = 7]; Arm C). All but 1 (Arm A) completed 6 induction instillations. Arm A dose escalation reached maximum feasible dose. Treatment-emergent adverse events (TEAEs) occurred in 14 (70%), 9 (82%), and 7 (70%) patients in Arms A, B, and C, respectively. No dose-limiting toxicities or TEAEs leading to discontinuation arose. Zalifrelimab was detected in urine with comparable exposure duration across arms. Systemic zalifrelimab was detected in 2 patients (≥60-fold lower than intravenous administration). At UGN-301 doses ≥300 mg, 33.3% (2/6), 100% (3/3), and 33.3% (1/3) of CIS ± Ta/T1 patients had CR and 50% (5/10), 75% (6/8), and 71.4% (5/7) of Ta/T1 patients were RF at Week 12 when treated with UGN-301, UGN-201/UGN-301, or gem/UGN-301, respectively. Among those in Arm A who had CR or were RF at 3 months, 50% (1/2) of CIS ± Ta/T1 patients maintained CR up to 6 months and 60% (3/5) of Ta/T1 patients remained RF at 15 months. Likewise, 33.3% (1/3) of CIS ± Ta/T1 patients and 83.3% (5/6) of Ta/T1 patients in Arm B were free of disease through 9 months and are being followed. Conclusions: Intravesical UGN-301 in RTgel provided sustained bladder exposure to zalifrelimab with minimal systemic absorption, limiting CTLA-4-related toxicity. UGN-301 alone or with UGN-201 or gem showed favorable safety and preliminary efficacy, supporting further evaluation of 500 mg UGN-301. Assessment of response duration in combination arms is ongoing. Clinical trial information: NCT05375903 .

Aumolertinib with carboplatin–pemetrexed versus aumolertinib for nonsmall cell lung cancer with <i>EGFR</i> and concomitant tumor suppressor genes (ACROSS2): An open‐label, multicenter, randomized phase 3 study

ABSTRACT Third‐generation epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR‐TKIs) are standard first‐line therapy for advanced, EGFR ‐mutated nonsmall cell lung cancer (NSCLC). However, their benefit is limited in patients who have co‐existing tumor suppressor gene (TSG) mutations, highlighting a need for intensified strategies to improve outcomes. ACROSS2 (ClinicalTrials.gov identifier NCT04500717) is the first prospective, multicenter, randomized phase 3 study to compare the third‐generation EGFR‐TKI aumolertinib in combination with carboplatin–pemetrexed versus aumolertinib monotherapy in patients who had NSCLC with EGFR mutations and concomitant TSG mutations. In total, 126 patients were enrolled and randomly assigned to either combination therapy ( n  = 62) or monotherapy ( n  = 64). The primary end point was median progression‐free survival (PFS). At a median follow‐up of 25.3 months, combination therapy significantly prolonged median PFS compared with monotherapy (19.78 vs 16.53 months; hazard ratio, 0.58; 95% confidence interval, 0.34–0.97). Landmark PFS rates at 12, 18, and 24 months were 78.7% versus 65.3%, 67.2% versus 40.8%, and 41.0% versus 29.9%, respectively. Subgroup analyses demonstrated a clear PFS benefit in patients who had co‐existing tumor protein p53 ( TP53 ) mutations. Grade 3 or greater adverse events occurred in 25.9% of patients who received combination therapy versus 17.2% of those who received monotherapy; no drug‐related deaths were observed. Overall survival data were immature (data maturity, 4%). The ACROSS2 trial provides the first prospective evidence supporting a genotype‐directed, chemotherapy‐targeted intensification approach favoring aumolertinib plus carboplatin–pemetrexed for this molecularly defined population.

2D High‐Entropy Phosphorus Chalcogenides for Efficient Solar‐Driven CO ₂ Reduction to Ethylene

ABSTRACT Solar‐driven CO 2 reduction to value‐added ethylene (C 2 H 4 ) is considered as a promising and mild approach for storing solar energy into chemical bonds in fuels and chemicals, yet the thermodynamic obstacles related to CO 2 activation and C─C coupling significantly limit the practical application of this approach. Developing high‐entropy materials (HEMs), featuring multi‐principal elements and high configurational entropy, has emerged as a topic of considerable interest for addressing the aforesaid challenge. Herein, an emerging 2D high‐entropy phosphorus chalcogenide (HEPC), Cu(CrVInFeMnNi)P 2 S 6 , is rationally developed as a multifunctional photocatalyst via integrating multiple cations into the frame of CuCrP 2 S 6 . The Cu site in the HEPC serves as the dominant active center for activating CO 2 and achieving C─C coupling for solar‐driven CO 2 to C 2 H 4 . Besides, the multi‐metal matrix of Cr, V, In, Fe, Mn, and Ni sites leads to a multi‐site integrated electron‐donation effect in HEPC, where these different metal sites form a d‐band gradient arrangement in HEPC as well as act as the auxiliary electron‐donating centers for increasing the charge density of the Cu site and significantly boosting C─C coupling. As a result, Cu(CrVInFeMnNi)P 2 S 6 achieves an ultrahigh apparent quantum yield (AQY) of 7.4% at 475 nm for solar‐driven CO 2 to C 2 H 4 (a superior C 2 H 4 selectivity of 71%) under the sacrificial‐agent‐free condition, outperforming the vast majority of state‐of‐the‐art photocatalysts. This work pioneers the application of high‐entropy phosphorus chalcogenides in catalysis and provides a new idea for the development of efficient multifunctional materials.

Excited State Opto‐Ionic Reservoir Computing in Hybrid Perovskite Electrochemically‐Gated Luminescent Cells

ABSTRACT We introduce a neuromorphic reservoir computing concept that leverages the complex interplay between electronic and ionic states in lead halide perovskites to run algorithms by harnessing opto‐ionic modulation of photoexcited state populations. The system leverages the heterogeneous material microstructure and ultrafast spatio‐temporal electronic state dynamics in perovskite microcrystals to generate a high‐dimensional internal state space reservoir within the charge carrier populations. This reservoir exhibits complex, nonlinear, and adaptive behavior. The computation output is read directly from the photogenerated luminescence using diffraction‐limited resolution with 10 6 nodes per cm 2 and energy of 800 pJ per node‐operation. The system performs robustly in distinguishing 4‐bit pulse sequences with a mean accuracy of 87%, showcasing its potential for neuromorphic computing tasks. Our work reveals excited‐state dynamics as a platform for exploring nanoscale computing with photoactive materials, also at high speeds using ultrafast photophysics, with large potential for the development of next‐generation neuromorphic technologies.

Adjuvant Durvalumab in Completely Resected Early-Stage Non–Small Cell Lung Cancer

PURPOSE Adjuvant immunotherapy improved patient outcomes in two trials in completely resected non–small cell lung cancer (NSCLC), but with conflicting primary end point results. The Canadian Cancer Trials Group BR.31 trial evaluated adjuvant durvalumab in completely resected early-stage NSCLC. METHODS Following resection of stage IB (≥4 cm) to IIIA NSCLC (American Joint Committee on Cancer 7th Edition) and optional adjuvant chemotherapy, patients were randomly assigned 2:1 to durvalumab 20 mg/kg or placebo 20 mg/kg once every 4 weeks for 12 cycles. Random assignment was stratified by stage, extent of nodal dissection, tumor cell (TC) PD-L1 expression, adjuvant chemotherapy use, and center. The primary end point was investigator-assessed disease-free survival (DFS). Secondary outcomes included overall survival (OS), adverse events, and quality of life. The primary analysis was in the subgroup with cancers that had a PD-L1 TC expression ≥25%, no common activating EGFR mutations ( EGFR –), and no ALK gene rearrangements ( ALK –). Secondary analyses in hierarchical order included DFS in the subgroup whose tumors were EGFR–/ALK– with PD-L1 TC ≥1%, followed by all patients whose tumors were EGFR–/ALK–, followed by OS in the same primary and secondary subgroups in the same hierarchical order. RESULTS Of 1,415 patients randomly assigned, 1,219 (86%) had EGFR–/ALK– tumors: 815 randomly assigned to durvalumab and 404 to placebo. With a median follow-up of 60 months, there were no differences in DFS between patients assigned durvalumab (316) versus placebo (161) in the primary population (stratified hazard ratio [HR], 0.93 [95% CI, 0.71 to 1.25]; P = .64) or in the secondary populations. Grade 3 to 4 adverse events were higher in durvalumab-treated patients (D = 26% v P = 20%). CONCLUSION Adjuvant durvalumab following complete resection was not associated with improvement in DFS compared with placebo in EGFR –/ ALK – NSCLC, regardless of PD-L1 status.

Artificial intelligence in the diagnosis and prognosis of upper tract urothelial carcinoma: A comprehensive review of current evidence, methodological standards, and future directions.

870 Background: Upper tract urothelial carcinoma (UTUC) is a rare malignancy (5–10% of urothelial cancers) with challenging diagnosis and heterogeneous outcomes. Artificial intelligence (AI)—including radiomics, machine learning (ML), deep learning (DL), and digital pathology—has emerged as a tool to improve detection, risk stratification, and treatment planning. Methods: A systematic literature review (PubMed, Scopus, Embase) to August 2025 identified original human studies using AI for UTUC diagnosis or prognosis. Extracted data included sample size, AI methodology, validation type, and key performance metrics. Results: Twenty-one studies met inclusion criteria (2018–2025): CT urography radiomics (n = 12), prognostic perirenal fat/peritumoral texture analysis (n = 2), AI-assisted urine cytology (n = 2), DL-based digital pathology (n = 2), and multimodal models integrating imaging and clinical/molecular data (n = 3). Radiomics achieved AUCs of 0.80–0.94 for grading/staging; multimodal approaches improved predictive accuracy (ΔAUC ≈ +0.06). AI-assisted cytology reached sensitivity &gt; 85% for recurrence detection, and digital pathology predicted lymph-node status with AUC up to 0.85. Most studies were retrospective and single-center; only 14% reported external validation. Conclusions: AI shows strong promise for UTUC diagnosis and prognostication, particularly via CT radiomics and multimodal integration. However, clinical adoption requires multicenter prospective validation, standardized imaging/pathology workflows, regulatory approval, and cost-effectiveness evaluation.

Immune checkpoint inhibitor combinations in sarcomatoid metastatic clear cell renal cell carcinoma: A systematic review and meta-analysis.

483 Background: Sarcomatoid dedifferentiation (sRCC) in metastatic clear-cell renal cell carcinoma (mccRCC) confers aggressive disease and poor prognosis. We maintain a living meta-analysis of first-line immune checkpoint inhibitor (ICI)–based combinations in mccRCC (Riaz et al., Eur Urol Oncol 2021), which demonstrated improved survival with ICI-based regimens over sunitinib. Here, we present an updated synthesis focused on the comparative efficacy of ICI combinations in the sarcomatoid subset. Methods: A systematic search of MEDLINE, EMBASE, and CENTRAL through October 2025 was performed as part of our living meta-analysis of first-line mccRCC therapy. Eligible phase III RCTs compared ICI combinations (IO/IO or IO/TKI) versus sunitinib, including CheckMate 214, CheckMate 9ER, KEYNOTE-426, CLEAR/KEYNOTE-581, JAVELIN Renal 101, and IMmotion151. Extracted outcomes included overall (OS) and progression-free survival (PFS), and objective (ORR), complete (CR), and partial (PR) response rates. Random-effects meta-analyses generated pooled hazard ratios (HRs) for time-to-event outcomes and risk ratios (RRs) for response rates with 95% confidence intervals. Subgroup interaction analyses compared sarcomatoid versus non-sarcomatoid subgroups, with p &lt; 0.1 considered significant. Results: Six phase III RCTs (n = 5,121; 624 sarcomatoid) were included. Across all ICI-based combinations, ICI therapy improved outcomes versus sunitinib in both sarcomatoid and non-sarcomatoid disease. In the pooled analysis, the OS interaction favored sRCC meeting the prespecified significance threshold for subgroup analyses (HR 0.53 vs 0.68; p-interaction = 0.06 &lt; 0.10), while no significant interaction was seen for PFS. Response outcomes showed the strongest differential benefit, particularly with IO/TKI regimens. IO/IO results were directionally consistent but limited by smaller non-sarcomatoid samples. Conclusions: ICI-based combinations significantly improve survival and response outcomes versus sunitinib in mccRCC. Using a prespecified α = 0.10 for interaction testing, the pooled analysis showed a significant OS interaction and higher response rates in sRCC, indicating enhanced ICI sensitivity. These updated meta-analysis data support ICI regimens as the preferred first-line therapy for mRCC with sarcomatoid de-differentiation. Endpoint Regimen Subgroup (S = sarcomatoid; NS = non-sarcomatoid) Effect (95% CI) p-interaction PFS IO/IO S 0.51 (0.40–0.65) – IO/TKI S vs NS 0.48 (0.36–0.64) vs 0.46 (0.39–0.52) 0.81 OS IO/IO S 0.54 (0.07–4.42) – IO/TKI S vs NS 0.51 (0.17–1.48) vs 0.68 (0.30–1.58) 0.24 ORR IO/IO S 2.93 (0.49–17.37) – IO/TKI S vs NS 2.43 (1.84–3.21) vs 1.95 (1.67–2.28) 0.03 CR IO/IO S 3.81 (0.82–17.71) – IO/TKI S vs NS 5.93 (4.73–7.42) vs 2.85 (0.10–83.73) 0.007 PR IO/IO S 3.48 (1.70–7.11) – IO/TKI S vs NS 2.10 (1.78–2.47) vs 1.75 (1.18–2.61) &lt;0.001

Adding carboplatin to sequential taxane–anthracycline neoadjuvant chemotherapy shows improved event‐free and overall survival benefits in premenopausal women with triple‐negative breast cancer

Correction to “Photocatalytic Carbon Dots‐Triggered Pyroptosis for Whole Cancer Cell Vaccines”

Scalable Fabrication of High‐Efficiency Thin‐Film Perovskite Solar Cells in Air via Polymer‐Mediated Synthesis of α‐FAPbI ₃ Microcrystals

ABSTRACT Formamidinium lead triiodide (FAPbI 3 ) perovskite solar cells (PSCs) demonstrate exceptional photovoltaic performance but face critical stability challenges impeding commercialization. Herein, we integrate polypropylene glycol (PPG) into an inverse temperature crystallization process to synthesize highly stable α‐FAPbI 3 microcrystals, which retain phase purity for over six months in air. Our approach enables large‐scale production (nearly 50 g) of PPG‐coated α‐FAPbI 3 (target) microcrystals from low‐cost PbI 2 , with over 95% yield—sufficient to manufacture 23 m 2 of perovskite solar modules. Redissolving the target α‐FAPbI 3 microcrystals, followed by spin‐coating and annealing, yields target perovskite films with reduced defect density, minimized residual strain, and enhanced carrier transport. Mechanistic investigations reveal that colloidal species form upon the redissolution of target microcrystals which modulate the film crystallization kinetics, i.e. accelerating (100)‐oriented nucleation and growth. Employing this integrated strategy, a champion PSC with a power conversion efficiency (PCE) of 26.50% (certified 26.22%) was obtained at a laboratory scale (0.06 cm 2 ) and 22.66% for a module with an aperture area of 28.99 cm 2 , together with prolonged operational stability. This work opens new avenues for the industrial‐scale fabrication of efficient and stable large‐area perovskite photovoltaics.

Non‐Equilibrium Carbothermal Shock Upcycling: Atomically Precise Synthesis of Tailored SiC Polytypes and Novel Hybrid Graphene from Complex Composites

Abstract The complex, heterogeneous nature of challenging precursors, as seen in end‐of‐life wind turbine blades, typically comprises glass or carbon fiber‐reinforced polymer composites with polyvinyl chloride foam cores. This complexity poses a significant material synthesis challenge, particularly for achieving high‐value recovery with precise structural control. A transformative one‐step, ultrafast carbothermal shock (CTS) process is presented that selectively converts these intricate, unseparated composites into high‐value SiC polytypes or novel graphene structures. Leveraging ultrafast Joule heating, CTS enables remarkable atomic‐scale phase control, facilitating kinetic trapping of specific non‐equilibrium structures such as metastable 6H‐SiC and a unique hybrid AB‐turbostratic graphene. This unique hybrid graphene combines the high charge carrier mobility of AB‐stacked nanodomains with the enhanced mechanical interlocking of turbostratic nanodomains. This results in exceptional electrical conductivity (1791 S m −1 ) and substantial mechanical reinforcement (+21.8%) in composites, significantly outperforming conventional reduced graphene oxide. Multiscale characterization and simulations elucidate the atomic‐scale mechanisms driving this phase evolution and kinetic trapping. The study establishes a new paradigm for advanced materials synthesis from complex feedstocks, transforming critical waste into on‐demand functional materials with compelling environmental benefits and dramatically lower operational costs. This sets the stage for sustainable material innovation and a circular economy.

Outcomes with subsequent therapies post-enfortumab vedotin/pembrolizumab (EVP) in patients (pts) with advanced urothelial carcinoma (aUC): Analysis of the UNITE study.

705 Background: EVP is now the preferred first line (1L) treatment (tx) for aUC. However, outcomes with subsequent therapies are not well defined and require evaluation. Methods: We included pts from UNITE, a multi-institutional retrospective aUC cohort, who received ≥1 cycle of 1L EVP followed by second line (2L) tx. Median progression free survival (mPFS) and overall survival (mOS) from EVP and 2L tx start were estimated using Kaplan Meier (KM) method. Median follow up (mf/u) time from EVP and 2L tx start were calculated using reverse KM. Overall response rate (ORR) was investigator assessed. Odds of response and survival to each 2L tx were compared to platinum-based chemotherapy (PB CTx) using univariable logistic regression. Results: Among 377 EVP 1L pts: 114 (30%) are still on tx, 58 (15%) progressed without 2L tx, 23 (6%) went to hospice/passed, 18 (5%) tx break/surveillance, 60 (16%) stopped due to intolerance, 17 (5%) other (lost to f/u, local consolidation, insurance delay), and 20 (5%) had unknown EVP tx status; 68 (18%) received 2L tx: 26 PB CTx (39%) 14 (21%) sacituzumab govitecan (SG), 7 (10%) erdafitinib (erda), 6 (9%) trastuzumab deruxtecan (T-DXd), 2 (3%) taxane-based (TB) CTx, 5 (7%) clinical trial, 7 (10%) radiation (RT), 1 unknown. We excluded PB CTx + immunotherapy (n = 2), clinical trial pts, RT, and unknown tx. Among 53 evaluable pts, median age was 72 (range 56-97), majority were male (83%), White (93%), had primary bladder tumor (69%), pure urothelial histology (58%), and ECOG PS &lt; 1 (83%). Mf/u time from EVP start was 18 months (mos) (95% CI 14.5-20.5). ORR to 1L EVP was 45% (3 CR, 21 PR) and mPFS was 5.5 mos (95% CI 4.4-7.1). Mf/u time from 2L tx start was 10 mos (95% CI 5.8-13.4). 34 pts were evaluable for 2L ORR; 24% responded (2 CR, 6 PR). Both CRs and 3 PRs occurred with PB CTx; 1 PR occurred with SG, T-DXd, and erda. Across 2L tx: mPFS was 2.8 mos (95% CI 1.8-6.2) and mOS 9.0 mos (95% CI 6.0-NR) with 57% (n = 30) alive at last f/u. No clear association was seen between 2L tx and OS (p = 0.52), PFS (p = 0.14), or ORR (Table). Conclusions: We observed modest ORR and survival with 2L tx in the post-EVP setting for pts with aUC, highlighting the need for additional therapies. Results may inform prognostic estimates and help guide the design of post-EVP trials. Larger cohorts are required to validate these findings. 2L Tx ORR: tx vs PB CTx, OR (95% CI) mPFS, mo (95% CI) PFS: tx vs PB CTx, OR (95% CI) mOS, mo (95% CI) OS: tx vs PB CTx, OR (95% CI) PB CTx (N=24) 4.1 (1.8-NR) NR (6.0-NR) SG (N=14) 0.29 (0.03-3.0, p=0.30) 2.8 (1.8-NR) 1.1 (0.4-2.8, p=0.87) 6.7 (3.6-NR) 1.6 (0.6-4.5, p=0.34) Erda (N=7) 0.5 (0.04-5.7, p=0.58) 1.6 (0.9-NR) 1.4 (0.4-4.3, p=0.59) 2.1 (1.8-NR) 1.8 (0.5-6.8, p=0.39) T-DXd (N=6) 0.5 (0.04-5.7, p=0.58) 5.8 (2.5-NR) 0.8 (0.3-2.5, p=0.70) 8.5 (3.4-NR) 1.4 (0.4-5.4, p=0.60) TB CTx (N=2) 0 (0-inf, p=0.99) 0.7 (0.0-NR) 6.5 (1.4-31.2, p=0.02) NR (NR-NR) 0 (0-inf, p=1.00)

Survivorship outcomes of stage I testis cancer management.

605 Background: Patients with stage I testicular cancer (TCa) have excellent survival, and surveillance after orchiectomy is often preferred. Limited data exist on survivorship outcomes of surveillance versus adjuvant therapy. We compared systemic health outcomes between patients managed with surveillance and those treated with upfront therapy. Methods: Claims data from the OptumLabs Data Warehouse (2007–2022) identified stage I TCa patients managed with surveillance, chemotherapy, or radiation. Adjuvant therapy was defined as chemotherapy or radiation within 4 months of diagnosis with no further therapy. Chemotherapy codes were required within 42 days to ensure multiple cycles were not given. Propensity score–matched cohorts were created using logistic regression. A 3-year analysis evaluated new diagnoses of cardiopulmonary complications, metabolic syndrome, men’s health, psychological, and miscellaneous systemic conditions. Outcomes were stratified by treatment group. Chi-square tests and Cox regression analyses compared survivorship outcomes between adjuvant therapy and surveillance. Results: Eight-hundred forty-two patients had 3 years of coverage: 531 surveillance, 159 chemotherapy, and 152 radiation. No significant differences were found in cardiopulmonary, metabolic, psychological, or other systemic outcomes between therapy and surveillance (Table 1). Men’s health diagnoses were more frequent with chemotherapy (35.2% vs 23.9%, p=0.027) compared to surveillance. However, Cox regression showed no significant time-to-event differences on time-to-event analysis between groups. Conclusions: Adjuvant chemotherapy may be associated with higher rates of men’s health complications (infertility, erectile dysfunction, hypogonadism), but over time the risk is not significantly different than surveillance. Propensity-score matched survivorship outcomes: A) surveillance vs chemotherapy; B) surveillance vs radiation. A) Surveillance (N=159) Chemotherapy (N=159) p value Cardiopulmonary Complications 0.157 Yes 14 (8.8%) 22 (13.8%) No 145 (91.2%) 137 (86.2%) Men’s Health Complications 0.027 Yes 38 (23.9%) 56 (35.2%) No 121 (76.1%) 103 (64.8%) Metabolic Syndrome Complications 0.631 Yes 53 (33.3%) 49 (30.8%) No 106 (66.7%) 110 (69.2%) Miscellaneous Systemic Disorders 0.879 Yes 25 (15.7%) 26 (16.4%) No 134 (84.3%) 133 (83.6%) Psychological Diagnoses 0.401 Yes 29 (18.2%) 35 (22.0%) No 130 (81.8%) 124 (78.0%) B) Surveillance (N=152) Radiation (N=152) p value Cardiopulmonary Complications 0.682 Yes 12 (7.9%) 14 (9.2%) No 140 (92.1%) 138 (90.8%) Men’s Health Complications 0.630 Yes 51 (33.6%) 55 (36.2%) No 101 (66.4%) 97 (63.8%) Metabolic Syndrome Complications 0.086 Yes 42 (27.6%) 56 (36.8%) No 110 (72.4%) 96 (63.2%) Miscellaneous Systemic Disorders 0.650 Yes 25 (16.4%) 28 (18.4%) No 127 (83.6%) 124 (81.6%) Psychological Diagnoses 0.650 Yes 28 (18.4%) 25 (16.4%) No 124 (81.6%) 127 (83.6%)

Impact of serum LDH on clinical outcomes in patients with good-risk metastatic non-seminomatous germ cell-cell tumors (NSGCT).

588 Background: In pts with NSGCT, serum AFP, hCG and LDH play an important role in staging, risk stratification and choice of treatment (tx). Given its low specificity, NCCN recommends against systemic tx in pts whos’ only evidence of metastatic disease is an elevated LDH. Pts with serum LDH &lt;1.5x the upper limit of normal (ULN) are considered to have good risk disease while pts with LDH 1.5-10x ULN and &gt;10x ULN are considered to have intermediate (int.) and poor risk disease respectively. In pts stratified into int. or poor risk disease based on LDH levels alone, the optimal tx approach remains unknown; notably, NCCN recommends treating int. risk disease as good risk if the int. classification is based solely on LDH being 1.5-3ULN. Here, we describe clinical outcomes in pts with advanced NSGCT based on their LDH levels. Methods: The prospectively maintained Indiana University testicular cancer database was queried for pts with advanced NSGCT who had elevated LDH but otherwise good risk disease, including AFP and hCG levels. We grouped pts into LDH risk groups defined as: good risk (LDH&lt;1.5x ULN), int. risk (LDH 1.5-10x ULN), and poor risk (&gt;10x ULN). Chemo regimens were also grouped into risk groups defined as: good risk (BEPX3, EPX4, VIPX3) or int/poor risk (BEPX4, VIPX4, BEPX3+EPX1). The Kaplan-Meier method was used to analyze progression free survival (PFS) and overall survival (OS) using the log rank test to compare groups. Results: We identified 101 pts w/ NSGCT with elevated LDH but otherwise good risk disease, including AFP and hCG levels. 60 pts (59.4%) had good risk LDH, 40 (39.6%) had int. risk and 1 (1%) had poor risk LDH. In pts with good risk LDH, 57 (95%) were treated with good risk chemo and 3 (5%) were treated with int. or poor risk chemo. In the 41 pts with int/poor risk LDH, 34 (82.9%) were treated with good risk chemo while 7 (17.1%) were treated with int. or poor risk chemo. The 2y PFS in pts with good risk LDH compared to pts with int. or poor risk LDH was 91.7 vs 89.5% (p=0.67) and the 2y OS was 97.7 vs 94.6% (p=0.87). When evaluating all pts treated with good risk chemo, there was no difference in survival outcomes between LDH risk categories. In pts with LDH 1.5-3x ULN, 2y PFS was 96.3% vs 74.5% in pts with LDH&gt;3ULN (p=0.0274); 2 y OS was 96.3 vs 90.9% (p=0.63). 14 pts had an LDH &gt;3ULN. 9 were treated with good risk chemo and 5 were treated with int/poor risk chemo. 2 y PFS was 91.7% in the good risk LDH cohort vs 74.5% for pts with LDH &gt;3ULN(p=0.026); 2y OS was not significantly different. Conclusions: In pts with NSGCT with elevated LDH but otherwise good risk disease, there was no difference in 2y PFS or OS among pts with good risk LDH vs int/poor risk LDH. In all pts treated with good risk chemo regimens, survival outcomes were not statistically different between LDH levels. PFS was shorter in pts with LDH &gt;3ULN vs pts with good risk LDH but there was no difference in 2 y OS.

Integrating multimodal management and molecular profiling in a patient with BRAF V600E–positive melanoma and brain metastases

Binder‐Free, Self‐Supporting, and Highly Conductive Sulfide Electrolytes Enabling Superior Anode Stability (Adv. Mater. 18/2026)

Ultrasound in Women's Health: Mechanisms, Applications, and Emerging Opportunities

ABSTRACT Women's health remains inadequately served due to the historical predominance of males as the biological reference in medical research, leading to persistent sex‐based gaps in the understanding, diagnosis, and management of disease. As healthcare moves toward decentralization, e.g., through the collection of person‐generated health data, point‐of‐care diagnostics, and wearable devices, there is a critical need for tools tailored to women's unique conditions and presentations. Ultrasound technologies, recognized for their versatility and safety, have evolved from imaging to multifunctional platforms, with growing roles in diagnosis and therapy. Diagnostic ultrasound non‐invasively assesses anatomical features and functional information, and therapeutic ultrasound can perform targeted interventions, including neuromodulation, immunomodulation, thermal ablation, and drug delivery. By exploring the fundamental physical principles of ultrasound, including acoustic streaming, cavitation, and thermal interactions, and linking these mechanisms to cellular and tissue responses, this review highlights the capability of ultrasound to address female‐specific health disparities, especially in conditions that are undertreated or differentially expressed in women. Advancements in ultrasound technologies could significantly enhance clinical outcomes and improve the quality of life for women affected by conditions currently underserved by traditional medical interventions.

Urinary tumor DNA (utDNA) and circulating tumor DNA (ctDNA) in patients (pts) with muscle-invasive bladder cancer (MIBC) who received perioperative durvalumab (D) in NIAGARA.

636 Background: In NIAGARA (NCT03732677), addition of perioperative D to neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) demonstrated a significant improvement in event-free survival (EFS) and overall survival and a numerical increase in pathological complete response (pCR) vs NAC and RC alone in pts with MIBC. In a prior exploratory analysis, negative plasma ctDNA status after neoadjuvant treatment prior to RC (pre-RC) was associated with prolonged EFS but not pCR. Here we assess utDNA as a complementary approach in this setting. Methods: Cisplatin-eligible pts with MIBC (cT2-T4aN0/1M0) were randomized 1:1 to receive perioperative D plus NAC (cisplatin + gemcitabine) and RC (D arm) or NAC and RC alone (comparator [C] arm). Dual primary endpoints were EFS and pCR. Exploratory analysis of utDNA and ctDNA was completed using the personalized Signatera assay (Natera, Inc, Austin, TX, USA) at baseline (BL; n=205) and pre-RC (n=183). Results: Of 1063 pts, 265 (25%) comprised the biomarker-evaluable population (BEP; 134 D arm; 131 C arm). At BL, lower utDNA levels were associated with longer EFS (low vs high utDNA HR 0.65, 95% CI 0.40−1.04). From BL to pre-RC, utDNA+ rate decreased from 85% to 55%. utDNA clearance was associated with longer EFS (HR 0.24, 95% CI 0.09−0.62) and was 12% higher in the D vs C arm (39% vs 27%). Pre-RC utDNA status was associated with a pCR (utDNA−; 72% [55/76] vs utDNA+; 18% [17/96]). Pre-RC utDNA and ctDNA status differentially correlated with disease stage at RC, with utDNA+ correlating with noninvasive disease (&lt;T2N0M0) and ctDNA+ with invasive disease (≥T2N0M0) or systemic spread (N+ and/or M+) (Table). Estimated 24-month EFS rate was highest for pts with dual-negative status at pre-RC (utDNA− ctDNA−; 90%, 95% CI 83–97), followed by pts with utDNA+ only (utDNA+ ctDNA−; 75%, 95% CI 65–87), and was lowest for pts with dual-positive status (utDNA+ ctDNA+; 55%, 95% CI 41–75). Conclusions: This analysis suggests that lower BL levels and pre-RC clearance of utDNA are associated with better EFS and shows the addition of D to NAC increased utDNA clearance. utDNA status at pre-RC was more closely associated with pCR vs prior findings for ctDNA status. Combined pre-RC ctDNA and utDNA analysis was associated with EFS and may provide complementary insights into disease stage at RC. utDNA status could provide clinically relevant information on the primary bladder tumor, particularly in ctDNA− pts, highlighting the potential value of combining utDNA and ctDNA to inform future management of MIBC. Clinical trial information: NCT03732677 . Pre-RC utDNA and ctDNA correlation with disease stage a at RC. Status n T0N0M0 (%) &lt;T2N0M0 (%) ≥T2N0M0 (%) T any N+ M+ (%) ctDNA− utDNA− 72 73.6 12.5 12.5 1.4 ctDNA− utDNA+ 62 24.2 30.7 37.1 8.1 ctDNA+ utDNA− 6 16.7 0.0 0.0 83.3 ctDNA+ utDNA+ 33 6.1 0.0 48.5 45.5 a By locally collected pathological assessment.

Validation of a computational histology artificial intelligence (CHAI) prognostic biomarker in muscle invasive bladder cancer.

791 Background: Standard management for MIBC is radical cystectomy (RC). This traditionally includes neoadjuvant chemotherapy (NAC) which confers additional survival benefit. However, the absolute survival benefit of NAC is 5-10%, and only 30-40% of US MIBC cases receive NAC. These limitations underscore the need for a more personalized approach to identify patients most likely to benefit from treatment escalation or avoid overtreatment in those likely cured with RC alone. The CHAI biomarker (BM) platform has previously been used to develop a now commercially-available prognostic tool in non-MIBC. We aimed to validate a novel prognostic BM, previously developed specifically for MIBC using the CHAI platform, in a multi-institutional real-world (RWD) MIBC cohort. Methods: The CHAI platform applies deep-learning to extract quantitative histologic features from pre-treatment transurethral resection bladder tumor (TURBT) specimen H&amp;E-stained whole-slide images. The previously-developed MIBC BM was locked; the model outputs a continuous histologic risk signature and is dichotomized into unfavorable BM positive (BM+) and favorable BM negative (BM-) groups. Validation was done on an independent, held-out, retrospective, pooled, RWD of clinical T2N0M0 MIBC patients who underwent RC at multiple NCI-Designated Centers. Multivariate (MVA) Cox proportional hazards (CPH) models assessed associations with recurrence-free survival (RFS), cause-specific survival (CSS), and OS. Kaplan-Meier methods and log-rank tests were used for survival analysis. Results: Among 134 patients with MIBC, 67 (50%) patients received cisplatin-based NAC. The BM stratified patients into 67 (50%) BM+ and 67 (50%) BM-. Among patients who received NAC, pathologic complete response (pCR) was seen at RC among 6/29 (20%) BM+ vs 13/38 (34%) BM-. On MVA, controlling for age, sex, presence of carcinoma in situ (CIS), variant histology, and NAC, BM+ was significantly associated with inferior RFS (Table; HR: 2.70 [1.46, 4.97]), CSS (HR: 2.60 [1.29, 5.26]) and OS (2.29 [1.29, 4.04]), all p&lt;0.01. With 36-mo median follow up, at 2yr, BM+ had worse outcomes: RFS 50% vs 18%; CSS 25% vs 8.3%; OS 36% vs 15%. Conclusions: A histologic prognostic BM derived from pre-treatment H&amp;E TURBT slides was validated, stratifying clinical T2 MIBC patients by risk of RFS, CSS, and OS, even when controlling for NAC. Future efforts will evaluate the ability to predict which patients benefit the most from additional treatment. Such a tool could be used to optimize patient selection by identifying those most likely to benefit from perioperative therapies, and sparing those who may be cured with surgery alone. MVA for RFS. HR (95% CI) P value Biomarker 2.70 [1.46, 4.97] p=0.01* Age 1.03 [1.00, 1.07] p=0.06 Sex 1.24 [0.65, 2.35] p=0.52 CIS 0.69 [0.32, 1.50] p=0.35 Variant histology 1.15 [0.56, 2.35] p=0.71 NAC 1.54 [0.80, 2.95] p=0.20