Browse Articles

Efficacy and safety of lenvatinib plus pembrolizumab in patients with advanced renal cell carcinoma and venous tumor thrombus: Results from the first analysis of the PELET trial.

509 Background: Venous tumor thrombus (VTT) in patients with renal cell carcinoma (RCC) represents an aggressive disease feature associated with poor prognosis and management challenges. The efficacy of immunotherapy-based combinations in this subgroup remains insufficiently characterized. Methods: The PELET trial is an ambispective study enrolling adult patients with histologically confirmed advanced RCC and unresected VTT. Patients received lenvatinib 20 mg orally once daily in combination with pembrolizumab 200 mg intravenously every 3 weeks. The primary endpoint was a ≥30% reduction in thrombus size. Secondary endpoints included changes in thrombus level, progression-free survival (PFS), and safety. Results: Twenty patients were included, predominantly male (85%), with a median age of 58.5 years. Most had clear cell histology (90%) and no sarcomatoid features. The median baseline thrombus size was 6.55 cm, which decreased to 3.0 cm after at least 12 weeks of therapy (p < 0.001). A ≥30% reduction in thrombus size was achieved in 45% of patients, meeting the primary endpoint. Moreover, 35% experienced a reduction in thrombus length > 50%, and 45% demonstrated a decrease in thrombus level by at least one level. Thrombus response was not correlated with baseline thrombus size. Median PFS was not reached at the time of analysis. Grade ≥3 adverse events occurred in 15% of patients. Conclusions: Twenty patients were included, predominantly male (85%), with a median age of 58.5 years. Most had clear cell histology (90%) and no sarcomatoid features. The median baseline thrombus size was 6.55 cm, which decreased to 3.0 cm after at least 12 weeks of therapy (p < 0.001). A ≥30% reduction in thrombus size was achieved in 45% of patients, meeting the primary endpoint. Moreover, 35% experienced a reduction in thrombus length > 50%, and 45% demonstrated a decrease in thrombus level by at least one level. Thrombus response was not correlated with baseline thrombus size. Median PFS was not reached at the time of analysis. Grade ≥3 adverse events occurred in 15% of patients. Clinical trial information: KCRB-092025-01.

Second opinions and treatment guidance in non- or minimally metastatic testicular cancer: Is ChatGPT 5 non-inferior to expert recommendations?

596 Background: Testicular cancer is rare. Many cases presented to the German online second-opinion platform (eKonsil) involve non- or minimally metastatic stages. Expert reviews aim to optimize care quality. Large language models (LLMs) such as ChatGPT version 5 may support this process if their recommendations are shown to be non-inferior to expert consensus. Methods: Eleven eKonsil cases with primary non- or minimally metastatic disease were evaluated. Consensus treatment recommendations were generated by three testicular cancer experts (AH, JH, HS) based on the EAU guidelines. The same cases were entered into GPT5 with reference to the EAU guidelines on different days, in different countries, and by different individuals in September 2025. Recommendations by GPT5 and expert consensus were assessed independently by three urologists using a four-point Likert scale based on 21 validated evaluation criteria. Results: We obtained 99 evaluations of adherence to expert opinion. Expert recommendations for direct treatment were available for 81 evaluations. Primary therapy suggested by GPT5 was acceptable (no or insignificant deviations from experts) in 70% (57/81). GPT5’s adherence to expert opinion was similar for localized and metastasized cases (3.14 vs. 3.38; p Wilcoxon = 0.38). Adherence differed significantly depending on suggested therapeutic alternatives (p Chi2 < .01) with chemotherapeutic compounds being suggested correctly in 85% (74/87), radiation in 78% (47/60), active surveillance in 76% (50/66) and surgery in 59% (30/51). GPT5 acceptably identified missing information ahead of therapeutic suggestions in 82% (22/27) of relevant cases. In case of deficits, an acceptable path of diagnostics was suggested in 74% (20/27). Performance in identifying informational deficits did not vary by metastatic status (p Chi2 = 0.19) and performance in suggesting diagnostics was no better than in suggesting primary therapy (3.30 vs. 3.14; p Wilcoxon = 0.48). With GPT5 failing to reach clinically acceptable ratings in over 95% for any metric, it did not meet criteria of non-inferiority to experts. Conclusions: GPT5-generated second-opinion recommendations for patients with non- or minimally metastatic testicular cancer cannot be assumed to be non-inferior to expert consensus. Caution is needed when using GPT5 as an assistant to screen cases for missing information or to generate therapeutical suggestions, particularly with surgical paths being involved. This study shows that LLMs, even when provided with guidelines, require more training and expert validation currently remains essential.

Temporal trends in mortality from bladder cancer with chronic kidney disease in the United States, 1999–2023: A population-based analysis.

649 Background: Bladder cancer frequently coexists with chronic kidney disease (CKD), a comorbidity that may affect treatment options and survival. Despite awareness of multimorbidity in oncology, national mortality trends for patients with both bladder cancer and CKD have not been well explored. Objective: To evaluate long-term trends in mortality due to bladder cancer with CKD in U.S. from 1999-2023 across demographic and geographic subgroups. Methods: Mortality data were retrieved from the CDC WONDER database using ICD-10 codes C67 (Neoplasm of bladder) and N-18 (CKD). We analyzed age-adjusted mortality rates (AAMR) per 100,000 population across sex, race, census region and urbanization level and crude rates (CR) across age groups (25-85+). Trends were analyzed through Joinpoint regression to estimate the Annual Percent Change (APC) and Average Annual Percent Change (AAPC) with 95% confidence intervals (CIs). Results: Between 1999 and 2023, 111947 deaths were attributed to bladder cancer with CKD, Overall AAMR (32.1) increased significantly (AAPC = 1.09%, p = 0.006). Males had higher AAMR (43.9) than females (27.3). Mortality rose significantly among both males (AAPC = 0.8%, p=0.02) and females (AAPC=1.2%, p=0.008). Black/African Americans showed highest AAMR (57.8). However, Trends increased significantly among White individuals (AAPC = 1.5%, p < 0.001). Regional variation in AAMRs was evident (Midwest: 34.1, South:33.01, West:30.7, Northeast:29.7). Mortality increased in the Midwest (AAPC=1.57%) and south (AAPC=1.01%).West Virginia had the highest AAMR (43.4) among states. Rural areas had a significant rise (AAPC = 1.70%, p = 0.001), while urban areas remained stable. The highest increase occurred in the 75–84 (AAPC = 0.9%, p = 0.02) and 85+ age group (AAPC = 3.04%, p < 0.001). Conclusions: The findings from this analysis highlight growing mortality disparities among patients with concurrent bladder cancer and CKD, particularly in older white males, and rural populations. Focused nephro-oncology interventions are warranted in high-risk groups.

Serial proteomic characterization of plasma extracellular vesicles (EV) to identify changes that predict outcomes in metastatic castrate-resistant prostate cancer (mCRPC) patients receiving ¹⁷⁷ Lu-PSMA-617.

258 Background: Extracellular vesicles (EVs) in plasma offer a minimally invasive window into tumor biology. We hypothesized that deep proteomic profiling of plasma EVs can characterize dynamic molecular changes and predict outcomes in patients with mCRPC treated with 177 Lu-PSMA-617. Methods: Of 100 prospectively enrolled patients receiving 177 Lu-PSMA-617 (Arafa, et al. ASCO 2025), 58 men had serial (baseline and on-treatment) plasma samples. EVs were isolated using differential ultracentrifugation and analyzed by shotgun mass spectrometry. Protein expression patterns (e.g. PSMA, B7-H3) were categorized as undetected at both baseline and follow-up (U->U) or detectable at both timepoints (D->D). Relative protein expression changes were dichotomized as increasing (>10% increase) versus no change/decreasing (not a >10% increase). Surface protein changes were quantified and associations with overall survival (OS) were sought using log-rank tests. Pathway-level analysis was conducted using pre-ranked gene set enrichment analysis (GSEA) to identify pathways associated with outcomes. Results: A total of 6,306 proteins were identified, with about 20% mapping to key cell-surface markers including PSMA, B7-H3, Trop-2, and STEAP1. When patients were stratified by the detection of the key 4 surface proteins (0–1, 2, or 3–4); increasing numbers of detected proteins were associated with progressively shorter OS using both baseline and follow-up samples (p<0.0001 for both). Outcomes based on serial protein detection (D->D) or non-detection (U->U) patterns are shown in the Table. Increases in EV-derived PSMA (HR 2.7, 95% CI 1.3–5.9, p=0.002), Trop-2 (HR 4.8, 95% CI 1.5–15.7, p<0.0001), and STEAP1 (HR 5.7, 95% CI 1.6–20.2, p<0.0001) were associated with worse OS, with a similar trend for increasing B7-H3 (HR 1.7, 95% CI 0.8–3.4, p=0.16). In GSEA analysis, fatty acid metabolism (NES=1.8, q=0.004), Hedgehog signaling (NES=1.7, q=0.02), bile acid metabolism (NES=1.6, q=0.03), and MYC targets (NES=1.5, q=0.04) were enriched in on-treatment samples from progressors, while angiogenesis (NES=1.6, q=0.02) was enriched in on-treatment samples from responders. Conclusions: On-treatment persistent detection or upregulation of EV-derived surface proteins (PSMA, B7-H3, Trop-2, and STEAP1) was associated with inferior overall survival in mCRPC patients treated with 177 Lu-PSMA-617. These findings highlight the potential clinical utility of dynamic plasma EV proteomics for prognostic stratification and clinical trial selection. U->U (days) D->D (days) OS HR (difference) P PSMA 297 141 4.52 0.002 B7-H3 NR 175 7.3 p<0.0001 Trop-2 247 79 5.27 p<0.0001 STEAP1 268 79 10.76 p<0.0001

Human organoids as 3D in vitro platforms for drug discovery: opportunities and challenges

Atomically Tailored Fe‐Dy Dual‐Atom Sites With 3d‐4f Orbital Coupling for Enhanced Bifunctional Oxygen Electrocatalysis

ABSTRACT Efficient bifunctional oxygen electrocatalysts are crucial for overcoming the high overpotentials and sluggish kinetics of the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) in rechargeable zinc‐air batteries (ZABs). Iron‐based single‐atom catalysts exhibit promising ORR activity, however, their excessive adsorption of oxygen‐containing intermediates, together with the scaling relationships between these intermediates, limits their bifunctional performance. Herein, a unique Fe‐Dy dual‐atom catalyst (FeDy‐DAC) is constructed, leveraging the strong orbital coupling between Fe‐3d and Dy‐4f orbitals to precisely modulate the electronic structure of the Fe sites. This modulation effectively weakens the overly strong adsorption of oxygen‐containing intermediates on Fe sites, facilitating * OH desorption. Meanwhile, the unique dual‐site co‐adsorption configuration of * O drives efficient O─O bond coupling, ultimately leading to a significant reduction in the rate‐determining energy barriers of both ORR and OER. Therefore, FeDy‐DAC exhibits outstanding bifunctional catalytic performance, with a high ORR half‐wave potential of 0.90 V and a narrow ORR/OER potential gap of 0.68 V. Moreover, FeDy‐DAC maintains stable operation for over 2500 h in ZABs, showcasing excellent long‐term durability. This work provides a novel strategy and insights for high‐performance bifunctional electrocatalyst design.

Network meta-analysis of second- and later-line therapies in advanced renal cell carcinoma: A comparative effectiveness approach.

504 Background: Despite advances with immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor (VEGF)-targeted therapies, most patients with advanced renal cell carcinoma (RCC) progress after first-line treatment. Optimal sequencing of subsequent therapies remains uncertain due to the lack of head-to-head randomized controlled trials (RCTs). This network meta-analysis (NMA) compared the efficacy and safety of second- and later-line systemic treatments. Methods: PubMed, Embase, and Cochrane were searched for RCTs enrolling patients with advanced RCC who had received ≥1 prior systemic therapy. Eligible studies evaluated approved or investigational ICIs, VEGFR tyrosine kinase inhibitors, mTOR inhibitors, or their combinations. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and grade ≥3 treatment-related adverse events (TRAEs). A frequentist NMA using a random-effects model (netmeta, R software ver. 4.5.0) generated pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs). Treatments were ranked using P-scores, and funnel plots assessed small-study bias. Results: Seventeen RCTs comprising 8,052 patients were included. Among 15 trials with available data, 62.4% of patients had only one prior line of therapy. Lenvatinib + everolimus (HR 0.49 vs placebo) and atezolizumab + cabozantinib (HR 0.56 vs placebo) demonstrated the greatest OS benefit. Compared with other active regimens, lenvatinib + everolimus significantly improved OS versus everolimus and temsirolimus monotherapy, ranking highest for OS (P-score = 0.88). For PFS, all active therapies outperformed placebo; lenvatinib + everolimus ranked first (P-score = 0.99) and improved PFS compared with all other therapies except telaglenastat + cabozantinib, ranking first (P-score = 0.89). Telaglenastat + cabozantinib (P-score = 0.89) and cabozantinib alone (P-score = 0.86) ranked second and third, respectively. Lenvatinib + everolimus also ranked first for ORR (P-score = 0.94), followed by belzutifan (P-score = 0.86). Combination regimens provided the greatest efficacy but were associated with higher rates of grade ≥3 TRAEs, whereas ICI monotherapy demonstrated the most favorable safety profile. No evidence of small-study bias was detected. Conclusions: In this NMA, lenvatinib + everolimus demonstrated the greatest overall efficacy across OS, PFS, and ORR, outperforming all other therapies except telaglenastat + cabozantinib in PFS. These findings suggest lenvatinib + everolimus as the leading option for second- or later-line therapy in advanced RCC. However, results should be interpreted with caution and warrant confirmation in future large, head-to-head randomized trials.

Real-world outcomes of systemic therapy in penile cancer: A single-center experience from a tertiary referral hospital in Mexico.

7 Background: Systemic strategies for penile cancer remain poorly defined across heterogeneous stages. We report real-world outcomes from a single-institution retrospective cohort, focusing on progression-free survival (PFS), overall survival (OS), and response rates. Methods: We reviewed all penile cancer cases treated at the National Cancer Institute of Mexico (2013–2024). All clinical stages were eligible per the 2018 TNM classification. Patients who received chemotherapy in any setting and those who did not were included. Survival was estimated with Kaplan–Meier; prognostic factors for PFS/OS were assessed using Cox proportional hazards models. Objective response rate (ORR) and disease control rate (DCR) were abstracted from routine clinical documentation. Results: A total of 156 patients were included; mean age 56.5 years (range, 27–87). Squamous cell carcinoma predominated (98.7%); two patients (1.3%) had neuroendocrine tumors. Grade 2 was most common (n=119, 76.3%). Stage distribution: I (n=14, 9%), II (n=37, 23.7%), III (n=41, 26.3%), IV (n=62, 39.7%), and 0/is (n=2, 1.3%). HPV status was positive in 9 (5.8%), negative in 2.6%, and unknown in 91.7%. Neoadjuvant therapy was delivered to 26 patients (16.7%): PF was most common (n=13, 50%), followed by concurrent chemoradiotherapy (n=6, 23.1%) and TIP (n=4, 15.4%). In this subgroup, ORR was 50% (13/26), DCR 66% (17/26), and median PFS 13 months (95% CI, 11.2–14.7). Adjuvant treatment was given to 28 patients (17.9%): chemotherapy in 11 (39.3%), chemoradiotherapy in 9 (32.1%), and radiotherapy in 8 (28.6%). Among stage IV cases, 31 patients (19.9%) were M1; the most frequent metastatic sites were lung (n=18, 52.9%) and non-regional lymph nodes (n=16, 47.1%). In the overall cohort, median OS was 155 months (95% CI, 131–179). Comparing patients who received neoadjuvant therapy with those who did not showed no statistically significant OS difference (HR 0.59; 95% CI, 0.31–1.14; 18-month comparison). Among M1 patients who received at least one line of systemic therapy, median OS was 18.4 months (95% CI, 10.3–26.5). Conclusions: In this single-center cohort spanning all stages, squamous histology predominated and nearly 40% presented with stage IV disease. Neoadjuvant therapy achieved a 50% ORR and 13-month PFS but did not improve OS. Outcomes in M1 disease remain modest, underscoring the need for prospective trials to refine systemic strategies across stages.

Divergent biology and outcomes of somatic transformations (SM) in germ cell tumors (GCT).

613 Background: Somatic transformation (SM) of teratoma, defined by dedifferentiation and expansile overgrowth of teratomatous elements, is rare yet clinically significant due to its aggressive behavior and metastatic potential. Differences by primary site, time to transformation, and outcomes remain poorly characterized. Optimal management and molecular insights are underexplored. Methods: We reviewed clinical and molecular data of all patients diagnosed with SM from June 2016 to May 2025. Time from initial GCT diagnosis to SM detection was defined as time to somatic transformation (TST). SM detected before first relapse was classified as “de-novo,” all others as “evolved.” Overall survival (OS) was measured from SM detection. Descriptive statistics, Kaplan-Meier estimates, and Cox proportional hazards analyses were used. Results: Seventy-two patients were identified: 40 (56%) testicular and 24 (33%) mediastinal primaries. Over 90% of mediastinal tumors showed sarcomatous transformation and were de-novo. Rhabdomyosarcoma (RMS) was enriched in de-novo cases with faster TST, whereas adenocarcinoma predominated in evolved cases with longer TST. (See Table) Primitive neuroectodermal tumor (PNET) histology carried the worst prognosis compared to non-PNET SM (median OS 1.8 vs 8 years; HR 1.94, 95% CI 0.88–4.31; p = 0.1), particularly in testicular primaries (HR 3.81, 95% CI 1.28–11.32; p = 0.01). Relapses within three months of chemotherapy in de-novo SM were associated with inferior OS (HR 2.65, 95% CI 1.01–6.92; p = 0.04). Among those who progressed, salvage surgery was associated with improved OS (HR 0.28, 95% CI 0.13–0.59; p = 0.008). Genomic data was available in 40 patients (55%). TP53 mutations occurred in 35%, enriched in extragonadal primaries (OR 20.8; 95% CI 2.3–184.4; p = 0.0006) and associated with faster progression (HR 3.6; 95% CI 1.7–7.9; p = 0.0009) without OS differences. PTEN/AKT pathway mutations (32%) correlated with sarcomatous transformation (OR 5.11; 95% CI 1.1–37.23; p = 0.05). ctDNA was detected in three relapsed patients; two cleared with salvage therapy, one remains on treatment. Conclusions: SM in GCT demonstrates temporal, histologic, and molecular distinctions across primary sites. PNET histology and chemotherapy resistance in de-novo SM portend worse outcomes. The feasibility of salvage surgery is consequential for those who experience relapse. Extragonadal SM, particularly mediastinal primaries, are enriched for TP53 mutations, and sarcomatous elements. Feature OR/95%CI/ p value Testicular vs extragonadal primaries: sarcomatous elements Frequency (%) 15/40 (37%) vs 27/32 (84%) OR: 9; 95% CI: 2.85–28.4; p < 0.0001 RMS vs non-RMS Mean TST in years (SD) 0.2 (0.5) vs 4.6 (9.4) p = 0.0007 Adenocarcinoma vs non-adenocarcinoma Mean TST in years (SD) 19.4 (13.3) vs 2.4 (6.7) p = 0.02

Response of venous tumor thrombi in renal cell carcinoma to immune checkpoint inhibitor therapy: A multicenter retrospective cohort study.

496 Background: Approximately 10% of patients with renal cell carcinoma (RCC) have an associated venous tumor thrombus (VTT), the presence of which impacts surgical management and increases perioperative risk. Historical systemic therapy regimens had limited success in downsizing VTT; however, the impact of immune checkpoint inhibitors (ICIs) on VTT shrinkage is unknown. Our primary objective is to assess VTT shrinkage comparing responses to ICI versus non-ICI regimens. Methods: This multicenter retrospective cohort study included patients with RCC and VTT from 2006-2024 who received upfront systemic therapy. Patients were evaluated at tertiary referral centers across Mayo Clinic Rochester, Florida, and Arizona. Systemic therapies were categorized as ICI versus non-ICI regimens. VTT length was quantified by distance relative to the superior border of the renal vein ostium. The primary outcome was change in VTT length on serial imaging as measured by absolute length reduction (cm), RECIST version 1.1 criteria, and Mayo VTT level reclassification. Linear mixed-effect models (LMMs) identified associations with VTT shrinkage and clinicopathologic features. Results: A total of 108 patients with median age 65 years (IQR 57-71) were included, of whom 49 (45%) received ICI regimens. ICI regimens were associated with greater VTT shrinkage (1cm vs 0.1 cm, p=0.025), increased RECIST responses (51% vs 32%, p=0.046), and a higher rate downstaging per Mayo VTT level (33% vs 12%, p=0.008) compared to non-ICI regimens. On multivariable LMM analysis, ICI regimens remained more likely to result in VTT shrinkage compared to non-ICI regimens (-0.12 cm/month, 95% CI –0.24-0.00, p=0.046). Absence of abdominal lymphadenopathy was also associated with VTT shrinkage (-0.18cm/month, 95% CI -0.06- -0.30, p=0.004). Initial Mayo VTT level, IMDC risk, and number of metastatic sites were not associated with VTT shrinkage. Conclusions: Treatment with ICI-regimens resulted in VTT shrinkage and Mayo VTT level reduction. This is a particularly important area of exploration as radical nephrectomy and tumor thrombectomy carry up to a 40% risk of peri-operative major complications. These data support using ICI regimens for patients with RCC with VTT who are not candidates for upfront surgery and prioritizing ICI regimens in neoadjuvant clinical trials.

Innovative antibody therapeutic development in China compared with the USA and Europe

High‐Precision In‐Sensor Computing Reaching Up to 10 Bits

ABSTRACT The growing demand for data‐centric and intelligent applications calls for seamless integration of sensing, memory, and computation within a single device to improve efficiency, reduce energy consumption, and enable real‐time processing. However, the adoption of such in‐sensor computing is hindered by limited reconfigurability, which constrains its use in complex tasks beyond basic image processing. Here, we identify cascaded switching driven by interactions among differently polarized domains as a fundamental barrier to achieving high reconfiguration precision. To overcome this, we introduce a polarization energy focusing strategy, enabled by a tailored compositional distribution of ferroelectric and semiconductor materials. This approach yields the first in‐sensor computing device with reconfigurable precision reaching 10 bits. Its capability in both conventional image processing and advanced reconstructed optics is demonstrated, highlighting its potential as a high‐linearity, high‐precision platform for next‐generation intelligent systems.

From innovation to evidence: Trends in AI/ML clinical trials in GU oncology, 2010-2025.

337 Background: Genitourinary (GU) cancers generate complex multimodal data — imaging, pathology, genomics, and clinical variables — that challenge clinical decision-making. Artificial intelligence/machine learning (AI/ML) may enhance care by synthesizing these data points. Yet, the scope, design, and real-world impact of AI/ML GU trials remain unclear. Methods: We queried ClinicalTrials.gov (as of 8/7/2025) for adult GU oncology trials between 2010-2025 using a predefined set of AI/ML keywords. Trials using AI/ML were identified by manual review and classified as “AI/ML primary” (i.e., AI/ML tool development or validation) and/or “therapeutic” (delivering cancer therapy). All classifications — including each trial’s primary AI/ML purpose and data modality — were guided by a standardized codebook and independently coded by two reviewers (Cohen’s κ = 0.48-0.69), with discrepancies adjudicated by a third. PubMed (searched 10/6/2025) was queried by NCT ID to identify peer-reviewed publications and assess dissemination lag. Descriptive statistics were used to summarize trial characteristics, and logistic regression analyses were performed in Stata to assess temporal trends. Results: Of 127 AI/ML GU trials, 107 (84%) were initiated between 2020 and 2025, comprising 2.8% of total GU trials during this period (Table). From 2020–2025, the odds of a GU trial involving AI/ML increased annually (OR 1.28; 95% CI 1.11-1.48; p<0.001). Most trials focused on prostate (n=68, 54%) or bladder (n=25, 20%) cancers and were conducted in China (n=37, 29%) or the USA (n=29, 23%). Common AI/ML applications included detection/diagnosis (n=64, 50%), risk stratification (n=24, 19%), and treatment planning/decision support (n=12, 9%). Radiology imaging was the predominant data modality (n=63, 50%), followed by multimodal (n=32, 25%) and clinical data/text (n=10, 8%). Among 102 AI/ML primary trials, only 33 (32%) were interventional, 12 (12%) were randomized, and 7 (7%) were therapeutic. Just 14 (14%) had a PubMed-indexed publication, of which one was randomized, and none were therapeutic. Conclusions: AI/ML trials in GU oncology are growing rapidly but remain a small fraction of the overall trial activity. Most focus on diagnostics rather than therapeutic integration, and publications remain rare. To realize the promise of AI/ML, future efforts must emphasize trial design rigor, translation into therapeutic applications, and timely dissemination — paralleling the evolution of immunotherapy a decade ago. Temporal trends in GU AI/ML trials (2020-2025). Year Total AI/ML trials (n) Therapeutic AI/ML trials (n) Total GU trials (n) % of GU trials that were AI/ML 2020 5 0 655 0.8 2021 13 0 679 1.9 2022 20 2 605 3.3 2023 21 0 728 2.9 2024 30 2 717 4.2 2025* 18 2 465 3.9 Total 107 6 3849 2.8 *Cutoff 8/7/2025.

Clinical outcomes of neoadjuvant intravesical mitomycin-C therapy administered immediately prior to TURBT in NMIBC: Over three years of follow-up data from a randomized phase II trial.

771 Background: Immediate neoadjuvant intravesical chemotherapy (INAIC) with mitomycin C (MMC), administered before transurethral resection of bladder tumor (TURBT) in non-muscle invasive bladder cancer (NMIBC) patients, may prevent reimplantation of free-floating cancer cells dislodged during piecemeal resection by reducing their tumorigenic potential preoperatively and increasing MMC concentration in the resected tumor bed. We previously reported per-protocol analysis that showed a 63% recurrence risk reduction with our strategy versus TURBT alone, though not statistically significant (P = 0.11), likely due to limited follow-up (PMID: 36250938). We updated our preliminary analysis to include oncological outcomes over three years for assessing the strategy's long-term sustainability. Methods: This single-center, randomized phase II trial was conducted at the National Cancer Center of South Korea between August 2016 and December 2020 (IRB No. NCC2016-0168). The intervention group received two 40 mg/20 mL doses of MMC one day before and four hours prior to TURBT. The control group underwent standard TURBT only; no patients in either group received immediate post-operative intravesical chemotherapy (IPOIC). The primary endpoint was three-year RFS; secondary endpoints included independent risk factors for recurrence, progression-free survival (PFS), and cystectomy-free survival (CFS). Statistical analyses used two-tailed tests, with p-values < 0.05 deemed significant. Results: The updated analysis involved 33 intervention and 38 control patients, with similar median follow-up times of 60 and 60.4 months, respectively (P = 0.65). The groups were well matched, with no significant differences in demographics, tumor features, risk classifications, or adjuvant intravesical therapies (all P > 0.05). During a prolonged follow-up period, recurrence occurred in 9.1% (3/33) in the intervention group vs. 31.5% (12/38) of controls. Two INAIC doses with MMC cut recurrence risk by 77% vs. TURBT alone, with 3- and 5-year RFS rates of 90.7% vs. 78.6% and 75.3%, respectively, confirming sustained benefits (P = 0.01). During follow-up, 15.8% (6/38) of control patients progressed and 7.8% (3/33) had cystectomy (ypT0N0, ypT2N0, pT1N0); none in the intervention group did. Two doses of INAIC with MMC significantly improved 3- and 5-year PFS rates compared to controls (100% vs. 92.1% and 85.8%; HR 0.078, P = 0.014) and 3- and 5-year CFS rates (100% vs. 97.4% and 91.1%; HR 0.078, P = 0.014) using Firth’s penalized likelihood method. Conclusions: Our up-to-date analysis further supports using INAIC with two MMC doses for favorable mid- to long-term oncological outcomes in diverse NMIBC patients. Clinical trial information: NCT03058757 .

Addressing barriers to adopting first-line standards of care in la/mUC: A community practice-informed initiative.

660 Background: Rapid advances in 1L therapy for locally advanced/metastatic urothelial carcinoma (la/mUC) have shifted standards and offer new opportunities to improve outcomes. These advances also introduce complexities in clinical decision-making including eligibility, sequencing, and AE management. In the community setting, these challenges are amplified by variations in resources, infrastructure, and care coordination. To address these challenges and support adoption of evolving standards of care, a targeted educational initiative was developed for GU oncology teams. Methods: A curriculum comprising two 30-minute CME sessions and a community-based practice-pattern analysis (PPA) survey was developed in collaboration with the Large Urology Group Practice Association (LUGPA) and the Bladder Cancer Advocacy Network (BCAN). The education launched on Medlive.com in April (Session 1) and September 2025 (Session 2) and will remain available for 12 months. Session 1 focused on guideline updates, practice implications, and AE mitigation in 1L la/mUC. The PPA survey, deployed in June 2025, assessed real-world treatment patterns and barriers to integrating newer regimens and informed development of Session 2, which highlighted strategies to address identified barriers. Outcomes were measured through pre-/post-activity assessments and evaluations. Results: To date, over 1,800 clinicians have participated in Session 1, with 93% designating their specialty as oncology/urology. Session 1 demonstrated a ~25% confidence gain in both individualizing 1L treatment selection and counseling patients on newer regimens. Most learners cited sequencing as the main challenge (25%), followed by AE management and patient counseling. Intended changes included adopting EV+P in 1L–eligible patients (42%) and reevaluating the role of platinum-based chemo (32%) in this setting. PPA survey findings (n = 95; 77% community-based) revealed cisplatin eligibility as the most influential factor guiding 1L treatment selection (65%). Among cis-eligible patients, 71% preferred platinum-based chemo ± IO, indicating lagging adoption of guideline-preferred therapy. The greatest barrier to adopting ADC+IO regimens was AE management (56%). Conclusions: A tethered, two-session curriculum, augmented by a PPA survey, demonstrated broad engagement and measurable improvements in confidence for 1L decision-making in la/mUC. Survey findings highlight a transitional phase in community practice and the need for pragmatic tools to (1) operationalize ADC+IO eligibility, (2) standardize AE monitoring/mitigation strategies, and (3) clarify sequencing. These results underscore the critical role of outcomes-driven education in closing the gap between emerging evidence, guidelines, and real-world implementation.

Emotional concerns due to kidney cancer (KC) and disparities in patient support across North America (NA): Results from the International Kidney Cancer Coalition (IKCC) global patient survey (GPS).

490 Background: Patient support services are an important component of care for people with KC that can lead to better outcomes, improved emotional wellbeing, and a higher quality of life. The IKCC and its network have conducted a biennial GPS since 2018 to assess patient/caregiver experiences on KC burden, diagnosis, and management, to identify unmet needs and country variances, and guide recommendations and actions to close gaps. We present 2025 GPS data on emotional wellbeing and patient support resources across NA compared to global responses. Methods: An IKCC steering committee of patient advocates, medical experts and the Picker Institute designed the 2025 GPS targeting KC patients and caregivers. It was cognitively tested, translated into 16 languages, and hosted online and on paper. Data were independently analyzed using cross-tabulations. Results: Between Sept 24 and Nov 15, 2024, 2677 responses were received from patients (n = 2049) and caregivers (n = 628) from 46 countries, including Canada (n = 266), the USA (n = 220), and Mexico (n = 131). In the last 12 months, 85% of respondents globally experienced an impact to their emotional wellbeing due to KC or kidney growth. Emotional concerns were observed across all stages of disease. The most common were disease-related anxiety (50%), fear of recurrence (49%), sadness/depression (36%), fear of dying (35%), and difficulty in daily living, on the job or in school (23%). Globally, only 45%–66% of respondents discussed these emotional concerns with an HCP, and 12%–20% of conversations were reported as unhelpful. Variations were observed across countries in NA; notably, more respondents from Mexico discussed emotional concerns with an HCP compared to Canada and the USA. Globally, 50% of respondents accessed a patient support group, either in person or online, with variations across NA. Overall, 47% said they were helpful, 3% said they were not helpful, 31% did not need a patient support group, and 16% could not find one. Patient organization websites (28%) and online support groups (27%) were considered most helpful, with variations observed across NA. Respondents indicated a desire for more counselling and/or psychological support, in-person support, peer-to-peer support, and online support. Conclusions: Most respondents in NA experienced an impact to their emotional wellbeing due to KC; however, many did not use a patient support group or discuss their emotional concerns with an HCP, particularly in Canada and the USA. Improved communication is needed between patients/caregivers and HCPs to address emotional concerns. Referrals to trusted patient support groups can reduce existing gaps in emotional support services, particularly with in-person support groups and counselling/psychological support.

Induced proximity-based therapeutic modalities

Molecular Bridge Regulation of Buried Interface in Perovskite Solar Cells

ABSTRACT Defects at the buried interface represent a critical challenge that impedes further improvements in both the performance and scalable manufacturing of perovskite solar cells (PSCs). Defect formation, lattice mismatch, and energy‐level misalignment at this interface aggravate nonradiative recombination and accelerate photothermal degradation, thereby limiting both efficiency and operational stability. Here, we employ interface engineering using multifunctional molecules to suppress defect formation. To minimize redundant material screening, we combine theoretical calculations with experimental validation to identify 4‐aminobutylphosphonic acid (4‐ABPA) for modifying the interface between the perovskite layer and the electrode. Both simulation and experimental results demonstrate 4‐ABPA as a multifunctional molecular bridge that simultaneously anchors to the charge transport layer and interacts with the perovskite lattice. And its role in dynamically regulating perovskite crystallization and enhancing interfacial performance is uncovered. The dual‐site chemical binding regulates crystallization, alleviates residual stress, suppresses interfacial defects, and optimizes energy‐level alignment at the buried interface. As a result, voltage loss is reduced to 31 mV, enabling power conversion efficiencies of 25.56% in n–i–p and 26.45% in p–i–n architectures with negligible hysteresis. The modified devices also exhibit outstanding durability, retaining 83.91% of their initial performance under 1440 h of continuous operation and 91.59% after 2600 h of ambient storage. Our work establishes a systematic and universal buried‐interface engineering strategy to further enhance efficiency and stability, thereby advancing the mass production of perovskite devices.

Does urinary diversion type influence long-term renal outcomes after radical cystectomy? A multicenter retrospective study.

728 Background: Long-term renal function decline is a known complication following urinary diversion, and its etiology is considered multifactorial, involving factors such as preoperative renal function, comorbidities, and postoperative complications. While previous studies have explored general risk factors for renal deterioration, the specific impact of different urinary diversion techniques on long-term renal outcomes remains unclear. Methods: This multicenter retrospective study analyzed 702 patients who underwent radical cystectomy (RC) and urinary diversion. Patients were categorized into three groups based on the type of urinary diversion: cutaneous ureterostomy, ileal conduit, and ileal neobladder. Major adverse kidney events (MAKE), defined as a ≥50% decline in estimated glomerular filtration rate (eGFR), doubling of serum creatinine, or eGFR ≤15 mL/min/1.73 m 2 , were used as indicators of renal prognosis. Events were considered present if criteria were met on two consecutive occasions at least three months apart. Multivariable Cox proportional hazards regression analysis was performed to evaluate the impact of urinary diversion type on MAKE-free survival. Results: The median age was 70 years, and the median follow-up duration was 48 months. Of the 702 patients, 219 (31%) underwent cutaneous ureterostomy, 123 (18%) ileal conduit, and 360 (51%) ileal neobladder. eGFR at 5, 7, and 10 years after RC differed significantly among the three groups ( P < 0.001 for all time points). Chronic kidney disease-free survival was significantly longer in the ileal neobladder group compared to both the cutaneous ureterostomy group ( P = 0.012) and the ileal conduit group ( P = 0.024). MAKE occurred in 121 patients (17%). After adjusting for confounding variables, no significant difference in MAKE-free survival was observed between the cutaneous ureterostomy and ileal conduit groups. However, the ileal neobladder group had a significantly lower risk of MAKE compared to the cutaneous ureterostomy group ( P = 0.014; hazard ratio: 0.518; 95% confidence interval: 0.307–0.876). Conclusions: The type of urinary diversion significantly affects long-term renal function. These findings may be useful in guiding surgical decision-making and predicting renal outcomes following urinary diversion. Multivariable analysis for MAKE-free survival. Factor P value HR 95% CI Age Continuous 0.992 1.00 0.97–1.03 Sex Male 0.469 0.84 0.53–1.34 PS Continuous 0.603 1.15 0.69–1.92 BMI Continuous 0.011 1.09 1.02–1.16 Hypertension Presence 0.222 1.32 0.85–2.05 Dislipidemia Presence 0.145 1.46 0.88–2.42 DM Presence 0.703 1.10 0.67–1.83 Preoperative eGFR Continuous 0.421 0.99 0.98–1.01 Hydronephrosis Presence 0.138 0.64 0.35–1.16 Grade of hydronephrosis Continuous <0.001 1.56 1.27–2.02 Type of urinary diversion Ureterostomy Ref. Conduit 0.995 0.99 0.57–1.75 Neobladder 0.014 0.52 0.31–0.88

Artificial intelligence (AI)–assisted eligibility screening for prostate cancer clinical trial matching.

405 Background: Clinical trials are critical to advancing prostate cancer treatment, yet patient enrollment remains a major bottleneck. Despite strong interest in AI for trial matching, real-world use remains limited due to reasons such as complex infrastructure requirements. To address this, we developed a lightweight, scalable AI framework leveraging the Google Healthcare Search API—requiring minimal technical expertise—to automate trial eligibility screening. Methods: We used a pre-trained GPT-5 large language model (LLM) to decompose the eligibility criteria of 13 prostate cancer clinical trials into 269 YES/NO questions, such that for an eligible patient of a given trial, the chart review would yield YES for inclusion and NO for exclusion questions. From 348 patients enrolled in one of the trials, we built a dataset linking each eligibility question to each patient, resulting in 4,947 patient–question pairs (2,034 inclusion pairs with YES labels and 2,913 exclusion pairs with NO labels). The task was framed as binary classification. During evaluation, for each patient–question pair, the LLM extracted search phrases from the question to retrieve relevant EHR information via the Google Healthcare Search API, then used the question and retrieved information to predict YES or NO responses. Performance was measured using accuracy, precision, recall, specificity, and F1 score. Results: Across 4,947 question–patient pairs, our framework achieved 0.81 accuracy, 0.85 precision, 0.65 recall, 0.92 specificity and a F1 score of 0.74. Results for different phases of trials is reported in Table 1, which demonstrates the approach’s robustness across trial phases. Predictions for exclusion criteria were highly precise, while inclusion criteria were more challenging. Most errors were observed in criteria involving complex nested logical conditions, interpretable clinical definitions and data not explicitly measurable or recorded in the EHR (e.g., planned treatments or clinician-assessed scores). Conclusions: This work demonstrates a practical AI framework to support clinical trial matching. The system can identify complex disease states (biochemical recurrence vs radiographic metastasis), castration status (sensitive, resistant) and genomics. Future work should focus on developing human-in-the-loop supervision and improving question decomposition to reduce errors in complex eligibility criteria. Screening performance of the proposed framework across different phases of trials. Trial Phase #Patient-Question Pairs #YES/NO labels Accuracy Precision Recall Specificity F1 score I, II, I/II 4,227 Yes: 1,735 No: 2,492 0.80 0.84 0.66 0.92 0.74 III 720 Yes: 299 No: 421 0.82 0.90 0.63 0.95 0.74 All 4,947 Yes: 2,034 No: 2,913 0.81 0.85 0.65 0.92 0.74 #YES/NO labels: The number of patient-question pairs that are labeled YES/NO among total patient-question pairs of the same row.