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MEVPRO-3: Phase III trial of mevrometostat plus enzalutamide (versus placebo plus enzalutamide) in metastatic castration-sensitive prostate cancer (mCSPC).
TPS284 Background: Enhancer of zeste homolog 2 (EZH2) enzymatic activity plays a crucial role in prostate cancer progression. Mevrometostat, an oral potent and selective EZH2 inhibitor may synergize with androgen receptor pathway inhibitors (ARPIs) to delay ARPI resistance In a phase I study (NCT03460977), mevrometostat combined with enzalutamide showed promising antitumor activity versus enzalutamide alone in heavily pre-treated patients with metastatic castration-resistant prostate cancer (mCRPC) (median [95% CI] radiographic progression-free survival [rPFS], 14.3 [7.5, not estimable] vs 6.2 [4.1, 13.9] months; HR [90% CI] 0.51 [0.28, 0.95]), and a manageable safety profile. Addition of mevrometostat to an ARPI in patients with mCSPC is hypothesized to prevent or delay progression to CRPC and improve survival. The ongoing phase III studies MEVPRO-1 (NCT06551324) and MEVPRO-2 (NCT06629779) are evaluating mevrometostat plus enzalutamide in patients with mCRPC. MEVPRO-3 (NCT07028853) will evaluate mevrometostat plus enzalutamide, versus placebo plus enzalutamide, in ARPI-naïve patients with mCSPC. Methods: MEVPRO-3 is a double-blind, randomized, global, phase III study enrolling patients aged ≥18 years with mCSPC and Eastern Cooperative Oncology Group performance status 0–1. Prior systemic therapy use in the metastatic setting is not allowed except for ≤3 months of androgen deprivation therapy (with or without first-generation antiandrogens), with no evidence of disease progression prior to Day 1. Prior palliative radiotherapy or surgery is allowed, but radical prostatectomy or prostate radiotherapy or metastasis-directed therapy for mCSPC is not. Around 1000 patients will be randomized 1:1 to mevrometostat (875 mg BID with food) plus enzalutamide (160 mg, QD) or placebo plus enzalutamide. Randomization will be stratified by low vs high disease volume and de novo vs relapsed mCSPC. The primary endpoint is rPFS per RECIST 1.1 (soft tissue) and PCWG3 criteria (bone) assessed by blinded independent central review. Secondary endpoints include overall survival; objective response rate; duration of response; time to PSA progression, initiation of new antineoplastic therapy, first symptomatic skeletal event, and CRPC; and patient-reported outcomes. Alpha-protected efficacy analyses will include tests for rPFS and OS. HRs and 95% CIs will be estimated via Cox proportional hazard model. P - values will be provided by stratified log-rank test. Pharmacokinetics and safety will also be assessed. Enrollment is ongoing in North America and the Asia-Pacific, and planned in Europe and Latin America. Disclosure: Pfizer’s generative AI tool, MAIA, was used in developing this abstract; the authors take full responsibility for the content. Clinical trial information: NCT07028853 .
Predicting cancer organ tropism in mCRPC patients using triple-tracer PET imaging radiomics clustering from the 3TMPO cohort study.
29 Background: The 3TMPO study has characterized the prevalence of intrapatient intermetastatic heterogeneity (IIH) in mCRPC using a Triple-Tracer PET Imaging approach (PMID 39327017). Artificial intelligence based radiomics clustering can help to further characterize both IIH and interpatient cancer heterogeneity. In this study we have exploited the triple-tracer radiomics signatures to cluster patients and predict cancer organ tropism. Methods: 3TMPO is a multisite prospective observational study in which 41 mCRPC patients underwent 18 F-FDG, 68 Ga- PSMA–617 and 68 Ga-DOTATATE PET/CT scans. Calculations for hierarchic clustering used 9 vectors (SUVmax 18 F-FDG, SUVmean 18 F-FDG, SUVpeak 18 F-FDG, SUVmax 68 Ga- PSMA–617, SUVmean 68 Ga- PSMA–617, SUVpeak 68 Ga- PSMA–617, SUVmax 68 Ga-DOTATATE, SUVmean 68 Ga-DOTATATE, SUVpeak 68 Ga-DOTATATE on a total of 355 (35% nodal, 34% bone, 31% visceral) unique lesions. The model was trained on 284 (80.0%) lesions and used the remaining 71 (20%) for internal validation. Results: Based on triple tracer radiomics in each metastasis, 5 clusters could be identified with a total variance of 69.4%. Cluster 2 (C2) showed a triple-tracer signature strongly suggestive (specificity: 79%) of visceral metastasis, as did cluster 1 (C1) (specificity: 66%). Lesions in cluster 4 (C4) had a specificity of 74% for nodal metastasis. Nodal lesions in C2 showed, in contrast to C4, a vector activity more resemblant of liver lesions, putting forward the hypothesis that nodal disease with a C4 signature could be biologically different from lymph nodes with a C2 signature. Patients with lesions who expressed a C2 signature had a decrease in overall survival (OS) (3.1 months, n=4) compared to patients with lesions in other (C1, C3, C4 & C5) clusters (7.3 months, n = 37) (p-value = 0.06). Conclusions: An internally validated model using the 3TMPO 18 F-FDG, 68 Ga- PSMA–617 and 68 Ga-DOTATATE PET/CT imaging vectors to identify organ tropism clusters is presented. Different triple tracer signatures could be identified, some of which are associated with a shorter OS. Signatures of lymphatic lesions in M1c disease differ from M1a/b cases, suggesting that triple-tracer imaging can highlight differences in tumour biology. These findings favour our hypothesis that radiomic clusters could be used to predict organ tropisms and prognosis to guide precision medicine treatment intensification.
Therapy for Stage IV Non–Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, 2026.3.0
This guideline has been updated. This ASCO Living Guideline is reviewed on an eight-week cycle. Please see the online dynamic version for the latest updates. ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual . ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by clinicians and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature, and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and Appendix 2 (online only) for more . PURPOSE To provide evidence-based recommendations for patients with stage IV non–small cell lung cancer with driver alterations. METHODS This ASCO living guideline offers continually updated recommendations based on an ongoing systematic review of randomized controlled trials (RCTs), with the latest time frame spanning March-October 2025. An Expert Panel of medical oncology, pulmonary, community oncology, research methodology, and advocacy experts was convened. The literature search included systematic reviews, meta-analyses, and RCTs. Outcomes of interest include efficacy and safety. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS This guideline consolidates all previous updates and reflects the body of evidence informing this guideline topic. Thirteen studies were identified in the latest search of literature to date. RECOMMENDATIONS Evidence-based recommendations were updated to address first, second, and subsequent treatment options for patients with driver alterations. Additional information is available at www.asco.org/thoracic-cancer-guidelines .
Nomadic Molecular Key‐Driven Instantaneous Covalent Reconstruction Enables Ultrahigh Impact‐Stiffening Polymeric Armor
ABSTRACT Impact‐stiffening materials hold great promise in safeguarding human safety and apparatus integrity, serving as intelligent armor to mitigate transient impact and damage. However, high activation strain/rate, stiffening hysteresis, and inefficient energy dissipation of current materials pose significant challenges for matching extreme events. Herein, we report a nomadic molecular key‐driven ultrahigh impact‐stiffening strategy that leverages strain‐rate‐sensitive and covalent‐active molecules to trigger covalent reconstruction and nanodomain agglomeration within polymers. Our design employs poly(styrene‐thioctic acid) (PSTx) with a few thioctic acids (TA) as a critical stiffening key, in which disulfide/hydrogen bonds form energy‐dissipating multi‐networks, while phenyls act as precursors for physical crosslinking. Distinct from conventional mechanisms, force‐activated TA functions as a molecular key that rapidly induces covalent crosslinking and phenyl nanodomain resembling, effectively “locking” networks and blunting cracks to achieve efficient impact‐resistance. PSTx exhibits ultralow relaxation time (15.8 ms), exceptional stiffening response (2925 times), and stretchability over 4000%. Even at low strains/rates of 2000 s −1 , it achieves high modulus (5.8 GPa), record strength (84.3 MPa), and excellent energy dissipation (12.4 MJ/m 3 ), yielding 97% impact‐force reduction. PSTx is processable into various wearable composites with outstanding impact force attenuation (+957%) and puncture resistance (+360%). This work resolves challenges of activation thresholds and stiffening hysteresis in impact‐stiffening materials, providing a molecular key‐switchable paradigm for intelligent systems.
Enfortumab vedotin (EV) related cutaneous toxicity to predict metabolic response on fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan in advanced urothelial carcinoma (aUC): A single-center experience.
736 Background: EV is an antibody–drug conjugate approved for aUC after chemotherapy and immune checkpoint inhibitors. Cutaneous toxicity is the most frequent adverse event (AE) of EV, but the correlation between cutaneous toxicity and treatment efficacy based on standardized FDG-PET computed tomography (CT) assessment has not yet been established. Methods: In this retrospective single-center study, data from patients (pts) with aUC treated with more than one dose of EV after platinum-based chemotherapy and immunotherapy between September 2021 and August 2025 were analyzed. Treatment response was assessed by FDG-PET performed 3 months after treatment initiation. All the PET CT scans were reviewed in a blinded fashion by two readers using standardized criteria. The aim of this study was to establish a correlation between EV-related cutaneous toxicity and metabolic response. Results: Seventy-four pts were included. The median age of the population was 69.5 years, 86.5 % were male. Lymph-nodes were the most common site of metastasis (68.9%). Starting dose of EV was 1.25 mg/kg for 83.8% of the pts. The overall metabolic response on FDG-PET CT was 55.4% (41 pts), with a median duration of response of 5.23 (3.73–8.00) months. EV-related cutaneous toxicity occurred in 42 pts (56.8%), predominantly grade 1 (73.8%) and grade 2 (21.4%). No grade 4 or 5 AEs were reported. Logistic regression confirmed a correlation between cutaneous toxicity and metabolic response (Odds Ratio 8.17; 95% CI 2.87–23.32; p < 0.001). Among the 14 pts that achieved a metabolic complete response (CR), 13 experienced cutaneous toxicity (7 pts grade 1 and 4 pts grade 2). Two pts with grade 3 toxicity achieved CR. Progression-free survival was also significantly longer in pts with cutaneous toxicity (7.45 vs. 4.51 months; p < 0.001). Conclusions: These findings support a correlation between EV-related cutaneous toxicity in urothelial carcinoma and metabolic response on FDG-PET. These data should be confirmed in prospective trials.
Influence of concomitant distant lymph node metastases in metastatic hormone-sensitive prostate cancer patients with bone metastases.
116 Background: Most patients with metastatic hormone-sensitive prostate cancer (mHSPC) are burdened by bone metastases. However, the impact of concomitant distant lymph node metastases at diagnosis in these patients is unknown. Methods: We relied on the FRAMCAP database (FRAnkfurt Metastatic Cancer database of the Prostate) to compare time to metastatic castration-resistant prostate cancer (mCRPC) and overall survival (OS) between M1b vs. M1a+b mHSPC patients. Univariable and multivariable Cox regression models were applied. Results: Among 432 patients, 64% harbored M1b vs. 36% M1a+b mHSPC. PSA was significantly higher in M1a+b vs. M1b patients (81 vs. 44 ng/ml, p<0.05), as well as rates of LATITUDE high-risk (76% vs. 55%) and CHAARTED high-volume disease (70% vs. 50%) (both p<0.001). Regarding time to mCRPC, median time to CRPC was 26 vs. 16 months for M1b vs. M1a+b patients (hazard ratio [HR]: 1.6, p<0.01). Regarding OS, median OS was not significantly different, with median OS of 53 vs. 47 months for M1b vs. M1a+b patients (p=0.9). After controlling for patient and tumor characteristics in multivariable Cox regression analyses, concomitant lymph node metastases were not an independent risk for shorter time to CRPC or OS in patients with bone metastases (both p>0.15). Conclusions: Patients with concomitant distant lymph node metastases in mHSPC with bone metastases (M1a+b) harbor more unfavorable baseline cancer characteristics relative to M1b without lymph node metastases, translating into significantly shorter time to mCRPC. However, after controlling for patient and tumor characteristics, neither time to mCRCP nor OS seems not be affected by concomitant lymph node metastases.
A randomized phase 2 study of enhanced AR blockade with enzalutamide in high-risk patients with biochemical relapse undergoing salvage radiation: Final results from RTOG 3506 (STEEL).
156 Background: Patients with high-risk features who experience biochemical relapse (BCR) after radical prostatectomy (RP) benefit from the addition of androgen deprivation therapy (ADT) to salvage radiotherapy (SRT). We hypothesized that enhanced androgen receptor (AR) blockade (eARB) with enzalutamide would improve SRT outcomes for high-risk patients. Methods: Post-RP patients who had BCR (PSA ≥ 0.2 ng/mL) with at least 1 high-risk feature (Gleason 8-10, seminal vesicle invasion, pN1, persistent PSA >0.1 ng/mL after RP, and PSA ≥ 0.7 ng/mL) were eligible. Patients were randomized 1:1 to 24 months of standard ADT (sADT) with an LHRH analog (LHRHa) or eARB comprised of LHRHa + enzalutamide 160 mg daily. Progression free survival (PFS) was analyzed with progression defined as PSA ≥ 0.2 ng/mL or initiation of new therapy following SRT. Results: Between April 2019 and August 2022, 188 patients were enrolled. The patient characteristics were well balanced between the two arms. Median age was 64 years. Nodal involvement (pN1), pT3a-b, and Gleason 9 were noted in 22%, 77%, and 52% of patients, respectively. Over 70% had ≥2 aggressive features. Median follow-up time at the time of this report was 34.6 months. Prostatic fossa and pelvic SRT were mandatory. Para-aortic radiotherapy (RT), and lymph node and prostatic fossa lesion RT boosts were left at the discretion of the radiation oncologist. The SRT+eARB arm had better PFS when compared to the SRT+sADT arm (HR=0.62, 80% CI: 0.42-0.91, one-sided p=0.052). The rate of biochemical failure at 2 years was 19% (95% CI: 12-28) in the SRT+sADT arm as compared to 11% (95% CI: 5-18) in the SRT+eARB arm. Grade 3 adverse events (AEs) related to sADT vs. eARB were 19% vs. 30%, while Grade 4 AEs were 4% vs. 2%, respectively. The most common AEs (all grades, >15%) included hot flashes, fatigue, diarrhea, and decreased lymphocytes. The grade 3+ AEs (>3%) included decreased lymphocytes and hypertension. Conclusions: The addition of enzalutamide to standard ADT resulted in an improvement of PFS following SRT, warranting a phase 3 trial. The increase in toxicity was consistent with other studies of enzalutamide and did not identify new safety concerns. Clinical trial information: NCT03809000 .
Randomized pilot trial of pre-visit patient education as preparation for decision making in newly diagnosed prostate cancer (PrepDM).
361 Background: Men with newly diagnosed prostate cancer (PCa) face preference-sensitive choices among currently available alternatives in management. High-quality decisions require understanding options, weighing trade-offs, and aligning choices with personal values. We evaluated whether brief pre-visit education improves patients’ Preparation for Decision Making (PrepDM). Methods: This was a single-center, 1:1 randomized pilot trial of men with biopsy-proven prostate cancer allocated to intervention (in which patients were provided curated educational material/videos before the follow-up visit) or usual care. Baseline demographics and tumor characteristics were collected; continuous and categorical variables were compared with Wilcoxon rank sum and Fisher’exact /Chi-square tests, respectively. The primary outcome was the PrepDM total score (10 items, each 1-5; range 1-50), assessing overall patient degree of strategy understanding and preparation. Secondary outcomes were item-level scores. Analyses were intention-to-treat. Group differences used Wilcoxon rank-sum with Hodges-Lehmann (HL) estimates; item-level multiple comparison testing was controlled with Benjamini-Hochberg FDR (q-values). Results: Fifty-two participants were randomized (26/arm). Median age was 70 years; median PSA 7.2 ng/dL; median prostate volume 42 cc; ISUP GG1/GG2/≥GG3 were 27%/37%/36%. Cohorts were comparable at baseline with no detectable differences in race/ethnicity, PSA, Gleason grade group, prostate volume, BMI, or age. The intervention increased overall preparation compared to control (total score difference: +6 points, 95%CI +2 to +10; p=0.002). After FDR adjustment, 7/10 items favored intervention: helping organizing thoughts (+1; q=0.006); knowing the decision depends on what matters most (+1; q=0.02); deciding desired involvement (+1; q=0.02); identifying questions (+1; q=0.03); preparing to talk about what matters most (+1; q=0.04); recognizing a decision is needed (+1;q=0.041); and weighing pros/cons (+1; q=0.045). Items on preparing for a follow-up visit (q=0.08), making a better decision (q=0.11), and prioritizing which pros/cons are most important (q=0.11) were not significant. Conclusions: Brief pre-visit patient education improved preparation for decision making, supporting shared decision-making and patient empowerment in prostate cancer care. Larger multicenter trials should confirm effectiveness and assess downstream outcomes (decisional conflict, decision quality, and satisfaction/regret).
Effects of a diet high in omega-3 polyunsaturated fatty acids (PUFAs) on inhibition of soluble epoxide hydrolase (sEH) and mitigation of painful docetaxel-induced peripheral neuropathy in mice.
140 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a painful and frequently persistent and debilitating toxicity of cancer treatment that greatly affects the quality of life of cancer survivors. There is an unmet need for effective treatments against established CIPN and for preventative approaches. The enzyme soluble epoxide hydrolase (sEH) converts epoxy fatty acids (EpFAs), which are polyunsaturated fatty acid (PUFA) derivatives with inflammation-resolving, analgesic and anti-cancer properties, into corresponding pro-inflammatory and hyperalgesic dihydroxy metabolites (diols). Thus, sEH is a master regulator of inflammation. The sEH inhibitor (sEHI) EC5026 has completed phase 1 studies in healthy volunteers, with no significant adverse effects noted. The EpFAs of the ω-3 PUFAs are particularly effective at promoting analgesia and resolution of inflammation, suggesting that a diet rich in ω-3 PUFAs would enhance the inflammation-resolving effects of a sEHI. Methods: We examined the prophylactic efficacy of the sEHI EC5026 in a mouse model of docetaxel-induced painful neuropathy, by measuring mechanical hind paw withdrawal thresholds (PWTs) using an electronic von Frey aesthesiometer (IITC, Woodland Hills, CA). EC5026 was formulated in the drinking water at a concentration calculated to provide the mice with a dose of ~5 mg/kg/day through their daily unrestricted water intake. In addition, we studied docetaxel-induced CIPN in adult sEH ( Ephx2 ) male homozygous knock-out (KO) mice and wild-type (WT) mice on a diet high in ω-3 PUFAs vs a diet high in ω-6 PUFAs (both from Research Diets Inc., New Brunswick, NJ), starting 3 weeks prior to beginning docetaxel treatment and continued throughout the duration of the experiment. We also measured the levels of non-esterified PUFAs and their corresponding EpFAs and diols by UPLC-MS/MS in mouse plasma. Results: Docetaxel decreased the PWT in male C57BL/6J WT mice, while prophylactic administration of EC5026 mitigated this neuropathic allodynia. After 3 weeks on the ω-3 vs ω-6 diet, the respective PUFAs and their corresponding dihydroxy metabolites were significantly enriched. As expected, genetic ablation of Ephx2 increased the plasma levels of the corresponding epoxides. Importantly, sEH KO mice exhibited less severe docetaxel-induced CIPN and recovered from it faster than their WT counterparts when fed a diet high in ω-3 PUFAs, but not when fed a diet high in ω-6 PUFAs. Conclusions: We propose that sEH is a druggable therapeutic target in CIPN pathophysiology. The benefits of targeting sEH can be augmented by a diet rich in omega-3 PUFAs.
High comorbidity as a predictor of poorer survival and ARPI efficacy in metastatic prostate cancer.
72 Background: The prognostic impact of comorbidity burden in metastatic prostate cancer (mPC) remains uncertain. This study aimed to evaluate the association between Charlson Comorbidity Index (CCI) and progression free survival (PFS) and to explore androgen receptor pathway inhibitor (ARPI) outcomes in patients with high comorbidity. Methods: This retrospective multicenter study evaluated the impact of clinical and laboratory characteristics on progression free survival using Kaplan Meier and Cox regression analyses. CCI was dichotomized as <3 vs ≥3 based on the cohort median. In the subgroup of patients with CCI≥3 receiving androgen deprivation therapy (ADT) plus ARPIs, PFS was compared between enzalutamide and abiraterone. Results: A total of 344 patients were included. The median age was 68.6 years (range, 43.7–88.7), and the median follow up was 29.4 months (range, 2.2–145.8). ECOG performance status was 0 in 51.5%, 1 in 43.6% and ≥2 in 4.9% of patients. The median CCI was 3; 141 patients (41.0%) had CCI<3, and 203 (59.0%) had CCI≥3. Median PFS was 40.5 months (95% CI, 25.9–55.1) for CCI<3 and 29.0 months (95% CI, 22.5–35.4) for CCI≥3. Variables significant in univariate analysis were entered into multivariable Cox regression, where CCI≥3 (p=0.046), elevated LDH (p<0.001), and elevated ALP (p=0.033) remained independent adverse prognostic factors for PFS (Table 1). Among patients with CCI≥3 receiving ADT+ARPI, median PFS was 54.3 months with enzalutamide and 34.0 months with abiraterone (log-rank p=0.043). Conclusions: Higher comorbidity burden (CCI≥3) is an independent predictor of shorter PFS in metastatic prostate cancer. Among patients with high CCI receiving ARPI plus ADT, abiraterone was associated with inferior PFS compared with enzalutamide. Comorbidity assessment may guide individualized treatment selection and risk stratification in clinical practice. Univariate and multivariate Cox regression analyses for progression-free survival. Variable Univariate HR (95% CI) Univariate p-value Multivariate HR (95% CI) Multivariate p-value Age (<70 vs. ≥70) 0.86 (0.62–1.19) 0.364 ECOG performance status (≥1 vs. 0) 1.32 (1.06–1.64) 0.015 1.16 (0.78–1.73) 0.470 Charlson Comorbidity Index (≥3 vs. <3) 1.09 (1.01–1.18) 0.034 1.60 (1.07–2.41) 0.022 Elevated ALP 1.72 (1.18–2.51) 0.005 1.00 (1.00–1.00) 0.711 Elevated LDH 1.90 (1.30–2.78) <0.001 1.95 (1.31–2.91) 0.001 Gleason score (≥8 vs. <8) 1.25 (0.86–1.83) 0.244 High-volume disease 2.12 (1.53–2.96 <0.001 1.98 (1.30–3.00) 0.001 De novo metastasis 1.18 (0.80–1.74) 0.395 Bone metastasis 2.08 (1.30–3.33) 0.002 1.28 (0.64–2.54) 0.483 Liver metastasis 1.90 (0.89–4.07) 0.098
Gemcitabine intravesical system (Gem-iDRS) in combination with cetrelimab (CET) versus chemoradiotherapy (CRT) in muscle-invasive bladder cancer (MIBC): SunRISe-2 final results.
635 Background: Bladder sparing is an important therapeutic goal in MIBC. Definitive treatment for localized MIBC is CRT or radical cystectomy (RC) with neoadjuvant chemotherapy. Gem-iDRS (previously TAR-200), approved for BCG-unresponsive non-MIBC with carcinoma in situ, is an intravesical drug-releasing system designed for sustained delivery of gemcitabine in bladder. CET is an investigational IgG4 anti–PD-1 antibody. We report final analysis of SunRISE-2 (NCT04658862), an open-label, randomized, phase 3 superiority study. Methods: Patients (pts; ≥18 yrs with cT2-T4a, N0, M0 MIBC, declined/ineligible for RC) were randomized 1:1 to Gem-iDRS + intravenous CET (arm 1) or concurrent CRT (cisplatin or gemcitabine plus RT, 64 or 55 Gy; arm 2). In arm 1, pts received Gem-iDRS every 3 wks (Q3W) for 18 wks, followed by Q12W until W144 and CET Q3W until W78. In arm 2, pts received CRT for up to 6.5 wks. Primary end point was bladder-intact event-free survival (BI-EFS; defined as time to muscle-invasive or distant relapse, RC or death). Secondary end points included overall response (OR; using biopsy and CT/MRI) at W18, metastasis-free survival (MFS), overall survival (OS), and safety. The study met the prespecified futility criteria. Final analysis was conducted after data collection was complete. Results: At July 7, 2025 data cutoff, 518 pts were randomized (arm 1, n=262; arm 2, n=256). Median follow-up was 11.3 months. Gem-iDRS + CET did not show superior BI-EFS over CRT (HR, 1.71 [95% CI, 1.16-2.53]); 24-mo rates were 58.5% vs 66.5%, respectively. At W18, OR rate was 56.7% in arm 1 and 65.3% in arm 2. In pts who achieved complete response (CR) at W18, 24-mo BI-EFS rates were 76.2% and 72.0% in arms 1 and 2 (Table). Incidence of any-grade and grade ≥3 treatment-related adverse events (TRAEs) is shown in Table. Most common grade ≥3 TRAE was urinary tract infection (6.3%) in arm 1 and neutropenia (8.7%) in arm 2. There was no treatment-related death in arm 1 and 1 death in arm 2. Conclusions: In SunRISe-2, Gem-iDRS + CET did not show superior BI-EFS over CRT in pts with MIBC not receiving RC. 24-mo BI-EFS rates in pts with CR at W18, and MFS and OS rates in all pts were similar in both arms. There were no unexpected safety findings in either arm. Clinical trial information: NCT04658862 . Efficacy [95% CI] Gem-iDRS + CET (n=262) CRT (n=256) Median BI-EFS, mo NE [22.9-NE] NE [26.6-NE] 24-mo BI-EFS rate, % 58.5 [49.4-66.5] 66.5 [55.6-75.4] OR rate at W18, n (%) a 122 (56.7) [49.8-63.5] 132 (65.3) [58.4-71.9] 24-mo BI-EFS rate in pts with CR at W18, % 76.2 [59.9-86.5] 72.0 [55.1-83.5] 24-mo MFS rate, % 65.5 [55.5-73.8] 70.2 [59.4-78.7] 24-mo OS rate, % 83.7 [76.3-88.9] 84.0 [73.7-90.5] TRAEs n=254 n=241 Any-grade | grade ≥3, n (%) 203 (79.9) | 68 (26.8) 212 (88.0) | 77 (32.0) a Gem-iDRS + CET, n=215; CRT, n=202; CR 50.7% and 59.4%, partial response 6.0% and 5.9%, non-response 43.3% and 34.7%, respectively. NE, not estimable.
SAVE: A multicenter randomized phase 2 trial of salvage radiotherapy (SRT) with androgen-deprivation therapy (ADT) versus apalutamide (Apa) for biochemical progression after radical prostatectomy (RP).
364 Background: Adding 6 months of ADT to SRT can negatively impact health-related quality of life (HRQoL). SAVE evaluated apalutamide as an alternative to maintain HRQoL. Methods: SAVE (NCT03899077) is an investigator-initiated, multi-center, open label, randomized phase 2 trial. Patients had a rising PSA after RP and were referred for SRT. Only patients with adequate erectile function (IIEF-5 score ≥ 8) were eligible. Patients were randomized to 6 months of ADT (investigator's choice) or 6 months of Apa. Primary endpoint was the EPIC-26 sexual domain (SD) score at 9 months after starting hormonal treatment (HT) compared between both arms by the Wilcoxon test. The study was powered to detect a 15-points difference between both arms with 90% power and one-sided type I error of 0.05. Secondary endpoints included overall HRQoL, assessed using EPIC-26, FACT-P, EORTC QLQ C30 and PR25, at 3, 6 and 9 months, and PSA response rates (at least 80% decline). Results: 201 participants from 7 sites were randomized from 04/17/2019 to 10/16/2024 to ADT (100) or Apa (101). Pretreatment scores were not significantly different in both arms. Median (Q1 – Q3) EPIC-26 SD score at 9 months after starting HT was significantly higher in the Apa (57 (39 – 79)) than in the ADT (19 (6 – 38)) group (p < 0.001). Similar differences in SD scores were observed at 3 (50 (26 – 71) vs 15 (4 – 32), p < 0.001) and 6 (45 (26 - 71) vs 13 (4 – 28), p < 0.001) months. EPIC-26 urinary incontinence (92 (79 – 100) vs 86 (65 – 100), p = 0.01 at 3 months; 92 (79 – 100) vs 86 (61 – 100), p = 0.056 at 6 months) and hormonal (90 (80 – 95) vs 80 (60 – 90), p < 0.001 at 3 months; 85 (75 – 95) vs 75 (60 – 85), p< 0.001 at 6 months; 95 (85 – 100) vs 80 (65 – 90), p< 0.001 at 9 months) domain scores were better in the Apa arm. FACT-P total score was 126 (112 – 137) vs 119 (109 – 131) at 3 (p = 0.018), 129 (116 – 138) vs 122 (110 – 132) at 6 (p = 0.025), and 133 (126 – 140) vs 128 (117 – 136) at 9 (p = 0.006) months. Significantly better scores were observed with Apa on the physical and functional well-being as well as prostate cancer-specific scales at all timepoints. PR25 showed significantly higher sexual activity and functioning scores as well as less urinary and hormonal treatment related symptoms with Apa at all timepoints. Global health status (C30) was 83 (67 – 83) vs 67 (58 – 83) at 3 (p = 0.011), 83 (67 – 92) vs 67 (58 – 83) at 6 (p < 0.001), and 83 (83 – 100) vs 75 (67 – 83) at 9 (p < 0.001) months. Significantly better physical, role, emotional, cognitive and social functioning, as well as less fatigue was observed with Apa at all timepoints. PSA response rates were similar at 3 (82% with Apa vs 75% with ADT, p = 0.3), 6 (84% vs 73%, p = 0.12) and 9 (76% vs 74%, p = 0.9) months. Conclusions: Apalutamide monotherapy significantly spares HRQoL compared to ADT, not only regarding sexual functioning but also more generally, without jeopardizing PSA response. Clinical trial information: NCT03899077 .
Activated Carbon‐Reinforced Super‐Structured Porous Hydrogel With Robust Mechanical and Excellent Pro‐Healing Properties for Abdominal Wall Defect Repair
ABSTRACT The repair of abdominal wall defects necessitates the use of advanced biomaterials that can concurrently provide mechanical support, modulate immune responses, and promote tissue regeneration, but current solutions are difficult to integrate these functions. Herein, we report a facile yet effective strategy that confers a unique combination of high porosity, superior mechanical strength, and immunomodulatory performance on poly(vinyl alcohol) (PVA) hydrogel by incorporating activated carbon (AC) to produce super‐structured porous PVA (SPVA‐AC) hydrogel. The robust hydrogen bonding, hydrophobic interaction, and mechanical interlocking between AC and PVA enable AC to function not only as a pore‐expanding agent but also as a rigid crosslinking center. Such dual roles facilitate the construction of enlarged porous structures for fibroblast infiltration while simultaneously enhancing mechanical stability for structural durability in wet environments. Meanwhile, AC serves as an efficient scavenger for reactive oxygen species and inflammatory factors, thereby reshaping the local immune microenvironment by promoting M2 macrophage polarization and accelerating tissue healing. In a rat model of abdominal wall defect, the anti‐adhesion SPVA‐AC hydrogel demonstrates robust mechanical stability, remarkable anti‐inflammatory activity, and accelerated tissue healing. This work offers a scalable and innovative strategy for designing high‐performance biomaterials aimed at soft tissue reconstruction.
Upcycling Mixed Alloy Scraps via Liquid Metal Dealloying for Cross‐Alloy Circular Economy
ABSTRACT The challenge of mixed, contaminated metal scrap and the unsustainable environmental footprint of traditional primary metal production based on fossil reductants necessitate innovative, scalable recycling strategies. This study presents a generic liquid metal dealloying‐vacuum (LMD‐V) approach for synergistic upcycling of complex multiple alloy scraps, representing a paradigm shift from conventional single‐stream recycling. Demonstrated using nickel (Ni) superalloy and magnesium (Mg) alloy scrap, the method leverages Mg's low melting point to extract Ni, leaving refractory metals (rhenium (Re), tungsten (W), tantalum (Ta)) as a porous residue. Vacuum treatment recovers 99.7% pure Mg and yields a brittle nickel‐aluminum (Ni‐Al) alloy, directly converted into Raney‐Ni catalyst with commercial‐grade performance. The weakened porous residue (2%–6% of its original strength) facilitates critical metal recovery. Compared to conventional recycling, it reduces energy and carbon footprints by 74.6% and 56.7%, respectively. By transforming carbon‐intensive scraps into high‐value products, LMD‐V establishes a closed‐loop, scalable pathway for mixed scrap recycling, profoundly advancing the circular economy.
Biofilm‐Antagonist Ginger‐Based 3D‐Printable Photoresins for Complex Implant Designs Exhibiting Advanced Multifunctional Biomedical Applications
Abstract Since the discovery of 3D‐printing, it has revolutionized personalized drug delivery and implants by enabling intricate, customizable designs. However, key challenges remain, including complex design, host immune response, biofilm formation, and infection‐induced inflammation at the implant site. This work offers, first‐ever, unique ginger‐based 3D‐printable resins by chemically modifying Zingerol (Zing‐OH, a ginger‐based component) into photopolymerizable compositions that can print high‐resolution complex designs via DLP 3D‐printing. Briefly, the Zing‐OH is amended via different functional group backbones, resulting in Zing‐OH‐based resins (ether, ester, and urethane) and their respective prints. Moreover, the Zing‐OH prints’ thermal, mechanical, and biodegradation properties can be fine‐tuned by simply customizing the backbone. Furthermore, the shape memory efficacy and the human bone (nasal cartilage, vestibular, cortical, femur, etc.) mimicking mechanical properties (exhibiting 2–200 MPa compressive strength) makes them more enticing. In tandem, the prints are also hemocompatible as well as cyto‐friendly against human skin (HaCaT) and lung (BEAS‐2B) cells, and mouse fibroblast (NIH‐3T3) cells. Concurrently, an in vivo biocompatibility study in a rat model indicates that the printed materials are biocompatible, showing no signs of severe inflammatory response over a 28‐day period. More importantly, the outstanding anti‐biofilm and antioxidant efficacies of the Zing‐OH prints make them more appealing due to their potential to prevent implant rejection, thus making them promising tools for bone‐tissue engineering (BTE) applications.
Comparison of quantitative functional RAD51 foci and genomic alterations in predicting PARPi response in mCRPC: A multicenter real-world study.
114 Background: Currently, the clinical outcomes of poly(ADP-ribose) polymerase (PARP) inhibitors varied widely in metastatic castration-resistant prostate cancer (mCRPC) patients with different HRR gene alterations (HRRalt). It is urgent and necessary to develop a novel biomarker for predicting the clinical efficiency of PARP inhibitors in the mCRPC patients. Tissue-based immunofluorescence (IF) assay for the functional RAD51 foci is emerging as a promising biomarker for assessing homologous recombination deficiency (HRD). However, the predictive value of the RAD51 foci using the IF assay for mCRPC patients following PARP inhibitors remains uncertain. This multicenter real-world study was to evaluate the predictive value of the RAD51 foci in the IF assay in mCRPC patients with HRRalt and not-altered HRR after the PARP inhibitor treatment. Methods: The multicenter real-world study involved 217 consecutive patients who had received the next-generation sequencing (NGS) and PARP inhibitor treatment from three tertiary referral hospitals. RAD51 foci were quantified in formalin-fixed, paraffin-bedded, untreated tumor specimens by IF. We assessed progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier method. Potential factors influencing PFS and OS were compared between the treatment arms using Cox proportional-hazards models. Prediction models were established to compare their predictive value in PFS and OS. The prostate-specific antigen (PSA) response and the treatment effect across subgroups were also evaluated. Results: RAD51 foci had significantly better predictive efficacy than the BRCA1/2alt and HRRalt, with a significantly higher predictive power in PFS and OS (RAD51: area under the curve [AUC]: PFS: 0.795; OS: 0.765, BRCA1/2alt: AUC: PFS: 0.669; OS: 0.628, HRRalt: AUC: PFS: 0.635; OS: 0.566). In the overall cohort, median PFS and OS were significantly longer in the RAD51-Low group than the RAD51-High group (PFS: 9.0 vs 2.0 mo; hazard ratio [HR] 0.25, 95% confidence interval [CI] 0.18–0.35; p < 0.01; OS: 25.0 vs 11.0 mo; HR 0.34, 95% CI 0.22–0.43; p < 0.01). In the not-altered HRR cohort, the RAD51-Low group also had significantly longer survival than the RAD51-High group (PFS: 6.5 vs 1.0 mo; HR 0.21, 95% CI 0.11–0.40; p < 0.01; OS: 24.0 vs 8.0 mo; HR 0.32, 95% CI 0.17–0.56; p < 0.01). PSA responses were also significantly higher in the RAD51-Low group than the RAD51-High group. Limitations include its retrospective design and small sample size. Conclusions: In mCRPC patients treated with PARP inhibitors, RAD51 foci demonstrates a superior predictive value for clinical outcomes compared to HRRalt and BRCA1/2alt. RAD51 foci also serve as a pivotal biomarker for extending the PARP inhibitor efficacy to not-altered HRR patients. A large-scale prospective randomized controlled trial is needed to confirm these results.
Trends in PSA and metastatic prostate cancer at presentation in the United States from 2004-2022.
76 Background: The introduction of prostate-specific antigen (PSA) screening in the mid-1980s led to an increase in the diagnoses of localized prostate cancer relative to metastatic disease. In 2008, the United States Preventive Services Task Force (USPSTF) discouraged screening for men aged 75 and older and in 2012 extended this to all men. In 2018, the USPSTF partially reversed their position to recommend individualized screening for men aged 55 to 69. We investigated the association between the implementation of these guidelines on the average PSA and metastatic stage of disease at initial diagnosis. Methods: We analyzed the 2025 release of the National Cancer Data Base (NCDB) and included patients diagnosed with prostate adenocarcinoma from 2004 to 2022. Data for PSA, metastatic disease, and year of diagnosis were recorded. We report trends by era (2004-2007, 2008-2011, 2012-2017, and 2018-2022). Results: A total of 2,259,526 men with a diagnosis of prostate cancer were identified in the NCDB. The mean age at diagnosis declined form 65.5 years during first era to 64.6 years in the second era and then increased to 66.4 years in the third era. The median PSA level at diagnosis declined from 6.1 ng/mL in 2004 to 5.8 ng/mL 2008, but this trend reversed after 2008 with median PSA rising steadily to 7.3 ng/mL by 2018. The incidence of metastatic disease at diagnosis steadily increased from 2,764 (2.7%) in 2004 to 13,043 (9.2%) in 2022. Conclusions: We detected a strong temporal association between PSA screening guidelines and both PSA level and metastatic stage at time of diagnosis. While PSA decreased and then increased, the proportion of patients diagnosed with metastatic disease at presentation rose steadily. The introduction of more sensitive imaging modalities, such as PSMA PET CT may have resulted more detection of metastatic disease at diagnosis, independent of the PSA at diagnosis. An underlying increase in the aggressive disease amongst US men over the past two decades cannot be excluded. Mean age, median PSA, and percentage of men presenting with metastatic disease at diagnosis in USA, 2004-2022. Era Mean age at diagnosis Median PSA at diagnosis Percentage of men presenting with metastatic disease 2004 – 2007 65.6 6.1 2.63% 2008 – 2011 64.7 5.9 3.33% 2012 – 2017 65.5 6.8 6.43% 2018 - 2022 67.0 7.5 8.40%
Palliative care utilization and hospitalization outcomes among patients with renal cell carcinoma: A 2020-2022 National Inpatient Sample analysis.
432 Background: Renal cell carcinoma (RCC) is an aggressive malignancy with significant symptom burden. Advances in targeted and immune-based therapies have improved survival, yet patients often experience complications that make early palliative care (PC) integration essential. This study evaluated inpatient outcomes and complications among RCC hospitalizations receiving PC in the United States (U.S.) from 2020 to 2022 using the National Inpatient Sample (NIS). Methods: A retrospective cohort study was conducted using the 2020-2022 NIS. Adult hospitalizations (≥18 years) with RCC (excluding renal pelvis) were identified by ICD-10 codes. PC use was defined by code Z51.5. Primary outcome was in-hospital mortality; secondary outcomes were length of stay (LOS), total charges, and complications (hypercalcemia, obstructive uropathy, spinal cord compression, malignant pleural effusion). Multivariable regression models adjusted for demographic, clinical, and hospital-level factors. Results: Among 271,515 RCC hospitalizations, 9.1% (24,745) received PC, indicating limited integration. PC was more common in older patients (≥65 years: 10.6% vs < 65 years: 7.0%; p < 0.05) and those with Medicare (10.2%) versus private (9.7%), Medicaid (6.4%), or self-pay (8.9%) (p < 0.05). Utilization did not differ by race (p = 0.19), sex (p = 0.20), or income quartile (p = 0.51), but increased with higher comorbidity burden (p < 0.05). On adjusted analyses, the PC group showed higher in-hospital mortality (OR 15.09, 95% CI 13.62–16.72; p < 0.05), longer hospital stays (+2.79 days, 95% CI 2.47–3.10; p < 0.05), and higher total charges (+$14,107, 95% CI $8,964–$19,249; p < 0.05). PC recipients also had higher odds of complications, including hypercalcemia (OR 2.71, 95% CI 2.40–3.05), obstructive uropathy (OR 1.34, 95% CI 1.19–1.52), spinal cord compression (OR 1.93, 95% CI 1.51–2.47), and malignant pleural effusion (OR 3.98, 95% CI 3.49–4.54) (p < 0.05 for all). Conclusions: PC recipients had higher mortality, longer stays, greater costs, and more complications, reflecting advanced disease and delayed referral rather than adverse effects of PC itself. Early consultation triggers for complications such as hypercalcemia, uncontrolled pain, and neurologic compromise, along with improved inpatient to outpatient continuity may facilitate timely PC integration and optimize resource utilization.
Real-world determinants of testosterone recovery following androgen deprivation therapy in patients with localized prostate cancer.
353 Background: Androgen deprivation therapy (ADT) is a cornerstone of localized prostate cancer management, yet testosterone recovery after cessation varies. Understanding clinical and treatment-related predictors of recovery may inform patient counseling and optimize therapeutic planning. This study aims to identify factors associated with likelihood of, and time to, testosterone recovery following ADT at a large safety-net institution. Methods: A retrospective chart review was completed on all patients treated with ADT and radiation for localized or regionally advanced prostate cancer at an urban, safety-net hospital between 2013 and 2024. We conducted multivariable regression analyses to evaluate predictors of testosterone recovery using logistic regression, and time to recovery using Cox proportional hazards models. Covariates included duration of ADT (short vs long course), use of GnRH agonist vs antagonist, combined androgen blockade, baseline testosterone level, age at diagnosis, and comorbidities (hypertension [HTN], diabetes mellitus [T2DM], cardiovascular disease [CVD], hyperlipidemia [HLD]). Hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. Results: A total of 191 patients were included in this study. Median age at diagnosis was 67.3 years. During the study period, 71.2% of patients had testosterone recovery. Those without recovery were monitored for median 30.0 months. Short-course ADT was significantly associated with faster recovery (HR=1.54, 95% CI 1.06-2.24, p=0.023) and greater odds of testosterone normalization (OR=3.48, 95% CI 1.38-8.76, p=0.008). Use of a GnRH antagonist was also associated with accelerated recovery (HR=2.86, 95% CI 1.52-5.38, p=0.001). Cardiovascular disease was linked to a modestly faster recovery (HR=1.50, 95% CI 1.00-2.25, p=0.048), while the impacts of HTN (HR=0.75, 95% CI 0.44-1.28, p=0.29), T2DM (HR=0.81, 95% CI 0.57-1.15, p=0.24), and HLD (HR=0.69, 95% CI 0.47-1.00, p=0.051) were not significant. Older age was inversely associated with testosterone recovery (OR=0.93, 95% CI 0.89-0.98, p=0.002), and low baseline testosterone levels were a strong negative predictor (OR=0.16, 95% CI 0.06-0.45, p<0.001). Other variables, including combined androgen blockade and comorbidity burden, were not significantly associated with outcomes. Conclusions: Shorter duration of ADT and GnRH antagonist use were associated with more rapid testosterone recovery, while older age and lower baseline testosterone level significantly reduced the likelihood of testosterone normalization. These findings suggest that both treatment selection and patient baseline characteristics play critical roles in recovery trajectories following ADT. Further prospective validation is warranted to guide personalized treatment duration and recovery expectations.
High‐Mobility 2D Molecular Crystals Enable Field‐Effect X‐Ray Detectors with Record Volumetric Sensitivity
ABSTRACT Direct X‐ray detectors that are lightweight, low‐cost, and ultra‐sensitive are essential for next‐generation portable imaging, wearable monitoring, and low‐dose medical diagnostics. Conventional high‐performance detectors use thick single‐crystal active layers to boost sensitivity, but this increases device volume, raises dark current, and complicates integration with flexible and portable electronics. Here, we break from this paradigm with an ultrathin, high‐mobility 2D molecular crystal (2DMC) integrated into a lateral field‐effect transistor. This design employs a highly confined in‐plane carrier transport path coupled with strong gate‐electrostatic control to achieve complete carrier depletion and sub‐pA dark currents. Thanks to high‐mobility and efficient charge collection in the ultrathin channel, the detector achieves a record volumetric sensitivity of 5.91 × 10 10 µC Gy −1 cm −3 and a detection limit of 1.43 nGy s −1 , surpassing all reported organic detectors and competing with state‐of‐the‐art inorganic ones. Importantly, we show that in the ultrathin regime, high‐mobility outweighs atomic number in governing sensitivity, overturning conventional design logic. We further fabricate large‐area, uniform 2DMC arrays with excellent operational stability, enabling high‐contrast imaging at doses as low as 10.17 nGy s −1 . This work establishes a new paradigm for lightweight, low‐dose organic X‐ray imaging and introduces mobility‐centric design rules for next‐generation detectors.