Hailong Hu

Purpose: Repeat transurethral resection of bladder tumor (TURBT) is recommended for selected patients with non–muscle-invasive bladder cancer (NMIBC), but clinicopathologic indications are broad and often identify no residual tumor. We tested whether postresection urinary tumor DNA (utDNA) adds value beyond guideline-derived repeat-TURBT selection and established recurrence risk models. Materials and Methods: This guideline-anchored cohort analysis included 161 patients with NMIBC who underwent repeat TURBT. Urine was collected 2 to 6 weeks after initial TURBT and before repeat TURBT. Tissue-naïve utDNA and cytology were compared with repeat-TURBT pathology and evaluated against repeat-TURBT indication sets, European Association of Urology (EAU) risk grouping, The European Organisation for Research and Treatment of Cancer (EORTC) models, and Club Urologico Espanol de Tratamiento Oncologico (CUETO) models. Results: Residual tumor was found in 57 patients (35.4%). Core, expanded, and carcinoma in situ-augmented core indication sets selected 73.3%, 88.2%, and 80.7% of patients. Within these indication-positive groups, utDNA-negative status identified 66.9% to 67.7% as lower-yield, although 9.1% to 10.4% still had residual tumor. Adding utDNA increased residual tumor AUCs from 0.544 to 0.891, 0.537 to 0.892, and 0.513 to 0.890 for the three indication sets, respectively. For any recurrence, c-indices increased from 0.602 to 0.774 for EAU risk grouping, 0.717 to 0.837 for EORTC models, and 0.770 to 0.824 for CUETO models after adding utDNA. Conclusion: Postresection utDNA refined residual tumor detection beyond repeat-TURBT indication sets and improved recurrence risk stratification beyond EAU/EORTC models, with directionally consistent CUETO results. Positive utDNA after negative repeat TURBT suggested occult molecular risk and supports prospective testing of utDNA-informed resection and surveillance algorithms.

Cisplatin (CDDP) chemosensitivity and severe toxicity severely limit its clinical application in muscle‐invasive bladder cancer (MIBC) and non‐muscle‐invasive bladder cancer (NMIBC). To address these unmet clinical needs, we synthesized a series of melatonin‐conjugated platinum(IV) prodrugs functionalized with isocyanate chains (compounds 5 ‒ 12 ), and identified MP‐12C (compound 11 ) as the lead candidate with optimal potency and safety. In vitro assays showed that MP‐12C exhibited far stronger antiproliferative activity than CDDP and mitomycin C in parental and CDDP‐resistant bladder cancer cells. Multiple in vivo models, including subcutaneous xenograft, orthotopic, and chemically induced spontaneous bladder cancer models, were adopted. Both intravenous injection and intravesical instillation of MP‐12C achieved robust tumor suppression while reducing toxicity compared to conventional chemotherapeutics. Mechanistically, MP‐12C downregulated the TCF4/COL6A3 axis to suppress collagen VI secretion by bladder cancer cells, thereby remodeling the extracellular matrix (ECM) and enhancing the sensitivity of bladder cancer cells to CDDP. MP‐12C triggered immunogenic cell death and persistently activated the cGAS‐STING pathway, promoting dendritic cell maturation and CD8 ⁺ T cell infiltration to remodel the antitumor immune microenvironment. Collectively, MP‐12C integrates ECM modulation and immune activation to exert superior anti‐bladder cancer efficacy with favorable safety, thus providing a promising platinum(IV) prodrug strategy for NMIBC and MIBC.

Objective: PD-1 based immunochemotherapy has improved bladder cancer (BC) outcomes, yet individual responses remain heterogeneous. Low-cost, non-invasive predictive biomarkers are urgently needed. Urinary protein semi-quantification (UPSQ) correlates with BC tumor load, but its predictive value during PD-1 based immunochemotherapy remains unclear. We conducted a post-hoc analysis of the TRUCE-01 (NCT04730219) and TRUCE-02 (NCT04730232) trials to explore the association between UPSQ and clinical outcomes. Methods: 104 patients received 3 cycles of tislelizumab plus nab-paclitaxel. UPSQ at baseline (UP-B) and 60 ± 7 days (UP-60) after treatment initiation, urinary red blood cell (URBC) and urinary white blood cell (UWBC) were dynamically detected. Dynamic indices (UPDV score, UPV risk stratification) were defined to evaluate UPSQ changes. The primary endpoint was clinical complete response (cCR), and the secondary endpoints included overall survival (OS), cancer-specific survival (CSS), and events-free survival (EFS). Bulk RNA-seq transcriptomic analysis was performed in 22 MIBC patients. Results: UPSQ decreased significantly at 60 days in the overall cohort and subgroups (all p < 0.05). Baseline URBC and UWBC were positively correlated with UPSQ, while tumor size was positively associated with UPSQ in MIBC patients. In regression analyses, several indicators reached nominal significance ( unadjusted p < 0.05), but failed to remain significant ( adjusted p > 0.05) after Benjamini-Hochberg correction due to limited sample size. Low UPV risk was correlated with a significantly higher cCR rate in both MIBC (OR 12.5, unadjusted p = 0.003, adjusted p = 0.055) and VHR-NMIBC (OR 3.47, unadjusted p = 0.031, adjusted p = 0.177) subgroups. UP-B grade showed a trend toward an inverse association with cCR (OR 0.48, unadjusted p = 0.028, adjusted p = 0.085) and OS (HR 1.70, unadjusted p = 0.045, adjusted p = 0.181) in the MIBC subgroup after multivariate adjustment. Transcriptomic analysis suggested that MIBC patients with high UP-B grade may exhibit a more aggressive tumor phenotype. Conclusions: UPSQ was linked to the clinical outcomes of patients receiving PD-1-based immunochemotherapy for BC. In MIBC, lower baseline UPSQ grade may be associated with a tumor transcriptomic phenotype contributing to better cCR and OS. Clinical Trial Registration: https://clinicaltrials.gov , identifier NCT04730219; https://clinicaltrials.gov , identifier NCT04730232.

Background: Patients with very high‐risk (VHR), nonmuscle–invasive bladder cancer (NMIBC) who are ineligible for or decline radical cystectomy face limited treatment options. Immune checkpoint inhibitor–based regimens have demonstrated promise but lack reliable biomarkers to guide patient selection. The objective of this study was to identify magnetic resonance imaging–derived radiomic phenotypes predictive of treatment response to immune checkpoint inhibitor–based therapy. Methods: The authors retrospectively analyzed two prospective cohorts of patients with extensive VHR NMIBC: a single‐center derivation cohort from the TRUCE‐02 trial ( n = 59) and a multicenter validation cohort from the TRUCE‐22 trial ( n = 37). All patients received tislelizumab and nanoparticle albumin‐bound paclitaxel every 3 weeks. Complete response (CR) was assessed at 3 months. Radiomic features were extracted from baseline, T2‐weighted images, and a hybrid framework integrating supervised feature selection with unsupervised clustering was used to identify imaging phenotypes. Associations with CR, progression‐free and overall survival, and immune‐related transcriptional signatures were evaluated. Results: Three radiomic clusters were identified: immune‐excluded (cluster 0), immune‐intermediate (cluster 1), and immune‐inflamed (cluster 2). In the derivation cohort, cluster 2 had a significantly higher CR rate (82.8%) than cluster 0 (21.4%; p = .001), a pattern that was validated in TRUCE‐22 (83.3% vs. 22.2%; p = .008). The cluster‐only model achieved the highest predictive performance for CR in both the derivation (area under the receiver operating characteristic curve, 0.77) and validation (area under the receiver operating characteristic curve, 0.78) cohorts. Cluster 2 had better progression‐free and overall survival. Transcriptomic and immunofluorescence analyses revealed functional immune suppression in cluster 0, including reduced CD8‐positive, phosphorylated STAT1–positive T cells. Conclusions: In patients with very high‐risk NMIBC, magnetic resonance imaging–derived radiomic phenotypes can be used to stratify responses to immunochemotherapy and capture functional immune states. Noninvasive radiomic profiling may guide precision treatment selection in patients who are unfit for radical cystectomy, and prospective validation is warranted before clinical adoption.

PURPOSE: The optimal adjuvant treatment approach for muscle-invasive bladder cancer (MIBC) remains unsettled. The IMvigor011 trial demonstrated that circulating tumor DNA (ctDNA)–guided adjuvant atezolizumab improves outcomes and advances precision oncology in this setting. However, the socioeconomic value of this biomarker-driven strategy is unclear. We therefore assessed the economic value of ctDNA-guided therapy in this postoperative setting. MATERIALS AND METHODS: We constructed a three-state Markov model to estimate costs, quality-adjusted life-years (QALYs), incremental net monetary benefit (INMB), and incremental cost-effectiveness ratios (ICERs) in patients with MIBC. The model compared a ctDNA-guided adjuvant atezolizumab strategy with the standard of care (SOC) from a US health care payer perspective. Cost-effectiveness was assessed across willingness-to-pay (WTP) thresholds of $50,000-$150,000 in US dollars (USD) per QALY, and model robustness was examined through comprehensive sensitivity analyses. RESULTS: Over a 5-year horizon, the ctDNA-guided strategy yielded 3.05 QALYs at a cost of $78,796 USD, compared with 2.92 QALYs and $131,601 USD for SOC. This corresponded to an ICER of –$397,163 USD per QALY gained, demonstrating dominance through greater benefit at lower cost. Sensitivity analyses confirmed that the ctDNA-guided approach was consistently cost-effective across all WTP thresholds. CONCLUSION: ctDNA-guided atezolizumab adjuvant therapy proves to be a cost-effective strategy for MIBC, optimizing health care resource allocation and reducing overtreatment while improving patient outcomes. More standardized ctDNA testing protocols and transparent reporting of ctDNA status distributions are essential.

Background: The current predictive models for venous thromboembolism (VTE) have limitations in predicting VTE risk in patients with urological cancer. Objectives: To establish and validate a risk stratification model for in-hospital VTE in patients with urological cancer. Design: Retrospective, multicenter study. Methods: The clinical data of 735 patients with urological cancer in the Department of Urology at four hospitals in China between January 2019 and December 2024 were analyzed. VTE ( n = 147) and non-VTE ( n = 588) groups were formed based on inclusion and exclusion criteria to develop a predictive model for VTE in patients with urological cancer. Results: In this study, we developed a risk stratification model using a logistic regression based on variables selected by LASSO and constructed a nomogram to visualize the model. The areas under the receiver operating characteristic curve for the training, validation, and external validation cohorts were 0.933 (95% confidence interval (CI): 0.909–0.957), 0.900 (95% CI: 0.850–0.950), and 0.857 (95% CI: 0.776–0.938), respectively. The corresponding Brier scores for them were 0.070, 0.089, and 0.200. The calibration curve indicated good model performance. Decision curve analysis evaluated the clinical utility of the model and showed that it provided a higher net benefit than the “treat-all” and “treat-none” strategies across a wide range of threshold probabilities, supporting its potential clinical usefulness. Conclusion: A predictive model was developed to estimate the risk of in-hospital VTE in patients with urological cancer, enabling personalized assessment and guiding preventive strategies. Further studies are needed to better validate our model.

Obesity significantly increases the risk of developing urinary tract stones, particularly distal ureteral stones, which can complicate treatment with extra

Repeat transurethral resection of bladder tumor (re‐TURBT) is commonly recommended for patients with non–muscle‐invasive bladder cancer (NMIBC) with high‐risk features, although many individuals may undergo unnecessary procedures that increase morbidity without clear benefit. Urinary tumor DNA (utDNA) has emerged as a promising biomarker, and we evaluated the performance of a multidimensional utDNA assay (utLIFE) in this context. In a retrospective cohort of 161 patients who underwent re‐TURBT between May 2020 and May 2025, urine samples collected 2–6 weeks after initial TURBT were analyzed using utLIFE, which integrates shallow whole‐genome sequencing and targeted sequencing of 155 genes with machine learning–based classification. Residual tumor was identified in 35% of patients, and utLIFE demonstrated high diagnostic accuracy, with sensitivity of 80.7%, specificity of 96.2%, and overall accuracy of 90.7%, markedly outperforming urine cytology. A positive utLIFE result was the strongest independent predictor of residual disease (OR = 77.5, 95% CI: 22.4–268.2, p < 0.001). During a median follow‐up of 32.5 months, recurrence occurred in 20.5% of patients; recurrence was defined as urothelial tumor relapse within the urinary tract and did not include distant metastasis. utLIFE positivity was significantly associated with shorter recurrence‐free survival (HR = 16.4, 95% CI: 2.7–101.8, p = 0.003). Longitudinal testing further revealed that utDNA positivity frequently preceded cystoscopic evidence of recurrence by several months. These findings highlight the strong diagnostic and prognostic value of utDNA in identifying residual disease and predicting recurrence, supporting its potential role in refining postoperative management strategies for NMIBC.

Early 2 factor (E2F) genes are transcription factors that interact with many DNAs and proteins. Studies have demonstrated that E2F genes can play an oncogenic role in different cancers, yet fewer have explored their effects on pan-cancers. In this study, E2F expression is systematically characterized in multiple types of cancer and its predictive value is determined. Several public databases (GEO, Cancer Genome Atlas (TCGA), cBioPortal, Kaplan–Meier Plotter and PrognoScan) were used to evaluate E2F genes differentially expressed between normal and tumor tissue in pan-cancer, we then investigated the correlation between expression levels of E2F and prognostic factors, clinicopathologic stage, gene mutation types, functional enrichment, drug sensitivity. This study also examined the relationship between microsatellite instability, tumor mutation burden, tumor microenvironment (TME), tumor-related immune checkpoint genes, and immunotherapy response as well as the expression of E2F. Then, we examined potential signaling pathways by analyzing gene set enrichment analyses (GSEAs). Finally, we performed the real-time PCR expression validation and in vitro functional experiments of E2F5. The expression of E2F was upregulated in most tumor tissues compared to adjacent normal tissues. The expression of E2F family genes was highest in E2F4 and lowest in E2F7 in 33 TCGA cancers. E2F gene expression correlates significantly with prognosis in multiple cancer types, as well as RNA-related stemness score and DNA-related stemness score, immune and stromal scores. The E2F genes expression also related with immune subtype in pan-cancer. There existed a positive correlation between E2F2 expression level and Dasatinib sensitivity, negatively related to drug sensitivity of Nelarabine, XK-469, Cyclophosphamide, etc. Pazopanib, Doxorubicin, and Paclitaxel sensitivity was all positively associated with E2F5 expression. E2F genes high expression group showed significant positive or negative enrichment in multiple tumor- and immune-related pathways. In addition, we also discovered that the expression level of nearly all E2F genes was positively or negatively correlated with objective responses to anti-PD-1/PD-L1 across multiple immunotherapy cohort. The immune infiltration analysis of specific bladder cancer further showed the significant relationships between E2Fs copy number variations or mutation status, and infiltration level of different immune cells. Furthermore, differential expression validation and in vitro phenotypic experiments indicated that E2F5 significantly promoted BCa cells proliferation and migration. According to these analysis and validation results, E2F genes are relevant to the occurrence and progression of various cancers, which may be biomarkers for tumor diagnostics and prognosis. The discovery of new therapeutic targets can lead to reshaping TME to promote tumor-suppressive metastasis rather than tumor-friendly metastasis.