In non-metastatic prostate cancer (nmPCa) setting, it is important to early identify the patients at risk of biochemical recurrence (BCR) for immediate postoperative intervention. Our study aimed to evaluate the potential clinical utility of circulating tumor DNA (ctDNA) for predicting disease recurrence. This real-world observational study evaluated 161 cases of nmPCa undergoing next-generation sequencing at our institution. A total of 139 ctDNA samples and 31 biopsied tumor tissue underwent genomic profiling. The study endpoint was BCR after radical prostatectomy. Relationships between the ctDNA status and the biochemical progression-free survival (bPFS) were analyzed by log-rank test and multivariate Cox regression. Of 161 enrolled patients, 19(11.8%) harbored deleterious alterations in NCOR2, followed by BRCA2(3.7%), ATR(2.5%) and CDK12(2.5%). Of available pre-operative blood samples(n=139), ctDNA was detectable in 91(65.5%). Until last follow-up, 56 of 68(85.3%) patients with detectable ctDNA had achieved BCR, whereas only 8 of 39(20.5%) patients with undetectable ctDNA had achieved BCR. Patients who had undetectable ctDNA experienced significantly longer bPFS compared with those who had detectable ctDNA (NA vs. 8.2 mo, hazard ratio[HR]: 0.14, p<0.01). Pre-operative ctDNA status was a significant prognostic factor of disease recurrence. Pre-operative ctDNA detection could identify patients at high risk of recurrence and has the potential to inform immediate postoperative interventions, but these approaches remain to be validated in prospective studies. ctDNA studies can provide insights into accurate monitoring and precise treatment rather than simply following routine clinical care.

Objectives: Prostate cancer (PCa) is one of the most common malignancies in men worldwide and has caused increasing clinical morbidity and mortality, making timely diagnosis and accurate staging crucial. The authors introduced a novel approach based on mass spectrometry for precise diagnosis and stratification of PCa to facilitate clinical decision-making. Methods: Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry analysis of trace blood samples was combined with machine learning algorithms to construct diagnostic and stratification models. A total of 367 subjects, comprising 181 with PCa and 186 with non-PCa were enrolled. Additional 60 subjects, comprising 30 with PCa and 30 with non-PCa were enrolled as an external cohort for validation. Subsequent metabolomic analysis was carried out using Autoflex MALDI-TOF, and the mass spectra were introduced into various algorithms to construct different models. Results: Serum metabolic fingerprints were successfully obtained from 181 patients with PCa and 186 patients with non-PCa. The diagnostic model based on the eight signals demonstrated a remarkable area under curve of 100% and was validated in the external cohort with the area under curve of 87.3%. Fifteen signals were selected for enrichment analysis, revealing the potential metabolic pathways that facilitate tumorigenesis. Furthermore, the stage prediction model with an overall accuracy of 85.9% precisely classified subjects with localized disease and those with metastasis. The risk stratification model, with an overall accuracy of 89.6%, precisely classified the subjects as low-risk and high-risk. Conclusions: Our study facilitated the timely diagnosis and risk stratification of PCa and provided new insights into the underlying mechanisms of metabolic alterations in PCa.

Personalized vaccines demonstrate remarkable potential in leveraging tumor-specific adaptive immunity for cancer therapy. Nevertheless, current platforms face persistent challenges, including premature systemic clearance and imprecise antigen-presenting cell targeting, culminating in transient and inefficient antitumor immunity. Furthermore, the technical complexity, extended timelines, and prohibitive costs required for tumor-specific neoantigen identification continue to impede the clinical translation of personalized cancer vaccines. Here, we report a tumor-derived extracellular vesicle-based scaffold vaccine that elicits robust and durable antitumor immunity for personalized cancer immunotherapy. Following subcutaneous administration, the in situ-formed hydrogel vaccine serves as a sustained reservoir for tumor-derived extracellular vesicle antigens and adjuvants while recruiting antigen-presenting dendritic cells to accumulate within the scaffold. Upon exposure to this antigen-rich depot, immature dendritic cells undergo efficient activation, with subsequently matured dendritic cells migrating to draining lymph nodes, where they induce potent and persistent tumor-specific CD8⁺ T-cell responses that suppress tumor progression across multiple murine models. Specifically, when using tumor-derived extracellular vesicles isolated from surgically excised tumor tissues, the patient-tailored vaccines demonstrate remarkable efficacy in preventing postoperative recurrence. Our findings validate the robust and durable therapeutic efficacy of this vaccine platform, highlighting its potential as a customizable strategy for personalized cancer immunotherapy.

To evaluate the efficacy and safety of high-frequency irreversible electroporation for ablation of benign prostatic hyperplasia. 160 subjects were randomly assigned to the test group to receive ablation and the control group to receive 0.2 mg/day tamsulosin. The maximum urinary flow rate (Qmax), prostate volume and International Prostate Symptom Score (IPSS) and International Index of Erectile Function 5-item (IIEF-5) score were evaluated before treatment and 1, 3, and 12 months after treatment. Differences inter-group and changes intra-group over different follow-up periods were evaluated, and adverse events were recorded. At the same time, patients were divided into three groups according to tertile method of the baseline prostate volume, and the above indicators were also analyzed. Qmax improvement in the test group and control group at 1, 3 and 12 months were 1.22±5.50 mL/s and 1.75±4.29 mL/s, 8.41±8.23 mL/s and 2.61±5.53 mL/s, 7.67±7.63 ml/s and 4.31±6.76 ml/s, respectively. IPSS improvement in the test group at 3 and 12 months were significantly higher than that in the control group, except for 1 month. Similarly, the reduction in prostate volume at 3 months was also observed. The incidences of adverse events were low in both groups. Subgroup analysis showed that there were no statistical differences in key indicators among subgroups. Qmax, prostate volume, IPSS were improved in the test group during 12-month follow-up, and the safety profile was favorable. H-FIRE ablation demonstrated significant efficacy and safety for all patients with large, medium and small prostate volumes.

Background: Bone metastasis is a major determinant of morbidity and therapeutic failure in advanced prostate cancer (PCa); however, the transcriptional programs and tumor microenvironmental alterations driving metastatic progression remain incompletely understood. This study aimed to systematically characterize transcriptomic differences between non-metastatic and bone-metastatic PCa and to identify key microenvironmental signaling pathways involved in tumor survival and chemoresistance. Methods: Bulk RNA sequencing was performed on 49 non-metastatic and 28 bone-metastatic PCa specimens. Differential expression analysis was integrated with weighted gene co-expression network analysis (WGCNA), gene set enrichment analysis, and immune/stromal deconvolution. Key findings were validated using in vitro functional assays, including Transwell co-culture models, small interfering RNA (siRNA)-mediated gene silencing, cell viability, apoptosis, and docetaxel resistance analyses. Results: Transcriptomic profiling identified 574 differentially expressed genes. Bone-metastatic tumors were enriched in ribosome-related and translational pathways, whereas non-metastatic tumors displayed immune-associated signatures, including natural killer (NK) cell-mediated cytotoxicity and cytokine signaling. WGCNA revealed immune-related gene modules preferentially enriched in non-metastatic disease. Immune deconvolution demonstrated significantly higher infiltration of NK cells and endothelial cells in non-metastatic tumors. Chemokine-receptor analysis highlighted upregulation of the CXCL10-CXCR3 axis in non-metastatic PCa. In vitro, PCa cells expressed CXCR3, while endothelial cells markedly increased CXCL10 expression upon co-culture. Functional assays showed that endothelial-derived CXCL10 promoted PCa cell survival, suppressed apoptosis, and conferred resistance to docetaxel via CXCR3-dependent signaling; these effects were reversed by CXCL10 or CXCR3 knockdown. Conclusions: These findings uncover a context-dependent endothelial-immune chemokine network distinguishing non-metastatic from bone-metastatic PCa and identify the CXCL10-CXCR3 axis as a critical mediator of tumor survival and chemoresistance, suggesting a potential therapeutic vulnerability in advanced prostate cancer.