Prostate最新文献

{"title":"Prostate Cancer Cells With the AR-Low and EMT-High Phenotype Are Vulnerable to NAD+ Synthesis Inhibitors.","authors":"Hyun-Kyung Ko, Rebecca L Foertsch, Kasen Shi, Janét Pittsenbarger, Changhui Xue, Kaiyo Shi, Hao Geng, Lina Gao, David Z Qian","doi":"10.1002/pros.70100","DOIUrl":"10.1002/pros.70100","url":null,"abstract":"<p><strong>Background: </strong>Metastatic prostate cancers are primarily treated by therapies targeting the androgen/androgen receptor (AR) signaling pathways. Despite the initial success, treatment resistance is almost universal, leading to disease progression and patient mortality. Currently, the molecular mechanism and vulnerability of treatment-resistant prostate cancers are poorly understood. These knowledge gaps are major obstacles in improving treatment and patient survival. Recently, we used the single-cell approach to establish a new anti-androgen/AR resistant cell model, in which tumor cells had an AR-low phenotype, expressing low levels of AR and AR-target genes, and were resistant to androgen-deprivation (ADT) and enzalutamide in vitro and in vivo.</p><p><strong>Methods: </strong>We determined the transcriptome of the treatment-resistant AR-low cells with bulk RNA-Seq, qRT-PCR, and chromatin immunoprecipitation (ChIP)-qPCR. We identified a metabolic vulnerability of the resistant cells with siRNA, plasmid-based overexpression and metabolic assays. We next determined whether the vulnerability can be exploited by small molecule inhibitors to enhance enzalutamide with proliferation and colony formation assays and Incucyte-based live cell imaging. We also determined the clinical relevance of the vulnerability with the prostate cancer TCGA data set.</p><p><strong>Results: </strong>The AR-low treatment resistant tumor cells had significantly different transcriptomes from the treatment-sensitive counterparts, notably represented by the EMT-high expression phenotype. The resistant cells were deficient in the expression of NAPRT, a rate determining enzyme in nicotinamide adenine dinucleotide (NAD+) biosynthesis, causing the resistant cells to be vulnerable to NAD+ biosynthesis inhibitors. Importantly, this vulnerability can be exploited to enhance enzalutamide efficacy in the castration sensitive setting as NAPRT-low was phenotypically associated with EMT-high and AR-low in subpopulations of tumor cells and patient samples.</p><p><strong>Conclusion: </strong>Our newly established treatment-resistant cell model has the AR-low/EMT-high phenotype, which is clinically associated with enzalutamide resistance in patients. NAPRT-deficiency (NAPRT-low) can be a novel vulnerability associated with the AR-low/EMT-high phenotype and thus can be targeted by NAD+ inhibitors to improve enzalutamide efficacy.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"428-439"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145716737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETRACTION: Lin28 Induces Resistance to Anti-Androgens via Promotion of AR Splice Variant Generation.","authors":"","doi":"10.1002/pros.70119","DOIUrl":"10.1002/pros.70119","url":null,"abstract":"<p><strong>Retraction: </strong>R. Tummala, N. Nadiminty, W. Lou, C. P. Evans, and A. C. Gao, \"Lin28 Induces Resistance to Anti-Androgens via Promotion of AR Splice Variant Generation,\" The Prostate 76, no. 5 (2016): 445-455, https://doi.org/10.1002/pros.23134. The above article, published online on 30 December 2015 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Dr. Samuel Denmeade; and Wiley Periodicals LLC. A third party reported that the Lin28 band in Figure 4D had been duplicated and resized as the AR-V7 band in Figure 4E and that one of the AR-V7 images in Figure 4A had been duplicated in one of the hnRNPA1 images in Figure 5C. Further investigation by the publisher confirmed these duplications and also found that bands had been duplicated between Figures 1A and 5A and between Figures 1B and 5C. The investigation also found evidence of image splicing in Figures 3A, 3C, 5B, and 5D. The authors responded to an inquiry by the publisher and provided explanations for some instances of duplicated western blot images. The authors further stated that evidence of image splicing in the mentioned bands could be due to artifacts from image editing software. The authors stated that original data were no longer available. The editors determined that the re-use of experimental data between Figures 1A and 5C and between Figures 1B and 5C may have been appropriate. However, the re-use of data between Figures 4D and 4E as well as between Figures 4A and 5C, in which the data were used for different experimental conditions, was not considered acceptable. Additionally, the evidence of splicing in Figures 3A, 5B, and 5D added further concerns about the veracity of the data. The retraction has been agreed to because the multiple instances of duplication and potential splicing in some images compromise the editors' confidence in the conclusions presented in the article. The authors did not respond to our notice regarding the retraction.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"508"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping Molecular Diversity in Prostate Cancer With a Combined Multiplex IHC and RNA-ISH Assay.","authors":"Shannon Carskadon, Sean Williamson, Sangeetha Jyothilingam, Nilesh Gupta, Nallasivam Palanisamy","doi":"10.1002/pros.70108","DOIUrl":"10.1002/pros.70108","url":null,"abstract":"<p><strong>Background: </strong>Molecular heterogeneity in prostate cancer is defined by distinct gene fusions and expression profiles involving ERG, SPINK1, ETV1, and ETV4. These markers are typically mutually exclusive and represent biologically distinct molecular subtypes with clinical and therapeutic relevance. Conventional methods assess these markers independently, limiting the ability to study their spatial relationships within the same tumor focus.</p><p><strong>Methods: </strong>We developed a combined dual immunohistochemistry (IHC) and dual RNA in situ hybridization (RNA-ISH) assay for simultaneous detection of ERG, SPINK1, ETV1, and ETV4 in formalin-fixed paraffin-embedded (FFPE) prostate cancer tissues. Validated antibodies were used for ERG and SPINK1 protein detection, while RNAscope probes were employed for ETV1 and ETV4 mRNA visualization. The assay was optimized for sequential staining compatibility, chromogen contrast, and morphological preservation, and subsequently applied to prostate cancer cores representing various molecular subtypes.</p><p><strong>Results: </strong>The combined assay enabled clear, concurrent visualization of ERG and SPINK1 protein expression together with ETV1 and ETV4 transcripts in a single tissue section. Expression patterns were mutually exclusive across tumor foci, consistent with known molecular subtypes of prostate cancer. The method maintained histological integrity and signal specificity, providing high-resolution spatial information that could not be obtained by separate assays. This approach allowed detailed assessment of intra- and inter-tumoral heterogeneity within the same histological context.</p><p><strong>Conclusions: </strong>This dual IHC and dual RNA-ISH approach represents a novel and reliable platform for multiplex detection of key prostate cancer biomarkers on a single slide. The method offers significant advantages for molecular classification, tissue-based biomarker validation, and comprehensive evaluation of tumor heterogeneity in translational and diagnostic research.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"493-504"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145745416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering Resistance: Beyond the Androgen Paradigm; Report From the 2025 Coffey-Holden Prostate Cancer Academy Meeting.","authors":"Tanya Stoyanova, Saul J Priceman, Ashley E Ross, Phuoc T Tran, Rana R McKay, Kenneth J Pienta, Howard R Soule, Andrea K Miyahira","doi":"10.1002/pros.70102","DOIUrl":"10.1002/pros.70102","url":null,"abstract":"<p><strong>Introduction: </strong>The 12th Annual 2025 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, \"Deciphering Resistance: Beyond the Androgen Paradigm,\" was held at the University of California, Los Angeles (UCLA), Luskin Conference Center, in Los Angeles, CA, from June 19 to 22, 2025.</p><p><strong>Methods: </strong>The CHPCA Meeting is a discussion-focused conference held annually by the Prostate Cancer Foundation (PCF), for in-depth academic analysis of emerging research with the greatest potential to drive new understandings and treatments for prostate cancer. The 2025 CHPCA Meeting included attendance by 79 academic investigators and 39 talks over 8 sessions.</p><p><strong>Results: </strong>The session topics included: drug discovery in academia, non-apoptotic cell death mechanisms, understanding and overcoming treatment resistance, chromosomal instability (CIN) as a driver of metastasis and treatment resistance, targeting metastatic sites, immunotherapy sensitizers, and optimizing therapy delivery and biomedical engineering.</p><p><strong>Discussion: </strong>This meeting report summarizes the presentations from the 2025 CHPCA Meeting. We hope that disseminating this information will directly contribute to novel research efforts and improved treatment strategies for patients with prostate cancer.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"411-427"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145702557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cystoscopic ICG-Guided Sentinel Lymph Node Dissection in Robotic Radical Prostatectomy: A Prospective Study.","authors":"Yi Hong Li, Yu Feng Chuang, Yen Chuan Ou, Yi Sheng Lin, Li Hua Huang, Wei Chun Weng, Chao Yu Hsu, Min Che Tung","doi":"10.1002/pros.70107","DOIUrl":"10.1002/pros.70107","url":null,"abstract":"<p><strong>Background: </strong>To evaluate the diagnostic accuracy, procedural feasibility, and clinical outcomes of a novel cystoscopic-guided indocyanine green (ICG) injection technique followed by fluorescence-guided sentinel lymph node dissection (SLND) during robotic-assisted radical prostatectomy (RaRP), hereafter referred to as CysICG-SLND.</p><p><strong>Methods: </strong>We prospectively enrolled patients with clinically localized prostate cancer (cT1-cT3, cN0) scheduled for RaRP between November 2019 and May 2020. Each patient received cystoscopic-guided intraprostatic injections of ICG, with injection volumes tailored according to prostate size. SLND was performed using the da Vinci Xi Surgical System equipped with near-infrared imaging and followed by a routine extended pelvic lymph node dissection (ePLND). Diagnostic accuracy, procedural complications, and medium-term oncological outcomes were analyzed.</p><p><strong>Results: </strong>A total of 34 patients were included (risk category: low = 2, intermediate = 11, high = 21). Cystoscopic ICG injection was technically successful in all cases. The overall fluorescence detection rate was 97.1%, with excellent per-patient sensitivity (100%) and negative predictive value (NPV) (100%) across all patients. However, per-node diagnostic performance was moderate (sensitivity 66.7%, specificity 47.8%). Notably, in the high-risk group, per-node performance was modest, with sensitivity, specificity, positive predictive value (PPV), and NPV of 66.7%, 55.2%, 20.5%, and 90.7%, respectively. No metastatic nodes were identified in low-risk and intermediate-risk groups, demonstrating a reliable 100% NPV in these subpopulations. High-risk patients had significantly higher biochemical recurrence (BCR) rates compared to lower-risk groups (p = 0.017). There were no allergic reactions or postoperative complications attributable to ICG.</p><p><strong>Conclusions: </strong>CysICG-SLND is a feasible, accurate approach for nodal staging in prostate cancer, particularly beneficial in low- to intermediate-risk groups, achieving excellent sensitivity and NPV. Although diagnostic performance is limited in high-risk patients, high per-patient accuracy still supports clinical utility. Larger prospective studies are warranted to validate these results and further elucidate the technique's clinical role.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"481-492"},"PeriodicalIF":2.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145821727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of Serenoa repens Extract Combined With Alfuzosin Versus Alfuzosin Alone in Men With Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia: A Multicenter Randomized Study.","authors":"Giulio Bevilacqua, Dalila Carino, Stefano Salciccia, Alessandro Gentilucci, Flavio Forte, Massimiliano Di Marco, Antonio Pastore, Marco Martini, Stefano Signore, Alessandro Calarco, Martino Recchia, Olivia Voglino, Valenzi Fabio Maria, Pietro Viscuso, Fabrizio Presicce, Ervin Shehu, Marco Frisenda, Alessandro Sciarra","doi":"10.1002/pros.70071","DOIUrl":"10.1002/pros.70071","url":null,"abstract":"<p><strong>Background: </strong>Chronic inflammation is commonly observed in benign prostatic hyperplasia (BPH) tissue and may contribute to lower urinary tract symptoms (LUTS) as well as disease progression. This study evaluated the efficacy of combining a standardized extract of Serenoa repens (Sr) with alfuzosin versus alfuzosin monotherapy in men with LUTS due to BPH.</p><p><strong>Methods: </strong>In this prospective Phase III, randomized, multicenter, real-world study, 300 treatment-naïve men with moderate-to-severe LUTS (IPSS > 7) and prostate volume > 30 cc were enrolled. Patients received either alfuzosin 10 mg/day or alfuzosin 10 mg plus HESr 320 mg/day for 12 months. Primary endpoints included changes in IPSS and uroflowmetry (Q_max). Secondary endpoints included quality of life (IPSS-Q8), storage symptoms (IPSS-Q2 and Q4), nocturia (IPSS-Q7), erectile function (IIEF-5), and ejaculatory function (MSHQ-Ej). Outcomes were analyzed using mixed-model ANOVA with post hoc Tukey's tests. Statistical analysis was performed using JMP Pro 14 (SAS Institute Inc.). The protocol was approved by our Ethical Committee Lazio Area 1, Protocol 0949/2023, Rif 7385 on December 12, 2023.</p><p><strong>Results: </strong>Both treatments significantly improved total IPSS over time (p < 0.0001). Across all time points, combination therapy was associated with consistently lower IPSS scores, demonstrating a significant time-by-treatment interaction (p = 0.007). Nocturia improved significantly over time (p < 0.0001); the combination group showed greater benefit from Month 3 onward (p = 0.006), though the main treatment effect was not statistically significant (p = 0.076). Q_max improved in both groups (p < 0.0001), with a significant time-treatment interaction (p = 0.006), but no significant main effect of treatment type (p = 0.113). A mild but significant decline in IIEF-5 was observed in both groups over time. Treatment adherence exceeded 86% in both arms.</p><p><strong>Conclusions: </strong>The combination of HESr and alfuzosin was significantly more effective than alfuzosin monotherapy in relieving LUTS, with greater benefits from Month 3 onward. Q_max and nocturia also showed greater, although mild, improvements with combination therapy. Sexual function outcomes were comparable between groups. High adherence and real-world applicability support the clinical value of this combination in managing BPH-related LUTS.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"204-218"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145304353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Effect of KELIM Score of Prostate-Specific Antigen in Hormone-Sensitive Prostate Cancer Patients Treated With Novel Androgen Receptor Inhibitors: Pioneering New Ways.","authors":"Yusuf Ilhan, Murat Araz, Ali Fuat Gurbuz, Semiha Urvay, Muslih Urun, Berrak Mermit Ercek, Ozden Ozilice, Onur Yazdan Balcik, Canan Yildiz, Hacer Demir, Ismail Beypinar","doi":"10.1002/pros.70098","DOIUrl":"10.1002/pros.70098","url":null,"abstract":"<p><strong>Background: </strong>The prognostic value of the PSA ELIMination rate constant K (PRO-KELIM) score was investigated in patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with novel androgen receptor inhibitors.</p><p><strong>Methods: </strong>This multicenter retrospective study included 160 patients diagnosed with prostate adenocarcinoma between 2011 and 2024 who received enzalutamide or abiraterone during the mCSPC and had at least three PSA measurements within the first 100 days of treatment. The patients were categorized into favorable (PRO-KELIM ≥ 1.0) and unfavorable (PRO-KELIM < 1.0) groups. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier survival analysis and Cox regression.</p><p><strong>Results: </strong>Median PFS was significantly higher in the favorable group than in the unfavorable group (not reached vs. 40.0 months, p < 0.001). The estimated 2-year PFS rates in the favorable and unfavorable groups were 78% and 52%, respectively. In multivariate analyses, a high PRO-KELIM score (HR 2.99; 95% CI 1.35-6.66, p = 0.007) and good initial response to treatment (p = 0.001) were independent favorable prognostic factors for PFS. The median OS did not differ significantly between the groups (p = 0.27). PRO-KELIM score was not an independent prognostic factor for OS (p = 0.76).</p><p><strong>Conclusion: </strong>These findings suggest that the PRO-KELIM score can be a valuable prognostic tool in the mCSPC to assess early treatment response and predict disease progression.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"393-400"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145589933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adapting the Bellmunt Risk Score for Prognostic Stratification in Metastatic Castration-Sensitive Prostate Cancer.","authors":"Satı Coşkun Yazgan, Hatice Bölek, Muharrem Coşkunpınar, Emre Yekedüz, Yüksel Ürün","doi":"10.1002/pros.70062","DOIUrl":"10.1002/pros.70062","url":null,"abstract":"<p><strong>Background: </strong>The management of mCSPC has improved with the addition of docetaxel and androgen receptor pathway inhibitors (ARPi) to androgen deprivation therapy. However, patient outcomes remain heterogeneous, highlighting the need for practical prognostic models. The Bellmunt risk score, based on ECOG status, hemoglobin, and liver metastases, was developed for urothelial carcinoma, but its role in mCSPC is unclear.</p><p><strong>Methods: </strong>This retrospective study analyzed 182 mCSPC patients treated with first-line docetaxel or ARPi from 2010 to 2024. Patients were stratified into low- and high-risk groups by the Bellmunt score. Overall survival (OS) was assessed with Kaplan-Meier and Cox models. Subgroup and interaction analyses were performed to evaluate the consistency of the Bellmunt risk score's prognostic value across treatment modalities. The Bellmunt, CHAARTED, and LATITUDE criteria were compared using the concordance index (C-index).</p><p><strong>Results: </strong>Patients with a low Bellmunt risk score had significantly longer OS than high-risk patients (median OS: 44.4 vs. 14.1 months; p < 0.001). This prognostic effect was consistent in both ARPi and docetaxel subgroups, with no significant interaction between treatment type and Bellmunt score (p-interaction = 0.185). In multivariate analysis, the Bellmunt score remained an independent predictor of OS (HR: 3.13; 95% CI: 1.16-8.43; p = 0.024). The Bellmunt score showed better discriminative ability for OS (C-index: 0.67) than CHAARTED (0.62) and LATITUDE (0.64) criteria. However, the absolute differences in C-index values were modest, and the analysis was restricted to patients with complete data, potentially introducing selection bias.</p><p><strong>Conclusion: </strong>The Bellmunt risk score appears to offer a practical approach to risk stratification in mCSPC, with promising prognostic value across treatment types. However, its incremental clinical utility over existing criteria is limited, and its role in guiding therapy remains unestablished. These exploratory findings warrant prospective validation.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"150-157"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetics-Driven, Intensity-Modulated Adaptive Management of Patients With Metastatic Prostate Cancer.","authors":"Reynier D Rodriguez Rosales, Arjun Venkatesh, Jean-Pierre Kanumuambidi, Yudai Ishiyama, Mohammed Al-Toubat, Hunter Sceats, Thomas D Metzner, Shelby Sparks, Nicole Murray, Mark Bandyk, K C Balaji","doi":"10.1002/pros.70070","DOIUrl":"10.1002/pros.70070","url":null,"abstract":"<p><strong>Background: </strong>Survival differs markedly between men with metastatic prostate cancer (mPC) confined to lymph nodes (LNM) versus bone (BM). We examined whether site-specific genomic alterations-and their combinations-explain this disparity and could inform intensity-modulated follow-up or therapy.</p><p><strong>Methods: </strong>Clinical and targeted-sequencing data for 1011 men with mPC in the cBioPortal for Cancer Genomics registry were analyzed (LNM-only = 622; BM-only = 389). Genes altered in > 5% of tumors (two-sided p < 0.05) were assessed individually and in every possible multigene cluster for associations with overall survival (OS). Survival was evaluated with Kaplan-Meier curves and the difference in restricted mean survival time (dRMST) to pinpoint the first significant curve divergence. Synthetic-lethal (SL) interactions were explored via the SLOAD database.</p><p><strong>Results: </strong>In total, 18 of 184 profiled genes (9.8%) exceeded the 5% alteration threshold. FOXA1 was enriched in BM, whereas TMPRSS2, ERG, PTEN, ZFHX3, CDK12, and KMT2C were enriched in LNM (p < 0.05). Among 9143 tested gene clusters, 65 were associated with inferior OS; 48 occurred in the LNM subgroup, 17 in the combined cohort, and none in the BM alone. High-risk clusters showed first OS divergence 10-60 months after diagnosis of metastasis. SLOAD identified 615 putative SL pairs involving these genes.</p><p><strong>Conclusions: </strong>We identified 65 site-specific multigene clusters-chiefly in lymph node-only mPC-that underlie the survival gap between nodal and bone metastases. These signatures suggest a 10-60-month interval that may lend itself for intensity-modulated follow-up. We also discovered hundreds of synthetic-lethal gene-alteration pairs, opening future research opportunities in combinatorial therapeutic targeting.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"196-203"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic Value of Micro-Ultrasound in Identifying Local Recurrence After Radical Prostatectomy.","authors":"Basil Kaufmann, Manish Choudhary, Ashutosh Maheshwari, Swati Bhardwaj, Adriana Pedraza, Reuben Ben-David, Asher Mandel, Neeraja Tillu, Vinayak G Wagaskar, Mani Menon, Michael A Gorin, Ashutosh K Tewari","doi":"10.1002/pros.70069","DOIUrl":"10.1002/pros.70069","url":null,"abstract":"<p><strong>Purpose: </strong>The limited resolution of standard transrectal ultrasound (TRUS) has made it difficult to perform biopsies of the prostate bed in cases of suspected local recurrence following radical prostatectomy. The aim of this study was to benchmark the performance of using high resolution micro-ultrasound (microUS) in place of standard TRUS for performing post-prostatectomy biopsies.</p><p><strong>Materials and methods: </strong>We conducted a retrospective review of pathology reports from January 2013 to October 2024, identifying patients who underwent biopsies of the prostate bed for suspected local recurrence after radical prostate. Sensitivity and specificity were compared for biopsies performed using standard TRUS. A biopsy was deemed diagnostic if it revealed prostate tissue (cancerous or benign) or non-prostatic tissue when a previously suspicious lesion was no longer detectable on subsequent imaging. The ground truth for local recurrence was defined by biochemical recurrence (prostate-specific antigen [PSA] ≥ 0.2 ng/mL in two consecutive measurements) accompanied by reproducible findings in the prostate bed on MRI and/or PET.</p><p><strong>Results: </strong>Of the 24 patients included, 10 (42%) underwent microUS-guided biopsy and 14 (58%) underwent TRUS-guided biopsy. The median PSA levels at biopsy for the microUS and TRUS cohorts were 0.39 ng/mL (range 0.39-6.40) and 0.45 ng/mL (range 0.20-30.82), respectively. The median lesion sizes on MRI were 0.9 cm (IQR 0.7-1.8) for microUS and 2.5 cm (IQR 1.2-6) for TRUS. MicroUS demonstrated a sensitivity of 89% (95% CI: 52-100), compared with 43% (95% CI: 18-71) for TRUS. Specificity could not be reliably assessed, as only one recurrence-negative patient was available in the microUS group and none in the TRUS group.</p><p><strong>Conclusion: </strong>MicroUS-guided transrectal biopsies appear to offer superior diagnostic performance in detecting local recurrences following radical prostatectomy compared to standard TRUS-guided biopsy. Further study is needed to confirm our findings and to evaluate the performance of microUS-guided biopsies independently of pre-biopsy imaging results.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"189-195"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12704237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}