Prostate最新文献

{"title":"Exploring the Gut-Prostate Axis: Microbial Signatures Linked to Prostate Volume and Bladder Function.","authors":"Jonathan Surber, Marie Lork, Yasser Morsy, Michael Scharl, Daniel Stephan Engeler, Janine Langenauer, Lukas John Hefermehl, Anna Ebner, Basil Kaufmann, Manuela Hunziker, Daniel Eberli, Uwe Bieri, Cédric Poyet","doi":"10.1002/pros.70160","DOIUrl":"10.1002/pros.70160","url":null,"abstract":"<p><strong>Background: </strong>Benign prostatic hyperplasia (BPH) is a common urologic condition in aging men, often linked to systemic inflammation and metabolic dysfunction. Emerging evidence suggests that the gut microbiome may contribute to prostate health and disease. Here we aim to explore potential associations between gut microbiota composition and clinical parameters, such as prostate volume (PV) and residual bladder volume (RBV).</p><p><strong>Methods: </strong>This cross-sectional study analyzed stool samples from 28 patients undergoing transurethral surgery. Gut microbiota composition was analyzed using 16S rRNA gene sequencing. Patients were stratified into groups based on PV ( ≤ 40 mL vs. > 40 mL) and RBV ( ≤ 100 mL vs. > 100 mL). α-diversity (Chao1 and Shannon indices) and β-diversity (Jaccard distance) were calculated. Linear discriminant analysis effect size (LEfSe) was used to identify differentially abundant taxa between groups.</p><p><strong>Results: </strong>No significant differences in gut microbial α- or β-diversity were observed between groups stratified by PV or RBV. Nevertheless, several specific bacterial taxa showed significant variation between groups. Methanobrevibacter smithii was markedly less abundant in patients with PV > 40 mL (p < 0.01). Similarly, patients with high RBV ( ≥ 100 mL) exhibited distinct gut microbial profiles compared to those with lower RBV, characterized by a reduced abundance of Collinsella and an increased abundance of Gastranaerophilales (both p < 0.01).</p><p><strong>Conclusion: </strong>Our findings suggest that while overall gut microbial diversity may remain stable, specific taxa are associated with prostate and bladder phenotypes, supporting the concept of a gut-prostate axis. Future research should focus on longitudinal studies to investigate how gut (and urinary) microbiota evolve alongside BPH and/or LUTS over time, with the goal of determining whether microbial signatures could serve as early indicators for symptomatic BPH.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"900-910"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13116016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147482233","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}

{"title":"Socioeconomic and Demographic Factors in Genetic Testing Utilization Among Advanced Prostate Cancer Patients.","authors":"Alexandra T Skowron, Karen Childers, Courtney M Rose, Kyle C McElyea, Avery K Supernois, Yousuf Hussain, Mohammed Baseer, Sunita Ghosh, Clara Hwang","doi":"10.1002/pros.70165","DOIUrl":"10.1002/pros.70165","url":null,"abstract":"<p><strong>Purpose: </strong>Germline genetic testing in patients with advanced prostate cancer (PCa) is underutilized and hypothesized to be impacted by socioeconomic and demographic factors. This single institution, retrospective study assessed the association of income and social vulnerability with genetic referrals and testing.</p><p><strong>Methods: </strong>The Henry Ford Health (HFH) tumor registry was queried for new diagnoses of stage III, IV PCa from 2017 to 2022. 1385 patients were eligible and 186 patients (13.43%) received a referral, while 1199 (86.57%) patients did not. Median household income (gMHI) and social vulnerability index (SVI) were assigned based on census tract level geocoding and analyzed by tertiles. Univariable and multivariable logistic regression analyses were performed assessing referral for genetic counseling and completion of genetic testing as outcomes. In the multivariable analysis, associations between age, stage and gMHI were analyzed.</p><p><strong>Results: </strong>Black and stage IV patients were more likely to receive genetics referral than White and stage III patients, respectively (20.3% vs 10.6%, p < 0.0001; 25.5% vs 7.3%, p < 0.0001). Multivariable analysis showed that middle gMHI tertile patients had 53% lower unadjusted OR for genetic referral than lowest gMHI tertile patients (OR = 0.47, 95% CI [0.29, 0.75]; p = 0.0017). There was no significant difference in the odds of referral between the highest and lowest gMHI tertiles (OR = 1.22, 95% CI [0.83, 1.79]; p = 0.3175). No other significant associations were found between gMHI, SVI and genetic counseling referrals or completion of testing. Adjusted comparisons showed significant associations between increased referral or testing rate and decreasing age and more advanced stage (OR = 0.97, 95% CI [0.95, 1.00]; p = 0.0218), (OR = 2.84, 95% CI [1.70, 4.74]; p = 0.0001).</p><p><strong>Conclusion: </strong>Although socioeconomic factors have been hypothesized as barriers to genetic testing, we found no evidence of an association in our patient population. Instead, the lowest gMHI tertile patients were equally as likely to complete genetic testing as highest gMHI tertile patients, indicating socioeconomic barriers can be overcome. Clinical factors including age and stage did independently predict completion of testing, supporting referral for testing based on clinical characteristics.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"941-948"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13116033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147583068","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}

{"title":"Does Insulin Resistance Predict Lower Urinary Tract Symptoms? Results From the Reduction by Dutasteride of Prostate Cancer (REDUCE) Trial.","authors":"Renning Zheng, James P Daniels, James M Mirocha, Alexander Hernández-Tirado, Daniel M Moreira, Jay H Fowke, Stephen J Freedland","doi":"10.1002/pros.70154","DOIUrl":"10.1002/pros.70154","url":null,"abstract":"<p><strong>Background: </strong>We previously found that higher insulin resistance (IR) was associated with larger prostate size and greater risk of benign prostatic hyperplasia (BPH). Since BPH is the most common cause of lower urinary tract symptoms (LUTS), we investigated whether IR is also linked to incidence and progression of LUTS in the REDUCE study, a 4-year randomized trial of dutasteride vs. placebo for prostate cancer prevention.</p><p><strong>Methods: </strong>Participants were required to complete the International Prostate Symptom Score (IPSS) questionnaire at recruitment and every subsequent 6 months. Fasting insulin and glucose levels were measured at study baseline, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was calculated based on these values. Multivariable Cox regression was used to assess associations between HOMA-IR and (1) LUTS incidence among asymptomatic patients (baseline IPSS < 8); or (2) LUTS progression among symptomatic patients (baseline IPSS ≥ 8) respectively.</p><p><strong>Results: </strong>As previously reported within this cohort, at baseline, higher HOMA-IR quartiles were correlated with larger prostate volumes among both asymptomatic (N = 2745; p < 0.001) and symptomatic patients (N = 1942; p = 0.007). However, among asymptomatic patients, HOMA-IR whether analyzed as a continuous (p = 0.74) or categorized variable (all p ≥ 0.60) was not associated with LUTS incidence in multivariable analysis. Similarly, in symptomatic participants, no associations were found between HOMA-IR and LUTS progression in multivariable analyses, whether HOMA-IR was assessed as a categorical (all p ≥ 0.46) or continuous variable (p = 0.83).</p><p><strong>Conclusions: </strong>Although IR was linked to larger prostate volumes, it was not an independent risk factor of LUTS development or progression despite the known associations between BPH and LUTS.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"858-864"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147445888","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":"Association Between Preoperative Membranous Urethral Length and Urinary Continence Recovery After Retzius Sparing Robotic Assisted Radical Prostatectomy: Results From a Retrospective Single-Center Study.","authors":"Konstantinos Pagonis, Mohamed Noureldin, Eddy Lilly, Celine Harmouche, Wissam Abou Chedid","doi":"10.1002/pros.70158","DOIUrl":"10.1002/pros.70158","url":null,"abstract":"<p><strong>Background: </strong>Urinary incontinence (UI) remains a common complication after radical prostatectomy, even with advancements such as robotic-assisted radical prostatectomy (RARP). Preoperative membranous urethral length (MUL) has been suggested as a predictor of early continence recovery, but its role in Retzius Sparing RARP (RSRARP) remains unclear. This study evaluated the association between preoperative MUL and early postoperative UI in patients undergoing RSRARP.</p><p><strong>Methods: </strong>We retrospectively analyzed 157 patients who underwent RSRARP between March 2024 and February 2025 at a high-volume center. All had preoperative multiparametric MRI (mpMRI) with MUL measurements and documented continence outcomes at 6 weeks and 3 months. Continence was defined by pad use: pad-free, mild incontinence (1 pad/day), or moderate-to-severe ( ≥ 2 pads/day). Correlation testing and ordinal logistic regression assessed MUL's predictive value. Secondary analysis included age, BMI, prostate volume, and bladder neck preservation.</p><p><strong>Results: </strong>At 3 months, 97% of patients were pad-free and 3% used one pad. Mean MUL was 12.6 mm (SD 2.7). No significant correlation existed between MUL and continence (Spearman's ρ = -0.046, p = 0.570). Regression confirmed MUL was not predictive (p = 0.745). Bladder neck preservation strongly correlated with pad-free continence, while larger prostate size trended toward higher UI but without significance.</p><p><strong>Conclusions: </strong>Preoperative MUL was not identified as a statistically significant predictor of early continence after RSRARP. Bladder neck preservation was associated with favorable continence outcomes; however, given the small number of incontinence events, these findings should be interpreted cautiously. Overall, the high continence rates observed highlight the potential benefit of the Retzius-sparing approach.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"851-857"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147445898","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":"Spatial Robustness of Prostate Cancer Biomarkers Evaluated by Spatial Transcriptomics.","authors":"Kristofer G Taylor, Bjarne Johannessen, Ian G Mills, Morten B Rye, Karol Axcrona, Rolf I Skotheim","doi":"10.1002/pros.70164","DOIUrl":"10.1002/pros.70164","url":null,"abstract":"<p><strong>Background: </strong>Prognostic biomarker panels identified through bulk sequencing approaches have shown utility in localized prostate cancer but are limited by underlying molecular heterogeneity. Spatial transcriptomics offers a complementary approach to investigate spatial gene expression patterns and the tissue- and cell-type-associated localization of their constituent biomarker genes.</p><p><strong>Methods: </strong>Using publicly available data, we analyzed biomarker genes from four prognostic panels (Oncotype DX, Prolaris, Decipher, and ProClass-an in-house candidate panel) across 37 tissue sections from two patients with localized high-grade disease. Analyses were performed to quantify biomarker gene abundance across tissue sections using the Visium Spatial Platform, assess spatial variability using global Moran's I, and identify biomarker localization to specific biological niches through spatial co-expression network analysis.</p><p><strong>Results: </strong>Tissue type composition varied markedly between tissue sections. Several genes from Oncotype DX (KLK2, AZGP1, TPM2, GSN, FLNC, COL1A1) and Decipher (ANO7, MYBPC1) were consistently spatially variable across the samples (mean global Moran's I > 0.1). In contrast, cell cycle-associated genes, predominantly in the Prolaris panel, exhibited weak expression limited to a small proportion of sample spots. ProClass genes also showed limited expression, impeding robust spatial analysis. Weighted gene co‑expression network analysis identified spatial modules closely aligned to histopathological annotations, linking most Oncotype DX genes to stromal networks, whereas Decipher genes spanned diverse networks.</p><p><strong>Conclusions: </strong>Spatial transcriptomics revealed significant variability in biomarker gene expression across highly heterogeneous prostate cancer tissue sections from two patients, providing proof-of-concept for its potential use in prognostic biomarker panel research. Several Oncotype DX genes were notably spatially variable, predominantly localizing to stromal regions, whilst the majority of biomarker genes from other panels exhibited non-spatial patterns. Although low-abundance genes may be impacted by current technological limitations, integrating spatial data into biomarker research holds promise for developing \"spatially robust\" panels to provide reliable prognostic information amidst molecular heterogeneity in prostate cancer.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"929-940"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147583093","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":"A Feasibility Study of the Repurposing of Prazosin to Improve Treatment Outcomes in Men Receiving Radiotherapy for Prostate Cancer (MiniRaP-00).","authors":"Liam D King, David Christie, Daniel Cehic, Wendy Dare, Russ Chess-Williams, Donna Sellers, Catherine McDermott, Alexandra McCarthy, Shailendra Anoopkumar-Dukie","doi":"10.1002/pros.70162","DOIUrl":"10.1002/pros.70162","url":null,"abstract":"<p><strong>Background: </strong>Further work is needed to improve treatment outcomes for prostate cancer (PCa), with the repurposing of the α₁-adrenoreceptor antagonists presenting a potential solution. This feasibility clinical trial presents the first prospective data of the use of an α₁-adrenoreceptor antagonist in men undergoing radiotherapy for PCa.</p><p><strong>Methods: </strong>The study enrolled men planned to receive radiotherapy for PCa. Participants received escalating doses of prazosin administered during radiotherapy. Blood pressure was recorded at each radiotherapy fraction. The primary outcome was treatment protocol feasibility and secondary outcomes were maximum tolerated dose (MTD) of prazosin, safety, and progression-free survival (PFS).</p><p><strong>Results: </strong>Ten participants were enrolled into the study and all achieved > 90% treatment compliance and > 80% assessment compliance. One participant and four participants achieved an MTD of 1 mg and 0.5 mg, respectively, and the remaining five participants had an MTD of 0 mg, with the overall protocol defined MTD being 0 mg. There were no Grades 3/4 adverse events. All treatment-related adverse events (TRAE) were either hypotension or orthostatic hypotension, of the 17 reported TRAEs 16 were asymptomatic. No participants had evidence of disease progression at the 36-week follow-up.</p><p><strong>Conclusions: </strong>Our study demonstrated that coadministration of prazosin during radiotherapy is feasible. However, the incidence of hypotension resulted in a protocol-defined MTD (under conservative blood pressure based DLT definition) of 0 mg, although 16 of the 17 reports were asymptomatic. Combined with monitoring used in other studies utilizing prazosin, this suggests that our safety monitoring and dose-limiting toxicity (DLT) definition may have been too strict and did not accurately reflect a clinically relevant MTD. As this study achieved its primary aim and demonstrated the feasibility of the administration of prazosin during radiotherapy, further prospective studies are justified, with greater consideration given to the definition of DLTs.</p><p><strong>Trial registration: </strong>Australian New Zealand Clinical Trials Registry (381954).</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"891-899"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13116038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147464270","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}

{"title":"A Pilot Study of ¹⁸F-rhPSMA-7.3-PET/MRI to Reduce Mischaracterization of Active Surveillance and Focal Therapy Candidates With Occult Higher Risk Disease.","authors":"Ridwan Alam, Derek Hesse, Nikki Hubbard, Emma McGarrity, Sai Kumar, Clayton Neill, Yutai Li, Nicole Handa, Hiten D Patel, Edward M Schaeffer, Hatice Savas, Ashley E Ross","doi":"10.1002/pros.70147","DOIUrl":"10.1002/pros.70147","url":null,"abstract":"<p><strong>Introduction: </strong>PSMA-PET offers an opportunity to reduce the mischaracterization of disease in active surveillance (AS) and focal therapy (FT) candidates. We describe the results of a pilot clinical trial evaluating ¹⁸F-radiohybrid(rh)PSMA-7.3-PET/MRI to detect occult adverse pathology among potential AS and FT candidates (NCT05852041).</p><p><strong>Methods: </strong>We enrolled 20 men with low risk or favorable intermediate risk prostate cancer and Decipher score ≥ 0.45 diagnosed after an MRI-informed prostate biopsy. All patients underwent PSMA-PET/MRI followed by either PET/MRI-guided biopsy or radical prostatectomy within 90 days. The outcome of interest was detection of grade group (GG) 3-5 disease, seminal vesicle invasion (pT3b), or lymph node involvement (pN1). A detection rate of 15% for this outcome was considered clinically significant. Management decisions and confidence in those decisions were recorded before and after the scan using a 3-point scale. A paired t-test was performed to compare the change in confidence decisions.</p><p><strong>Results: </strong>At enrollment, 17 patients (85%) had favorable intermediate risk and 3 (15%) had low risk prostate cancer. The median Decipher score was 0.58 (IQR 0.49-0.65). Five patients (25%) demonstrated the outcome of interest based on upgrading alone. None had upstaging to pT3b or pN1. Major changes in management plan occurred in 7 patients (35%). Average confidence in decisions improved from moderate (2.05) to high (2.80) after the scan (p < 0.001).</p><p><strong>Conclusions: </strong>¹⁸F-rhPSMA-7.3-PET/MRI can detect occult higher risk disease in men who are otherwise candidates for AS or FT. The scan prompted major changes in management and increased confidence in the final treatment strategy.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"865-871"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13116030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147464310","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}

{"title":"The Prognostic Significance of Radiographic Progression Without PSA Progression in Patients With Metastatic Hormone-Sensitive Prostate Cancer Treated With First-Line ARPI Therapy.","authors":"Takeshi Tsutsumi, Shogo Yamazaki, Takuya Matsuda, Takuya Tsujino, Taizo Uchimoto, Takafumi Yanagisawa, Keiichiro Mori, Wataru Fukuokaya, Fumihiko Urabe, Masanobu Saruta, Atsuhiko Yoshizawa, Shingo Toyoda, Saizo Fujimoto, Kyosuke Nishio, Moritoshi Sakamoto, Tatsuo Fukushima, Ko Nakamura, Kazuki Nishimura, Keita Nakamori, Tomohisa Matsunaga, Yuki Yoshikawa, Ryoichi Maenosono, Kiyoshi Takahara, Teruo Inamoto, Takahiro Kimura, Kazutoshi Fujita, Kazumasa Komura, Haruhito Azuma","doi":"10.1002/pros.70157","DOIUrl":"10.1002/pros.70157","url":null,"abstract":"<p><strong>Background: </strong>Radiographic progression (RP) without prostate-specific antigen (PSA) elevation has emerged as a clinically important pattern in the androgen receptor pathway inhibitors (ARPI) era, but its prevalence and prognostic significance in real-world metastatic hormone-sensitive prostate cancer (mHSPC) cohorts remain unclear.</p><p><strong>Objective: </strong>To assess the prevalence and prognostic implications of RP alone progression in mHSPC patients treated with first-line ARPIs.</p><p><strong>Methods: </strong>We retrospectively analyzed 518 mHSPC patients treated with abiraterone acetate plus prednisolone, enzalutamide, or apalutamide. PSA progression was defined using PCWG3 criteria. Patients were categorized into PSA progression or RP alone progression groups, and clinical outcomes were compared.</p><p><strong>Results: </strong>Among 169 patients who developed castration-resistant prostate cancer (CRPC), 34 (20.1%) experienced RP alone. RP alone patients had significantly worse overall survival compared to those with PSA progression (median 21 vs. 39 months, p = 0.007), despite exhibiting deeper biochemical responses-PSA nadir (0.055 vs. 0.86 ng/mL, p < 0.001) and a higher rate of PSA nadir < 0.2 ng/mL (61.8% vs. 27.4%, p < 0.001). The baseline characteristic differing between groups was CHAARTED volume classification; high volume disease was markedly more common in RP alone patients (94.1% vs. 77.8%). In univariate and multivariate analyses of the overall cohort, CHAARTED high volume disease was identified as an independent risk factor for RP alone (HR 10.3, 95% CI 1.20-89.3; p = 0.034).</p><p><strong>Conclusion: </strong>RP alone progression occurred in approximately one-fifth of patients and was associated with significantly poorer survival despite excellent PSA responses, underscoring the limitation of PSA-based monitoring and supporting routine imaging for early detection of PSA-incongruent disease progression in mHSPC.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"882-890"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13116049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147464234","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}

{"title":"Exosomal ZFPL1 Identifies Neuroendocrine and Stem Cell-Like Prostate Cancer Subtypes?","authors":"Neshat Masud, Johnmesha Sanders, Kenneth A Iczkowski, Girish V Shah","doi":"10.1002/pros.70148","DOIUrl":"10.1002/pros.70148","url":null,"abstract":"<p><strong>Background: </strong>Calcitonin (CT) and its receptor promote prostate cancer (PC) progression and metastasis. Identifying downstream CT-regulated genes may provide clinically useful biomarkers.</p><p><strong>Methods: </strong>Subtraction hybridization was used to identify CT-inducible genes. Expression of zinc finger protein-like 1 (ZFPL1) was examined in malignant versus benign prostate tissues and evaluated for regulation by CT and androgens. Exosomal secretion of ZFPL1 protein was assessed, and plasma levels were measured in PC patients compared with cancer-free individuals. Immunohistochemistry was performed to assess ZFPL1 localization with neuroendocrine (NE) and stem cell markers.</p><p><strong>Results: </strong>ZFPL1 was strongly expressed in malignant prostates but nearly absent in benign tissues. Its expression was upregulated by both CT and androgens. ZFPL1 protein was secreted through exosomes, and plasma concentrations in PC patients were at least fourfold higher than in cancer-free controls. Immunohistochemistry confirmed ZFPL1 co-localization with NE and stem cell markers, suggesting an association with aggressive, androgen-resistant PC.</p><p><strong>Conclusions: </strong>ZFPL1 is a CT- and androgen-regulated protein selectively expressed in malignant prostate cells and secreted via exosomes. Its elevated plasma levels and association with aggressive disease highlight its promise as a non-invasive biomarker for PC detection and monitoring.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"872-881"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147464263","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":"SPOP Mutations in Veterans With Prostate Cancer and Outcomes With Doublet and Triplet Therapy in De Novo Metastatic Hormone Sensitive Prostate Cancer.","authors":"Joseph J Park, Chin-Lin Tseng, Alexandros Giagtzis, Michael J Kelley, Rhonda L Bitting","doi":"10.1002/pros.70161","DOIUrl":"10.1002/pros.70161","url":null,"abstract":"<p><strong>Background: </strong>Inactivating missense mutations in the tumor suppressor gene speckle-type pox virus and zinc finger protein (SPOP) occur in 5%-15% of men with prostate cancer (PC). SPOP mutations increase androgen receptor-mediated transcription and enhance sensitivity to hormonal therapies. Here we describe the clinical characteristics, outcomes, and mutational patterns in Veterans with SPOP-mutated PC.</p><p><strong>Methods: </strong>This retrospective cohort was defined as men diagnosed with PC between January 1, 2000 and September, 30 2024 in the Veterans Affairs health care system with an SPOP mutation identified on genomic testing. The primary and secondary outcomes were overall survival (OS) from date of metastasis and metastatic castration-resistant PC (mCRPC) to death or censoring on December 31, 2024, and adjusted for left truncation.</p><p><strong>Results: </strong>Of 984 Veterans with SPOP-mutated PC, most Veterans (78.4%) received at least one androgen receptor pathway inhibitor (ARPI) and 20.2% received docetaxel. Median OS from date of metastasis (n = 898) was 42.0 mo (95% CI: 38.1-48.2). Median OS from mCRPC diagnosis (n = 425) was 23.5 mo (95% CI: 19.4-29.5). We also identified a subgroup of 114 patients with de novo metastatic hormone-sensitive PC (mHSPC), 96 who received androgen deprivation therapy (ADT) + ARPI (doublet) and 18 who received ADT + ARPI + docetaxel (triplet) as initial therapy. Median OS from diagnosis to death was 48.3 mo (CI not estimable) in the doublet subgroup and not estimable in the triplet subgroup. The most common co-occurring genetic alterations with SPOP in de novo mHSPC were APC (21.9%; 25/114), TP53 (18.4%; 21/114), and PTEN (8.3%; 8/114).</p><p><strong>Conclusions: </strong>This is the largest cohort of men with SPOP mutations, including those with de novo mHSPC treated with an ARPI, reported to date. Further prospective study of SPOP-mutated PC may help guide which patients with de novo mHSPC may either benefit from or can forego the addition of chemotherapy.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"920-928"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147488357","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}