Prostate最新文献

{"title":"c-Kit-Mediated PI3K/AKT and Wnt/β-Catenin Signaling Drives Resistance to 5α-Reductase Inhibitors in Benign Prostatic Hyperplasia.","authors":"Jun Zhu, Junduo Wang, Meng Gu, Huan Xu, Yanbo Chen, Bin Xu, Qi Chen","doi":"10.1002/pros.70046","DOIUrl":"https://doi.org/10.1002/pros.70046","url":null,"abstract":"<p><strong>Background: </strong>Resistance to 5α-reductase inhibitors (5ARIs) represents a significant therapeutic challenge in benign prostatic hyperplasia (BPH) clinical management. While the c-Kit-mediated signaling has been implicated in various pathological conditions, its role in BPH and 5ARI resistance remains undefined.</p><p><strong>Methods: </strong>Patient-derived organoids (PDOs) were established from BPH specimens and characterized through immunofluorescence, immunohistochemistry, and RT-qPCR analysis. Transcriptomic profiling was performed to identify differentially expressed genes between 5ARI-sensitive and resistant samples. The functional significance of c-Kit-mediated signaling was evaluated using selective inhibitor ISCK03. Further analysis identified cellular targets of c-Kit inhibition, and downstream signaling mechanisms were characterized through pathway analysis.</p><p><strong>Results: </strong>RNA sequencing revealed differentially expressed genes between 5ARI-sensitive and resistant BPH PDOs, with significant enrichment in KIT and related genes. Enhanced c-Kit expression was confirmed in 5ARI-resistant specimens through multiple methodologies. Selective c-Kit inhibition with ISCK03 specifically suppressed 5ARI-resistant PDOs proliferation while sparing sensitive ones. Tests utilizing single-cell-derived organoids identified basal epithelial cells as primary targets of c-Kit inhibition. Mechanistic studies demonstrated that c-Kit maintains 5ARI resistance through the PI3K/AKT and Wnt/β-catenin signaling axis, with c-Kit inhibition significantly downregulating this pathway.</p><p><strong>Conclusions: </strong>c-Kit-mediated signaling is associated with 5ARI resistance in BPH, potentially through modulation of PI3K/AKT and Wnt/β-catenin pathways. These findings highlight c-Kit as a potential therapeutic target for overcoming 5ARI resistance.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187771","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 of Weight Loss and BMI on PSA Levels and Overall Survival in Veterans With Metastatic Castrate-Resistant Prostate Cancer.","authors":"Nicholas Fedele, R Jackson Wilson, Jason Doherty, Priya Baxi, Daniel Eaton, Nina Cheranda, Srinivas Govindan, Suhong Luo, Martin W Schoen","doi":"10.1002/pros.70060","DOIUrl":"https://doi.org/10.1002/pros.70060","url":null,"abstract":"<p><strong>Background: </strong>There is a complex relationship between body weight and survival in prostate cancer. While increased BMI is associated with increased prostate cancer incidence and death, obesity is associated with improved survival in metastatic castrate-resistant prostate cancer (mCRPC). However, little is known about the effect of weight change before the treatment of mCRPC on survival. We assessed the association between BMI, weight loss before treatment, PSA levels, and overall survival in mCRPC.</p><p><strong>Methods: </strong>Veterans treated with abiraterone or enzalutamide for de novo mCRPC from May 2011 to June 2017 were identified within the VHA. BMI and weight loss in the year before treatment were determined. Kruskal-Wallis, χ² tests, ANOVA, Kaplan-Meier, and Cox proportional hazard modeling tests were used to assess the association between BMI, weight loss, PSA at the start of treatment, and overall survival, with covariates including age, race, and Charlson Comorbidity Index.</p><p><strong>Results: </strong>We identified 8857 veterans treated for mCRPC with weight loss values available and 8438 patients with BMI values available. There was shorter survival in veterans with weight loss > 10% of body weight (median = 9.8 months, n = 1332) compared with 5%-10% loss (median = 16.1 months, n = 1619) and stable weight (median = 25.1 months, n = 5906). Mean PSA levels increased (106.3, 160.0, 267.8) as BMI decreased (BMI > 30, BMI 25-30, BMI < 25), respectively. As weight loss increased (stable weight vs. weight loss 5%-10% vs. weight loss > 10%), mean PSA levels increased (112.2, 205.8, 405.9), respectively. Compared with a stable weight, both losing 5%-10% of weight (HR: 1.30, 95% CI: 1.22-1.38) and losing > 10% of weight (HR: 1.98, 95% CI: 1.85-2.12) are independently associated with increased mortality. Analyses in subgroups revealed BMI > 30 with stable weight to be the most favorable group in terms of survival, while BMI < 25 with > 10% weight loss had the highest mortality risk (HR: 2.63, 95% CI: 2.39-2.89).</p><p><strong>Conclusion: </strong>Weight loss the year before treatment is associated with increased mortality and higher PSA levels in patients with mCRPC. The effect of weight loss is independent of BMI, where we found that lower BMI is associated with increased mortality and higher PSA levels in patients with mCRPC. This risk increases with the magnitude of weight loss, with lower BMI categories compounding the risk. Both weight loss and BMI should be incorporated into survival models to improve prognostication in mCRPC.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187744","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":"Influence of 5-Alpha Reductase Inhibitors on PI-RADS Scores and Prostate Cancer Detection: A Systematic Review and Meta-Analysis.","authors":"Lian Qiong, Li Qingyi, Guo Bohong, Hao YouCheng, Liu Qiangzhao","doi":"10.1002/pros.70066","DOIUrl":"https://doi.org/10.1002/pros.70066","url":null,"abstract":"<p><strong>Background: </strong>The impact of 5-alpha reductase inhibitors (5-ARIs) on Prostate Imaging Reporting and Data System (PI-RADS) tumor classifications and prostate cancer (PCa) detection were reviewed and analyzed.</p><p><strong>Method: </strong>A comprehensive systematic review and meta-analysis were conducted by evaluating published studies examining the influence of 5-ARIs on PI-RADS lesions and PCa detection. The Web of Science, PubMed, and Embase databases were accessed for relevant study retrieval. Statistical analyses were performed through the use of STATA v.16.0.</p><p><strong>Results: </strong>Seven studies, comprising 12,132 participants, were included. Compared to men who had not received 5-ARIs, those exposed to 5-ARIs exhibited no significant differences in PCa diagnosis (OR 0.97, 95% CI 0.86-1.08; p = 0.55) or clinically significant PCa (csPCa) diagnosis (OR 1.01, 95% CI 0.89-1.16; p = 0.85). Further subgroup analyses demonstrated that 5-ARI-exposed men had comparable PCa diagnosis in PI-RADS 3 (OR 0.85, 95% CI 0.65-1.12; p = 0.25), PI-RADS 4 (OR 1.01, 95% CI 0.85-1.21; p = 0.84), and PI-RADS 5 (OR 1.01, 95% CI 0.81-1.26; p = 0.87) groups relative to 5-ARI-naïve men.</p><p><strong>Conclusions: </strong>These findings suggest that 5-ARIs do not significantly alter PI-RADS lesion distribution or impact PCa and csPCa diagnosis. Consequently, exposure to 5-ARIs should not influence MRI-based diagnostic approaches in patients with suspected PCa.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187725","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":"https://doi.org/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":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-24","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":"Integration of Primary Care Into the Follow-Up Protocol for Prostate Cancer Patients in Aragon, Spain. It Is Time to Follow Other Successful Models in the Region.","authors":"Angel Borque-Fernando, Patricia Guerrero-Ochoa, Luis Mariano Esteban, Aitor Hernández, Raúl López-Blasco, Raquel Espílez Ortiz, Pedro Gil Martínez, Jesús Gil-Fabra, Miguel Angel Trivez-Boned, Eva Mallén-Mateo, María Jesús Gil-Sanz","doi":"10.1002/pros.70057","DOIUrl":"https://doi.org/10.1002/pros.70057","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objective: &lt;/strong&gt;Over the past decade, prostate cancer (PCa) survival rates have increased, largely due to advancements in modern healthcare. As a result, the majority of PCa patients worldwide are now survivors, placing a considerable burden on healthcare systems. Specialists at Miguel Servet Hospital in Zaragoza, Spain, follow the European Association of Urology (EAU) guidelines in managing PCa patients; however, these recommendations do not specifically address the follow-up of patients by nonspecialist medical staff. This study evaluates the safety of a follow-up protocol that refers PCa survivors to primary care after undergoing radical prostatectomy (RP) as a curative treatment, with a particular focus on those diagnosed with pathologic high-grade localized and locally advanced PCa.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The study includes data from 579 patients diagnosed with high-risk PCa-both localized and locally advanced-according to EAU criteria. These patients underwent RP between 1992 and 2018 at the Aragón Health Service (SALUD), Sector Zaragoza II-Hospital Universitario Miguel Servet. The follow-up protocol involves initial monitoring by the urology department. Patients who remain free of biochemical recurrence (BCR) are subsequently followed up by primary care (PC) medical staff. To evaluate the short- and long-term effectiveness of this protocol, we analyzed biochemical recurrence-free survival, stratified by risk groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The BCR rate after referral to PC is under 20.5% in the overall high-risk group. A more detailed analysis shows that the localized subgroup has a 14.5% BCR probability, while the locally advanced subgroup experiences a fourfold increase, reaching 41.98%. The risk of BCR is 2-5 times higher in the locally advanced group compared to the localized group. BCR patterns indicate that nearly half of all cases occur within 4 years post-RP, though trends vary by risk group. In high-risk localized PCa, almost half of BCRs occur between four and ten years post-RP, whereas in locally advanced PCa, over 65% occur within the first 4 years, indicating earlier recurrence in this group. Kaplan-Meier survival curves confirm a significant difference (p &lt; 0.001): locally advanced PCa shows a threefold higher cumulative BCR risk at 10 years (2.78) and a fourfold higher risk at 5 years (4.41). Although the overall BCR rate after referral to PC is below 20.5% in the high-risk group, recurrence risk varies significantly-14.5% in the localized subgroup versus 41.98% in the locally advanced subgroup. These findings underscore the earlier and more frequent recurrence in locally advanced PCa compared to high-risk localized PCa.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Referring PCa survivors for follow-up in primary care has proven to be an effective and safe approach. The success of this protocol can be attributed to clear communication with the primary care team regarding the parameters f","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132830","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":"Robot-Assisted Salvage Prostatectomy: External Validation of the EAU Selection Criteria and Identification of the Optimal Candidate: A Junior ERUS/YAU Collaborative Study.","authors":"Mike Wenzel, Christoph Würnschimmel, Arjun Nathan, Marcio Covas Moschovas, Christian Wagner, Giorgio Calleris, Fabrizio Di Maida, Juan Gomez Rivas, Carlo Andrea Bravi, Ruben De Groote, Federico Piramide, Filippo Turri, Keith Kowalczyk, Gopal Sharma, Iulia Andras, Edward Lambert, Nikolaos Liakos, Danny Darlington, Marco Paciotti, Gabriele Sorce, Philipp Mandel, Antonio Galfano, Senthil Nathan, Giancarlo Marra, Paolo Dell'Oglio, Alexandre Mottrie, Felix K H Chun, Vipul Patel, Alberto Breda, Alessandro Larcher","doi":"10.1002/pros.70048","DOIUrl":"https://doi.org/10.1002/pros.70048","url":null,"abstract":"<p><strong>Background: </strong>EAU guidelines recommend salvage radical prostatectomy (sRP) only in highly selected patients with recurrent prostate cancer in experienced centers.</p><p><strong>Methods: </strong>The Junior ERUS/Young Academic Urologist Working Group on Robot-Assisted Surgery conducted a multicentric project to investigate biochemical recurrence-free (BCR), metastases-free (MFS), and overall survival (OS) outcomes in robotic sRP patients stratified according to EAU criteria.</p><p><strong>Results: </strong>Of 180 patients, 49% fulfilled EAU criteria. Patients not fulfilling EAU criteria more frequently underwent focal therapy as primary treatment (53% vs. 33%) and exhibited significantly higher rates of pT3-4 (70% vs. 48%), positive surgical margins (48% vs. 24%), and pathological Gleason score 8-10 (72% vs. 48%, all p < 0.01), with no differences in postoperative complications. Rates of PSA persistence were significantly higher in patients not fulfilling EAU criteria (16% vs. 0%, p < 0.001). Regarding BCR, patients not fulfilling EAU criteria harbored significantly worse BCR-free survival (hazard ratio (HR): 1.96, p = 0.046) with 24- and 48-month BCR-free survival rates of 81.7% and 73.9% vs. 65.0% and 58.5% for patients fulfilling EAU criteria. After multivariable adjustment, patients not fulfilling EAU criteria harbored higher risk of BCR (HR: 2.94, p = 0.045). Regarding MFS and OS outcomes, no significant differences were observed in the comparison between both groups. Incorporating presalvage surgery features into a new classification yielded better discrimination for BCR analysis, but were comparable to EAU criteria for MFS and OS outcomes.</p><p><strong>Conclusions: </strong>The majority of patients do not fulfill EAU criteria, and even more so after focal therapy. These patients harbor worse BCR rates after robotic sRP. However, within our short-term follow-up, no differences in MFS and OS were observed.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132802","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":"Comprehensive Histopathological and Biochemical Analyzes of Prostatic Amyloid Bodies (Corpora Amylacea) From Autopsy Samples From Japanese Patients.","authors":"Junji Yatsuda, Kyosuke Kanenawa, Toshiya Nomura, Masamitsu Okada, Teruaki Masuda, Yohei Misumi, Masayoshi Tasaki, Mitsuharu Ueda, Yukio Ando, Tomomi Kamba","doi":"10.1002/pros.70058","DOIUrl":"https://doi.org/10.1002/pros.70058","url":null,"abstract":"<p><strong>Background: </strong>Amyloid bodies (corpora amylacea) are found in the prostate and other organs, and their abnormal accumulation can lead to amyloidosis. However, it remains unclear how the constituents and pathological significance of amyloid bodies differ between tissues.</p><p><strong>Methods: </strong>We performed pathological, proteomic, and biochemical analyzes of prostatic amyloid bodies isolated from 53 consecutive patients who underwent pathological autopsy at Kumamoto University from 2006 to 2017. Amyloid bodies were isolated using laser microdissection, and their constituents were analyzed by liquid chromatography-tandem mass spectrometry, immunohistochemistry, and immunoblotting.</p><p><strong>Results: </strong>Prostatic amyloid bodies were found in samples from 47 of the 53 patients (89%). The most frequently detected proteins were lactoferrin (100%), S100-A9 (90.9%), prostate-specific antigen (90.9%), and cytoskeleton-associated protein 2-like (90.9%). Amyloid-associated proteins, such as apolipoprotein E (72.7%), vitronectin (54.5%), and serum amyloid P component (36.4%), were also present but were less prevalent. Prostatic amyloid bodies were more common in patients with benign prostatic hyperplasia (N = 25) than in other patients (N = 28).</p><p><strong>Conclusions: </strong>These results suggest that amyloid bodies from different tissues may share some constituents. Our findings support further investigation to determine the relationship between the constituents of prostatic amyloid bodies and the pathophysiology of prostatic diseases.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145132843","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":"Hormone Therapy With Salvage Radiotherapy After Radical Prostatectomy: A Systematic Review and Meta-Analysis.","authors":"Reyhaneh Bayani, Kasra Kolahdouzan, Sepehr Nayebirad, Naeim Nabian, Fatemeh Jafari, Reza Ghalehtaki, Filippo Alongi, Nima Mousavi Darzikolaee","doi":"10.1002/pros.70056","DOIUrl":"https://doi.org/10.1002/pros.70056","url":null,"abstract":"<p><strong>Background: </strong>Salvage radiotherapy (RT) is a standard treatment for non-metastatic prostate cancer recurrence after radical prostatectomy (RP), yet the efficacy of concurrent hormone therapy remains debated. This systematic review and meta-analysis evaluates the impact of adding hormone therapy to adjuvant or salvage RT on key survival outcomes.</p><p><strong>Methods: </strong>We searched PubMed, Scopus, Web of Science, and clinical trial registries for randomized phase 2 or 3 trials comparing RT alone versus RT with hormone therapy (anti-androgens or androgen deprivation therapy) in patients undergoing RP. A random-effects meta-analysis with the inverse variance method was performed for overall survival (OS), metastasis-free survival (MFS), and progression-free survival (PFS) after extracting the corresponding hazard ratios (HR) and 95% confidence intervals (CI).</p><p><strong>Results: </strong>Four trials with generally low risk of bias were identified. Pooled HRs were 0.85 (95% CI: 0.72-0.99) for OS, 0.82 (95% CI: 0.70-0.96) for MFS, and 0.58 (95% CI: 0.51-0.66) for PFS, favoring hormone therapy. Following a sensitivity analysis that excluded the results of one of the four trials, the significance for OS was no longer observed.</p><p><strong>Conclusion: </strong>Hormone therapy with post-RP RT significantly improves OS, MFS, and PFS in prostate cancer patients. Although the benefit in OS appears less robust, these findings support the significant role of hormone therapy in delaying disease progression. PROSPERO Registration Number: CRD42024597336.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145126237","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":"Pathology of a Canine Model of Localized Prostate Carcinoma.","authors":"Nathan K Hoggard, Felipe M Berg, Marlon R Szczepaniak, Xinning Wang, Noriko Kantake, Gopalakrishnan Ramamurthy, Li Gong, Eric T Hostnik, Krishan Kumar, Arijit Ghosh, Dong Luo, Michael V Knopp, Jill M Keller, Evan T Keller, Agata A Exner, James P Basilion, Michael F Tweedle, Thomas J Rosol","doi":"10.1002/pros.70054","DOIUrl":"https://doi.org/10.1002/pros.70054","url":null,"abstract":"<p><strong>Background: </strong>Dogs spontaneously develop prostate carcinoma (PC) and share prostate gland anatomy, physiology, and size to men. Over the last 15 years, we have developed and refined a canine model of focal PC to evaluate therapeutic-diagnostic (theranostic) interventions. A comprehensive description of the pathology and synthesis of the various studies has not been performed. The goal of this manuscript was to describe the canine model tumor pathology within the framework of its methodological development to help guide future translational PC research.</p><p><strong>Methods: </strong>In published and unpublished studies, we previously inoculated prostate glands of immunosuppressed, intact beagle dogs (n = 56) with a canine PC cell line (Ace-1) transduced with human or canine genes for targeted theranostics. Gross tumor assessment and histology were performed in all cases. Molecular tumor and microenvironmental pathology was investigated using digital image analysis, immunohistochemistry, laser-capture microdissection, and quantitative real-time PCR.</p><p><strong>Results: </strong>The model reliably (85.7% engraftment rate) formed prostatic tumors resembling intermediate and high-grade localized PC, with poorly differentiated morphology, stromal invasion, and peripheral growth. Soft tissue metastasis occurred in 13/48 (27.1%) dogs. Most dogs formed multifocal prostatic tumors with occasional tumors outside the prostate gland. Tumor location influenced growth behavior and the microenvironment. Allografts were histologically classified as intraglandular intraprostatic, invasive intraprostatic, capsular, or extraprostatic. Compared to intraprostatic tumors, capsular/extraprostatic tumors had increased proliferation (Ki-67 index), epithelial-to-mesenchymal transition, and microenvironmental alterations that included increased collagenous stroma, fibroplasia, and reduced immune cell infiltration.</p><p><strong>Conclusions: </strong>The canine model of PC captured important pathologic features of men undergoing curative-intent therapy alongside model- and species-specific characteristics of interest to researchers. Beyond defining pathology, the results highlighted applications of the canine model in studying the tumor microenvironment and advancing preclinical, anti-cancer strategies in a large animal species.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114812","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":"Enhancing Prostate Cancer Diagnosis: The Combined Value of PHI and mpMRI.","authors":"Y M Yáñez-Castillo, M T Melgarejo-Segura, M A Arrabal-Polo, A Jiménez-Pacheco, J V García-Larios, T De Haro Muñoz, P Lardelli-Claret, J L Martín-Rodríguez, M Arrabal-Martín","doi":"10.1002/pros.70055","DOIUrl":"https://doi.org/10.1002/pros.70055","url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer (PCa) diagnosis is often hindered by the need to detect clinically significant disease (csPCa) while minimizing unnecessary biopsies. The Prostate Health Index (PHI) and multiparametric magnetic resonance imaging (mpMRI) are promising tools to address these challenges.</p><p><strong>Objective: </strong>To develop and internally validate a predictive model for PCa and csPCa by combining PHI and mpMRI in a high-risk population.</p><p><strong>Methods: </strong>This retrospective study included 179 patients who underwent prostate biopsy between 2019 and 2023. Inclusion criteria comprised elevated PSA (> 3 ng/mL), suspicious digital rectal examination and/or family history, PHI values, and pre-biopsy mpMRI. Logistic regression models were developed, and model performance was assessed using C-statistics, calibration plots, and decision curve analysis (DCA).</p><p><strong>Results: </strong>PCa was diagnosed in 40.2% of patients, and csPCa in 34.7% of them. A multivariate model including PHI, prostate volume, and mpMRI achieved an AUC of 0.81 for PCa. For csPCa, the best model combined PHI and prostate volume (AUC 0.76). In the PI-RADS 3 subgroup, PHI showed high discriminatory performance (AUC 0.81), surpassing PSA density (PSA-D). The DCA showed a superior net benefit of the multivariable models compared to single-parameter strategies.</p><p><strong>Conclusion: </strong>Integrating PHI and mpMRI improves PCa diagnostic accuracy and clinical decision-making, especially in ambiguous cases such as PI-RADS 3 lesions, and reduces unnecessary biopsies in clinical practice.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114777","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}