Prostate最新文献

{"title":"The Effects of the Blood-Based S2,3PSA% Test on Prostate Cancer Screening: A Novel Approach to Reduce the Need for MRI and Unnecessary Biopsies.","authors":"Hikari Miura, Tomoko Hamaya, Tohru Yoneyama, Tadashi Shimoyama, Fumiyasu Tsushima, Kyo Togashi, Yuki Miura, Anna Yoneyama, Hiroyuki Sato, Sosuke Omizo, Kazuyuki Mori, Hirotake Kodama, Naoki Fujita, Teppei Okamoto, Hayato Yamamoto, Shingo Kakeda, Chikara Ohyama, Shingo Hatakeyama","doi":"10.1002/pros.24917","DOIUrl":"10.1002/pros.24917","url":null,"abstract":"<p><strong>Objective: </strong>Prostate-specific antigen (PSA)-based screening has reduced prostate cancer (PCa) mortality but is associated with overdiagnosis/overtreatment. We developed and evaluated a blood-based S2,3PSA% test to address the limitations of PSA-based screening for PCa.</p><p><strong>Methods: </strong>This retrospective study included men aged ≤ 75 years who underwent opportunistic PSA and S2,3PSA% screening between April 2022 and March 2023. Secondary screening was recommended for participants with PSA ≥ 2.0 ng/mL and S2,3PSA% ≥ 38.0%, or PSA ≥ 4.0 ng/mL. The primary outcome was the reduction in MRI utilization based on an S2,3PSA% cutoff of ≥ 38.0%. Secondary outcomes included the PCa detection rate, as well as reductions in prostate biopsies and medical costs.</p><p><strong>Results: </strong>Among 808 participants who underwent PSA and S2,3PSA% screening, 190 met the criteria for secondary screening. Of these, 72 underwent further evaluation, including MRI in 65 participants. MRI findings excluded 22 (33.8%) participants from requiring prostate biopsy. Ultimately, 25 participants underwent prostate biopsy, and PCa was diagnosed in 17 (68.0%), including 12 with clinically significant PCa. The combined use of PSA, S2,3PSA%, and MRI resulted in a 44% reduction in MRI use, a 63% reduction in unnecessary biopsies, and a 72% reduction in medical costs. Study limitations include the small sample size and lack of evaluation of participants with negative S2,3PSA% or MRI findings.</p><p><strong>Conclusions: </strong>S2,3PSA% screening may have potential as a tool to reduce the need for MRI, unnecessary biopsies, and medical costs.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"1062-1068"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128739","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":"Altered Ten Eleven Translocation Methylcytosine Dioxygenase Expression and DNA Hydroxymethylation in a Mouse Model of Prostate Cancer.","authors":"Matthew Aguilera, David L Klinkebiel, Victoryn Williams, Jeffrey Rovatti, Benjamin Purizhansky, Barbara A Foster, Adam R Karpf, Shannon R M Kinney","doi":"10.1002/pros.24912","DOIUrl":"10.1002/pros.24912","url":null,"abstract":"<p><strong>Background: </strong>DNA hydroxymethylation (5hmC) is known to be altered in human prostate cancer. An animal model is required to study the functional roles of the ten eleven translocation (TET) DNA dioxygenases and the 5hmC modification in prostate cancer development and progression.</p><p><strong>Methods: </strong>We characterized Tet expression, global genomic 5hmC, and genome-wide 5hmC patterns, and the transcriptome, in the TRansgenic Adenocarcinoma of Mouse Prostate (TRAMP) autochthonous model of prostate cancer.</p><p><strong>Results: </strong>We observed increased mRNA and protein levels of Tet1 in TRAMP samples, as compared to normal mouse prostate. Additionally, we found minimal expression of Tet2 mRNA overall, and Tet3 mRNA levels appeared similar in both sample types. However, TRAMP tumors expressed what appeared to be the inactive form of Tet3, versus the active form expressed in normal prostates. TRAMP tumors displayed global genomic hypohydroxymethylation (i.e., loss of 5hmC), and genome-wide analysis revealed widespread hypohydroxymethylation was interspersed with regions of locus-specific hyperhydroxymethylation (i.e., increased 5hmC). The differentially hydroxymethylated regions correlated with altered gene expression, and pathway analyses indicated that these genes often participate in oncogenic pathways.</p><p><strong>Conclusions: </strong>Tet expression and 5hmC patterns are altered in the TRAMP model and closely match what has been observed in human prostate cancer, suggesting that TRAMP is a suitable model to study the role of Tets and 5hmC in prostate cancer development and progression.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"1036-1051"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041169","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":"Prevalence and Characteristics of Prostatic Utricles: A Retrospective MRI Study in Middle-Aged to Elderly Men.","authors":"Tomer Bashi, Shoni Kamshov, Adi Kidron, Sophie Barnes, Amihay Nevo, Snir Dekalo, Yuval Bar-Yosef","doi":"10.1002/pros.24907","DOIUrl":"10.1002/pros.24907","url":null,"abstract":"<p><strong>Background: </strong>Congenital urological malformations encompass a wide range of anomalies affecting the urinary tract and reproductive organs. MRI has emerged as a diagnostic tool in identifying these conditions. Prostatic utricle is an enlarged diverticulum in the posterior urethra, which results from incomplete degradation of the Müllerian ducts or decreased androgenic stimulation of the urogenital sinus. Prostatic utricle is an uncommon congenital anomalies, with 1% incidence in autopsy findings and clinical prevalence of 5% in urologic patients.</p><p><strong>Methods: </strong>This retrospective study analyzed 5819 prostate MRI interpretations from 4990 unique patients. The primary objective was to identify congenital abnormalities, focusing on the presence of a utricle and other related anomalies. Prostates suspected to have utricles were reevaluated by genitourinary specialized radiologist and utricles size were measured.</p><p><strong>Results: </strong>The study identified 127 patients positive for a utricle with an average age of 66 years at examination among the unique cohort. The average prostate size for patients with a utricle was 78.3 cc and the average utricle size was 0.4 cm³. Statistical analysis did not demonstrate any statistical trend between prostate size, age or PSA to utricle size. Additional congenital anomalies detected included one patient with a seminal vesicle cyst, one patient with right seminal vesicle agenesis and bilateral vas deferens agenesis, and two patients with ureterocele.</p><p><strong>Conclusion: </strong>The prevalence of prostate utricle within a cohort of 4990 middle-aged to elderly men is 2.54%.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"1000-1004"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041854","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":"LHRH Antagonists Restore Serum Testosterone Faster Than LHRH Agonists in Prostate Cancer Patients After Radiotherapy.","authors":"Sangjon Pae, Shinichi Sakamoto, Xue Zhao, Takaaki Tamura, Tomohiko Kamasako, Akinori Takei, Yasutaka Yamada, Tomokazu Sazuka, Yusuke Imamura, Koichiro Akakura, Tomohiko Ichikawa","doi":"10.1002/pros.24899","DOIUrl":"10.1002/pros.24899","url":null,"abstract":"<p><strong>Introduction: </strong>Maintaining a castration level of testosterone (TST) during radiation therapy combined with androgen deprivation therapy (ADT) is an essential strategy in the treatment of prostate cancer; however, hypogonadism can cause various complications. The aim was to compare serum TST recovery between LHRH agonists and LHRH antagonists.</p><p><strong>Methods: </strong>A total of 131 patients who underwent radiation therapy with ADT for prostate cancer were retrospectively analyzed. Serum TST levels after termination of ADT including LHRH agonists and antagonists were compared. Cox proportional hazards model and the Kaplan-Meier method were used for statistical analysis.</p><p><strong>Results: </strong>Median age, baseline TST, nadir TST, and duration of ADT were 71 years, 535 ng/dL, 10.92 ng/dL, and 12 months, respectively. Multivariate analysis identified significant associations of initial PSA ≥ 10.92 ng/mL (p = 0.0366), ADT ≥ 360 days (p = 0.0408), nadir TST ≤ 19 ng/dL (p = 0.0003), and LHRH agonist (p = 0.0027) with delayed TST recovery to castration level (50 ng/dL). We created a risk model based on these four independent risk factors (Low: 0-1 factor/Intermediate: 2 factors/High Risk: 3-4 factors). Each risk group significantly differentiated the TST recovery to castration level. Even after propensity score matching, recovery of TST to castration level and therapeutic level (200 ng/dL) was significantly delayed in the LHRH agonist group compared with the LHRH antagonist group (p = 0.0016, p = 0.0389, respectively).</p><p><strong>Conclusion: </strong>LHRH antagonists restored serum TST to castration and therapeutic levels faster than LHRH agonists in prostate cancer patients undergoing radiation therapy with ADT.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"919-931"},"PeriodicalIF":2.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774877","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":"National Cancer System Characteristics and Prostate Cancer Outcomes: An Analysis of Global Data.","authors":"Edward Christopher Dee, Ranvir Iyengar, Aditya Narayan, Erin Jay G Feliciano, James Fan Wu, Frances Dominique V Ho, Kenrick Ng, Jonas Willmann, Megan Lorenza L Cabaero, Anderson Kirk Nigel G Tan, Kaitlyn Lapen, Daniel Gorovets, Dana E Rathkopf, Sean M McBride, Himanshu Nagar, Brandon A Mahal, Paul L Nguyen","doi":"10.1002/pros.24901","DOIUrl":"10.1002/pros.24901","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Importance and objective: &lt;/strong&gt;Prostate cancer is the second most common cancer among men globally and the number of cases is expected to double from 2020 to 2040. A greater understanding of health system factors that can be leveraged to improve prostate cancer control may guide health system planning in anticipation of the growing global burden of prostate cancer.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;This ecological cross-sectional study made use of the most recent available national health system metrics for countries with prostate cancer incidence and mortality estimates available from the International Agency for Research on Cancer (IARC). IARC data represent the most updated estimates as of April 2025.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcomes: &lt;/strong&gt;National estimates of age-standardized mortality-to-incidence ratios (MIR) were derived from the GLOBOCAN 2022 database for male patients with prostate cancer of all ages. Health spending as a percent of gross domestic product, physicians per 1000 population, nurses and midwives per 1000 population, surgical workforce per 1000 population, gross domestic product (GDP) per capita, Universal Health Coverage Service Coverage Index (UHC index), availability of pathology services, human development index (HDI), gender inequality index, and number of radiotherapy centers per 1000 population were collected. The association between prostate MIR and each metric was evaluated using simple univariable linear regression models. Those with p &lt; 0.005 (Bonferroni corrected) were included in multivariable models. Variation inflation factor analysis facilitated exclusion of variables with significant multicollinearity. R&lt;sup&gt;2&lt;/sup&gt; defined goodness of fit.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Based on IARC estimate availability, data for 185 countries were collected; data availability ranged from 144 (77.8%, surgical workforce per 1000 population known) to 185 (100%, GDP per capita, RT centers per 1000 population). On univariable analysis, each of the 10 metrics was significantly associated with MIR of prostate cancer (&lt; 0.001 forall). All but one (HDI, due to mutlicollinearity) were included in the multivariable model. The final multivariable model included 123 countries with complete data. Of those included in the regression with complete data, 44 of 123 (35.8%) were high-income countries; of those excluded due to incomplete data, 16 of 62 (25.8%) were high-income countries (χ² p = 0.17 comparing the proportion of high-income countries in the included and excluded groups). Therefore, the following variables were independently associated with lower (improved) MIR for prostate cancer: (1) surgical workforce per 1000 population, (2) UHC index, (3) radiotherapy centers per 1000 population, (4) GDP per capita. The final model had R&lt;sup&gt;2&lt;/sup&gt; of 0.8408.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions and relevance: &lt;/strong&gt;Analysis of global data and health-system metrics suggest that surgical workforce, degree of UHC, availability of radiot","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"947-953"},"PeriodicalIF":2.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042946","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 and Safety of Enzalutamide and Abiraterone Plus Prednisolone in Elder Castration-Resistant Prostate Cancer Patients: A Sub-Analysis From the ENABLE Study.","authors":"Takehiko Okamura, Kouji Izumi, Satoshi Kurokawa, Takashi Shima, Yuki Kato, Koji Mita, Manabu Kamiyama, Shogo Inoue, Seiji Hoshi, Nobumichi Tanaka, Yuko Yoshio, Hideki Enokida, Ippei Chikazawa, Noriyasu Kawai, Kohei Hashimoto, Takashi Fukagai, Kazuyoshi Shigehara, Shizuko Takahara, Atsushi Mizokami","doi":"10.1002/pros.24897","DOIUrl":"10.1002/pros.24897","url":null,"abstract":"<p><strong>Background: </strong>Clinical trials rarely focus on elder patients with castration-resistant prostate cancer (CRPC), and data on the outcomes of second-generation androgen receptor signaling inhibitors (ARSIs) remain limited.</p><p><strong>Methods: </strong>The ENABLE study for prostate cancer was an investigator-initiated, multicenter, randomized controlled trial conducted in Japan to compare enzalutamide (ENZ) and abiraterone plus prednisolone (ABI). This sub-analysis was performed to evaluate the efficacy and the safety profiles between patients aged ≥ 75 (older) and < 75 years (younger), and then between the ENZ and ABI arms in the older and the younger cohort separately.</p><p><strong>Results: </strong>The ENZ arm included 41 younger and 51 older patients, while the ABI arm included 36 younger and 56 older patients. No significant differences in survival endpoints were observed between younger and older patients. Median time to prostate-specific antigen (PSA) progression (TTPP) was 15.2 months for younger and 21.2 months for older patients (HR 0.84, 95% CI 0.53-1.33, p = 0.4647). Median overall survival (OS) was 33.7 months for younger and 37.8 months for older patients (HR 0.80, 95% CI 0.50-1.29, p = 0.3651). Among older patients (n = 107), the ENZ arm had a TTPP of 21.2 months compared to 10.1 months for the ABI arm and an OS of 37.8 months compared to 44.7 months for the ABI arm (p = 0.1506 and p = 0.9321, respectively). Any grade and grade ≥ 3 adverse events were observed in 47 (61%) and 11 (14%) younger patients and 73 (68%) and 18 (17%) older patients, respectively. No significant differences were found in any grade or grade ≥ 3 adverse events between younger and older patients (p = 0.3487 and p = 0.6885, respectively).</p><p><strong>Conclusions: </strong>ARSIs demonstrated similar efficacy and safety in both younger and older patients. ENZ may be a more suitable option for older patients due to its higher PSA response rate.</p><p><strong>Clinical trial registration: </strong>This trial was registered with the University Hospital Medical Information Network (UMIN) Center under identifier UMIN000015529.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"903-911"},"PeriodicalIF":2.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782027","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":"Muscadine Grape Skin Extract in Biochemically Recurrent Prostate Cancer: A Randomized, Placebo-Controlled, Biomarker-Enriched Trial in Patients With the SOD2 Ala/Ala Variant.","authors":"A Mandl, M L Zahurak, N A Metri, N D Shore, S Mao, R R McKay, M E Taplin, R Z Szmulewitz, B L Maughan, Z R Reichert, E R Kessler, E I Heath, R Dreicer, C A Stein, G L Milne, K S Sfanos, S E Ernst, L A Mummert, A Cruz-Lebrón, S L J Michel, M A Kane, M Hursey, M A Worth, W D Wagner, J R Eshleman, M Debeljak, L Xu, H Cao, D Dowling, C H Marshall, M C Markowski, S R Denmeade, M A Eisenberger, E S Antonarakis, M A Carducci, C J Paller","doi":"10.1002/pros.24903","DOIUrl":"10.1002/pros.24903","url":null,"abstract":"<p><strong>Background: </strong>Many patients with biochemically recurrent prostate cancer (BCRPC) prefer to delay androgen deprivation therapy (ADT) due to its adverse effects, highlighting the need for better-tolerated, effective alternatives. A subgroup analysis of our prior Phase II trial showed that muscadine grape skin extract (MPX) increased PSA doubling time (PSADT) in patients with SOD2 Ala/Ala variant which provided the rationale for this trial.</p><p><strong>Methods: </strong>This randomized, double-blind, placebo-controlled trial, conducted at 14 sites, evaluated patients with BCRPC and SOD2 Ala/Ala genotype. Patients received 4000 mg MPX or placebo daily. The primary endpoint was on-study PSA slope with comparisons between treatment arms. Secondary endpoints were PSADT, PSA response (≥ 50% decrease), and PSA progression free survival (PFS). Correlative studies included markers of oxidative stress and gastrointestinal microbiota composition.</p><p><strong>Results: </strong>At interim analysis, fifty-nine patients were randomized (MPX, n = 29; placebo, n = 30). On-study PSA slopes at 12, 24, 36, and 48 weeks showed no significant differences between the MPX and placebo arms (p = 0.49). The study was stopped due to futility. No significant differences were observed in PSADT, PSA response, median PSA PFS, or oxidative stress biomarkers. MPX was well-tolerated, with no grade 3-4 AEs attributable to the study drug. Microbiome analysis showed no significant differences in alpha diversity but revealed increased relative abundance of Roseburia faecis and Akkermansia muciniphila in the MPX group.</p><p><strong>Conclusions: </strong>Although MPX supplementation had no significant effect on PSA slope in men with BCRPC and SOD2 Ala/Ala variant, this study provides a rigorous evaluation of a natural product and highlights the importance of well-designed clinical trials in advancing evidence-based integrative oncology.</p><p><strong>Trial registration: </strong>ClinicalTrials. gov, NCT03535675.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"966-976"},"PeriodicalIF":2.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057344","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":"Primary Analysis of (NCT03380806) a Phase II Randomized Trial of Stereotactic Body Radiotherapy Boost Versus Conventional Fractionation External Beam Radiotherapy Boost in Unfavorable-Intermediate and High-Risk Prostate Cancer.","authors":"Andre Gouveia, Aruz Mesci, Naghmeh Isfahanian, Ian Dayes, Kimmen Quan, Mira Goldberg, Kara Lynne Schnarr, Himu Lukka, David Cuthbert, Abhiram Hallock, Georgia Douvi, Jim Wright, Anand Swaminath, Tom Chow, Kevin Diamond, George Hajdok, Lindsay Maharaj, Joycelyne Ewusie, Theodoros Tsakiridis","doi":"10.1002/pros.24905","DOIUrl":"10.1002/pros.24905","url":null,"abstract":"<p><strong>Background: </strong>Standard treatment for unfavorable-intermediate and high-risk prostate cancer involves androgen deprivation therapy (ADT) in combination with pelvic conventional fractionation (CF) external beam radiotherapy (EBRT) and a CF-EBRT or brachytherapy boost to the prostate. This trial compared CF-EBRT boost with stereotactic body radiotherapy (SBRT) boost after pelvic CF-EBRT.</p><p><strong>Methods: </strong>Patients were randomized to receive a boost using either CF-EBRT (32-34 Gy in 15-17 fractions) or SBRT (19.5-21 Gy in three weekly fractions) following pelvic CF-EBRT (45-46 Gy in 23-25 fractions). The primary objective was to assess early (3-month post-radiotherapy) gastrointestinal (GI) and genitourinary (GU) quality of life (QoL), using the expanded prostate index composite (EPIC) score. Secondary objectives included long-term QoL, International Prostate Symptom Score (IPSS) changes, toxicity assessments, and long-term disease control outcomes. Linear regression and Fisher's exact test were used for analysis.</p><p><strong>Results: </strong>Of the 100 patients randomized, 53 received CF-EBRT, and 47 received SBRT. After a mean follow-up of 18.5 months, no significant differences were observed in EPIC score changes between CF-EBRT and SBRT at 3 months posttreatment for urinary (11.5 vs. 8.6, p = 0.23), bowel (5.2 vs. 6.4, p = 0.57), and overall QoL (8.3 vs. 7.5, p = 0.61). IPSS scores were similar (p = 0.11), and CTCAE v.5.0 toxicity rates were comparable, with an odds ratio of 0.90 (p > 0.99). Biochemical failure rates were under 5% for both groups.</p><p><strong>Conclusions: </strong>This is the first randomized trial to report QoL outcomes after SBRT boost radiotherapy in patients with unfavorable-intermediate and high-risk prostate cancer. SBRT boost after pelvic CF-EBRT is well-tolerated and demonstrates comparable outcomes in QoL and toxicity to the CF-EBRT boost. Further follow-up is needed to assess the long-term effects on QoL, toxicity, and disease control.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT03380806.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"977-985"},"PeriodicalIF":2.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12131954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992273","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":"Valosin-Containing Protein (VCP/p97) Mediates Neuroendocrine Differentiation in Prostate Cancer Cells Through Pim1 Signaling Inducing Autophagy.","authors":"K K Sruthi, Ramesh Ummanni","doi":"10.1002/pros.24900","DOIUrl":"10.1002/pros.24900","url":null,"abstract":"<p><strong>Background: </strong>Neuroendocrine Prostate Cancer (NEPC) is an aggressive type of androgen-independent prostate cancer (AIPC) associated with resistance to treatment. Valosin-containing protein (VCP/p97) has been found to be overexpressed in prostate cancer (PCa) cells undergoing neuroendocrine differentiation (NED) in response to interleukin-6 (IL-6). This study explores the molecular mechanisms through which VCP/p97 contributes to the progression of NEPC.</p><p><strong>Methods: </strong>To investigate the role of VCP/p97 in the NED of PCa, we overexpressed the VCP/p97 in PCa cells. The molecular mechanisms underlying VCP/p97 induced NED were assessed by using western blot analysis and RT-PCR. Morphological changes were analyzed by using both bright field and confocal microscope. Lysotracker staining was performed to identify autophagy in VCP positive PCa cells.</p><p><strong>Results: </strong>In the present study, we found that VCP/p97 expression was notably higher in neuroendocrine (NE) cells NCI-H660 and PC3 than in other PCa cells. IL-6 treatment led to significant VCP/p97 overexpression in LNCaP and VCaP cells, with a marked increase in NE markers NSE and CHR-A. Inhibition of VCP/p97 using NMS-873 attenuated NED features, suggesting that VCP/p97 is required for NED progression. Moreover, VCP's role in NED is linked to its regulation via Pim1 in differentiating cells. Exogenous expression of VCP/p97 enhanced Pim1 and c-Myc expression, which were diminished upon VCP/p97 inhibition which is corroborated by reduced NED markers. Pim1 inhibition using AZD1208 and c-Myc knockdown further supported Pim1's involvement in VCP mediated NED. To promote NED, VCP/p97 regulated autophagy, as evidenced by increased LC3B and decreased SQSTM1/p62 levels upon VCP overexpression. Inhibition of VCP/p97 or autophagy disrupted NED and autophagic flux, arresting NED of LNCaP cells. Lysotracker staining and autophagic flux assays confirmed VCP's role in enhancing lysosomal-mediated autophagy and autophagolysosome formation. Furthermore, we show that AMPK activation, via LKB1 is essential for VCP/p97 mediated NED and autophagy.</p><p><strong>Conclusion: </strong>VCP drives NED in PCa cells through a complex interplay involving the Pim1 axis and autophagy pathways. These findings highlight the potential of targeting VCP/p97 and its associated mechanisms as therapeutic strategies to inhibit NED progression.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"932-946"},"PeriodicalIF":2.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025865","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":"Evaluating CRPC Definition: Comparing Upfront ARSI and Conventional Hormonal Therapy for Metastatic Hormone Sensitive Prostate Cancer (mHSPC) in Real World Propensity Score Matched Cohort.","authors":"Tatsuya Shimomura, Fumihiko Urabe, Katsuki Muramoto, Takafumi Yanagisawa, Wataru Fukuokaya, Keiichiro Mori, Kojiro Tashiro, Kota Katsumi, Hidetsugu Takahashi, Kentaro Yoshihara, Keiichiro Miyajima, Yu Imai, Kosuke Iwatani, Sotaro Kayano, Taro Igarashi, Masaya Murakami, Shunsuke Tsuzuki, Hiroki Yamada, Jun Miki, Takahiro Kimura","doi":"10.1002/pros.24898","DOIUrl":"10.1002/pros.24898","url":null,"abstract":"<p><strong>Introduction: </strong>The biology of castration-resistant prostate cancer (CRPC) status between conventional hormonal therapy and upfront androgen signaling inhibitor (ARSI) treatment might be different, and the biological status of prostate cancer after failure of sequential ARSI in conventional hormonal therapy would be the same as CRPC in upfront ARSI. In this study, we evaluate our proposed definition of CRPC in our cohort with propensity score-matched analysis.</p><p><strong>Patients and methods: </strong>A total of 885 patients diagnosed with metastatic hormone-sensitive prostate cancer (mHSPC) who received conventional hormonal therapy, upfront androgen receptor signaling inhibitors (ARSI) with or without docetaxel therapy at Jikei University Hospital and its affiliated institutions, were included in this study. We compared survival outcomes between conventional hormonal therapy and upfront ARSI doublet treatment using conventional CRPC definition or our proposed CRPC definition.</p><p><strong>Result: </strong>CRPC-free survival (CRPCFS) and cancer-specific survival (CSS) is significantly better in upfront ARSI (upfront (+)) than upfront (-) group (median CRPCFS is 68 months vs. 18 months, median CSS is not reached (NR) and NR, (p < 0.0001 and p = 0.0381), respectively) in propensity score-matched cohort, although overall survival (OS) is not different. Median CSS and OS after conventional CRPC diagnosis is NR (upfront (-)) and 30 months (upfront (+)) (p = 0.0614), and 37 months (upfront (-)) and 24 months (upfront (+)) (p = 0.00503). OS is significantly better in upfront (-) than upfront (+) group with conventional CRPC definition. Median CSS and OS after our proposed CRPC diagnosis is 20 months (upfront (-)) and 30 months (upfront (+)) (p = 0.389), and 20 months (upfront (-)) and 24 months (upfront (+)) (p = 0.932).</p><p><strong>Conclusion: </strong>This proposed CRPC definition is thought to reflect the actual biological characteristics of prostate cancer with or without upfront ARSI treatment, and it is thought that the introduction of this definition should be considered when comparing the survival outcome between with or without upfront ARSI treatment.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"912-918"},"PeriodicalIF":2.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812878","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}