Prostate最新文献

{"title":"Comparing PSA Screening Patterns and Their Role as Predictor of Prostate Cancer Diagnosis: Analysis of a Contemporary North American Cohort.","authors":"Giuseppe Ottone Cirulli, Alex Stephens, Giuseppe Chiarelli, Marco Finati, Alessandro Bertini, Morrison Chase, Shane Tinsley, Sohrab Arora, Akshay Sood, Giovanni Lughezzani, Nicolò Buffi, Giuseppe Carrieri, Andrea Salonia, Alberto Briganti, Francesco Montorsi, Craig Rogers, Firas Abdollah","doi":"10.1002/pros.24856","DOIUrl":"https://doi.org/10.1002/pros.24856","url":null,"abstract":"<p><strong>Introduction: </strong>PSA screening remains a pivotal tool for early prostate cancer (PCa) detection. International guidelines rely on evidence from three major randomized clinical trials: ERSPC, PLCO, and CAP. We aim to examine the percentage of patients in real-world practice who get PSA screening as defined by each of the aforementioned trials. Moreover, we seek to evaluate if the different PSA screening patterns have a different impact on PCa incidence and its features at diagnosis.</p><p><strong>Materials and methods: </strong>Our institutional database was queried to identify men aged 55-69 who received at least one PSA test, did not develop PCa or die within 6 years of the initial test, had follow-up within our system at least 6 years after the initial test, and did not have a previous PCa diagnosis. A total of 28,612 patients met our selection criteria. We categorized patients into three distinct PSA screening patterns based on testing frequency (PLCO: 1 PSA test per year for 6 years; ERSPC: 2 or 3 PSA tests over 6 years; CAP: 1 PSA test over 6 years). Our primary outcomes were any PCa incidence and clinically significant PCa (csPCa, defined as ISUP ≥ 3) incidence. Secondary outcome was the rate of cM1 disease. Competing risks cumulative incidence curves were used to depict any PCa and csPCa diagnosis with death before a diagnosis considered a competing risk. Multivariable competing risks regression (CRR) was used to assess the impact of the different screening patterns on any PCa and csPCa incidence, after adjusting for confounding factors.</p><p><strong>Results: </strong>The most prevalent PSA screening pattern was ERSPC, including 15,530 patients (54.3%), followed by the CAP with 9003 patients (31.5%), and the PLCO with only 4079 patients (14.2%). The median (IQR) follow-up time was 4.8 (1.7-10.8) years. At 10 years, any PCa incidence was 7.4% versus 5.6% versus 2.5% for PLCO versus ERSPC versus CAP, respectively, while for csPCa, the rates were 2.5% versus 2.5% versus 1.2% (both p < 0.001). On multivariable analyses, PLCO and ERSPC patterns were associated with 2.92-fold and 2.31-fold higher risks from 1 year to the next of any PCa diagnosis, respectively, compared to CAP pattern (both p < 0.001). Similarly, patients with PLCO and ERSPC patterns had 2.07-fold and 2.31-fold higher risks, respectively, of csPCa diagnosis compared to CAP pattern (both p < 0.001). In men with PCa diagnosis, the rates of cM1 disease were respectively 1.7% vs 5.6% vs 10.8% for PLCO versus ERSPC versus CAP, respectively (p = 0.0009).</p><p><strong>Conclusion: </strong>We observed that the most common screening pattern in \"real-world\" clinical practice is close to what ERSPC recommend, and this pattern seems to achieve a reasonable reduction in the risk of advanced PCa, while limiting overdiagnosis.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"e24856"},"PeriodicalIF":2.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054170","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":"The Safety and Efficacy of Targeted Alpha Therapy, Ac-225 Prostate-Specific Membrane Antigen, in Patients With Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis.","authors":"Huseyin Besiroglu, Mustafa Kadihasanoglu","doi":"10.1002/pros.24857","DOIUrl":"https://doi.org/10.1002/pros.24857","url":null,"abstract":"<p><strong>Background: </strong>Metastatic castration resistance prostate cancer (mCRPC) is a challenging disease with a significant burden of mortality and morbidity. Most of the patients attain resistance to the available treatments, necessitating further novel therapies in this clinical setting. Actinium 225 (²²⁵Ac) prostate-specific membrane antigen (PSMA) radioligand therapy has emerged as a promising option and has been utilized for the last decade. Although a few meta-analyses were performed on the efficacy and safety of ²²⁵Ac-PSMA RLT in mCRPC patients, several current studies have been added to the literature since the latest meta-analysis. We aimed to gather all individual studies to perform up-to-date meta-analyses.</p><p><strong>Methods: </strong>We searched the literature using Pubmed-Medline, Web of Science, Elsevier-Sceince Direct, and Cochrane-Central databases. The data for any PSA decline, over 50% PSA decline, overall survival (OS), progression-free survival (PFS), and toxicity profile were captured from the studies eligible for meta-analysis. We utilized the random effect model to generate pooled estimates.</p><p><strong>Results: </strong>The sixteen eligible studies contained 1102 patients. Sixty-three percent of patients achieved more than 50% PSA decline, while 82% had any PSA decline after the completion of therapy. The pooled mean OS and PFS were 12.72 months (9.52-15.91) and 11.02 months (6.88-15.15), respectively. The most common adverse event was xerostomia, with a pooled proportion of 84%. Grade ≥ 3 anemia, thrombocytopenia, leucopenia, and nephrotoxicity were encountered in 9%, 5%, 4%, and 4% of the patients.</p><p><strong>Conclusions: </strong>²²⁵Ac-PSMA RLT is an efficacious and safe treatment for mCRPC. Future well-designed randomized controlled studies comparing ²²⁵Ac-PSMA RLT with other approved therapeutic options would better comprehend the exact role of this therapy in the treatment sequence of mCRPC.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"e24857"},"PeriodicalIF":2.6,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048270","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":"Baseline Imaging Derived Factors of Response Following [225Ac]Ac-J591 Therapy in Metastatic Castration-Resistant Prostate Cancer: A Lesion Level Analysis.","authors":"Judith Stangl-Kremser, Andres Ricaurte-Fajardo, Sandra Huicochea Castellanos, Alexander Martinez-Fundichely, Michael Sun, Joseph R Osborne, Jones T Nauseef, Scott T Tagawa, Neil H Bander","doi":"10.1002/pros.24853","DOIUrl":"https://doi.org/10.1002/pros.24853","url":null,"abstract":"<p><strong>Purpose: </strong>Actinium-225 labeled prostate-specific membrane antigen (PSMA) targeted radionuclide therapy has emerged as a potential treatment option in the management of men with metastatic castrate-resistant prostate cancer (mCRPC). This study investigated molecular imaging-derived parameters and compared imaging response of lesions categorized by tumor site.</p><p><strong>Methods: </strong>Men with mCRPC treated with [225Ac]Ac-J591 from 2017 to 2022 at our center on two prospective trials (NCT03276572 and NCT04506567) with pre- and post-treatment [68Ga]Ga-PSMA-11 Positron Emission Tomography (PET) imaging studies available were included. SUVpeak of the 3 most- and 3 least-avid lesions of the tumor sites were manually assessed. The median change of the SUVpeak from pre- to post-treatment per tumor site was evaluated using the paired Wilcox test. An objective response (OR) in the follow-up image was defined as complete or partial response using PET Response Criteria in Solid Tumors (PERCIST) 1.0.</p><p><strong>Results: </strong>A total of 46 cases met the criteria for image review; most of them (n = 25, 54.3%) had more than one tumor site category. In total, 445 PSMA PET-positive lesions were assessed: 220 osseous, 163 nodal, 41 visceral, and 21 prostatic lesions. After treatment with [225Ac]Ac-J591, absolute SUVpeak values per tumor site declined significantly (p < 0.05) except for prostatic lesions (p = 1). The PERCIST-OR rate for osseous, nodal, visceral, and prostatic lesions was 53%, 28%, 56%, and 38%, respectively.</p><p><strong>Conclusion: </strong>[225Ac]Ac-J591 is an active treatment in men with mCRPC. Tumor distribution patterns may influence treatment response and potentially prognosis. Our findings warrant further validation in a larger cohort but may be considered in treatment planning and trial design.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"e24853"},"PeriodicalIF":2.6,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034801","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":"Clinical Sensitivity and Specificity of the PROSTest in an American Cohort.","authors":"Kambiz Rahbar, Mark Kidd, Vikas Prasad, R David Rosin, Ignat Drozdov, Abdel Halim","doi":"10.1002/pros.24858","DOIUrl":"https://doi.org/10.1002/pros.24858","url":null,"abstract":"<p><strong>Introduction: </strong>Prostate cancer (PCa) is the most commonly diagnosed cancer in men in the United States, following skin cancer, with an incidence rate of 112.7 per 100,000 men per year. The need for a reliable, non-invasive diagnostic tool for early PCa detection (screening, biochemical residual disease) remains unmet due to the limitations of PSA testing, which often leads to overdiagnosis and overtreatment. The PROSTest is a novel, blood-based qPCR assay that assesses gene expression to diagnose PCa and predict patient outcomes to different treatments. This study aimed to validate the sensitivity and specificity of the PROSTest in a diverse cohort of US-based PCa patients compared to healthy controls.</p><p><strong>Materials and methods: </strong>This prospective study included 143 PCa patients and 92 healthy controls. Blood samples were collected, and the PROSTest was conducted following RNA isolation and cDNA production, using a predefined 27-gene algorithm to provide a binary output. The assay's sensitivity and specificity were evaluated using receiver operating characteristic (ROC) analysis, with a 50% score cut-off distinguishing PCa from non-PCa patients. Analytical reproducibility was assessed with intra- and inter-assay comparisons of Ct values and PROSTest scores.</p><p><strong>Results: </strong>The PROSTest demonstrated a sensitivity of 94% (95% CI 89-98%) and a specificity of 88% (95% CI 80-94%) in distinguishing PCa patients from controls, with an area under the ROC curve (AUROC) of 0.97. The false positive rate among controls was 12%. Intra- and inter-assay reproducibility was confirmed with no significant differences in Ct values or PROSTest scores between operators or assays. PROSTest scores were significantly higher in PCa patients compared to controls and in those undergoing treatment versus untreated patients.</p><p><strong>Conclusion: </strong>This validation study confirms the high sensitivity and specificity of the PROSTest in detecting PCa in a diverse USA cohort. The assay's robustness and reproducibility support its potential as a reliable diagnostic tool for PCa detection and monitoring. Further studies are warranted to evaluate its utility across broader populations and treatment settings.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"e24858"},"PeriodicalIF":2.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016422","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":"Screening for Predictive Factors of Efficacy of Second-Generation Androgen Receptor Axis-Targeted Agents in Patients With High-Risk Metastatic Hormone-Sensitive Prostate Cancer.","authors":"Takashi Ueda, Keita Hayakawa, Go Horiguchi, Junki Murashita, Takumi Shiraishi, Saizo Fujimoto, Masatsugu Miyashita, Yumiko Saito, Yusuke Gabata, Satoshi Sako, Hikaru Takahashi, Atsuko Fujihara, Takafumi Minami, Yutaka Yamamoto, Masayoshi Okumi, Fumiya Hongo, Koji Okihara, Kazutoshi Fujita, Osamu Ukimura","doi":"10.1002/pros.24855","DOIUrl":"https://doi.org/10.1002/pros.24855","url":null,"abstract":"<p><strong>Background: </strong>Differences in the effectiveness of second-generation androgen receptor axis-targeted agents (ARATs) in high-risk metastatic hormone-sensitive prostate cancer (mHSPC) remain unclear. This study aimed to identify the factors influencing the efficacy of ARATs in patients with high-risk mHSPC and compare their long-term effectiveness.</p><p><strong>Methods: </strong>Four hundred and sixty-six patients with mHSPC treated with ARATs were retrospectively recruited from our hospital and affiliated hospitals of the Kindai Oncology Study Group and Kyoto Prefectural University of Medicine Oncology Study Group between December 2013 and March 2024. Cox proportional hazards analysis was performed to identify prognostic factors for overall survival in patients with mHSPC. Propensity score matching was used to adjust for the differences in clinical backgrounds of the patients.</p><p><strong>Results: </strong>Univariate and multivariable analyses revealed that Gleason pattern 5 and pretreatment ALP levels were notable prognostic factors for overall survival in patients with mHSPC treated with ARATs. In the subgroup of patients with high-risk mHSPC with Gleason pattern 5, apalutamide and enzalutamide showed significantly better outcomes in terms of PSA-PFS, PFS2, and overall survival compared to abiraterone acetate though selection bias and the small number of patients may be associated with the results in this study. Univariate and multivariable analyses suggested that ARATs selection (ABI vs. APA or ENZ) may serve as an independent predictor of overall survival in patients with high-risk mHSPC with Gleason pattern 5 treated with ARATs.</p><p><strong>Conclusion: </strong>Gleason pattern 5 may be a predictive factor for ARAT efficacy in patients with high-risk mHSPCs.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"e24855"},"PeriodicalIF":2.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016428","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":"Relationship Between Radiation Therapy and Fecal Incontinence in Patients Treated for Localized Prostate Cancer: Results of the French ICONES Study.","authors":"Yazid Belkacemi, Gabriele Coraggio, Kamel Debbi, Laura Sirmai, Clemence Hollande, Elise Rambaud, Asma Hadhri, Xie Li, Wissal Hassani, Michael Levy, Dimitri Vordos, Alexandre Ingels, Gokoulakrichenane Loganadane, Alexandre De La Taille","doi":"10.1002/pros.24852","DOIUrl":"https://doi.org/10.1002/pros.24852","url":null,"abstract":"<p><strong>Background: </strong>Radiation-induced late fecal incontinence (LFI) is one of the most quality-of-life impairing symptoms in prostate cancer. We aimed to assess the impact of radiotherapy (RT) technique and dose-volume effects on LFI using a robust score.</p><p><strong>Methods: </strong>We identified 409 patients who underwent curative intent using standard fractionated radiation therapy, 190 of them were finally included and analyzed. The severity of LFI was assessed using the Jorge & Wexner score.</p><p><strong>Results: </strong>With a median follow-up of 55 months (range 15-96) months, LFI crude rate was 11.5%. In the multivariate analyses, image-guided radiotherapy (IGRT), rectal maximum dose (Dmax) and anal canal minimum dose (Dmin) were significantly associated with LFI risk. The use of IGRT was associated with lower risk of LFI (p = 0.02); higher rectum Dmax (≥ 68.4 Gy; p = 0.02) and anal canal Dmin (≥ 6.4 Gy; p = 0.04) were associated with increased risk.</p><p><strong>Conclusion: </strong>Our results suggest a significant impact of the total dose delivered to the anorectal volumes and the use of IGRT to spare organs at risk during radiation delivery.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"e24852"},"PeriodicalIF":2.6,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985354","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":"Development and Validation of a Predictive Model of Prostate Screening Compliance: A Nationwide Population-Based Study.","authors":"Diego Arriaga-Izabal, Francisco Morales-Lazcano, Adrian Canizalez-Román","doi":"10.1002/pros.24854","DOIUrl":"https://doi.org/10.1002/pros.24854","url":null,"abstract":"<p><strong>Introduction: </strong>Prostate cancer (PCa) is the second most common cancer in men worldwide, with significant incidence and mortality, particularly in Mexico, where diagnosis at advanced stages is common. Early detection through screening methods such as digital rectal examination and prostate-specific antigen testing is essential to improve outcomes. Despite current efforts, compliance with prostate screening (PS) remains low due to several barriers. This study aims to develop and validate a predictive model for PCa screening compliance in Mexican men.</p><p><strong>Materials and methods: </strong>Retrospective observational design with data from the Mexican Health and Aging Study (MHAS). Participants were men aged 50-69 from three cohorts: development/internal validation, temporal validation, and external validation. Key predictors were identified using relaxed Least Absolute Shrinkage and Selection Operator (LASSO) regression, and model performance was assessed using the area under the curve (AUC) from receiver operating characteristic (ROC) analyses, along with calibration and decision curve analysis (DCA). A web nomogram was also developed.</p><p><strong>Results: </strong>The final model included seven key predictors. AUC values indicated good predictive performance: 0.783 for the training subgroup, 0.722 for the test subgroup, 0.748 for the time cohort, and 0.756 for the external cohort, with sensitivities of 73.5%. The DCA demonstrated the superior clinical utility of the model compared to the reference strategies.</p><p><strong>Conclusions: </strong>The predictive model developed for performance to PCa screening is robust across different cohorts and highlights critical factors influencing performance. The accompanying web-based nomogram enhances clinical applicability and supports interventions aimed at improving PCa screening rates among Mexican men.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"e24854"},"PeriodicalIF":2.6,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980660","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":"Does a Negative Prostate Biopsy Reduce the Risk of Prostate Cancer Reclassification in an Active Surveillance Protocol? An Updated Systematic Review and Meta-Analysis.","authors":"Razman Arabzadeh Bahri, Abdolreza Mohammadi, Ehsan Zemanati Yar, Mina Rezayat, Ramin Heshmat, Seyed Mohammad Kazem Aghamir","doi":"10.1002/pros.24851","DOIUrl":"https://doi.org/10.1002/pros.24851","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the association of the negative confirmatory and follow-up biopsy with prostate cancer reclassification in active surveillance protocol.</p><p><strong>Materials and methods: </strong>A systematic search was performed in databases, including Scopus, PubMed, Embase, and Web of Science, on June 25th, 2024, to identify relevant studies regarding negative biopsy and reclassification of prostate cancer among men on AS. The patient data including, sample sizes, follow-up duration, the status of performing the confirmatory biopsy, hazard ratio (HR), and 95% confidence intervals (CI) of each reported HR were evaluated in each study. The relationships between negative biopsies and reclassification were assessed using a forest plot. A random-effect meta-analysis was used when high heterogeneity existed among the studies. Otherwise, a fixed-effect meta-analysis was utilized. A p value of less than 0.05 was considered statistically significant. All statistical analyses were performed by using STATA statistical software, version 16.</p><p><strong>Results: </strong>A total of 13 articles were included in the study. These articles were published between 2008 and 2023, with the majority being published in recent years (2020-2023). The included articles evaluated a total of 17,900 patients. Our results regarding reclassification and upgrading are represented according to the confirmatory biopsy and subsequent follow-up biopsies. After a negative confirmatory biopsy, the pooled HR for reclassification was 0.46 (95% CI: 0.38-0.55, p < 0.01). Secondly, the study demonstrated that a decreased chance of cancer upgrading was also connected with negative confirmatory biopsies with a pooled HR of 0.57 (95% CI: 0.45-0.72, p < 0.01). Negative follow-up biopsies were linked to a 55% decrease in the risk of reclassification, according to the pooled HR for reclassification in patients with negative biopsies compared to those with positive biopsies of 0.45 (95% CI: 0.42-0.48, p < 0.01). Also, patients with negative follow-up biopsies had a pooled HR for upgrading of 0.57 (95% CI: 0.48-0.67, p < 0.01), indicating a 43% lower chance of upgrading than in patients with positive biopsies.</p><p><strong>Conclusion: </strong>In active surveillance of PCa patients, a negative confirmatory biopsy decreased the chance of cancer reclassification and upgrading, with the pooled OR 0.46 and 0.57 [p < 0.01], respectively. Also, negative follow-up biopsies were linked to a decreased chance of cancer reclassification and upgrading. Our review recommends extend the follow-up evaluations in PCa patients with negative findings in surveillance biopsy who scheduled for active surveillance.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"e24851"},"PeriodicalIF":2.6,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973359","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":"Time to Castration Resistance is Associated With Overall Survival Even After the Achievement of Castration Resistance in Metastatic Prostate Cancer.","authors":"Hiroto Kato, Yusuke Goto, Satoko Kojima, Yusuke Onoda, Ken Wakai, Kyokushin Hou, Kazuhiro Araki, Shinichi Sakamoto, Tomohiko Ichikawa, Yukio Naya","doi":"10.1002/pros.24850","DOIUrl":"https://doi.org/10.1002/pros.24850","url":null,"abstract":"<p><strong>Background: </strong>Recent clinical trials have shown that patients with metastatic castration-sensitive prostate cancer in real-world settings have different overall survival (OS) rates after stratifying for tumor burden or visceral metastasis. However, some patients with a low tumor burden and without visceral metastasis still have a poor survival. Androgen receptor signaling is still a main therapeutic target of prostate cancer treatment even after the achievement of castration resistance. In this regard, we hypothesized that time to castration resistance can be a prognostic factor of metastatic castration-sensitive prostate cancer even after achieving castration resistance. The current study aimed to assess the novel prognostic factors, particularly time to castration resistance, of prostate cancer in patients at a real-world single institution.</p><p><strong>Methods: </strong>The data of 261 patients who were newly diagnosed with metastatic castration-sensitive prostate cancer from January 2007 to December 2023 were retrospectively analyzed.</p><p><strong>Results: </strong>The median OS was 60.7 months, and the median time to castration resistance was 13.1 months. Among 261 patients, 158 developed castration-resistant prostate cancer. A shorter time to castration resistance, the presence of distant lymph node metastasis, ISUP grade group 5, and older age were associated with a shorter OS in patients who developed castration-resistant prostate cancer. A shorter time to castration resistance was significantly associated with a shorter OS regardless of the tumor burden. Further, it was associated with a shorter OS even after the achievement of castration resistance.</p><p><strong>Conclusions: </strong>The study results support the presence of persistent androgen receptor signaling even after achieving castration resistance in prostate cancer, and time to castration resistance can be a biomarker for the activation of androgen receptor signaling regardless of tumor burden.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"e24850"},"PeriodicalIF":2.6,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958970","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":"Nectin-4 Expression in Prostatic Adenocarcinoma: An Immunohistochemical Study.","authors":"Ezra G Baraban, Evangelia Vlachou, Sunil Patel, Max Kates, Burles Johnson, Armine Smith, Eugene Shenderov, Shivang Sharma, Samuel R Denmeade, Alex Brame, Misop Han, Angelo M De Marzo, Andres Matoso, Jean Hoffman-Censits","doi":"10.1002/pros.24846","DOIUrl":"https://doi.org/10.1002/pros.24846","url":null,"abstract":"<p><strong>Background: </strong>The Nectin-4 directed antibody drug conjugate enfortumab vedotin (EV) has emerged as frontline systemic therapy in combination with immune checkpoint blockade for urothelial carcinoma (UC), capitalizing on the ubiquitous expression of this protein in UC. There is limited data available regarding expression of Nectin-4 by immunohistochemistry in prostate cancer, but this is of interest as a substantial number of UC patients likely to receive EV have concomitant prostate cancer.</p><p><strong>Methods: </strong>Nectin-4 protein expression was evaluated by immunohistochemistry in tissue microarrays encompassing a cohort of 302 prostatic adenocarcinomas spanning Grade Groups 1-5. Intensity of expression was scored from 1 (weak) to 3 (intense staining readily apparent at low magnification). H-scores were calculated by multiplying the percentage of cells staining by the intensity of expression.</p><p><strong>Results: </strong>Nectin-4 expression was frequently observed in benign prostate tissue (86% of cases, mean H-score of 40, median 20, interquartile range [IQR]: 10-60) and in prostatic adenocarcinoma (91% of cases, mean H-score of 90, median 70, IQR: 20-150). Significant differences in Nectin-4 expression among prostatic adenocarcinoma Grade Groups 1-5 were not observed. Across all prostatic adenocarcinomas evaluated, the mean Nectin-4 H-score of 90 was statistically significantly higher than the mean H-score of 40 observed in benign prostate tissue (p < 0.001). Three of four prostatic ductal adenocarcinomas showed Nectin-4 expression, with a median H-score of 250 (IQR: 152-300).</p><p><strong>Conclusions: </strong>Nectin-4 protein expression is common in benign prostate tissue and prostatic adenocarcinoma. These findings provide a rationale for future studies investigating potential activity of EV in prostate cancer.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142923855","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}