Prostate最新文献

{"title":"The detection rate for prostate cancer in systematic and targeted prostate biopsy in biopsy-naive patients, according to the localization of the lesion at the mpMRI: A single-center retrospective observational study.","authors":"Matteo Massanova, Biagio Barone, Vincenzo Francesco Caputo, Luigi Napolitano, Andrea Ponsiglione, Francesco Del Giudice, Matteo Ferro, Giuseppe Lucarelli, Francesco Lasorsa, Gian Maria Busetto, Sophie Robertson, Francesco Trama, Ciro Imbimbo, Felice Crocetto","doi":"10.1002/pros.24761","DOIUrl":"10.1002/pros.24761","url":null,"abstract":"<p><strong>Objective: </strong>Evaluate the detection rates of systematic, targeted and combined cores at biopsy according to tumor positions in biopsy-naïve patients.</p><p><strong>Material and methods: </strong>A retrospective analysis of a single-center patient cohort (n = 501) that underwent transrectal prostate biopsy between January 2017 and December 2019 was performed. Multi-parametric MRI was executed as a prebiopsy investigation. Biopsy protocol included, for each patient, 12 systematic cores plus 3 to 5 targeted cores per lesion identified at the mpMRI. Pearson and McNemar chi-squared tests were used for statistical analysis to compare tumor location-related detection rates of systematic, targeted and combined (systematic + targeted) cores at biopsy.</p><p><strong>Results: </strong>Median age of patients was 70 years (IQR 62-72), with a median PSA of 8.5 ng/ml (IQR 5.7-15.6). Positive biopsies were obtained in 67.7% of cases. Overall, targeted cores obtained higher detection rates compared to systematic cores (54.3% vs. 43.1%, p < 0.0001). Differences in detection rates were, however, higher for tumors located at the apex (61.1% vs. 26.3%, p < 0.05) and anteriorly (44.4% vs. 19.3%, p < 0.05). Targeted cores similarly obtained higher detection rates in the posterior zone of the prostate gland for clinically significant prostate cancer. A poor agreement was reported between targeted and systematic cores for the apex and anterior zone of the prostate with, respectively κ = 0.028 and κ = -0.018.</p><p><strong>Conclusion: </strong>A combined approach of targeted and systematic biopsy delivers the highest detection rate in prostate cancer (PCa). The location of the tumor could however greatly influence overall detection rates, indicating the possibility to omit (as for the base or posterior zone of the gland) or add (as for the apex or anterior zone of the gland) further targeted cores.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"1234-1243"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141460791","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 and histopathological parameters in transrectal ultrasound-guided biopsies associated with tumor upgrading after radical prostatectomy: A comparative analysis of risk groups.","authors":"Mustafa Ozkaya, Muhammed Fatih Simsekoglu, Goktug Kalender, Kadir Can Sahin, Iclal Gurses","doi":"10.1002/pros.24751","DOIUrl":"10.1002/pros.24751","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Thanks to technological advances, prostate cancer (PCa) can be diagnosed at a younger age. It is known that most of these patients are in the low-intermediate risk group, and the histological grade of the tumor increases in half of those undergoing radical prostatectomy (Rp) compared to their diagnostic biopsies. This is especially important in terms of active surveillance (AS) and/or the timely evaluation of curative treatment options in patients diagnosed at an early age. Our aim was to investigate clinical and histopathological parameters that may be associated with an increase in the histological grade of the tumor in patients with acinar adenocarcinoma who were diagnosed by transrectal ultrasound-guided biopsy (TRUS-Bx) and underwent Rp.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A total of 205 patients with classical acinar adenocarcinoma diagnosed by TRUS-Bx without metastasis and who underwent Rp were grouped according to the D'Amico risk classification. Age at diagnosis, serum prostate-specific antigen (PSA), PSA density, prostate volume, Prostate Imaging Reporting and Data System (PI-RADS) score, clinical stage, Gleason Grade Group (GGG), high-grade intraepithelial neoplasia in tumor-free cores (HGPIN) (single and ≥2 cores), perineural invasion (PNI), and lymphovascular invasion (LVI) was obtained. Additionally, GGG, pathological stage, lymph node metastasis, surgical margin positivity, and tumor volume obtained from Rp were evaluated. Comparisons were made between the case groups in which the tumor grade increased and remained the same, in terms of age, serum PSA, PSA density, HGPIN in tumor-free cores (single and ≥2 cores), PNI, and LVI in all biopsies (with or without tumors), as well as risk groups. In addition, the relationships of HGPIN in tumor-free cores (single and ≥2 cores), PNI, and LVI on TRUS-Bx with age, serum PSA and PSA density, tumor volume, surgical margin positivity, pathological stage, lymph node metastasis, and risk groups were examined separately.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Of the patients, 72 (35.1%) were in the low-risk group, 95 (46.3%) in the intermediate-risk group, and 38 (18.5%) in the high-risk group. Most of the patients with an increased histological grade (n = 38, 48.1%) were in the low-risk group (p &lt; 0.05) and had an advanced median age. HGPIN in single and ≥2 tumor-free cores and PNI were more common in these patients (p &lt; 0.01, p &lt; 0.001, and p &lt; 0.05, respectively). According to the multivariable analysis, advanced age (odds ratio [OR]: 1.087, 95% confidence interval [CI]: 1.029-1.148, p &lt; 0.05), high serum PSA (OR: 1.047, 95% CI: 1.006-1.090, p &lt; 0.05), HGPIN in ≥2 tumor-free cores (OR: 6.346, 95% CI: 3.136-12.912, p &lt; 0.001), and PNI (OR: 3.138, 95% CI: 1.179-8.356, p &lt; 0.05) were independent risk factors for a tumor upgrade. Furthermore, being in the low-risk group was an independent risk factor when compared to the intermediate- and high-risk groups (OR: 0.187, 95% CI: ","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"1146-1156"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154441","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":"LGALS3 cfDNA methylation in seminal fluid as a novel prostate cancer biomarker outperforming PSA.","authors":"Irena Abramovic, Ivan Pezelj, Leo Dumbovic, Lucija Skara Abramovic, Tonci Vodopic, Stela Bulimbasic, Goran Stimac, Floriana Bulic-Jakus, Tomislav Kulis, Ana Katusic Bojanac, Davor Tomas, Monika Ulamec, Nino Sincic","doi":"10.1002/pros.24749","DOIUrl":"10.1002/pros.24749","url":null,"abstract":"<p><strong>Background: </strong>The unmet challenge in prostate cancer (PCa) management is to discriminate it from benign prostate hyperplasia (BPH) due to the lack of specific diagnostic biomarkers. Contemporary research on potential PCa biomarkers is directed toward methylated cell-free DNA (cfDNA) from liquid biopsies since epigenetic mechanisms are strongly involved in PCa development.</p><p><strong>Methods: </strong>In the present research, cfDNA methylation of the LGALS3 gene in blood and seminal plasma of PCa and BPH patients was assessed using pyrosequencing, as well as LGALS3 DNA methylation in tissue biopsies. Liquid biopsy samples were taken from patients with clinical suspicion of PCa, who were subsequently divided into two groups, that is, 42 with PCa and 55 with BPH, according to the histopathological analysis.</p><p><strong>Results: </strong>Statistically significant higher cfDNA methylation of LGALS3 in seminal plasma of BPH than in PCa patients was detected by pyrosequencing. ROC curve analysis showed that it could distinguish PCa and BPH patients with 56.4% sensitivity and 70.4% specificity, while PSA did not differ between the two patient groups. In contrast, there was no statistically significant difference in LGALS3 cfDNA methylation in blood plasma between the two patient groups. In prostate tumor tissue, there was a statistically significant DNA hypermethylation of LGALS3 compared to surrounding nontumor tissue and BPH tissue.</p><p><strong>Conclusions: </strong>The DNA hypermethylation of the LGALS3 gene represents an event specific to PCa development. In conclusion, LGALS3 cfDNA methylation in seminal fluid discriminates early PCa and BPH presenting itself as a powerful novel PCa biomarker highly outperforming PSA.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"1128-1137"},"PeriodicalIF":2.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141187037","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":"Cutibacterium acnes invades prostate epithelial cells to induce BRCAness as a possible pathogen of prostate cancer.","authors":"Shingo Ashida, Chiaki Kawada, Hiroko Tanaka, Atsushi Kurabayashi, Ken-Ichi Yagyu, Shuji Sakamoto, Kazuhiro Maejima, Satoru Miyano, Masanori Daibata, Hidewaki Nakagawa, Keiji Inoue","doi":"10.1002/pros.24723","DOIUrl":"10.1002/pros.24723","url":null,"abstract":"<p><strong>Background: </strong>Abundant evidence suggests that chronic inflammation is linked to prostate cancer and that infection is a possible cause of prostate cancer.</p><p><strong>Methods: </strong>To identify microbiota or pathogens associated with prostate cancer, we investigated the transcriptomes of 20 human prostate cancer tissues. We performed de novo assembly of nonhuman sequences from RNA-seq data.</p><p><strong>Results: </strong>We identified four bacteria as candidate microbiota in the prostate, including Moraxella osloensis, Uncultured chroococcidiopsis, Cutibacterium acnes, and Micrococcus luteus. Among these, C. acnes was detected in 19 of 20 prostate cancer tissue samples by immunohistochemistry. We then analyzed the gene expression profiles of prostate epithelial cells infected in vitro with C. acnes and found significant changes in homologous recombination (HR) and the Fanconi anemia pathway. Notably, electron microscopy demonstrated that C. acnes invaded prostate epithelial cells and localized in perinuclear vesicles, whereas analysis of γH2AX foci and HR assays demonstrated impaired HR repair. In particular, BRCA2 was significantly downregulated in C. acnes-infected cells.</p><p><strong>Conclusions: </strong>These findings suggest that C. acnes infection in the prostate could lead to HR deficiency (BRCAness) which promotes DNA double-strand breaks, thereby increasing the risk of cancer development.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"1056-1066"},"PeriodicalIF":2.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140900289","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":"Morphologic patterns observed in prostate biopsy cases with discrepant grade group and molecular risk classification.","authors":"Nancy Y Greenland, Matthew R Cooperberg, Peter R Carroll, Janet E Cowan, Jeffry P Simko, Bradley A Stohr, Emily Chan","doi":"10.1002/pros.24725","DOIUrl":"10.1002/pros.24725","url":null,"abstract":"<p><strong>Background: </strong>Molecular-based risk classifier tests are increasingly being utilized by urologists and radiation oncologists to guide clinical decision making. The Decipher prostate biopsy test is a 22-gene RNA biomarker assay designed to predict likelihood of high-grade disease at radical prostatectomy and risk of metastasis and mortality. The test provides a risk category of low, intermediate, or high. We investigated histologic features of biopsies in which the Grade Group (GG) and Decipher risk category (molecular risk) were discrepant.</p><p><strong>Methods: </strong>Our institutional urologic outcomes database was searched for men who underwent prostate biopsies with subsequent Decipher testing from 2016 to 2020. We defined discrepant GG and molecular risk as either GG1-2 with high Decipher risk category or GG ≥ 3 with low Decipher risk category. The biopsy slide on which Decipher testing was performed was re-reviewed for GG and various histologic features, including % Gleason pattern 4, types of Gleason pattern 4 and 5, other \"high risk\" features (e.g., complex papillary, ductal carcinoma, intraductal carcinoma [IDC]), and other unusual and often \"difficult to grade\" patterns (e.g., atrophic carcinoma, mucin rupture, pseudohyperplastic carcinoma, collagenous fibroplasia, foamy gland carcinoma, carcinoma with basal cell marker expression, carcinoma with prominent vacuoles, and stromal reaction). Follow-up data was also obtained from the electronic medical record.</p><p><strong>Results: </strong>Of 178 men who underwent prostate biopsies and had Decipher testing performed, 41 (23%) had discrepant GG and molecular risk. Slides were available for review for 33/41 (80%). Of these 33 patients, 23 (70%) had GG1-2 (GG1 n = 5, GG2 n = 18) with high Decipher risk, and 10 (30%) had GG ≥ 3 with low Decipher risk. Of the 5 GG1 cases, one case was considered GG2 on re-review; no other high risk features were identified but each case showed at least one of the following \"difficult to grade\" patterns: 3 atrophic carcinoma, 1 collagenous fibroplasia, 1 carcinoma with mucin rupture, and 1 carcinoma with basal cell marker expression. Of the 18 GG2 high Decipher risk cases, 2 showed GG3 on re-review, 5 showed large cribriform and/or other high risk features, and 10 showed a \"difficult to grade\" pattern. Of the 10 GG ≥ 3 low Decipher risk cases, 5 had known high risk features including 2 with large cribriform, 1 with IDC, and 1 with Gleason pattern 5.</p><p><strong>Conclusions: </strong>In GG1-2 high Decipher risk cases, difficult to grade patterns were frequently seen in the absence of other known high risk morphologic features; whether these constitute true high risk cases requires further study. In the GG ≥ 3 low Decipher risk cases, aggressive histologic patterns such as large cribriform and IDC were observed in half (50%) of cases; therefore, the molecular classifier may not capture all high risk histologic patterns.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"1076-1085"},"PeriodicalIF":2.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140908963","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":"Increased α2,3-sialyl N-glycosylated prostate-specific membrane antigen (PSMA) in post-DRE urine is associated with high grade group prostate cancer.","authors":"Stephen Mackay, Ian O Oduor, Tanya C Burch, Brian P Main, Dean A Troyer, Oliver J Semmes, Julius O Nyalwidhe","doi":"10.1002/pros.24724","DOIUrl":"10.1002/pros.24724","url":null,"abstract":"<p><strong>Introduction: </strong>Aberrant glycosylation of proteins is an important hallmark in multiple cancers. Prostate-specific membrane antigen (PSMA), a highly glycosylated protein with 10 N-linked glycosylation sites, is an Food and Drug Administration approved theranostic for prostate cancer. However, glycosylation changes in PSMA that are associated with prostate cancer disease progression have not been fully characterized.</p><p><strong>Methods: </strong>We investigated whether urinary PSMA sialylation correlate with high-grade prostate cancer. Urine samples were collected from men after digital rectal examination (DRE) before prostate biopsy. Lectin-antibody enzyme-linked immunoassay was used to quantify α2,3-sialyl PSMA in post-DRE urine samples from subjects with benign prostate tumors, Grade Group 1 prostate cancer and those with Grade Group ≥2 disease.</p><p><strong>Results: </strong>There are significant increases in α2,3-sialylated PSMA in patients with Grade Group ≥2 disease compared to benign (p = 0.0009) and those with Grade Group 1 disease (p = 0.0063). There were no significant differences in α2,3-sialyl PSMA levels between Grade Group 1 and benign prostate tumors (p = 0.7947).</p><p><strong>Conclusions: </strong>Our study shows that there are significant differences in the abundance of α2,3-sialylated PSMA in post-DRE urines from disease stratified prostate cancer patients, and the increase is correlated with progression and disease severity. The detection of increased PSMA sialyation in post-DRE urines from patients with higher Grade Group ≥2 disease states provides novel untapped potential for the development of prognostic biomarkers for prostate cancer. Specifically, quantitation of α2,3-sialylated PSMA shows potential for discriminating between benign to intermediate grade disease, which is a significant clinical challenge in staging and risk stratification of prostate cancer.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"1067-1075"},"PeriodicalIF":2.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140908961","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":"Reproducible preclinical models of androgen receptor driven human prostate cancer bone metastasis.","authors":"JuanJuan Yin, Asha Daryanani, Fan Lu, Anson T Ku, John R Bright, Aian Neil S Alilin, Joel Bowman, Ross Lake, Chennan Li, Tri M Truong, Joseph D Twohig, Elahe A Mostaghel, Masaki Ishikawa, Mark Simpson, Shana Y Trostel, Eva Corey, Adam G Sowalsky, Kathleen Kelly","doi":"10.1002/pros.24718","DOIUrl":"10.1002/pros.24718","url":null,"abstract":"<p><strong>Background: </strong>Preclinical models recapitulating the metastatic phenotypes are essential for developing the next-generation therapies for metastatic prostate cancer (mPC). We aimed to establish a cohort of clinically relevant mPC models, particularly androgen receptor positive (AR⁺) bone metastasis models, from LuCaP patient-derived xenografts (PDX) that reflect the heterogeneity and complexity of mPC.</p><p><strong>Methods: </strong>PDX tumors were dissociated into single cells, modified to express luciferase, and were inoculated into NSG mice via intracardiac injection. The progression of metastases was monitored by bioluminescent imaging. Histological phenotypes of metastases were characterized by immunohistochemistry and immunofluorescence staining. Castration responses were further investigated in two AR-positive models.</p><p><strong>Results: </strong>Our PDX-derived metastasis (PDM) model collection comprises three AR⁺ adenocarcinomas (ARPC) and one AR^- neuroendocrine carcinoma (NEPC). All ARPC models developed bone metastases with either an osteoblastic, osteolytic, or mixed phenotype, while the NEPC model mainly developed brain metastasis. Different mechanisms of castration resistance were observed in two AR⁺ PDM models with distinct genotypes, such as combined loss of TP53 and RB1 in one model and expression of AR splice variant 7 (AR-V7) expression in another model. Intriguingly, the castration-resistant tumors displayed inter- and intra-tumor as well as organ-specific heterogeneity in lineage specification.</p><p><strong>Conclusion: </strong>Genetically diverse PDM models provide a clinically relevant system for biomarker identification and personalized medicine in metastatic castration-resistant prostate cancer.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"1033-1046"},"PeriodicalIF":2.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11216894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140873065","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":"Effects of oral administration of nonselective Trk inhibitor on bladder overactivity in rodent models of prostatic inflammation.","authors":"Taro Igarashi, Shinsuke Mizoguchi, Kanako Matsuoka, Tadanobu Kamijo, Shota Kawano, Akira Furuta, Yasuyuki Suzuki, Takahiro Kimura, Laura E Pascal, Zhou Wang, Naoki Yoshimura","doi":"10.1002/pros.24708","DOIUrl":"10.1002/pros.24708","url":null,"abstract":"<p><strong>Background: </strong>Our research focused on the assessment of the impact of systemic inhibition of Trk receptors, which bind to nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), on bladder hypersensitivity in two distinct rodent models of prostatic inflammation (PI).</p><p><strong>Methods: </strong>Male Sprague-Dawley rats were divided into three groups (n = 6 each): the control group (no PI, vehicle administration), the untreated group (PI, vehicle administration), and the treated group (PI, nonselective Trk inhibitor, GNF 5837, administration). PI in rats was induced by a intraprostatic injection of 5% formalin. Posttreatment, we carried out conscious cystometry and a range of histological and molecular analyses. Moreover, the study additionally evaluated the effects of a nonselective Trk inhibitor on bladder overactivity in a mouse model of PI, which was induced by prostate epithelium-specific conditional deletion of E-cadherin.</p><p><strong>Results: </strong>The rat model of PI showed upregulations of NGF and BDNF in both bladder and prostate tissues in association with bladder overactivity and inflammation in the ventral lobes of the prostate. GNF 5837 treatment effectively mitigated these PI-induced changes, along with reductions in TrkA, TrkB, TrkC, and TRPV1 mRNA expressions in L6-S1 dorsal root ganglia. Also, in the mouse PI model, GNF 5837 treatment similarly improved bladder overactivity.</p><p><strong>Conclusions: </strong>The findings of our study suggest that Trk receptor inhibition, which reduced bladder hypersensitivity and inflammatory responses in the prostate, along with a decrease in overexpression of Trk and TRPV1 receptors in sensory pathways, could be an effective treatment strategy for male lower urinary tract symptoms associated with PI and bladder overactivity.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"1016-1024"},"PeriodicalIF":2.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11227098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141159264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The additional value of ⁶⁸Ga-PSMA PET/CT SUVmax in predicting ISUP GG ≥ 2 and ISUP GG ≥ 3 prostate cancer in biopsy.","authors":"Joris G Heetman, Leonor J Paulino Pereira, Johannes C Kelder, Timo F W Soeterik, Lieke Wever, Jules Lavalaye, Erik J R J van der Hoeven, Marnix G E H Lam, Harm H E van Melick, Roderick C N van den Bergh","doi":"10.1002/pros.24716","DOIUrl":"10.1002/pros.24716","url":null,"abstract":"<p><strong>Background: </strong>Prebiopsy magnetic resonance imaging (MRI) increases the detection rate of clinically significant prostate cancer (csPCa). Prostate-specific membrane antigen-positron emission tomography/computed tomography (PSMA PET/CT) maximum standardized uptake value (SUVmax) of the prostate may offer additional value in predicting the likelihood of csPCa in biopsy.</p><p><strong>Methods: </strong>A single-center cohort study involving patients with biopsy-proven PCa who underwent both MRI and PSMA PET/CT between 2020 and 2021. Logistic regression models were developed for International Society of Urological Pathology (ISUP) Grade Group (GG) ≥ 2 and GG ≥ 3 using noninvasive prebiopsy parameters: age, (log-)prostate-specific antigen (PSA) density, PI-RADS 5 lesion presence, extraprostatic extension (EPE) on MRI, and SUVmax of the prostate. Models with and without SUVmax were compared using Likelihood ratio tests and area under the curve (AUC). DeLong's test was used to compare the AUCs.</p><p><strong>Results: </strong>The study included 386 patients, with 262 (68%) having ISUP GG ≥ 2 and 180 (47%) having ISUP GG ≥ 3. Including SUVmax significantly improved both models' goodness of fit (p < 0.001). The GG ≥ 2 model had a higher AUC with SUVmax 89.16% (95% confidence interval [CI]: 86.06%-92.26%) than without 87.34% (95% CI: 83.93%-90.76%) (p = 0.026). Similarly, the GG ≥ 3 model had a higher AUC with SUVmax 82.51% (95% CI: 78.41%-86.6%) than without 79.33% (95% CI: 74.84%-83.83%) (p = 0.003). The SUVmax inclusion improved the GG ≥ 3 model's calibration at higher probabilities.</p><p><strong>Conclusion: </strong>SUVmax of the prostate on PSMA PET/CT potentially improves diagnostic accuracy in predicting the likelihood of csPCa in prostate biopsy.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"1025-1032"},"PeriodicalIF":2.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140856698","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 validation of circulating GDF15/MIC-1 as a marker of response to docetaxel and survival in men with metastatic castration-resistant prostate cancer.","authors":"Kate L Mahon, Sarah Im Sutherland, Hui Ming Lin, Martin R Stockler, Howard Gurney, Girish Mallesara, Karen Briscoe, Gavin Marx, Celestia S Higano, Johann S de Bono, Kim N Chi, Georgina Clark, Samuel N Breit, David A Brown, Lisa G Horvath","doi":"10.1002/pros.24691","DOIUrl":"10.1002/pros.24691","url":null,"abstract":"<p><strong>Background: </strong>Elevated circulating growth differentiation factor (GDF15/MIC-1), interleukin 4 (IL4), and IL6 levels were associated with resistance to docetaxel in an exploratory cohort of men with metastatic castration-resistant prostate cancer (mCRPC). This study aimed to establish level 2 evidence of cytokine biomarker utility in mCRPC.</p><p><strong>Methods: </strong>IntVal: Plasma samples at baseline (BL) and Day 21 docetaxel (n = 120). ExtVal: Serum samples at BL and Day 42 of docetaxel (n = 430). IL4, IL6, and GDF15 levels were measured by ELISA. Monocytes and dendritic cells were treated with 10% plasma from men with high or low GDF15 or recombinant GDF15.</p><p><strong>Results: </strong>IntVal: Higher GDF15 levels at BL and Day 21 were associated with shorter overall survival (OS) (BL; p = 0.03 and Day 21; p = 0.004). IL4 and IL6 were not associated with outcomes. ExtVal: Higher GDF15 levels at BL and Day 42 predicted shorter OS (BL; p < 0.0001 and Day 42; p < 0.0001). Plasma from men with high GDF15 caused an increase in CD86 expression on monocytes (p = 0.03), but was not replicated by recombinant GDF15.</p><p><strong>Conclusions: </strong>Elevated circulating GDF15 is associated with poor prognosis in men with mCRPC receiving docetaxel and may be a marker of changes in the innate immune system in response to docetaxel resistance. These findings provide a strong rationale to consider GDF15 as a biomarker to guide a therapeutic trial of drugs targeting the innate immune system in combination with docetaxel in mCRPC.</p>","PeriodicalId":54544,"journal":{"name":"Prostate","volume":" ","pages":"747-755"},"PeriodicalIF":2.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140307901","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}