Prostate Cancer and Prostatic Diseases最新文献

{"title":"The effect of human leukocyte antigen genotype on survival in advanced prostate cancer treated with primary androgen deprivation therapy: the KYUCOG-1401-A study.","authors":"Masaki Shiota, Tokiyoshi Tanegashima, Shuichi Tatarano, Toshiyuki Kamoto, Hideyasu Matsuyama, Hideki Sakai, Tsukasa Igawa, Tomomi Kamba, Naohiro Fujimoto, Akira Yokomizo, Seiji Naito, Masatoshi Eto","doi":"10.1038/s41391-024-00808-0","DOIUrl":"https://doi.org/10.1038/s41391-024-00808-0","url":null,"abstract":"<p><strong>Background: </strong>Immune editing, in which human leukocyte antigens (HLA) have critical roles, has been suggested to shape the landscape of human cancer. This study prospectively investigated whether HLA gene zygosity is associated with the prognosis of primary androgen deprivation therapy in advanced prostate cancer.</p><p><strong>Methods: </strong>KYUCOG-1401-A was conducted in conjunction with a prospective clinical trial (KYUCOG-1401). Among the patients enrolled in KYUCOG-1401 and treated with primary androgen deprivation therapy, only Japanese patients were included. HLA genotypes of HLA-A, B, C, DRB1, DQB1, and DPB1 were determined. The effect of divergence of HLA genotypes on time to progression, prostate cancer-specific survival, and overall survival was evaluated.</p><p><strong>Results: </strong>Among 127 patients, homozygosity for HLA-DRB1 (HR, 95% CI; 4.05, 1.54-10.7, P = 0.0047) and HLA-DQB1 (HR, 95% CI; 3.75, 1.47-9.58, P = 0.0058) was associated with an increased risk of prostate cancer-specific mortality. Patients with higher HLA evolutionary divergence scores at HLA-DQB1 (HR, 95% CI; 0.90, 0.82-0.97, P = 0.0093) had lower risks of prostate cancer-specific mortality. Androgen-responsive gene sets were upregulated in CD4low and CD8low tumors in the prostate cancer cohort, but not in the bladder and kidney cancer cohorts.</p><p><strong>Conclusions: </strong>This study suggested that the diversity of HLA-II loci including HLA-DRB1 and HLA-DQB1 plays an important role in advanced prostate cancer survival, contributing to improved risk stratification in advanced prostate cancer. Moreover, it was shown that CD4⁺ T cells play an important role in androgen deprivation therapy, suggesting that immunotherapy targeting CD4⁺ T cells is promising for prostate cancer.</p>","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139898208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of anterior fibromuscular stroma on incontinence outcomes in RASP and HoLEP: a critical analysis of Grosso et al.‘s findings","authors":"Yu-Hsiang Lin,&nbsp;Horng-Heng Juang","doi":"10.1038/s41391-024-00807-1","DOIUrl":"10.1038/s41391-024-00807-1","url":null,"abstract":"","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139735942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of minimally invasive surgical procedures for Male Lower Urinary Tract Symptoms due to benign prostatic hyperplasia on ejaculatory function: a systematic review","authors":"Luca Gemma,&nbsp;Alessio Pecoraro,&nbsp;Arcangelo Sebastianelli,&nbsp;Pietro Spatafora,&nbsp;Francesco Sessa,&nbsp;Rossella Nicoletti,&nbsp;Stavros Gravas,&nbsp;Riccardo Campi,&nbsp;Sergio Serni,&nbsp;Mauro Gacci","doi":"10.1038/s41391-024-00795-2","DOIUrl":"10.1038/s41391-024-00795-2","url":null,"abstract":"Surgical treatments for lower urinary tract symptoms (LUTS) due to benign prostatic obstruction (BPO) are affected by potentially bothersome side effects on sexual, and, above all, ejaculatory function. Several minimally invasive techniques have been proposed in the last years in order to overcome these consequences. Our aim is to summarize and evaluate the efficacy on LUTS relieve and the impact on sexual/ejaculatory function of Rezum, prostate artery embolization (PAE), implantation of a prostatic urethral lift (PUL) and the temporary implantable nitinol device (TIND). A systematic review of the English-language literature was conducted using the MEDLINE, Embase, and Web of Science databases from January 2000 to October 2022, according to the PRISMA guidelines (PROSPERO ID: CRD42023466515). Randomized controlled trials&nbsp;(RCTs), prospective studies and non-comparative or comparative studies assessing the impact on functional and ejaculatory function after minimally invasive surgical therapies for Male LUTS were evaluated. Risk of bias assessment was performed according to the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool for comparative studies, and the revised Cochrane risk-of-bias tool for randomized trials (RoB 2) for RCTs. Overall, 47 studies were included (n = 4 for TIND; n = 9 for Rezum; n = 13 for PUL; n = 21 for PAE). Most studies relied on prospective patient cohorts and were rated as low risk of bias. Across studies assessing the efficacy of Rezum, a significant improvement in terms of IPSS (ranging from −47% to −56%) and Qmax (ranging from +39% to +87%) was reported. On the other hand, according to IIEF-5 score, Rezum had a minimal impact on sexual function (ranging from −1% to −3%). PUL showed a positive impact on IPSS (ranging from −35% to −58.2%) and Qmax (ranging from +49.9% to +114.7%) and sexual function. Finally, PAE showed encouraging functional results with IPSS score reducing from −12.8% to 63.3% and Qmax improving from +8% to 114.9% but the available evidence regarding the potential impact of PAE on sexual outcomes were limited. Rezum, PAE, PUL and TIND are safe and feasible techniques associated with a significant functional improvement. While available data suggest a minimal impact of Rezum and PUL on ejaculatory function, the evidence after PAE and TIND are still limited. Therefore, our review lays the foundation for further research aiming to identify the criteria to select best candidates for uMIST to tailor the management in light of specific patient- and disease- factors.","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41391-024-00795-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139735941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic and predictive analyses of circulating plasma biomarkers in men with metastatic castration resistant prostate cancer treated with docetaxel/prednisone with or without bevacizumab.","authors":"Andrew B Nixon, Yingmiao Liu, Qian Yang, Bin Luo, Mark D Starr, John C Brady, Wm Kevin Kelly, Himisha Beltran, Michael J Morris, Daniel J George, Andrew J Armstrong, Susan Halabi","doi":"10.1038/s41391-024-00794-3","DOIUrl":"10.1038/s41391-024-00794-3","url":null,"abstract":"<p><strong>Background: </strong>CALGB 90401 (Alliance) was a phase III trial of 1050 patients with metastatic castration-resistant prostate cancer (mCRPC) comparing docetaxel, prednisone, bevacizumab (DP+B) versus DP alone. While this trial did not show an improvement in overall survival (OS), there were improved intermediate outcomes suggesting that subsets of men may derive benefit from this combination. The purpose of this analysis was to identify prognostic and predictive biomarkers associated with OS and progression-free survival (PFS) benefit from DP+B.</p><p><strong>Methods: </strong>Baseline EDTA plasma samples from 650 consenting patients were analyzed for 24 biomarkers. The proportional hazards model was utilized to test for the prognostic and predictive importance of the biomarkers for OS. The statistically significant biomarkers of OS were further investigated for prognostic and predictive importance for other secondary outcomes.</p><p><strong>Results: </strong>15 markers [ICAM-1, VEGF-R3, TIMP-1, TSP-2, Ang-2, Her-3, Osteopontin (OPN), PlGF, VCAM-1, HGF, VEGF, Chromogranin A, IL-6, VEGF-R1, BMP-9] were prognostic of OS, while 9 markers (ICAM-1, VEGF-R3, Her-3, TIMP-1, Ang-2, OPN, PlGF, HGF, and VEGF) were also prognostic of PFS. All markers were statistically significant in univariate analyses after adjustment for multiplicity (FDR < 0.1). In multivariable analyses of OS adjusting for risk score, seven markers had FDR < 0.1, including ICAM-1, VEGF-R3, TIMP-1, Ang-2, VEGF, TSP-2 and HGF. In unadjusted analysis, OPN was predictive of PFS improvement with DP+B, in both univariate and multivariable analysis. However, none of the biomarkers tested were predictive of clinical outcomes after adjusting for multiple comparisons.</p><p><strong>Conclusions: </strong>Multiple biomarkers were identified in CALGB 90401 as prognostic of clinical outcomes but not predictive of OS. While OPN may have promise as a potential biomarker for anti-angiogenic therapies, further mechanistic and clinical studies are needed to determine the underlying biology and potential clinical application.</p>","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11317541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139723768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Initial management approach for localized/locally advanced disease is critical to guide metastatic castration-resistant prostate cancer care.","authors":"Vincenza Conteduca, Piergiorgio Di Tullio, Rossana Allamprese, Giuseppina Bruno, Cristian Lolli, Giuseppe Schepisi, Aldo Rosano, Guido Giordano, Marianna Garofoli, Vincenzo Emanuele Chiuri, Lucia Fratino, Elisa Zanardi, Luca Galli, Francesco Massari, Ugo Falagario, Pasquale Rescigno, Giuseppe Fornarini, Francesca Sanguedolce, Daniele Santini, Giuseppe Procopio, Orazio Caffo, Giuseppe Carrieri, Matteo Landriscina, Ugo De Giorgi","doi":"10.1038/s41391-024-00800-8","DOIUrl":"10.1038/s41391-024-00800-8","url":null,"abstract":"<p><strong>Background: </strong>Currently, several therapies are available for metastatic castration-resistant prostate cancer (mCRPC) but no specific clinical factors to personalize treatment. We first sought the prognostic value of duration on androgen-deprivation therapy (ADT) for hormone-sensitive prostate cancer (HSPC) in patients receiving androgen-receptor-signaling inhibitors (ARSI) for mCRPC.</p><p><strong>Methods: </strong>A multicenter cohort of mCRPC patients who started ARSI between July 2011 and October 2021 was identified. Based on their initial disease burden and duration on ADT for HSPC, primary progressive (PP) men were classified into four groups: low/intermediate-risk localized disease (LOC) and high-risk localized/locally advanced disease (LAD) and short-term (ST) < 24 vs. long-term (LT) ADT ≥ 24 months, whereas de novo (DN) mHSPC were subdivided into short-time vs. long-time to CRPC.</p><p><strong>Results: </strong>We included 919 mCRPC patients with a median age of 77 years [interquartile range (IQR) = 71-82)]. Median ADT duration in HSPC was 24 months (IQR = 14-40). Median follow-up was 91 months (IQR = 62-138), median OS and PFS from ARSI start were 20 (IQR 10-32) and 10 months (IQR = 5-19), respectively. In PP developing metastatic disease (n = 655, 71.3%), LOC and LAD with ST ADT had a greater than almost double-risk of death compared to LT ADT (LOC/ST: hazard ratio [HR] = 2.01; 95% CI 1.54-2.64; LAD/ST: HR = 1.73; 95% CI 1.34-2.24; p < 0.001). In the multivariate analysis including age, prognostic cohort, Gleason, ECOG, radical radiotherapy and prostatectomy, groups with ST ADT were associated with worse OS compared to LT ADT (LOC/ST: HR = 1.84; 95% CI 1.38-2.45; p < 0.001; LAD/ST: HR = 1.59; 95% CI 1.21-2.10; p < 0.001), along with ECOG > 2 (HR = 1.55; 95% CI 1.06-2.26; p = 0.03). There were also similar results of PFS. Moreover, long-time to CRPC in patients with history of DN mHSPC (n = 264, 28.7%) resulted in a better OS/PFS (HR = 0.76, 95% CI 0.56-1.02, p = 0.064 and HR = 0.74, 95% CI 0.55-0.99, p = 0.042, respectively).</p><p><strong>Conclusions: </strong>Our study showed that duration on ADT for mHSPC was significantly associated with survival in mCRPC undergoing ARSI. These findings suggest a possible connection between initial management of prostate tumour and a better prognostication in mCRPC. Prospective trials are warranted.</p>","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139723767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does prostate cancer without cribriform pattern have metastatic potential?","authors":"Lisa J Kroon, Sebastiaan Remmers, Eva Hollemans, Chris H Bangma, Monique J Roobol, Geert J L H van Leenders","doi":"10.1038/s41391-024-00802-6","DOIUrl":"https://doi.org/10.1038/s41391-024-00802-6","url":null,"abstract":"","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139716372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase 1/2 multicenter trial of DKN-01 as monotherapy or in combination with docetaxel for the treatment of metastatic castration-resistant prostate cancer (mCRPC).","authors":"David R Wise, Russell K Pachynski, Samuel R Denmeade, Rahul R Aggarwal, Jiehui Deng, Victor Adorno Febles, Arjun V Balar, Minas P Economides, Cynthia Loomis, Shanmugapriya Selvaraj, Michael Haas, Michael H Kagey, Walter Newman, Jason Baum, Andrea B Troxel, Sarah Griglun, Dayna Leis, Nina Yang, Viktoriya Aranchiy, Sabrina Machado, Erika Waalkes, Gabrielle Gargano, Nadia Soamchand, Amrutesh Puranik, Pratip Chattopadhyay, Ezeddin Fedal, Fang-Ming Deng, Qinghu Ren, Luis Chiriboga, Jonathan Melamed, Cynthia A Sirard, Kwok-Kin Wong","doi":"10.1038/s41391-024-00798-z","DOIUrl":"https://doi.org/10.1038/s41391-024-00798-z","url":null,"abstract":"<p><strong>Background: </strong>Dickkopf-related protein 1 (DKK1) is a Wingless-related integrate site (Wnt) signaling modulator that is upregulated in prostate cancers (PCa) with low androgen receptor expression. DKN-01, an IgG4 that neutralizes DKK1, delays PCa growth in pre-clinical DKK1-expressing models. These data provided the rationale for a clinical trial testing DKN-01 in patients with metastatic castration-resistant PCa (mCRPC).</p><p><strong>Methods: </strong>This was an investigator-initiated parallel-arm phase 1/2 clinical trial testing DKN-01 alone (monotherapy) or in combination with docetaxel 75 mg/m² (combination) for men with mCRPC who progressed on ≥1 AR signaling inhibitors. DKK1 status was determined by RNA in-situ expression. The primary endpoint of the phase 1 dose escalation cohorts was the determination of the recommended phase 2 dose (RP2D). The primary endpoint of the phase 2 expansion cohorts was objective response rate by iRECIST criteria in patients treated with the combination.</p><p><strong>Results: </strong>18 pts were enrolled into the study-10 patients in the monotherapy cohorts and 8 patients in the combination cohorts. No DLTs were observed and DKN-01 600 mg was determined as the RP2D. A best overall response of stable disease occurred in two out of seven (29%) evaluable patients in the monotherapy cohort. In the combination cohort, five out of seven (71%) evaluable patients had a partial response (PR). A median rPFS of 5.7 months was observed in the combination cohort. In the combination cohort, the median tumoral DKK1 expression H-score was 0.75 and the rPFS observed was similar between patients with DKK1 H-score ≥1 versus H-score = 0.</p><p><strong>Conclusion: </strong>DKN-01 600 mg was well tolerated. DKK1 blockade has modest anti-tumor activity as a monotherapy for mCRPC. Anti-tumor activity was observed in the combination cohorts, but the response duration was limited. DKK1 expression in the majority of mCRPC is low and did not clearly correlate with anti-tumor activity of DKN-01 plus docetaxel.</p>","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139716370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A real-world experience of pembrolizumab monotherapy in microsatellite instability-high and/or tumor mutation burden-high metastatic castration-resistant prostate cancer: outcome analysis.","authors":"Osama Mosalem, Winston Tan, Alan H Bryce, Roxana S Dronca, Daniel S Childs, Lance C Pagliaro, Jacob J Orme, Adam M Kase","doi":"10.1038/s41391-024-00799-y","DOIUrl":"https://doi.org/10.1038/s41391-024-00799-y","url":null,"abstract":"<p><strong>Background: </strong>The efficacy of pembrolizumab monotherapy in metastatic castration-resistant prostate cancer patients (mCRPC) when stratified by MSI-H and/or TMB-H is poorly defined. Additionally, outcomes based on sequencing source (i.e., tissue or liquid biopsy) have not been well described. We sought to assess outcomes of pembrolizumab monotherapy in patients with mCRPC and compare efficacy based on MSI-H and/or TMB-H when identified by tissue or liquid biopsy.</p><p><strong>Methods: </strong>A retrospective analysis was performed of mCRPC patients treated at Mayo Clinic with pembrolizumab monotherapy between 2018 and 2023. Objective response rates (ORR), median progression-free survival (mPFS), and overall survival (mOS), were determined by RECIST v1.1 criteria.</p><p><strong>Results: </strong>Twenty-two patients with mCRPC received pembrolizumab monotherapy for at least 3 cycles for a MSI-H or TMB-H indication. All patients had next generation sequencing (NGS) performed via tissue (n = 11) or liquid (n = 10) biopsy source. The ORR was 50% (27.3% complete response and 22.7% had partial response). The mPFS for TMB 10-14.9 mut/Mb (n = 4), TMB 15-24.9 mut/Mb (n = 6), and TMB ≥ 25 mut/Mb (n = 10) was 2.1, not reached (NR), and NR, respectively (p = 0.0003). The mOS for these same groups was 5.1 months, 20.5 months, and not reached, respectively. Among patients with TMB-H without co-occurring MSI-H or CDK12 (n = 6), none experienced a response and only one patient had stable disease compared to patients with MSI-H (n = 12) for whom the ORR was 75%. Immunotherapy responsive alterations such as ATRX and PTCH1 mutations were frequently noticed among patients who had complete response (CR).</p><p><strong>Conclusions: </strong>Our hypothesis-generating study suggests that MSI-H drives the efficacy of pembrolizumab in mCRPC with better survival outcomes as TMB increases. Clinicians should consider alternative treatment strategies for advanced prostate cancer when TMB-H is present without co-occurring MSI-H or CDK12.</p>","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139716371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence of prostate cancer in transgender women in the US: a large database analysis.","authors":"Matthew Loria, David Gilbert, Tomasz Tabernacki, Mart Andrew Maravillas, Megan McNamara, Shubham Gupta, Kirtishri Mishra","doi":"10.1038/s41391-024-00804-4","DOIUrl":"10.1038/s41391-024-00804-4","url":null,"abstract":"<p><p>The risk of prostate cancer among transgender women undergoing medical and surgical gender-affirming interventions remains unclear, though up to a fivefold decreased risk has been reported in comparison to cisgender men. In this study, we conducted a comparative analysis of the risk of prostate cancer among transgender women (TW) using data from TriNetX, a large database, versus SEER. Our findings indicate that, overall, transgender women exhibited a 2.56-fold lower risk of prostate cancer compared to cisgender men. Specifically, among TW on hormone therapy between ages 50-64, we observed a 2.06-fold decrease in risk. Contrary to the previous perception of prostate cancer being rare in transgender women, our study suggests that it may not be as uncommon as previously believed.</p>","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139703280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A non-invasive 25-Gene PLNM-Score urine test for detection of prostate cancer pelvic lymph node metastasis","authors":"Jinan Guo, Liangyou Gu, Heather Johnson, Di Gu, Zhenquan Lu, Binfeng Luo, Qian Yuan, Xuhui Zhang, Taolin Xia, Qingsong Zeng, Alan H. B. Wu, Allan Johnson, Nishtman Dizeyi, Per-Anders Abrahamsson, Heqiu Zhang, Lingwu Chen, Kefeng Xiao, Chang Zou, Jenny L. Persson","doi":"10.1038/s41391-023-00758-z","DOIUrl":"https://doi.org/10.1038/s41391-023-00758-z","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Prostate cancer patients with pelvic lymph node metastasis (PLNM) have poor prognosis. Based on EAU guidelines, patients with &gt;5% risk of PLNM by nomograms often receive pelvic lymph node dissection (PLND) during prostatectomy. However, nomograms have limited accuracy, so large numbers of false positive patients receive unnecessary surgery with potentially serious side effects. It is important to accurately identify PLNM, yet current tests, including imaging tools are inaccurate. Therefore, we intended to develop a gene expression-based algorithm for detecting PLNM.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>An advanced random forest machine learning algorithm screening was conducted to develop a classifier for identifying PLNM using urine samples collected from a multi-center retrospective cohort (<i>n</i> = 413) as training set and validated in an independent multi-center prospective cohort (<i>n</i> = 243). Univariate and multivariate discriminant analyses were performed to measure the ability of the algorithm classifier to detect PLNM and compare it with the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram score.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>An algorithm named 25 G PLNM-Score was developed and found to accurately distinguish PLNM and non-PLNM with AUC of 0.93 (95% CI: 0.85–1.01) and 0.93 (95% CI: 0.87–0.99) in the retrospective and prospective urine cohorts respectively. Kaplan–Meier plots showed large and significant difference in biochemical recurrence-free survival and distant metastasis-free survival in the patients stratified by the 25 G PLNM-Score (log rank <i>P</i> &lt; 0.001 and <i>P</i> &lt; 0.0001, respectively). It spared 96% and 80% of unnecessary PLND with only 0.51% and 1% of PLNM missing in the retrospective and prospective cohorts respectively. In contrast, the MSKCC score only spared 15% of PLND with 0% of PLNM missing.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>The novel 25 G PLNM-Score is the first highly accurate and non-invasive machine learning algorithm-based urine test to identify PLNM before PLND, with potential clinical benefits of avoiding unnecessary PLND and improving treatment decision-making.</p>","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139663860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}