Pub Date : 2024-08-01DOI: 10.1038/s41391-024-00875-3
Lorenzo Storino Ramacciotti, Andre Luis Abreu, Sébastien Crouzet, Petr Macek, Brian J Miles, Rahim Horuz, Diogo Nunes-Carneiro, Phillip Stricker, Stephen Scionti, M Pilar Laguna
Objective: To review the literature on salvage treatments after focal therapy (FT) for prostate cancer (PCa).
Materials and methods: A non-systematic literature review was conducted on PubMed, Scopus, and Web of Science up to March 15, 2024, for studies that assessed salvage treatment outcomes in patients with recurrent PCa after primary FT. Original prospective and retrospective studies with more than 10 patients were included. Reviews, editorial comments, conference abstracts, and studies focusing solely on whole-gland treatments were excluded.
Results: Twenty-one studies with a total of 1012 patients were included. The most reported salvage treatments were salvage radical prostatectomy followed by re-do ablation therapy. Only one study evaluated salvage radiation therapy. Except for one prospective study, all studies were retrospective. Oncological outcomes showed acceptable biochemical recurrence rates. Functional outcomes varied, with significant impacts observed on erectile function across modalities, though continence rates were less impacted. Complications were generally low across all treatment options.
Conclusion: Salvage treatment post-primary FT is feasible, safe, and has reasonable oncologic outcomes. However, significant declines in sexual function are common, while continence is comparatively less affected. The literature primarily consists of retrospective studies; hence, future research should focus on large-scale prospective evaluations to better define treatment protocols and improve patient outcomes.
{"title":"Salvage treatments after focal therapy for prostate cancer - a comprehensive review.","authors":"Lorenzo Storino Ramacciotti, Andre Luis Abreu, Sébastien Crouzet, Petr Macek, Brian J Miles, Rahim Horuz, Diogo Nunes-Carneiro, Phillip Stricker, Stephen Scionti, M Pilar Laguna","doi":"10.1038/s41391-024-00875-3","DOIUrl":"https://doi.org/10.1038/s41391-024-00875-3","url":null,"abstract":"<p><strong>Objective: </strong>To review the literature on salvage treatments after focal therapy (FT) for prostate cancer (PCa).</p><p><strong>Materials and methods: </strong>A non-systematic literature review was conducted on PubMed, Scopus, and Web of Science up to March 15, 2024, for studies that assessed salvage treatment outcomes in patients with recurrent PCa after primary FT. Original prospective and retrospective studies with more than 10 patients were included. Reviews, editorial comments, conference abstracts, and studies focusing solely on whole-gland treatments were excluded.</p><p><strong>Results: </strong>Twenty-one studies with a total of 1012 patients were included. The most reported salvage treatments were salvage radical prostatectomy followed by re-do ablation therapy. Only one study evaluated salvage radiation therapy. Except for one prospective study, all studies were retrospective. Oncological outcomes showed acceptable biochemical recurrence rates. Functional outcomes varied, with significant impacts observed on erectile function across modalities, though continence rates were less impacted. Complications were generally low across all treatment options.</p><p><strong>Conclusion: </strong>Salvage treatment post-primary FT is feasible, safe, and has reasonable oncologic outcomes. However, significant declines in sexual function are common, while continence is comparatively less affected. The literature primarily consists of retrospective studies; hence, future research should focus on large-scale prospective evaluations to better define treatment protocols and improve patient outcomes.</p>","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875776","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}
Pub Date : 2024-07-31DOI: 10.1038/s41391-024-00877-1
Angie K Puerto Nino, Valentina Garcia Perez, Silvia Secco, Cosimo De Nunzio, Riccardo Lombardo, Kari A O Tikkinen, Dean S Elterman
{"title":"Reply to RE: Can ChatGPT provide high-quality patient information on male lower urinary tract symptoms suggestive of benign prostate enlargement?","authors":"Angie K Puerto Nino, Valentina Garcia Perez, Silvia Secco, Cosimo De Nunzio, Riccardo Lombardo, Kari A O Tikkinen, Dean S Elterman","doi":"10.1038/s41391-024-00877-1","DOIUrl":"https://doi.org/10.1038/s41391-024-00877-1","url":null,"abstract":"","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860717","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}
Pub Date : 2024-07-29DOI: 10.1038/s41391-024-00873-5
J W Yaxley, B Fitzgerald
{"title":"Cardiovascular risks of androgen receptor targeted agents in prostate cancer: a systematic review and meta-analysis \"PCAN-23-0763R\".","authors":"J W Yaxley, B Fitzgerald","doi":"10.1038/s41391-024-00873-5","DOIUrl":"https://doi.org/10.1038/s41391-024-00873-5","url":null,"abstract":"","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793184","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}
Pub Date : 2024-07-24DOI: 10.1038/s41391-024-00872-6
Georges Mjaess, Laura Haddad, Teddy Jabbour, Arthur Baudewyns, Henri-Alexandre Bourgeno, Yolène Lefebvre, Mariaconsiglia Ferriero, Giuseppe Simone, Alexandre Fourcade, Georges Fournier, Marco Oderda, Paolo Gontero, Adrian Bernal-Gomez, Alessandro Mastrorosa, Jean-Baptiste Roche, Rawad Abou Zahr, Guillaume Ploussard, Gaelle Fiard, Adam Halinski, Katerina Rysankova, Charles Dariane, Gina Delavar, Julien Anract, Nicolas Barry Delongchamps, Alexandre Patrick Bui, Fayek Taha, Olivier Windisch, Daniel Benamran, Gregoire Assenmacher, Jan Benijts, Karsten Guenzel, Thierry Roumeguère, Alexandre Peltier, Romain Diamand
Background: Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions, identified through multiparametric magnetic resonance imaging (mpMRI), present a clinical challenge due to their equivocal nature in predicting clinically significant prostate cancer (csPCa). Aim of the study is to improve risk stratification of patients with PI-RADS 3 lesions and candidates for prostate biopsy.
Methods: A cohort of 4841 consecutive patients who underwent MRI and subsequent MRI-targeted and systematic biopsies between January 2016 and April 2023 were retrospectively identified from independent prospectively maintained database. Only patients who have PI-RADS 3 lesions were included in the final analysis. A multivariable logistic regression analysis was performed to identify covariables associated with csPCa defined as International Society of Urological Pathology (ISUP) grade group ≥2. Performance of the model was evaluated using the area under the receiver operating characteristic curve (AUC), calibration, and net benefit. Significant predictors were then selected for further exploration using a Chi-squared Automatic Interaction Detection (CHAID) analysis.
Results: Overall, 790 patients had PI-RADS 3 lesions and 151 (19%) had csPCa. Significant associations were observed for age (OR: 1.1 [1.0-1.1]; p = 0.01) and PSA density (OR: 1643 [2717-41,997]; p < 0.01). The CHAID analysis identified PSAd as the sole significant factor influencing the decision tree. Cut-offs for PSAd were 0.13 ng/ml/cc (csPCa detection rate of 1% vs. 18%) for the two-nodes model and 0.09 ng/ml/cc and 0.16 ng/ml/cc for the three-nodes model (csPCa detection rate of 0.5% vs. 2% vs. 17%).
Conclusions: For individuals with PI-RADS 3 lesions on prostate mpMRI and a PSAd below 0.13, especially below 0.09, prostate biopsy can be omitted, in order to avoid unnecessary biopsy and overdiagnosis of non-csPCa.
{"title":"Refining clinically relevant cut-offs of prostate specific antigen density for risk stratification in patients with PI-RADS 3 lesions.","authors":"Georges Mjaess, Laura Haddad, Teddy Jabbour, Arthur Baudewyns, Henri-Alexandre Bourgeno, Yolène Lefebvre, Mariaconsiglia Ferriero, Giuseppe Simone, Alexandre Fourcade, Georges Fournier, Marco Oderda, Paolo Gontero, Adrian Bernal-Gomez, Alessandro Mastrorosa, Jean-Baptiste Roche, Rawad Abou Zahr, Guillaume Ploussard, Gaelle Fiard, Adam Halinski, Katerina Rysankova, Charles Dariane, Gina Delavar, Julien Anract, Nicolas Barry Delongchamps, Alexandre Patrick Bui, Fayek Taha, Olivier Windisch, Daniel Benamran, Gregoire Assenmacher, Jan Benijts, Karsten Guenzel, Thierry Roumeguère, Alexandre Peltier, Romain Diamand","doi":"10.1038/s41391-024-00872-6","DOIUrl":"https://doi.org/10.1038/s41391-024-00872-6","url":null,"abstract":"<p><strong>Background: </strong>Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions, identified through multiparametric magnetic resonance imaging (mpMRI), present a clinical challenge due to their equivocal nature in predicting clinically significant prostate cancer (csPCa). Aim of the study is to improve risk stratification of patients with PI-RADS 3 lesions and candidates for prostate biopsy.</p><p><strong>Methods: </strong>A cohort of 4841 consecutive patients who underwent MRI and subsequent MRI-targeted and systematic biopsies between January 2016 and April 2023 were retrospectively identified from independent prospectively maintained database. Only patients who have PI-RADS 3 lesions were included in the final analysis. A multivariable logistic regression analysis was performed to identify covariables associated with csPCa defined as International Society of Urological Pathology (ISUP) grade group ≥2. Performance of the model was evaluated using the area under the receiver operating characteristic curve (AUC), calibration, and net benefit. Significant predictors were then selected for further exploration using a Chi-squared Automatic Interaction Detection (CHAID) analysis.</p><p><strong>Results: </strong>Overall, 790 patients had PI-RADS 3 lesions and 151 (19%) had csPCa. Significant associations were observed for age (OR: 1.1 [1.0-1.1]; p = 0.01) and PSA density (OR: 1643 [2717-41,997]; p < 0.01). The CHAID analysis identified PSAd as the sole significant factor influencing the decision tree. Cut-offs for PSAd were 0.13 ng/ml/cc (csPCa detection rate of 1% vs. 18%) for the two-nodes model and 0.09 ng/ml/cc and 0.16 ng/ml/cc for the three-nodes model (csPCa detection rate of 0.5% vs. 2% vs. 17%).</p><p><strong>Conclusions: </strong>For individuals with PI-RADS 3 lesions on prostate mpMRI and a PSAd below 0.13, especially below 0.09, prostate biopsy can be omitted, in order to avoid unnecessary biopsy and overdiagnosis of non-csPCa.</p>","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760520","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}
Pub Date : 2024-07-18DOI: 10.1038/s41391-024-00868-2
O Windisch, M Diana, D Tilki, G Marra, A Martini, M Valerio
Positive surgical margin (PSM) is a frequent concern for surgeons performing radical prostatectomy for prostate cancer (PCa). PSM are recognized as risk factors for earlier biochemical recurrence and expose patients to adjuvant or salvage treatments such as external radiotherapy and hormonotherapy. Several strategies have been established to reduce PSM rate, while still allowing safe nerve-sparing surgery. Precise preoperative staging by multiparametric magnetic resonance imaging (mpMRI) and fusion biopsy is recommended to identify suspicious areas of extracapsular extension (ECE) that warrant special attention during dissection. However, even with optimal imaging, ECE can be missed, some cancers are not well defined or visible, and capsular incision during surgery remains an issue. Hence, intraoperative frozen section techniques, such as the neurovascular structure-adjacent frozen section examination (NeuroSAFE) have been developed and lately widely disseminated. The NeuroSAFE technique reduces PSM rate while allowing higher rate of nerve-sparing surgery. However, its use is limited to high volume or expert center because of its high barrier-to-entry in terms of logistics, human resources and expertise, as well as cost. Also, NeuroSAFE is a time-consuming process, even in expert hands. To address these issues, several technologies have been developed for an ex vivo and in vivo use. Ex vivo technology such as fluorescent confocal microscopy and intraoperative PET-CT require the extraction of the specimen for preparation, and digital images acquisition. In vivo technology, such as augmented reality based on mpMRI images and PSMA-fluorescent guided surgery have the advantage to provide an intracorporeal analysis of the completeness of the resection. The current manuscript provides a narrative review of established techniques, and details several new and promising techniques for intraoperative PSM assessment.
{"title":"Intraoperative technologies to assess margin status during radical prostatectomy - a narrative review.","authors":"O Windisch, M Diana, D Tilki, G Marra, A Martini, M Valerio","doi":"10.1038/s41391-024-00868-2","DOIUrl":"https://doi.org/10.1038/s41391-024-00868-2","url":null,"abstract":"<p><p>Positive surgical margin (PSM) is a frequent concern for surgeons performing radical prostatectomy for prostate cancer (PCa). PSM are recognized as risk factors for earlier biochemical recurrence and expose patients to adjuvant or salvage treatments such as external radiotherapy and hormonotherapy. Several strategies have been established to reduce PSM rate, while still allowing safe nerve-sparing surgery. Precise preoperative staging by multiparametric magnetic resonance imaging (mpMRI) and fusion biopsy is recommended to identify suspicious areas of extracapsular extension (ECE) that warrant special attention during dissection. However, even with optimal imaging, ECE can be missed, some cancers are not well defined or visible, and capsular incision during surgery remains an issue. Hence, intraoperative frozen section techniques, such as the neurovascular structure-adjacent frozen section examination (NeuroSAFE) have been developed and lately widely disseminated. The NeuroSAFE technique reduces PSM rate while allowing higher rate of nerve-sparing surgery. However, its use is limited to high volume or expert center because of its high barrier-to-entry in terms of logistics, human resources and expertise, as well as cost. Also, NeuroSAFE is a time-consuming process, even in expert hands. To address these issues, several technologies have been developed for an ex vivo and in vivo use. Ex vivo technology such as fluorescent confocal microscopy and intraoperative PET-CT require the extraction of the specimen for preparation, and digital images acquisition. In vivo technology, such as augmented reality based on mpMRI images and PSMA-fluorescent guided surgery have the advantage to provide an intracorporeal analysis of the completeness of the resection. The current manuscript provides a narrative review of established techniques, and details several new and promising techniques for intraoperative PSM assessment.</p>","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724354","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}
Pub Date : 2024-07-17DOI: 10.1038/s41391-024-00870-8
Andrew W Hahn, Rebecca S Tidwell, Patrick G Pilie, Yao Yu, Jingjing Liu, Devaki Shilpa Surasi, Mark Titus, Jianhua Zhang, Neha Venkatesh, Theocharis Panaretakis, Justin R Gregg, Amado J Zurita, Bilal A Siddiqui, Paul G Corn, Sumit K Subudhi, Pavlos Msaouel, Efstratios Koutroumpakis, Chad D Huff, Ana Aparicio, Jennifer L McQuade, Daniel E Frigo, Christopher J Logothetis
Background: Androgen signaling is central to prostate cancer and men's health. Prior data indicates that increasing body fat is unfavorable in the localized setting yet associated with favorable outcomes in men with metastatic disease. Understanding the biological links between adiposity and prostate cancer may optimize the therapeutic index with ASI. We hypothesized that host adiposity and androgen synthesis are linked to the efficacy and toxicity of ASI for men with metastatic castration-resistant prostate cancer (mCRPC).
Methods: A post-hoc analysis was done of NCT02703623 where men with mCRPC (n = 186) were treated for 8 weeks with abiraterone acetate, prednisone, and apalutamide (AAPA), and a satisfactory response was defined as a PSA decline >50%. Body composition was measured on baseline CT scans. Germline DNA WES was performed with a focus on variants in steroidogenic genes. Adipokine levels were measured in pre-treatment plasma.
Results: Germline polymorphisms in 3 genes involved in androgen synthesis (AKR1C3 rs12529, CYP17A1 rs6162, SRD5A2 rs523349) were associated with differences in body composition at baseline on ADT alone (prior to receipt of AAPA). Elevated subcutaneous adipose tissue index (SATi, p = 0.02), visceral adipose tissue index (VATi, p = 0.03), and BMI (p = 0.04) were associated with satisfactory response to AAPA. Leptin had positive correlation with VATi (r = 0.47) and SATi (r = 0.48).
Conclusion: Inherited polymorphisms in androgen synthesis correlated with differences in body composition after exposure to ADT and warrant further investigation as candidate markers for body composition toxicity. Elevated subcutaneous and visceral adiposity were associated with improved response to ASI.
背景:雄激素信号对前列腺癌和男性健康至关重要。先前的数据表明,增加体内脂肪不利于局部治疗,但却与男性转移性疾病的良好预后有关。了解脂肪与前列腺癌之间的生物学联系可优化 ASI 的治疗指数。我们假设,宿主脂肪和雄激素合成与 ASI 对转移性耐受性前列腺癌(mCRPC)患者的疗效和毒性有关:对NCT02703623进行了事后分析,mCRPC男性患者(n = 186)接受了为期8周的醋酸阿比特龙、泼尼松和阿帕鲁胺(AAPA)治疗,PSA下降>50%即为满意反应。通过基线CT扫描测量身体成分。进行了种系 DNA WES 检测,重点是类固醇生成基因的变异。对治疗前血浆中的脂肪因子水平进行了测量:结果:3个参与雄激素合成的基因(AKR1C3 rs12529、CYP17A1 rs6162、SRD5A2 rs523349)的种系多态性与单用ADT时(接受AAPA治疗前)基线身体成分的差异有关。皮下脂肪组织指数(SATi,p = 0.02)、内脏脂肪组织指数(VATi,p = 0.03)和体重指数(BMI,p = 0.04)的升高与对 AAPA 的满意反应相关。瘦素与VATi(r = 0.47)和SATi(r = 0.48)呈正相关:结论:雄激素合成的遗传多态性与暴露于 ADT 后身体成分的差异相关,值得作为身体成分毒性的候选标记进一步研究。皮下和内脏脂肪含量升高与 ASI 反应改善有关。
{"title":"Body composition as a determinant of the therapeutic index with androgen signaling inhibition.","authors":"Andrew W Hahn, Rebecca S Tidwell, Patrick G Pilie, Yao Yu, Jingjing Liu, Devaki Shilpa Surasi, Mark Titus, Jianhua Zhang, Neha Venkatesh, Theocharis Panaretakis, Justin R Gregg, Amado J Zurita, Bilal A Siddiqui, Paul G Corn, Sumit K Subudhi, Pavlos Msaouel, Efstratios Koutroumpakis, Chad D Huff, Ana Aparicio, Jennifer L McQuade, Daniel E Frigo, Christopher J Logothetis","doi":"10.1038/s41391-024-00870-8","DOIUrl":"https://doi.org/10.1038/s41391-024-00870-8","url":null,"abstract":"<p><strong>Background: </strong>Androgen signaling is central to prostate cancer and men's health. Prior data indicates that increasing body fat is unfavorable in the localized setting yet associated with favorable outcomes in men with metastatic disease. Understanding the biological links between adiposity and prostate cancer may optimize the therapeutic index with ASI. We hypothesized that host adiposity and androgen synthesis are linked to the efficacy and toxicity of ASI for men with metastatic castration-resistant prostate cancer (mCRPC).</p><p><strong>Methods: </strong>A post-hoc analysis was done of NCT02703623 where men with mCRPC (n = 186) were treated for 8 weeks with abiraterone acetate, prednisone, and apalutamide (AAPA), and a satisfactory response was defined as a PSA decline >50%. Body composition was measured on baseline CT scans. Germline DNA WES was performed with a focus on variants in steroidogenic genes. Adipokine levels were measured in pre-treatment plasma.</p><p><strong>Results: </strong>Germline polymorphisms in 3 genes involved in androgen synthesis (AKR1C3 rs12529, CYP17A1 rs6162, SRD5A2 rs523349) were associated with differences in body composition at baseline on ADT alone (prior to receipt of AAPA). Elevated subcutaneous adipose tissue index (SATi, p = 0.02), visceral adipose tissue index (VATi, p = 0.03), and BMI (p = 0.04) were associated with satisfactory response to AAPA. Leptin had positive correlation with VATi (r = 0.47) and SATi (r = 0.48).</p><p><strong>Conclusion: </strong>Inherited polymorphisms in androgen synthesis correlated with differences in body composition after exposure to ADT and warrant further investigation as candidate markers for body composition toxicity. Elevated subcutaneous and visceral adiposity were associated with improved response to ASI.</p>","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141634342","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}
Pub Date : 2024-07-17DOI: 10.1038/s41391-024-00869-1
Amanda Broderick, Elizabeth Pan, Jinju Li, Alec Chu, Clara Hwang, Pedro C Barata, Frank Cameron Cackowski, Matthew Labriola, Alyssa Ghose, Mehmet Asim Bilen, Deepak Kilari, Bicky Thapa, Michael Piero, Laura Graham, Abhishek Tripathi, Rohan Garje, Vadim S Koshkin, Erik Hernandez, Tanya B Dorff, Michael Thomas Schweizer, Ajjai Shivaram Alva, Rana R McKay, Andrew J Armstrong
Background: Aberrant Wnt signaling has been implicated in prostate cancer tumorigenesis and metastasis in preclinical models but the impact of genetic alterations in Wnt signaling genes in men with advanced prostate cancer is unknown.
Methods: We utilized the Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) clinical-genomic database for this retrospective analysis. Patients with activating mutations in CTNNB1 or RSPO2 or inactivating mutations in APC, RNF43, or ZNRF3 were defined as Wnt-altered, while those lacking such alterations were defined as Wnt non-altered. We compared patient characteristics and clinical outcomes as well as co-occurring genetic alterations according to Wnt alteration status.
Results: Of the 1498 patients included, 193 (12.9%) were Wnt-altered. These men had a statistically significant 2-fold increased prevalence of liver and lung metastases as compared with Wnt non-altered patients at the time of initial diagnosis, (4.66% v 2.15% ; 6.22% v 3.07%), first metastatic disease diagnosis (10.88% v 5.29%; 13.99% v 6.21%), and CRPC development (11.40% v 6.36%; 12.95% v 5.29%). Wnt alterations were associated with more co-occurring alterations in RB1 (10.4% v 6.2%), AR (38.9% vs 25.7%), SPOP (13.5% vs 4.1%), FOXA1 (6.7% vs 2.8%), and PIK3CA (10.9% vs 5.1%). We found no significant differences in overall survival or other clinical outcomes from initial diagnosis, first metastatic disease, diagnosis of CRPC, or with AR inhibition for mCRPC between the Wnt groups.
Conclusions: Wnt-altered patients with prostate cancer have a higher prevalence of visceral metastases and are enriched in RB1, AR, SPOP, FOXA1, and PIK3CA alterations. Despite these associations, Wnt alterations were not associated with worse survival or treatment outcomes in men with advanced prostate cancer.
背景:在临床前模型中,Wnt 信号转导异常与前列腺癌的肿瘤发生和转移有关,但 Wnt 信号转导基因的遗传改变对晚期前列腺癌男性患者的影响尚不清楚:我们利用前列腺癌精准医学多机构协作努力(PROMISE)临床基因组数据库进行了这项回顾性分析。CTNNB1或RSPO2发生激活突变或APC、RNF43或ZNRF3发生灭活突变的患者被定义为Wnt改变患者,而没有发生此类改变的患者被定义为Wnt非改变患者。我们根据 Wnt 改变状态比较了患者特征、临床结果以及并发遗传改变:在纳入的 1498 名患者中,有 193 人(12.9%)发生了 Wnt 改变。与未发生 Wnt 改变的患者相比,这些男性患者在初次诊断(4.66% 对 2.15%;6.22% 对 3.07%)、首次转移性疾病诊断(10.88% 对 5.29%;13.99% 对 6.21%)和 CRPC 发展(11.40% 对 6.36%;12.95% 对 5.29%)时的肝脏和肺部转移发生率在统计学上显著增加了 2 倍。Wnt改变与更多的RB1(10.4% vs 6.2%)、AR(38.9% vs 25.7%)、SPOP(13.5% vs 4.1%)、FOXA1(6.7% vs 2.8%)和PIK3CA(10.9% vs 5.1%)共存改变相关。我们发现,从最初诊断、首次转移性疾病、诊断为CRPC或使用AR抑制剂治疗mCRPC开始,Wnt组之间的总生存期或其他临床结果没有明显差异:结论:Wnt改变的前列腺癌患者内脏转移率较高,且富含RB1、AR、SPOP、FOXA1和PIK3CA改变。尽管存在这些关联,但Wnt改变与晚期前列腺癌男性患者更差的生存期或治疗效果无关。
{"title":"Clinical implications of Wnt pathway genetic alterations in men with advanced prostate cancer.","authors":"Amanda Broderick, Elizabeth Pan, Jinju Li, Alec Chu, Clara Hwang, Pedro C Barata, Frank Cameron Cackowski, Matthew Labriola, Alyssa Ghose, Mehmet Asim Bilen, Deepak Kilari, Bicky Thapa, Michael Piero, Laura Graham, Abhishek Tripathi, Rohan Garje, Vadim S Koshkin, Erik Hernandez, Tanya B Dorff, Michael Thomas Schweizer, Ajjai Shivaram Alva, Rana R McKay, Andrew J Armstrong","doi":"10.1038/s41391-024-00869-1","DOIUrl":"https://doi.org/10.1038/s41391-024-00869-1","url":null,"abstract":"<p><strong>Background: </strong>Aberrant Wnt signaling has been implicated in prostate cancer tumorigenesis and metastasis in preclinical models but the impact of genetic alterations in Wnt signaling genes in men with advanced prostate cancer is unknown.</p><p><strong>Methods: </strong>We utilized the Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) clinical-genomic database for this retrospective analysis. Patients with activating mutations in CTNNB1 or RSPO2 or inactivating mutations in APC, RNF43, or ZNRF3 were defined as Wnt-altered, while those lacking such alterations were defined as Wnt non-altered. We compared patient characteristics and clinical outcomes as well as co-occurring genetic alterations according to Wnt alteration status.</p><p><strong>Results: </strong>Of the 1498 patients included, 193 (12.9%) were Wnt-altered. These men had a statistically significant 2-fold increased prevalence of liver and lung metastases as compared with Wnt non-altered patients at the time of initial diagnosis, (4.66% v 2.15% ; 6.22% v 3.07%), first metastatic disease diagnosis (10.88% v 5.29%; 13.99% v 6.21%), and CRPC development (11.40% v 6.36%; 12.95% v 5.29%). Wnt alterations were associated with more co-occurring alterations in RB1 (10.4% v 6.2%), AR (38.9% vs 25.7%), SPOP (13.5% vs 4.1%), FOXA1 (6.7% vs 2.8%), and PIK3CA (10.9% vs 5.1%). We found no significant differences in overall survival or other clinical outcomes from initial diagnosis, first metastatic disease, diagnosis of CRPC, or with AR inhibition for mCRPC between the Wnt groups.</p><p><strong>Conclusions: </strong>Wnt-altered patients with prostate cancer have a higher prevalence of visceral metastases and are enriched in RB1, AR, SPOP, FOXA1, and PIK3CA alterations. Despite these associations, Wnt alterations were not associated with worse survival or treatment outcomes in men with advanced prostate cancer.</p>","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141634343","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}
Pub Date : 2024-07-16DOI: 10.1038/s41391-024-00871-7
Yuchen Liu, Qingfang Zhang, Xuan Huang
Purpose: Metformin has been suggested to reduce the risk of cancer. However, previous studies have been inconsistent regarding the relationship between metformin use and the risk of occurrence of prostate cancer (PCa). The purpose of this study was to assess the effect of metformin on clinical outcomes in patients with PCa in a meta-analysis and to explore the possible dose-response relationship.
Methods: A systematic literature search was conducted in 10 electronic databases and 4 registries. The combined relative risks (RRs) were calculated using a random-effects model with 95% confidence interval (CIs) to assess the effect of metformin on the risk of PCa. Relevant subgroup analyses and sensitivity analyses were performed.
Results: The across studies results show that metformin use associated with lower incidence of PCa (RR: 0.82, 95% CI: 0.74-0.91). Metformin use was also found to reduce PCa recurrence, but the results were not statistically significant (RR: 0.97, 95% CI: 0.81-1.15). Metformin use was not associated with PCa mortality (RR: 0.94, 95% CI: 0.81-1.09). The results of subgroup analyses indicated that the type of study was a cohort study and the population came from both Asia and Europe showed that taking metformin reduced the incidence of PCa. A linear correlation was found between the duration of metformin use and its protective effect.
Conclusions: This meta-analysis revealed an independent correlation between metformin use and reduced incidence of PCa. Metformin use was not associated with either PCa recurrence rate or mortality. Furthermore, the effect of metformin on PCa incidence was found to be related to duration.
{"title":"Effect of metformin on incidence, recurrence, and mortality in prostate cancer patients: integrating evidence from real-world studies.","authors":"Yuchen Liu, Qingfang Zhang, Xuan Huang","doi":"10.1038/s41391-024-00871-7","DOIUrl":"https://doi.org/10.1038/s41391-024-00871-7","url":null,"abstract":"<p><strong>Purpose: </strong>Metformin has been suggested to reduce the risk of cancer. However, previous studies have been inconsistent regarding the relationship between metformin use and the risk of occurrence of prostate cancer (PCa). The purpose of this study was to assess the effect of metformin on clinical outcomes in patients with PCa in a meta-analysis and to explore the possible dose-response relationship.</p><p><strong>Methods: </strong>A systematic literature search was conducted in 10 electronic databases and 4 registries. The combined relative risks (RRs) were calculated using a random-effects model with 95% confidence interval (CIs) to assess the effect of metformin on the risk of PCa. Relevant subgroup analyses and sensitivity analyses were performed.</p><p><strong>Results: </strong>The across studies results show that metformin use associated with lower incidence of PCa (RR: 0.82, 95% CI: 0.74-0.91). Metformin use was also found to reduce PCa recurrence, but the results were not statistically significant (RR: 0.97, 95% CI: 0.81-1.15). Metformin use was not associated with PCa mortality (RR: 0.94, 95% CI: 0.81-1.09). The results of subgroup analyses indicated that the type of study was a cohort study and the population came from both Asia and Europe showed that taking metformin reduced the incidence of PCa. A linear correlation was found between the duration of metformin use and its protective effect.</p><p><strong>Conclusions: </strong>This meta-analysis revealed an independent correlation between metformin use and reduced incidence of PCa. Metformin use was not associated with either PCa recurrence rate or mortality. Furthermore, the effect of metformin on PCa incidence was found to be related to duration.</p>","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627475","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}
Pub Date : 2024-07-16DOI: 10.1038/s41391-024-00874-4
Hinpetch Daungsupawong, Viroj Wiwanitkit
{"title":"RE: \"Can ChatGPT provide high-quality patient information on male lower urinary tract symptoms suggestive of benign prostate enlargement?\"","authors":"Hinpetch Daungsupawong, Viroj Wiwanitkit","doi":"10.1038/s41391-024-00874-4","DOIUrl":"10.1038/s41391-024-00874-4","url":null,"abstract":"","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627476","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}
Pub Date : 2024-07-15DOI: 10.1038/s41391-024-00867-3
Dong-Woo Kang, Catherine J Field, Dhruvesh Patel, Adrian S Fairey, Normand G Boulé, Christina M Dieli-Conwright, Kerry S Courneya
Purpose: To report the effects of a 12-week high-intensity interval training (HIIT) program on cardiometabolic biomarkers in patients with prostate cancer on active surveillance (AS) from the Exercise During Active Surveillance for Prostate Cancer (ERASE) Trial.
Methods: Fifty-two men with prostate cancer on AS were randomized to either an exercise (HIIT; n = 26) or usual care (UC; n = 26) group. The HIIT intervention consisted of progressive, supervised, aerobic HIIT at an intensity of 85 to 95% VO2peak for 28 to 40 min per session performed three times/week for 12 weeks. Blood samples were collected at baseline and postintervention to analyze cardiometabolic biomarkers. Analysis of covariance was used to examine between-group mean differences.
Results: Blood data were obtained from 49/52 (94%) participants at postintervention. Participants were aged 63.4 ± 7.1 years and 40% were obese. The HIIT group attended 96% of the planned exercise sessions. No significant between-group changes in weight were observed after the intervention. Compared to UC, HIIT significantly improved total cholesterol (-0.40 mmol/L; 95% confidence interval[CI], -0.70 to -0.10; p = 0.011), non-high-density lipoprotein-c (-0.35 mmol/L; 95% CI, -0.60 to -0.11; p = 0.006), insulin (-13.6 pmol/L; 95% CI, -25.3 to -1.8; p = 0.025), insulin-like growth factor (IGF)-1 (-15.0 ng/mL; 95% CI, -29.9 to -0.1; p = 0.048), and IGF binding protein (IGFBP)-3 (152.3 ng/mL; 95% CI, 12.6 to 292.1; p = 0.033). No significant differences were observed for fasting glucose, HbA1c, other lipid markers, IGFBP-1, adiponectin, and leptin.
Conclusions: The ERASE Trial showed that a 12-week aerobic HIIT program improved several cardiometabolic biomarkers in patients with prostate cancer on AS that may contribute to cardiovascular health benefits and potentially influence signaling pathways in the progression of prostate cancer. Further research is needed to confirm the effects of exercise on cardiometabolic markers in men with prostate cancer on AS and determine if these effects are associated with improved long-term clinical outcomes.
{"title":"Effects of high-intensity interval training on cardiometabolic biomarkers in patients with prostate cancer undergoing active surveillance: a randomized controlled trial.","authors":"Dong-Woo Kang, Catherine J Field, Dhruvesh Patel, Adrian S Fairey, Normand G Boulé, Christina M Dieli-Conwright, Kerry S Courneya","doi":"10.1038/s41391-024-00867-3","DOIUrl":"https://doi.org/10.1038/s41391-024-00867-3","url":null,"abstract":"<p><strong>Purpose: </strong>To report the effects of a 12-week high-intensity interval training (HIIT) program on cardiometabolic biomarkers in patients with prostate cancer on active surveillance (AS) from the Exercise During Active Surveillance for Prostate Cancer (ERASE) Trial.</p><p><strong>Methods: </strong>Fifty-two men with prostate cancer on AS were randomized to either an exercise (HIIT; n = 26) or usual care (UC; n = 26) group. The HIIT intervention consisted of progressive, supervised, aerobic HIIT at an intensity of 85 to 95% VO<sub>2peak</sub> for 28 to 40 min per session performed three times/week for 12 weeks. Blood samples were collected at baseline and postintervention to analyze cardiometabolic biomarkers. Analysis of covariance was used to examine between-group mean differences.</p><p><strong>Results: </strong>Blood data were obtained from 49/52 (94%) participants at postintervention. Participants were aged 63.4 ± 7.1 years and 40% were obese. The HIIT group attended 96% of the planned exercise sessions. No significant between-group changes in weight were observed after the intervention. Compared to UC, HIIT significantly improved total cholesterol (-0.40 mmol/L; 95% confidence interval[CI], -0.70 to -0.10; p = 0.011), non-high-density lipoprotein-c (-0.35 mmol/L; 95% CI, -0.60 to -0.11; p = 0.006), insulin (-13.6 pmol/L; 95% CI, -25.3 to -1.8; p = 0.025), insulin-like growth factor (IGF)-1 (-15.0 ng/mL; 95% CI, -29.9 to -0.1; p = 0.048), and IGF binding protein (IGFBP)-3 (152.3 ng/mL; 95% CI, 12.6 to 292.1; p = 0.033). No significant differences were observed for fasting glucose, HbA1c, other lipid markers, IGFBP-1, adiponectin, and leptin.</p><p><strong>Conclusions: </strong>The ERASE Trial showed that a 12-week aerobic HIIT program improved several cardiometabolic biomarkers in patients with prostate cancer on AS that may contribute to cardiovascular health benefits and potentially influence signaling pathways in the progression of prostate cancer. Further research is needed to confirm the effects of exercise on cardiometabolic markers in men with prostate cancer on AS and determine if these effects are associated with improved long-term clinical outcomes.</p>","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620786","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}