Pub Date : 2024-08-13DOI: 10.1038/s41391-024-00878-0
Vérane Achard, Thomas Zilli
{"title":"Current status and perspectives on the use of androgen receptor pathway inhibitors in the salvage radiotherapy setting.","authors":"Vérane Achard, Thomas Zilli","doi":"10.1038/s41391-024-00878-0","DOIUrl":"10.1038/s41391-024-00878-0","url":null,"abstract":"","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141976471","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 : 2024-08-12DOI: 10.1038/s41391-024-00865-5
Julie N. Graff, Christopher J. Hoimes, Winald R. Gerritsen, Ulka N. Vaishampayan, Tony Elliott, Clara Hwang, Albert J. ten Tije, Aurelius Omlin, Raymond S. McDermott, Yves Fradet, Scott T. Tagawa, Deepak Kilari, Cristiano Ferrario, Hiroji Uemura, Robert J. Jones, Satoshi Fukasawa, Avivit Peer, Cuizhen Niu, Christian H. Poehlein, Ping Qiu, Leah Suttner, Ronald de Wit, Charles Schloss, Johann S. de Bono, Emmanuel S. Antonarakis
Background
KEYNOTE-199 (NCT02787005) is a multicohort phase 2 study evaluating pembrolizumab in patients with metastatic castration-resistant prostate cancer (mCRPC). Results from cohorts 4 (C4) and 5 (C5) are presented.
Methods
Eligible patients had not received chemotherapy for mCRPC and had responded to enzalutamide prior to developing resistance as defined by Prostate Cancer Clinical Trials Working Group 3 guidelines. Patients with RECIST-measurable disease were enrolled in C4, and patients with bone-only or bone-predominant disease were enrolled in C5. All patients received pembrolizumab 200 mg every 3 weeks for ≤35 cycles with ongoing enzalutamide until progression, unacceptable toxicity, or withdrawal. The primary end point was objective response rate (ORR) per RECIST v1.1 by blinded independent central review in C4. Secondary end points included disease control rate (DCR), overall survival, and safety in each cohort and both cohorts combined.
Results
A total of 126 patients were treated (C4, n = 81; C5, n = 45). Median age was 72 years (range 43–92), and 87.3% had received ≥6 months of enzalutamide prior to study entry. Confirmed ORR was 12.3% (95% CI 6.1–21.5%) for C4. Median duration of response in C4 was 8.1 months (range, 2.5+ to 15.2), and 5 of these patients experienced an objective response lasting ≥6 months. DCR was 53.1% (95% CI 41.7–64.3%) in C4 and 51.1% (95% CI 35.8–66.3%) in C5. Median overall survival was 17.6 months (95% CI 14.0–22.6) in C4 and 20.8 months (95% CI 14.1–28.9) in C5. Grade ≥3 treatment-related adverse events occurred in 35 patients (27.8%); 2 patients in C4 died from immune-related adverse events (myasthenic syndrome and Guillain-Barré syndrome).
Conclusions
The addition of pembrolizumab to ongoing enzalutamide treatment in patients with mCRPC that progressed on enzalutamide after initial response demonstrated modest antitumor activity with a manageable safety profile.
Clinical trial registry and ID
ClinicalTrials.gov, NCT02787005.
背景KEYNOTE-199 (NCT02787005)是一项多队列2期研究,评估了pembrolizumab在转移性去势抵抗性前列腺癌(mCRPC)患者中的应用。方法符合条件的患者未接受过mCRPC化疗,并且在出现前列腺癌临床试验工作组3指南定义的耐药性之前对恩杂鲁胺有反应。有RECIST可测量疾病的患者被纳入C4组,有仅骨或骨为主疾病的患者被纳入C5组。所有患者均接受pembrolizumab 200 mg治疗,每3周1次,疗程≤35个周期,并持续服用恩杂鲁胺,直至病情进展、出现不可接受的毒性或停药。主要终点是根据RECIST v1.1标准得出的客观反应率(ORR),由C4盲法独立中央审查。次要终点包括疾病控制率 (DCR)、总生存期以及每个组群和两个组群合并的安全性。结果 共有 126 名患者接受了治疗(C4,n = 81;C5,n = 45)。中位年龄为72岁(43-92岁),87.3%的患者在进入研究前已接受了≥6个月的恩杂鲁胺治疗。C4的确诊ORR为12.3%(95% CI为6.1-21.5%)。C4患者的中位应答持续时间为8.1个月(2.5+至15.2个月),其中5例患者的客观应答持续时间≥6个月。C4和C5患者的DCR分别为53.1%(95% CI 41.7-64.3%)和51.1%(95% CI 35.8-66.3%)。C4患者的中位总生存期为17.6个月(95% CI 14.0-22.6),C5患者为20.8个月(95% CI 14.1-28.9)。35名患者(27.8%)发生了≥3级治疗相关不良事件;2名C4患者死于免疫相关不良事件(肌萎缩综合征和吉兰-巴雷综合征)。结论对于恩杂鲁胺治疗后出现进展的mCRPC患者,在恩杂鲁胺治疗的基础上加用pembrolizumab显示了适度的抗肿瘤活性和可控的安全性。
{"title":"Pembrolizumab plus enzalutamide for metastatic castration-resistant prostate cancer progressing on enzalutamide: cohorts 4 and 5 of the phase 2 KEYNOTE-199 study","authors":"Julie N. Graff, Christopher J. Hoimes, Winald R. Gerritsen, Ulka N. Vaishampayan, Tony Elliott, Clara Hwang, Albert J. ten Tije, Aurelius Omlin, Raymond S. McDermott, Yves Fradet, Scott T. Tagawa, Deepak Kilari, Cristiano Ferrario, Hiroji Uemura, Robert J. Jones, Satoshi Fukasawa, Avivit Peer, Cuizhen Niu, Christian H. Poehlein, Ping Qiu, Leah Suttner, Ronald de Wit, Charles Schloss, Johann S. de Bono, Emmanuel S. Antonarakis","doi":"10.1038/s41391-024-00865-5","DOIUrl":"https://doi.org/10.1038/s41391-024-00865-5","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>KEYNOTE-199 (NCT02787005) is a multicohort phase 2 study evaluating pembrolizumab in patients with metastatic castration-resistant prostate cancer (mCRPC). Results from cohorts 4 (C4) and 5 (C5) are presented.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Eligible patients had not received chemotherapy for mCRPC and had responded to enzalutamide prior to developing resistance as defined by Prostate Cancer Clinical Trials Working Group 3 guidelines. Patients with RECIST-measurable disease were enrolled in C4, and patients with bone-only or bone-predominant disease were enrolled in C5. All patients received pembrolizumab 200 mg every 3 weeks for ≤35 cycles with ongoing enzalutamide until progression, unacceptable toxicity, or withdrawal. The primary end point was objective response rate (ORR) per RECIST v1.1 by blinded independent central review in C4. Secondary end points included disease control rate (DCR), overall survival, and safety in each cohort and both cohorts combined.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>A total of 126 patients were treated (C4, <i>n</i> = 81; C5, <i>n</i> = 45). Median age was 72 years (range 43–92), and 87.3% had received ≥6 months of enzalutamide prior to study entry. Confirmed ORR was 12.3% (95% CI 6.1–21.5%) for C4. Median duration of response in C4 was 8.1 months (range, 2.5+ to 15.2), and 5 of these patients experienced an objective response lasting ≥6 months. DCR was 53.1% (95% CI 41.7–64.3%) in C4 and 51.1% (95% CI 35.8–66.3%) in C5. Median overall survival was 17.6 months (95% CI 14.0–22.6) in C4 and 20.8 months (95% CI 14.1–28.9) in C5. Grade ≥3 treatment-related adverse events occurred in 35 patients (27.8%); 2 patients in C4 died from immune-related adverse events (myasthenic syndrome and Guillain-Barré syndrome).</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>The addition of pembrolizumab to ongoing enzalutamide treatment in patients with mCRPC that progressed on enzalutamide after initial response demonstrated modest antitumor activity with a manageable safety profile.</p><h3 data-test=\"abstract-sub-heading\">Clinical trial registry and ID</h3><p>ClinicalTrials.gov, NCT02787005.</p>","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":"25 1","pages":""},"PeriodicalIF":4.8,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141943429","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 : 2024-08-12DOI: 10.1038/s41391-024-00880-6
Sriram Deivasigamani, Eric S Adams, Shannon Stock, Srinath Kotamarti, Denis Séguier, Tarek Taha, Lauren E Howard, Alireza Aminsharifi, Ghalib Jibara, Christopher L Amling, William J Aronson, Matthew R Cooperberg, Christopher J Kane, Martha K Terris, Zachary Klaassen, Lourdes Guerrios-Rivera, Stephen J Freedland, Thomas J Polascik
Importance and objective: Partial gland ablation (PGA) is increasingly popular as a treatment for men with intermediate-risk prostate cancer (IR-PCa) to preserve functional outcomes while controlling their cancer. We aimed to determine the impact of race and clinical characteristics on the risk of upstaging (≥pT2c) and having adverse pathological outcomes including seminal vesicle invasion (SVI), extra prostatic extension (EPE) and lymph node invasion (LNI) at radical prostatectomy (RP) among men with IR disease eligible for PGA with hemi-ablation (HA).
Design: Retrospective analysis.
Setting: Multicenter.
Participants and measures: We studied patients diagnosed with unilateral IR-PCa treated with RP between 1988 and 2020 at 9 different Veterans Affairs hospitals within the SEARCH cohort. We analyzed differences in clinicopathological characteristics and outcome variables (odds of ≥pT2c and SVI, EPE and LNI) by race using multivariable logistic regression after adjusting for covariates.
Results: Among 3127 patients, 33% were African American (AA) men with unilateral IR-PCa undergoing RP. Compared to non-AA men, AA individuals were younger (61 vs. 65 years, p < 0.001), presented with a higher prostate specific antigen (PSA) category (≥10 ng/ml; 34 vs. 26%, p < 0.001), and had a lower clinical stage (p < 0.001). Among the 2,798 (89.5%) with ≥pT2c stage, AA men exhibited higher ≥ pT2c rates (93 vs. 89%, p < 0.001), primarily due to increased pT2c staging (64 vs. 57%), where upstaging beyond pT2 was lower than non-AA men (29 vs. 32%). On multivariable analysis, AA men were found to have higher odds of ≥pT2c (odds ratio [OR]: 1.39 CI, 1.02-1.88, p = 0.04), lower odds of EPE (OR: 0.73 CI, 0.58-0.91, p < 0.01) and no statistically significant associations with LNI (OR: 0.79 CI, 0.42-1.46, p = 0.45) and SVI (OR: 1 CI, 0.74-1.35, p = 0.99) compared to non-AA men. On multivariable analysis, clinical features associated with higher odds of ≥pT2c were pre-operative PSA ≥ 15 (OR = 2.07, P = 0.01) and higher number of positive cores (HPC) on biopsy (OR = 1.36, P < 0.001). Similarly, PSA ≥ 15, Gleason grade ≥3 and HPC on biopsy were associated with higher odds of SVI, EPE and LNI, respectively.
Conclusions: In men with IR-PCa undergoing RP, AA men demonstrated an overall higher likelihood of ≥pT2c with lower upstaging beyond pT2, lower likelihood of EPE and no significant difference in likelihood of SVI and LNI compared to non-AA men. These findings support select AA men to be potential candidates for PGA, such as HA. Clinical factors are predictive of higher pathological stage and adverse pathological outcomes at RP and could be considered when selecting candidates for PGA.
重要性和目的:部分腺体消融术(PGA)作为中危前列腺癌(IR-PCa)男性患者的一种治疗方法越来越受欢迎,它可以在控制癌症的同时保留功能性结果。我们的目的是确定种族和临床特征对符合半消融(HA)PGA治疗条件的中危前列腺癌患者的分期上移(≥pT2c)风险和不良病理结果(包括精囊侵犯(SVI)、前列腺外扩展(EPE)和淋巴结侵犯(LNI))的影响:设计:回顾性分析:多中心:我们研究了1988年至2020年间在SEARCH队列中9家不同的退伍军人事务医院接受RP治疗的单侧IR-PCa患者。在调整协变量后,我们使用多变量逻辑回归分析了不同种族在临床病理特征和结局变量(≥pT2c 和 SVI、EPE 和 LNI 的几率)方面的差异:在3127名患者中,33%为接受RP手术的单侧IR-PCa非裔美国人(AA)男性。与非非裔美国人男性相比,非裔美国人更年轻(61 岁对 65 岁,P 结论:非裔美国人的年龄更小:在接受 RP 的 IR-PCa 男性患者中,与非 AA 男性患者相比,AA 男性患者≥pT2c 的可能性总体较高,pT2 以上分期较低,EPE 的可能性较低,SVI 和 LNI 的可能性无显著差异。这些发现支持选择 AA 男性作为 PGA(如 HA)的潜在候选者。临床因素可预测较高的病理分期和 RP 时的不良病理结果,因此在选择 PGA 候选者时可加以考虑。
{"title":"Select black men are potential candidates for prostate hemi-ablation based on radical prostatectomy histopathology for intermediate-risk prostate cancer-a multicenter SEARCH cohort study.","authors":"Sriram Deivasigamani, Eric S Adams, Shannon Stock, Srinath Kotamarti, Denis Séguier, Tarek Taha, Lauren E Howard, Alireza Aminsharifi, Ghalib Jibara, Christopher L Amling, William J Aronson, Matthew R Cooperberg, Christopher J Kane, Martha K Terris, Zachary Klaassen, Lourdes Guerrios-Rivera, Stephen J Freedland, Thomas J Polascik","doi":"10.1038/s41391-024-00880-6","DOIUrl":"10.1038/s41391-024-00880-6","url":null,"abstract":"<p><strong>Importance and objective: </strong>Partial gland ablation (PGA) is increasingly popular as a treatment for men with intermediate-risk prostate cancer (IR-PCa) to preserve functional outcomes while controlling their cancer. We aimed to determine the impact of race and clinical characteristics on the risk of upstaging (≥pT2c) and having adverse pathological outcomes including seminal vesicle invasion (SVI), extra prostatic extension (EPE) and lymph node invasion (LNI) at radical prostatectomy (RP) among men with IR disease eligible for PGA with hemi-ablation (HA).</p><p><strong>Design: </strong>Retrospective analysis.</p><p><strong>Setting: </strong>Multicenter.</p><p><strong>Participants and measures: </strong>We studied patients diagnosed with unilateral IR-PCa treated with RP between 1988 and 2020 at 9 different Veterans Affairs hospitals within the SEARCH cohort. We analyzed differences in clinicopathological characteristics and outcome variables (odds of ≥pT2c and SVI, EPE and LNI) by race using multivariable logistic regression after adjusting for covariates.</p><p><strong>Results: </strong>Among 3127 patients, 33% were African American (AA) men with unilateral IR-PCa undergoing RP. Compared to non-AA men, AA individuals were younger (61 vs. 65 years, p < 0.001), presented with a higher prostate specific antigen (PSA) category (≥10 ng/ml; 34 vs. 26%, p < 0.001), and had a lower clinical stage (p < 0.001). Among the 2,798 (89.5%) with ≥pT2c stage, AA men exhibited higher ≥ pT2c rates (93 vs. 89%, p < 0.001), primarily due to increased pT2c staging (64 vs. 57%), where upstaging beyond pT2 was lower than non-AA men (29 vs. 32%). On multivariable analysis, AA men were found to have higher odds of ≥pT2c (odds ratio [OR]: 1.39 CI, 1.02-1.88, p = 0.04), lower odds of EPE (OR: 0.73 CI, 0.58-0.91, p < 0.01) and no statistically significant associations with LNI (OR: 0.79 CI, 0.42-1.46, p = 0.45) and SVI (OR: 1 CI, 0.74-1.35, p = 0.99) compared to non-AA men. On multivariable analysis, clinical features associated with higher odds of ≥pT2c were pre-operative PSA ≥ 15 (OR = 2.07, P = 0.01) and higher number of positive cores (HPC) on biopsy (OR = 1.36, P < 0.001). Similarly, PSA ≥ 15, Gleason grade ≥3 and HPC on biopsy were associated with higher odds of SVI, EPE and LNI, respectively.</p><p><strong>Conclusions: </strong>In men with IR-PCa undergoing RP, AA men demonstrated an overall higher likelihood of ≥pT2c with lower upstaging beyond pT2, lower likelihood of EPE and no significant difference in likelihood of SVI and LNI compared to non-AA men. These findings support select AA men to be potential candidates for PGA, such as HA. Clinical factors are predictive of higher pathological stage and adverse pathological outcomes at RP and could be considered when selecting candidates for PGA.</p>","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971766","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 : 2024-08-11DOI: 10.1038/s41391-024-00876-2
Osama Mohamad, Yun Rose Li, Felix Feng, Julian C Hong, Anthony Wong, Zakaria El Kouzi, Mohamed Shelan, Thomas Zilli, Peter Carroll, Mack Roach
Delays in the work-up and definitive management of patients with prostate cancer are common, with logistics of additional work-up after initial prostate biopsy, specialist referrals, and psychological reasons being the most common causes of delays. During the COVID-19 pandemic and the subsequent surges, timing of definitive care delivery with surgery or radiotherapy has become a topic of significant concern for patients with prostate cancer and their providers alike. In response, recommendations for the timing of definitive management of prostate cancer with radiotherapy and radical prostatectomy were published but without a detailed rationale for these recommendations. While the COVID-19 pandemic is behind us, patients are always asking the question: "When should I start radiation or undergo surgery?" In the absence of level I evidence specifically addressing this question, we will hereby present a narrative review to summarize the available data on the effect of treatment delays on oncologic outcomes for patients with localized prostate cancer from prospective and retrospective studies.
前列腺癌患者的检查和最终治疗延迟是常见现象,最常见的延迟原因包括前列腺活检后的额外检查、专家转诊和心理原因。在 COVID-19 大流行期间以及随后的激增中,手术或放疗的最终治疗时机已成为前列腺癌患者及其医疗服务提供者都非常关注的话题。为此,美国公布了前列腺癌放疗和根治性前列腺切除术明确治疗时机的建议,但没有详细说明这些建议的理由。虽然 COVID-19 大流行已经过去,但患者一直在问这个问题:"我应该什么时候开始放疗或手术?由于缺乏专门针对这一问题的 I 级证据,我们将在此提交一篇叙述性综述,总结前瞻性和回顾性研究中有关治疗延迟对局部前列腺癌患者肿瘤预后影响的现有数据。
{"title":"Delayed definitive management of localized prostate cancer: what do we know?","authors":"Osama Mohamad, Yun Rose Li, Felix Feng, Julian C Hong, Anthony Wong, Zakaria El Kouzi, Mohamed Shelan, Thomas Zilli, Peter Carroll, Mack Roach","doi":"10.1038/s41391-024-00876-2","DOIUrl":"10.1038/s41391-024-00876-2","url":null,"abstract":"<p><p>Delays in the work-up and definitive management of patients with prostate cancer are common, with logistics of additional work-up after initial prostate biopsy, specialist referrals, and psychological reasons being the most common causes of delays. During the COVID-19 pandemic and the subsequent surges, timing of definitive care delivery with surgery or radiotherapy has become a topic of significant concern for patients with prostate cancer and their providers alike. In response, recommendations for the timing of definitive management of prostate cancer with radiotherapy and radical prostatectomy were published but without a detailed rationale for these recommendations. While the COVID-19 pandemic is behind us, patients are always asking the question: \"When should I start radiation or undergo surgery?\" In the absence of level I evidence specifically addressing this question, we will hereby present a narrative review to summarize the available data on the effect of treatment delays on oncologic outcomes for patients with localized prostate cancer from prospective and retrospective studies.</p>","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917361","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 : 2024-08-01DOI: 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":" ","pages":""},"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":" ","pages":""},"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":" ","pages":""},"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":" ","pages":""},"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":" ","pages":""},"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":" ","pages":""},"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}