European urology oncology最新文献

{"title":"Development and Validation of a Survey to Assess Sexual Health in Female Partners of Patients with Prostate Cancer.","authors":"Stacy Loeb, Natasha Gupta, Daniela Wittmann, Christian J Nelson, John P Mulhall, Carolyn A Salter, Nataliya Byrne, Tatiana Sanchez Nolasco, Laura Zebib, Leigh Garrett, Elizabeth Schofield","doi":"10.1016/j.euo.2024.04.022","DOIUrl":"https://doi.org/10.1016/j.euo.2024.04.022","url":null,"abstract":"<p><strong>Background: </strong>Prostate cancer (PCa) diagnosis and treatment can have a significant negative impact on sexual health, affecting patients and their partners; however, the impact on partners is insufficiently addressed in current practice.</p><p><strong>Objective: </strong>We describe the development and validation of an instrument to measure sexual health in female partners of patients with PCa.</p><p><strong>Design, setting, and participants: </strong>Questions assessing sexual health were developed through a literature review, two qualitative studies, and an expert consensus process. Candidate survey items were tested through cognitive interviews and used to iteratively refine the questionnaire.</p><p><strong>Intervention: </strong>The final questionnaire was tested in a validation study among 200 female partners.</p><p><strong>Outcome measurements and statistical analysis: </strong>We performed an exploratory factor analysis, followed by an analysis for internal validity, test-retest reliability, and convergent and discriminant validity.</p><p><strong>Results and limitations: </strong>An initial set of 32 items was developed and refined through cognitive interviews. The resulting 27-item questionnaire was tested among 200 female partners of patients with PCa from across the USA. The exploratory factor analysis eliminated eight items and revealed seven key factors: (1) distress/satisfaction, (2) loss of connection as a couple, (3) active communication, (4) discomfort with communication, (5) frustration with sexual counseling, (6) expansion of sexual repertoire, and (7) nonpenetrative sexual activity. The overall scale demonstrated strong internal consistency (ordinal alpha 0.94) and test-retest reliability (0.89). Strengths of the study include development and evaluation of the first questionnaire to evaluate sexual quality of life among female partners of patients with PCa. However, additional work is needed to assess sexual health and quality of life among male and nonbinary partners.</p><p><strong>Conclusions: </strong>We developed a new instrument, the Sexual Concerns In Partners of Patients with Prostate cancer (SCIPPP-F), and found it to be valid in a diverse sample of female partners across the USA.</p><p><strong>Patient summary: </strong>Our new instrument can be used to characterize sexual health among female partners of patients with prostate cancer.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase 2 Study of Preoperative Tislelizumab in Combination with Low-dose Nab-Paclitaxel in Patients with Muscle-invasive Bladder Cancer.","authors":"Zhouliang Wu, Gangjian Zhao, Zhe Zhang, Chong Shen, Lili Wang, Guoping Xu, Yang Zhao, Rui Liang, Changping Li, Huanhuan Liu, Hongmei Wang, Hua Dong, Huaying Fu, Man Li, Hongjun Li, Yan Zhuang, La Da, Shiwang Huang, Kaipeng Jia, Houyuan Chen, Yiduo Bai, Shizheng Guo, Huanqing Cheng, Huina Wang, Haitao Wang, Yuanjie Niu, Hailong Hu","doi":"10.1016/j.euo.2024.04.020","DOIUrl":"https://doi.org/10.1016/j.euo.2024.04.020","url":null,"abstract":"<p><strong>Background and objective: </strong>Combinations of immune checkpoint inhibitors and nab-paclitaxel have achieved significant therapeutic effects in the treatment of advanced urothelial carcinoma. Our aim was to assess the efficacy and safety of tislelizumab combined with low-dose nab-paclitaxel in patients with muscle-invasive bladder cancer (MIBC).</p><p><strong>Methods: </strong>TRUCE-01 was a single-arm phase 2 study that included 62 patients with T2-4a N0/X M0 MIBC tumors with predominant urothelial carcinoma histology. Eligible patients received three 21-d cycles of intravenous 200 mg tislelizumab on day 1 plus intravenous 200 mg nab-paclitaxel on day 2, followed by surgical assessment. The primary study endpoint was a clinical complete response (cCR). Treatment-related adverse event (TRAE) profiles were recorded according to Common Terminology Criteria for Adverse Events version 5.0.</p><p><strong>Key findings and limitations: </strong>The safety analysis included all 62 patients and the efficacy analysis included 48 patients. The primary efficacy endpoint (cCR) was met by 25 patients (52%) patients. Among the 62 patients in the safety analysis, six (9.7%) had grade ≥3 TRAEs.</p><p><strong>Conclusions: </strong>Tislelizumab combined with low-dose nab-paclitaxel showed promising antitumor effectiveness and was generally well tolerated, which makes it an excellent preoperative therapy option for MIBC.</p><p><strong>Patient summary: </strong>We found that a combination of the drugs tislelizumab and low-dose nab-paclitaxel had satisfactory efficacy and safety for preoperative treatment of muscle-invasive bladder cancer.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clofarabine Has a Superior Therapeutic Window as compared to Gemcitabine in Preclinical Bladder Cancer Models.","authors":"Michael Gutmann, Iris E Ertl, Paula Herek, Petra Vician, Christine Pirker, Christoph Nössing, Robert Brettner, Ursula Lemberger, Reinhard Grausenburger, Kai Batlogg, Oliver Baumfried, Isabella Prantl, Neha Singh, Ekaterina Laukhtina, André Oszwald, Gabriel Wasinger, Eva Compérat, Walter Berger, Shahrokh F Shariat, Bernhard Englinger","doi":"10.1016/j.euo.2024.05.001","DOIUrl":"https://doi.org/10.1016/j.euo.2024.05.001","url":null,"abstract":"<p><p>Current standard-of-care systemic therapy options for locally advanced and metastatic bladder cancer (BC), which are predominantly based on cisplatin-gemcitabine combinations, are limited by significant treatment failure rates and frailty-based patient ineligibility. We previously addressed the urgent clinical need for better-tolerated BC therapeutic strategies using a drug screening approach, which identified outstanding antineoplastic activity of clofarabine in preclinical models of BC. To further assess clofarabine as a potential BC therapy component, we conducted head-to-head comparisons of responses to clofarabine versus gemcitabine in preclinical in vitro and in vivo models of BC, complemented by in silico analyses. In vitro data suggest a distinct correlation between the two antimetabolites, with higher cytotoxicity of gemcitabine, especially against several nonmalignant cell types, including keratinocytes and endothelial cells. Accordingly, tolerance of clofarabine (oral or intraperitoneal application) was distinctly better than for gemcitabine (intraperitoneal) in patient-derived xenograft models of BC. Clofarabine also exhibited distinctly superior anticancer efficacy, even at dosing regimens optimized for gemcitabine. Neither complete remission nor cure, both of which were observed with clofarabine, were achieved with any tolerable gemcitabine regimen. Taken together, our findings demonstrate that clofarabine has a better therapeutic window than gemcitabine, further emphasizing its potential as a candidate for drug repurposing in BC. PATIENT SUMMARY: We compared the anticancer activity of clofarabine, a drug used for treatment of leukemia but not bladder cancer, and gemcitabine, a drug currently used for chemotherapy against bladder cancer. Using cell cultures and mouse models, we found that clofarabine was better tolerated and more efficacious than gemcitabine, and even cured implanted tumors in mouse models. Our results suggest that clofarabine, alone or in combination schemes, might be superior to gemcitabine for the treatment of bladder cancer.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short-term Darolutamide (ODM-201) Concomitant to Radiation Therapy for Patients with Unfavorable Intermediate-risk Prostate Cancer: The Darius (AFU-GETUG P15) Phase 2 Trial Protocol.","authors":"Paul Sargos, Carine Bellera, Rita Bentahila, Marie Guerni, Nicolas Benziane-Ouaritini, Diego Teyssonneau, Nam-Son Vuong, Guillaume Ploussard, Morgan Roupret, Guilhem Roubaud","doi":"10.1016/j.euo.2024.04.023","DOIUrl":"https://doi.org/10.1016/j.euo.2024.04.023","url":null,"abstract":"<p><strong>Background: </strong>Combination of androgen deprivation therapy (ADT) with external beam radiation therapy (EBRT) is a standard of care for patients with intermediate-risk prostate cancer (PCa). However, 6 months of ADT generates multiple side effects impacting quality of life (QoL). Darolutamide (an androgen receptor targeting agent [ARTA]) is associated with low blood-brain barrier penetrance and less drug-drug interaction.</p><p><strong>Objective: </strong>To assess the efficacy of a combination of 6 months of darolutamide with EBRT to treat patients with unfavorable intermediate-risk PCa.</p><p><strong>Design, setting, and participants: </strong>The DARIUS trial is a multicenter randomized non comparative phase 2 trial, randomizing the 6-months darolutamide + EBRT arm versus 6-months ADT + EBRT in patients with unfavorable intermediate-risk PCa.</p><p><strong>Outcome measurements and statistical analysis: </strong>The primary endpoint is a biological response defined as prostate-specific antigen ≤0.1 ng/ml at month six of darolutamide or ADT. The key secondary endpoints are biochemical recurrence-free survival, disease-free survival, safety, and QoL. Ancillary studies using radiomics and genomic classifier are planned. Sixty-two patients will be included.</p><p><strong>Results and limitations: </strong>In this population of patients requiring ADT combined with EBRT, the use of an ARTA alone, such as darolutamide, may demonstrate antitumoral efficacy while minimizing toxicity and maintaining QoL. Limitations are mainly inherent to the open-label design of this study.</p><p><strong>Conclusions: </strong>Six months of darolutamide + EBRT compared with 6 months of ADT + EBRT may be efficient in terms of a biological response, avoiding toxicity and altered QoL attributable to ADT in patients with unfavorable intermediate-risk PCa.</p><p><strong>Patient summary: </strong>The ongoing DARIUS clinical trial assesses short-term (6 months) darolutamide treatment in association with external beam radiation therapy in men with localized prostate cancer. The trial investigates whether single-agent darolutamide can improve the biological response while maintaining a favorable tolerability profile.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional Outcomes and Quality of Life in High-risk Prostate Cancer Patients Treated by Robot-assisted Radical Prostatectomy with or Without Adjuvant Treatments.","authors":"Wout Devlies, Geert Silversmit, Filip Ameye, Peter Dekuyper, Thierry Quackels, Thierry Roumeguère, Ben Van Cleynenbreugel, Nancy Van Damme, Frank Claessens, Wouter Everaerts, Steven Joniau","doi":"10.1016/j.euo.2024.04.018","DOIUrl":"https://doi.org/10.1016/j.euo.2024.04.018","url":null,"abstract":"<p><strong>Background: </strong>Robot-assisted laparoscopic prostatectomy (RALP) is used frequently to treat prostate cancer; yet, prospective data on the quality of life and functional outcomes are lacking.</p><p><strong>Objective: </strong>To assess the quality of life and functional outcomes after radical prostatectomy in different risk groups with or without adjuvant treatments.</p><p><strong>Design, setting, and participants: </strong>The Be-RALP database is a prospective multicentre database that covers 9235 RALP cases from 2009 until 2016. Of these 9235 patients, 2336 high-risk prostate cancer patients were matched with low/intermediate-risk prostate cancer patients.</p><p><strong>Intervention: </strong>Patients were treated with RALP only or followed by radiotherapy and/or hormone treatment.</p><p><strong>Outcome measurements and statistical analysis: </strong>We used a mixed-model analysis to longitudinally analyse quality of life, urinary function, and erectile function between risk groups with or without additional treatments.</p><p><strong>Results and limitations: </strong>Risk group was not significant in predicting quality of life, erectile function, or urinary function after RALP. Postoperative treatment (hormone and/or radiotherapy treatment) was significant in predicting International Index of Erectile Function (IIEF-5), sexual activity, and sexual functioning.</p><p><strong>Conclusions: </strong>Risk group was not linked with clinically relevant declines in functional outcomes after RALP. The observed functional outcomes and quality of life are in favour of considering RALP for high-risk prostate cancer. Postoperative treatment resulted in lower erectile function measures without clinically relevant changes in quality of life and urinary functions. Hormone therapy seems to have the most prominent negative effects on these outcomes.</p><p><strong>Patient summary: </strong>This study investigated the quality of life, and urinary and erectile function in patients with aggressive and less aggressive prostate cancer after surgery only or in combination with hormones or radiation. We found that quality of life recovers completely, while erectile and urinary function recovers only partially after surgery. Aggressiveness of the disease had a minimal effect on the outcomes; yet, postoperative treatments lowered erectile function further.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retifanlimab in Advanced Penile Squamous Cell Carcinoma: The Phase 2 ORPHEUS Study.","authors":"Xavier García Del Muro, David Páez López-Bravo, Miler Andrés Cuéllar-Rivas, Pablo Maroto, Patrizia Giannatempo, Daniel Castellano, Miguel A Climent, Begoña P Valderrama, Alfonso Gómez de Liaño, Laura López-Montero, Leonardo Mina, Daniel Alcalá-López, Miguel Sampayo-Cordero, Andrea Necchi","doi":"10.1016/j.euo.2024.04.021","DOIUrl":"10.1016/j.euo.2024.04.021","url":null,"abstract":"<p><strong>Background and objective: </strong>Patients with advanced penile squamous cell carcinoma (PSCC) have poor outcomes and very limited therapeutic options are available. Most PSCC cases have high PD-L1 expression, which is associated with worse prognosis. Immunotherapy targeting PD-L1 could benefit patients with PSCC. Our aim was to evaluate the efficacy and safety of the anti-PD-1 antibody retifanlimab in patients with advanced/metastatic PSCC.</p><p><strong>Methods: </strong>ORPHEUS was a single-arm, multicenter, phase 2 trial in 18 patients with advanced/metastatic PSCC, previously untreated with anti-PD-1/anti-PD-L1 agents. Patients received retifanlimab 500 mg intravenously every 4 wk for up to 2 yr. The primary endpoint was the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors v1.1. Secondary endpoints included the clinical benefit rate (CBR), disease control rate, duration of response (DoR), time to response, progression-free survival (PFS), overall survival (OS), maximum tumor shrinkage, and safety. The Wilson method was used for the primary endpoint, and the Clopper-Pearson and Kaplan-Meier methods for secondary endpoints.</p><p><strong>Key findings and limitations: </strong>Median follow-up was 7.2 mo. The ORR was 16.7% (95% confidence interval [CI] 5.8-39.2); three patients had a partial response. Median DoR was 3.3 mo (range 1.8-8.5). The CBR was 22.2% (95% CI 6.4-47.6%). Median PFS was 2.0 mo (95% CI 1.6-3.3) and median OS was 7.2 mo (95% CI 3.0-9.8). One patient (5.6%) experienced grade 3 treatment-related adverse events (AEs). There were no grade >= 4 treatment-related AEs. The small sample size is the main limitation.</p><p><strong>Conclusions and clinical implications: </strong>Single-agent retifanlimab exhibited signals of clinical activity in advanced/metastatic PSCC, with no new safety signals. Further investigation of retifanlimab in this setting is warranted.</p><p><strong>Patient summary: </strong>Advanced penile cancer of the squamous cell type is a rare tumor with poor prognosis. The aggressiveness of this cancer is usually associated with high levels of a protein called PD-L1. We investigated whether retifanlimab, an immunotherapy drug against PD-1, has activity against this type of penile cancer. Tumor regression or stabilization occurred in one-third of the patients and the side effects were manageable.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influential Factors Impacting Treatment Decision-making and Decision Regret in Patients with Localized or Locally Advanced Prostate Cancer: A Systematic Literature Review.","authors":"Benjamin A Gartrell, Angaja Phalguni, Paulina Bajko, Suneel D Mundle, Sharon A McCarthy, Sabine D Brookman-May, Francesco De Solda, Ruhee Jain, Wellam Yu Ko, Guillaume Ploussard, Boris Hadaschik","doi":"10.1016/j.euo.2024.04.016","DOIUrl":"https://doi.org/10.1016/j.euo.2024.04.016","url":null,"abstract":"<p><strong>Context: </strong>Treatment decision-making (TDM) for patients with localized (LPC) or locally advanced (LAPC) prostate cancer is complex, and post-treatment decision regret (DR) is common. The factors driving TDM or predicting DR remain understudied.</p><p><strong>Objective: </strong>Two systematic literature reviews were conducted to explore the factors associated with TDM and DR.</p><p><strong>Evidence acquisition: </strong>Three online databases, select congress proceedings, and gray literature were searched (September 2022). Publications on TDM and DR in LPC/LAPC were prioritized based on the following: 2012 onward, ≥100 patients, journal article, and quantitative data. The Preferred Reporting Items Reviews and Meta-analyses guidelines were followed. Influential factors were those with p < 0.05; for TDM, factors described as \"a decision driver\", \"associated\", \"influential\", or \"significant\" were also included. The key factors were determined by number of studies, consistency of evidence, and study quality.</p><p><strong>Evidence synthesis: </strong>Seventy-five publications (68 studies) reported TDM. Patient participation in TDM was reported in 34 publications; overall, patients preferred an active/shared role. Of 39 influential TDM factors, age, ethnicity, external factors (physician recommendation most common), and treatment characteristics/toxicity were key. Forty-nine publications reported DR. The proportion of patients experiencing DR varied by treatment type: 7-43% (active surveillance), 12-57% (radical prostatectomy), 1-49% (radiotherapy), 28-49% (androgen-deprivation therapy), and 21-47% (combination therapy). Of 42 significant DR factors, treatment toxicity (sexual/urinary/bowel dysfunction), patient role in TDM, and treatment type were key.</p><p><strong>Conclusions: </strong>The key factors impacting TDM were physician recommendation, age, ethnicity, and treatment characteristics. Treatment toxicity and TDM approach were the key factors influencing DR. To help patients navigate factors influencing TDM and to limit DR, a shared, consensual TDM approach between patients, caregivers, and physicians is needed.</p><p><strong>Patient summary: </strong>We looked at factors influencing treatment decision-making (TDM) and decision regret (DR) in patients with localized or locally advanced prostate cancer. The key factors influencing TDM were doctor's recommendation, patient age/ethnicity, and treatment side effects. A shared, consensual TDM approach between patients and doctors was found to limit DR.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140920673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in Tumor Gene Expression Profiles Between De Novo Metastatic Castration-sensitive Prostate Cancer and Metastatic Relapse After Prior Localized Therapy.","authors":"Vinay Mathew Thomas, Nicolas Sayegh, Beverly Chigarira, Georges Gebrael, Nishita Tripathi, Roberto Nussenzveig, Yeonjung Jo, Emre Dal, Gliceida Galarza Fortuna, Haoran Li, Kamal Kant Sahu, Ayana Srivastava, Benjamin L Maughan, Neeraj Agarwal, Umang Swami","doi":"10.1016/j.euo.2024.04.013","DOIUrl":"https://doi.org/10.1016/j.euo.2024.04.013","url":null,"abstract":"<p><strong>Background and objective: </strong>It has been reported that patients with de novo metastatic castration-sensitive prostate cancer (dn-mCSPC) have worse prognosis and outcomes than those whose cancer relapses after prior local therapy (PLT-mCSPC). Our aim was to interrogate and validate underlying differences in tumor gene expression profiles between dn-mCSPC and PLT-mCSPC.</p><p><strong>Methods: </strong>The inclusion criteria were histologically confirmed prostate adenocarcinoma and the availability of RNA sequencing data for treatment-naïve primary prostate tissue. RNA sequencing was performed by Tempus or Caris Life Sciences, both of which have Clinical Laboratory Improvement Amendments certification. The Tempus cohort was used for interrogation, while the Caris cohort was used for validation. Differential gene expression analysis between the cohorts was conducted using the DEseq2 pipeline. The resulting gene expression profiles were further analyzed using Gene Set Enrichment software to identify pathways with enrichment in each cohort.</p><p><strong>Key findings and limitations: </strong>Overall, 128 patients were eligible, of whom 78 were in the Tempus cohort (dn-mCSPC 37, PLT-mCSPC 41) and 50 were in the Caris cohort (dn-mCSPC 30, PLT-mCSPC 20). Tumor tissues from patients with dn-mCSPC had higher expression of genes associated with inflammation pathways, while tissues from patients with PLT-mCSPC had higher expression of genes involved in oxidative phosphorylation, fatty acid metabolism, and androgen response pathways.</p><p><strong>Conclusions and clinical implications: </strong>Our study revealed upregulation of distinct genomic pathways in dn-mCSPC in comparison to PLT-mCSPC. These hypothesis-generating data could guide personalized therapy for men with prostate cancer and explain different survival outcomes for dn-mCSPC and PLT-mCSPC.</p><p><strong>Patient summary: </strong>We measured gene expression levels in tumors from patients with metastatic castration-sensitive prostate cancer. In patients with metastatic disease at first diagnosis, inflammatory pathways were upregulated. In patients whose metastasis occurred on relapse after treatment, androgen response pathways were upregulated. These findings could help in personalizing therapy for prostate cancer and explaining differences in survival.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140911060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combination of Abiraterone Acetate, Prostate Bed Radiotherapy, and Luteinizing Hormone-releasing Hormone Agonists in Biochemically Relapsing Patients After Prostatectomy (CARLHA): A Phase 2 Clinical Trial.","authors":"Loic Ah-Thiane, Loic Campion, Nedjla Allouache, Emmanuel Meyer, Pascal Pommier, Nathalie Mesgouez-Nebout, Anne-Agathe Serre, Gilles Créhange, Valentine Guimas, Emmanuel Rio, Paul Sargos, Sylvain Ladoire, Céline Mahier Ait Oukhatar, Stéphane Supiot","doi":"10.1016/j.euo.2024.04.014","DOIUrl":"https://doi.org/10.1016/j.euo.2024.04.014","url":null,"abstract":"<p><strong>Background: </strong>The relevance of next-generation hormone therapies and circulating tumor cells (CTCs) are not elucidated in biochemical recurrence after prostatectomy.</p><p><strong>Objective: </strong>To evaluate the combination of abiraterone acetate plus prednisone (AAP), prostate bed radiotherapy (PBRT), and goserelin in biochemically relapsing men after prostatectomy, and to investigate the utility of CTCs.</p><p><strong>Design, setting, and participants: </strong>In this single-arm multicenter phase 2 trial, 46 biochemically relapsing men were enrolled between December 2012 and January 2019. The median follow-up was 47 mo.</p><p><strong>Intervention: </strong>All patients received AAP 1000 mg daily (but 750 mg during PBRT), salvage PBRT, and goserelin.</p><p><strong>Outcome measurements and statistical analysis: </strong>The primary outcome was 3-yr biochemical recurrence-free survival (bRFS) when prostate-specific antigen (PSA) levels were ≥0.2 ng/ml. The secondary outcomes included alternative bRFS (alt-bRFS) when PSA levels were ≥0.5 ng/ml and safety assessment. CTC count was assessed.</p><p><strong>Results and limitations: </strong>The 3-yr bRFS and alt-bRFS were 81.5% (95% confidence interval or CI [66.4-90.3%]) and 95.6% (95% CI [83.5-98.9%]), respectively. The most common acute radiotherapy-related adverse effect (AE; all grades was pollakiuria (41.3%). The most common late AE (all grades) was urinary incontinence (15.2%). Grade 3-4 acute or late radiotherapy-related AEs were scarce. Most frequent AEs nonrelated to radiotherapy were hot flashes (76%), hypertension (63%), and hepatic cytolysis (50%, of which 20% were of grades 3-4). Of the patients, 11% had a CTC count of ≥5, which was correlated with poorer bRFS (p = 0.042) and alt-bRFS (p = 0.008). The association between CTC count and higher rates of relapse was independent of the baseline PSA level and PSA doubling time (p = 0.42 and p = 0.09, respectively). This study was nonrandomized with a limited number of patients, and few clinical events were reported.</p><p><strong>Conclusions: </strong>Adding AAP to salvage radiation therapy and goserelin resulted in high bRFS and alt-bRFS. AEs remained manageable, although a close liver surveillance is advised. CTC count appears as a promising biomarker for prognosis and predicting response to treatment.</p><p><strong>Patient summary: </strong>Our study was a phase 2 clinical trial that exhibited the efficacy and tolerance of a novel androgen-receptor targeting agent (abiraterone acetate plus prednisone) in patients with prostate cancer who experienced rising prostate-specific antigen after radical prostatectomy, in combination with prostate bed radiotherapy. The results also indicated the feasibility and potential value of circulating tumor cell detection, which constitutes a possible advance in managing prostate cancers.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the Clinical Utility of Published Prostate Cancer Polygenic Risk Scores in a Large Biobank Data Set.","authors":"Randy A Vince, Helen Sun, Udit Singhal, Fredrick R Schumacher, Erika Trapl, Johnie Rose, Jennifer Cullen, Nicholas Zaorsky, Johnathan Shoag, Holly Hartman, Angela Y Jia, Daniel E Spratt, Lars G Fritsche, Todd M Morgan","doi":"10.1016/j.euo.2024.04.017","DOIUrl":"https://doi.org/10.1016/j.euo.2024.04.017","url":null,"abstract":"<p><strong>Background and objective: </strong>Polygenic risk scores (PRSs) have been developed to identify men with the highest risk of prostate cancer. Our aim was to compare the performance of 16 PRSs in identifying men at risk of developing prostate cancer and then to evaluate the performance of the top-performing PRSs in differentiating individuals at risk of aggressive prostate cancer.</p><p><strong>Methods: </strong>For this case-control study we downloaded 16 published PRSs from the Polygenic Score Catalog on May 28, 2021 and applied them to Michigan Genomics Initiative (MGI) patients. Cases were matched to the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry to obtain granular clinical and pathological data. MGI prospectively enrolls patients undergoing surgery at the University of Michigan, and MUSIC is a multi-institutional registry that prospectively tracks demographic, treatment, and clinical variables. The predictive performance of each PRS was evaluated using the area under the covariate-adjusted receiver operating characteristic curve (aAUC), and the association between PRS and disease aggressiveness according to prostate biopsy data was measured using logistic regression.</p><p><strong>Key findings and limitations: </strong>We included 18 050 patients in the analysis, of whom 15 310 were control subjects and 2740 were prostate cancer cases. The median age was 66.1 yr (interquartile range 59.9-71.6) for cases and 56.6 yr (interquartile range 42.6-66.7) for control subjects. The PRS performance in predicting the risk of developing prostate cancer according to aAUC ranged from 0.51 (95% confidence interval 0.51-0.53) to 0.67 (95% confidence interval 0.66-0.68). By contrast, there was no association between PRS and disease aggressiveness.</p><p><strong>Conclusions and clinical implications: </strong>Prostate cancer PRSs have modest real-world performance in identifying patients at higher risk of developing prostate cancer; however, they are limited in distinguishing patients with indolent versus aggressive disease.</p><p><strong>Patient summary: </strong>Risk scores using data for multiple genes (called polygenic risk scores) can identify men at higher risk of developing prostate cancer. However, these scores need to be refined to be able to identify men with the highest risk for clinically significant prostate cancer.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}