Pub Date : 2025-04-01Epub Date: 2024-12-18DOI: 10.1097/JU.0000000000004373
Ekene A Enemchukwu, Susan Kalota, Kaiser Robertson, Sijian Ge, Jingmei Lu, Hanh Badger, Salim Mujais, Kenneth M Peters
Purpose: We assessed efficacy and safety of URO-902, an investigational gene therapy expressing the α subunit of the large-conductance Ca2+-activated K+ channel, in a phase 2a placebo-controlled trial in women with overactive bladder (OAB).
Materials and methods: Women, age 40 to 79 years, with OAB and urge urinary incontinence who were refractory to OAB medications were randomized to single-dose URO-902 24 and 48 mg or placebo administered by intradetrusor injection via cystoscopy under local anesthesia. Efficacy end points included change from baseline to week 12 in mean daily micturitions, urgency episodes, urge urinary incontinence episodes, and patient-reported outcomes. Safety assessments included adverse events and postvoid residual urine volume.
Results: Of 80 patients randomized (URO-902 24 mg, n = 26; URO-902 48 mg, n = 27; placebo, n = 27), 74 received treatment, and 67 reached week 24. At week 12, URO-902 24 and 48 mg were associated with significant improvement vs placebo in daily micturitions (least-squares mean change from baseline, -2.3 and -2.4 vs -0.8, respectively; least-squares mean difference [95% CI], ‒1.5 [‒2.7 to ‒0.3] and ‒1.6 [‒2.8 to ‒0.4], nominal P = .017 and P = .009, respectively). URO-902 48 mg was associated with significant improvements vs placebo in urgency episodes (‒3.4 vs ‒1.1; ‒2.2 [‒4.0 to ‒0.4]; nominal P = .016) and percentage of Patient Global Impression of Change responders (58% vs 31%; nominal P = .026). Among patients receiving URO-902 24 mg, URO-902 48 mg, and placebo, 46%, 54%, and 54%, respectively, experienced ≥ 1 treatment-emergent adverse events, most commonly UTI (0%, 15%, 4%) and hematuria (6%, 8%, 8%).
Conclusions: In this phase 2a trial, treatment with URO-902 was associated with improvements vs placebo in efficacy and patient-reported outcomes and was safe and well tolerated.
目的:在一项2a期安慰剂对照试验中,评估uroo -902的有效性和安全性。uroo -902是一种表达大电导Ca2+激活K+通道α亚基的基因疗法。材料和方法:40-79岁的OAB和急发性尿失禁(UUI)女性,对OAB药物难治,随机分为单剂量uro - 90224mg和48mg或安慰剂组,局部麻醉下经膀胱镜下肌内注射。疗效终点包括从基线到第12周的平均每日排尿、急症发作、UUI发作和患者报告的结果的变化。安全性评估包括不良事件(ae)和尿后残留量。结果:80例随机患者(uroo -902 24 mg, n=26;eu -902 48 mg, n=27;安慰剂组(n=27), 74人接受治疗,67人活到第24周。在第12周,与安慰剂相比,24和48 mg的URO-902在每日排尿方面有显著改善(基线的最小二乘平均变化,-2.3和-2.4 vs -0.8;最小二乘平均差[95%置信区间],-1.5[-2.7至-0.3]和-1.6[-2.8至-0.4],名义P分别=0.017和P=0.009)。与安慰剂相比,48 mg的eu -902在急症发作中有显著改善(-3.4 vs -1.1;-2.2[-4.0至-0.4];名义P=0.016)和患者对变化的总体印象应答者的百分比(58% vs 31%;名义P = 0.026)。在接受uro - 90224mg、48mg和安慰剂治疗的患者中,分别有46%、54%和54%的患者发生≥1次治疗性不良反应,最常见的是尿路感染(0%、15%、4%)和血尿(6%、8%、8%)。结论:在这项2a期试验中,与安慰剂相比,使用eu -902治疗在疗效和患者报告的结果方面有所改善,并且安全性和耐受性良好。
{"title":"Gene Therapy With URO-902 (pVAX/<i>hSlo</i>) for the Treatment of Female Patients With Overactive Bladder and Urge Urinary Incontinence: Safety and Efficacy From a Randomized Phase 2a Trial.","authors":"Ekene A Enemchukwu, Susan Kalota, Kaiser Robertson, Sijian Ge, Jingmei Lu, Hanh Badger, Salim Mujais, Kenneth M Peters","doi":"10.1097/JU.0000000000004373","DOIUrl":"10.1097/JU.0000000000004373","url":null,"abstract":"<p><strong>Purpose: </strong>We assessed efficacy and safety of URO-902, an investigational gene therapy expressing the α subunit of the large-conductance Ca<sup>2+</sup>-activated K<sup>+</sup> channel, in a phase 2a placebo-controlled trial in women with overactive bladder (OAB).</p><p><strong>Materials and methods: </strong>Women, age 40 to 79 years, with OAB and urge urinary incontinence who were refractory to OAB medications were randomized to single-dose URO-902 24 and 48 mg or placebo administered by intradetrusor injection via cystoscopy under local anesthesia. Efficacy end points included change from baseline to week 12 in mean daily micturitions, urgency episodes, urge urinary incontinence episodes, and patient-reported outcomes. Safety assessments included adverse events and postvoid residual urine volume.</p><p><strong>Results: </strong>Of 80 patients randomized (URO-902 24 mg, n = 26; URO-902 48 mg, n = 27; placebo, n = 27), 74 received treatment, and 67 reached week 24. At week 12, URO-902 24 and 48 mg were associated with significant improvement vs placebo in daily micturitions (least-squares mean change from baseline, -2.3 and -2.4 vs -0.8, respectively; least-squares mean difference [95% CI], ‒1.5 [‒2.7 to ‒0.3] and ‒1.6 [‒2.8 to ‒0.4], nominal <i>P</i> = .017 and <i>P</i> = .009, respectively). URO-902 48 mg was associated with significant improvements vs placebo in urgency episodes (‒3.4 vs ‒1.1; ‒2.2 [‒4.0 to ‒0.4]; nominal <i>P</i> = .016) and percentage of Patient Global Impression of Change responders (58% vs 31%; nominal <i>P</i> = .026). Among patients receiving URO-902 24 mg, URO-902 48 mg, and placebo, 46%, 54%, and 54%, respectively, experienced ≥ 1 treatment-emergent adverse events, most commonly UTI (0%, 15%, 4%) and hematuria (6%, 8%, 8%).</p><p><strong>Conclusions: </strong>In this phase 2a trial, treatment with URO-902 was associated with improvements vs placebo in efficacy and patient-reported outcomes and was safe and well tolerated.</p>","PeriodicalId":17471,"journal":{"name":"Journal of Urology","volume":" ","pages":"417-427"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854657","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 : 2025-04-01Epub Date: 2024-12-23DOI: 10.1097/JU.0000000000004379
Parth V Shah, Elizabeth L Koehne
{"title":"Editorial Comment.","authors":"Parth V Shah, Elizabeth L Koehne","doi":"10.1097/JU.0000000000004379","DOIUrl":"10.1097/JU.0000000000004379","url":null,"abstract":"","PeriodicalId":17471,"journal":{"name":"Journal of Urology","volume":" ","pages":"454"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877646","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 : 2025-04-01Epub Date: 2025-03-07DOI: 10.1097/JU.0000000000004408
Gregory E Tasian, Jonathan D Harper, Hussein R Al-Khalidi, Hongqiu Yang, Naim M Maalouf, Michele Curatolo, H Henry Lai, Alana Desai, Jodi A Antonelli, Jing Huang, Justin B Ziemba, Hunter Wessells, Ziya Kirkali, Charles D Scales, Peter P Reese
{"title":"Reply by Authors.","authors":"Gregory E Tasian, Jonathan D Harper, Hussein R Al-Khalidi, Hongqiu Yang, Naim M Maalouf, Michele Curatolo, H Henry Lai, Alana Desai, Jodi A Antonelli, Jing Huang, Justin B Ziemba, Hunter Wessells, Ziya Kirkali, Charles D Scales, Peter P Reese","doi":"10.1097/JU.0000000000004408","DOIUrl":"https://doi.org/10.1097/JU.0000000000004408","url":null,"abstract":"","PeriodicalId":17471,"journal":{"name":"Journal of Urology","volume":"213 4","pages":"483-484"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573188","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 : 2025-04-01Epub Date: 2024-12-12DOI: 10.1097/JU.0000000000004374
Rachel A Saunders, Andrea K Balthazar, Christopher D Jaeger, Monah Javidan-Nejad, Candace Y Chung, Judith A Vessey, Richard S Lee, Hsin-Hsiao Scott Wang
Purpose: Genitourinary rhabdomyosarcoma (GU-RMS) often requires multimodal therapy treatment including radiation, chemotherapy, and radical surgery for disease control. The long-term effects of the disease and associated treatments are unclear. We sought to investigate the long-term genitourinary quality of life for adult survivors of pediatric GU-RMS.
Materials and methods: In total, 14 participants (43% female, median age = 32.5 years [IQR = 23.25-39.25], range = 20-52 years, 2 bladder, 1 cervical, 5 paratesticular, 3 vaginal, 2 pelvic, and 1 prostate RMS) agreed to interview about impact of GU-RMS treatment during childhood on quality of life. A semistructured interview guide based on the long-term service and support quality-of-life model and grounded in known GU-RMS experiences was created. Two coders independently coded using thematic analysis methodology.
Results: Six themes emerged: (1) unknown fertility status; (2) lack of education; (3) relationships and difficult communication; (4) incontinence, clean intermittent catheterization, and a bag; (5) lifestyle and learned adaptation; and (6) threats to body image. Across these themes, participants reported insufficient knowledge regarding GU-RMS treatment and its impact on function. Participants were principally concerned with anatomical changes, fertility, pregnancy expectations, and survivorship challenges such as communication with romantic partners.
Conclusions: Survivors of GU-RMS have significant urinary and sexual function concerns that are important to address in long-term survivorship. Clinicians can potentially improve survivors' quality of life through open and honest age-appropriate education on expectations for treatment, fertility preservation options, and long-term effects of treatment.
{"title":"Long-Term Urinary and Sexual Outcomes in Pediatric Genitourinary Rhabdomyosarcoma Survivors: A Qualitative Study.","authors":"Rachel A Saunders, Andrea K Balthazar, Christopher D Jaeger, Monah Javidan-Nejad, Candace Y Chung, Judith A Vessey, Richard S Lee, Hsin-Hsiao Scott Wang","doi":"10.1097/JU.0000000000004374","DOIUrl":"10.1097/JU.0000000000004374","url":null,"abstract":"<p><strong>Purpose: </strong>Genitourinary rhabdomyosarcoma (GU-RMS) often requires multimodal therapy treatment including radiation, chemotherapy, and radical surgery for disease control. The long-term effects of the disease and associated treatments are unclear. We sought to investigate the long-term genitourinary quality of life for adult survivors of pediatric GU-RMS.</p><p><strong>Materials and methods: </strong>In total, 14 participants (43% female, median age = 32.5 years [IQR = 23.25-39.25], range = 20-52 years, 2 bladder, 1 cervical, 5 paratesticular, 3 vaginal, 2 pelvic, and 1 prostate RMS) agreed to interview about impact of GU-RMS treatment during childhood on quality of life. A semistructured interview guide based on the long-term service and support quality-of-life model and grounded in known GU-RMS experiences was created. Two coders independently coded using thematic analysis methodology.</p><p><strong>Results: </strong>Six themes emerged: (1) unknown fertility status; (2) lack of education; (3) relationships and difficult communication; (4) incontinence, clean intermittent catheterization, and a bag; (5) lifestyle and learned adaptation; and (6) threats to body image. Across these themes, participants reported insufficient knowledge regarding GU-RMS treatment and its impact on function. Participants were principally concerned with anatomical changes, fertility, pregnancy expectations, and survivorship challenges such as communication with romantic partners.</p><p><strong>Conclusions: </strong>Survivors of GU-RMS have significant urinary and sexual function concerns that are important to address in long-term survivorship. Clinicians can potentially improve survivors' quality of life through open and honest age-appropriate education on expectations for treatment, fertility preservation options, and long-term effects of treatment.</p>","PeriodicalId":17471,"journal":{"name":"Journal of Urology","volume":" ","pages":"494-503"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818528","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 : 2025-04-01Epub Date: 2024-12-20DOI: 10.1097/JU.0000000000004359
Jennifer M Jones, Andrew Matthew, Simon Tanguay, Celestia S Higano, Larry Goldenberg, Doris Howell, Manjula Maganti
Purpose: Although the provision of a survivorship care plan (SCP) has been recommended after prostate cancer (PCa) treatment, there have been no randomized controlled trials to examine their impact. The objective of this study was to evaluate the effect of a tailored PCa-SCP intervention provided to early-stage PCa survivors.
Materials and methods: A prospective, parallel 1:1 randomized controlled trial was conducted at 3 sites across Canada. Early-stage PCa survivors were randomized (n = 189; 64% response rate) to receive PCa-SCP intervention or usual care. Assessments were performed at baseline, 6 months, and 12 months. The primary outcome was change in patient activation (Patient Activation Measure-13); secondary outcomes included satisfaction with information, self-management support, prostate-specific quality of life, cancer worry, health care utilization, and health behaviors.
Results: For the primary patient activation analyses, no significant group-by-time differences were detected. There were significant between-group differences in (1) satisfaction with information from baseline to 6 months (mean [95% CI]: 7.13 [5.53-8.71]; effect size [ES], 0.34; P < .001) and baseline to 12 months (4.91 [3.06, 7.06]; ES, 0.19; P < .001); (2) social integration and support from baseline to 6 months (mean [95% CI]: 0.16 [0.06-0.26]; ES, 0.25; P = .002); and (3) skill and technique acquisition from baseline to 6 months (mean [95% CI]: 0.12 [-0.02 to 0.24]; ES, 0.33; P = .05). No other group-by-time differences were detected.
Conclusions: The PCa-SCP intervention did not have a significant effect on patient activation but did increase satisfaction with information and some aspects of self-management support. Although the benefits of the provision of an SCP alone remain unclear, the PCa-SCP intervention is likely a valuable tool that can be built upon as part of a comprehensive approach to enhance the quality of care for PCa survivors.
{"title":"A Tailored Electronic Survivorship Care Plan for Prostate Cancer Survivors: A Multicenter Randomized Controlled Trial.","authors":"Jennifer M Jones, Andrew Matthew, Simon Tanguay, Celestia S Higano, Larry Goldenberg, Doris Howell, Manjula Maganti","doi":"10.1097/JU.0000000000004359","DOIUrl":"10.1097/JU.0000000000004359","url":null,"abstract":"<p><strong>Purpose: </strong>Although the provision of a survivorship care plan (SCP) has been recommended after prostate cancer (PCa) treatment, there have been no randomized controlled trials to examine their impact. The objective of this study was to evaluate the effect of a tailored PCa-SCP intervention provided to early-stage PCa survivors.</p><p><strong>Materials and methods: </strong>A prospective, parallel 1:1 randomized controlled trial was conducted at 3 sites across Canada. Early-stage PCa survivors were randomized (n = 189; 64% response rate) to receive PCa-SCP intervention or usual care. Assessments were performed at baseline, 6 months, and 12 months. The primary outcome was change in patient activation (Patient Activation Measure-13); secondary outcomes included satisfaction with information, self-management support, prostate-specific quality of life, cancer worry, health care utilization, and health behaviors.</p><p><strong>Results: </strong>For the primary patient activation analyses, no significant group-by-time differences were detected. There were significant between-group differences in (1) satisfaction with information from baseline to 6 months (mean [95% CI]: 7.13 [5.53-8.71]; effect size [ES], 0.34; <i>P</i> < .001) and baseline to 12 months (4.91 [3.06, 7.06]; ES, 0.19; <i>P</i> < .001); (2) social integration and support from baseline to 6 months (mean [95% CI]: 0.16 [0.06-0.26]; ES, 0.25; <i>P</i> = .002); and (3) skill and technique acquisition from baseline to 6 months (mean [95% CI]: 0.12 [-0.02 to 0.24]; ES, 0.33; <i>P</i> = .05). No other group-by-time differences were detected.</p><p><strong>Conclusions: </strong>The PCa-SCP intervention did not have a significant effect on patient activation but did increase satisfaction with information and some aspects of self-management support. Although the benefits of the provision of an SCP alone remain unclear, the PCa-SCP intervention is likely a valuable tool that can be built upon as part of a comprehensive approach to enhance the quality of care for PCa survivors.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT03017456.</p>","PeriodicalId":17471,"journal":{"name":"Journal of Urology","volume":" ","pages":"407-416"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869515","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 : 2025-04-01Epub Date: 2024-12-23DOI: 10.1097/JU.0000000000004378
David-Dan Nguyen, Christopher J D Wallis
{"title":"Editorial Comment.","authors":"David-Dan Nguyen, Christopher J D Wallis","doi":"10.1097/JU.0000000000004378","DOIUrl":"10.1097/JU.0000000000004378","url":null,"abstract":"","PeriodicalId":17471,"journal":{"name":"Journal of Urology","volume":" ","pages":"415-416"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877642","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 : 2025-04-01Epub Date: 2025-01-22DOI: 10.1097/JU.0000000000004386
Mitchell G Goldenberg
{"title":"Editorial Comment.","authors":"Mitchell G Goldenberg","doi":"10.1097/JU.0000000000004386","DOIUrl":"10.1097/JU.0000000000004386","url":null,"abstract":"","PeriodicalId":17471,"journal":{"name":"Journal of Urology","volume":" ","pages":"510-511"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007500","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 : 2025-04-01Epub Date: 2024-12-20DOI: 10.1097/JU.0000000000004382
Jason Y Lee
{"title":"Editorial Comment.","authors":"Jason Y Lee","doi":"10.1097/JU.0000000000004382","DOIUrl":"10.1097/JU.0000000000004382","url":null,"abstract":"","PeriodicalId":17471,"journal":{"name":"Journal of Urology","volume":" ","pages":"510"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864648","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 : 2025-04-01Epub Date: 2024-12-24DOI: 10.1097/JU.0000000000004376
Luis H Braga, Melissa McGrath
{"title":"Editorial Comment.","authors":"Luis H Braga, Melissa McGrath","doi":"10.1097/JU.0000000000004376","DOIUrl":"10.1097/JU.0000000000004376","url":null,"abstract":"","PeriodicalId":17471,"journal":{"name":"Journal of Urology","volume":" ","pages":"492-493"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882523","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}