Pub Date : 2025-02-01DOI: 10.1016/j.euo.2024.08.001
Roberto Contieri , Mark S. Soloway , Paolo Gontero , Harry Herr , Wassim Kassouf , Laura S. Mertens , Marco Moschini , Michael O’Donnell , Joan Palou , Sarah P. Psutka , Morgan Rouprêt , Jeremy Y.C. Teoh , Ashish M. Kamat
Background and objective
Management of low-grade (LG) urothelium-confined (Ta stage) non–muscle-invasive bladder cancer (NMIBC) poses a distinct therapeutic challenge. Transurethral resection of bladder tumor (TURBT), the standard treatment, frequently has to be repeated because of high tumor recurrence rates. This places a considerable strain on both patients and health care infrastructure, underscoring the need for alternative management approaches. Herein, the IBCG (International Bladder Cancer Group), conducted a review to explore the efficacy and safety of deintensified treatment strategies for recurrent LG Ta NMIBC.
Methods
We conducted a collaborative review of relevant literature in the PubMed/MEDLINE and Cochrane CENTRAL databases. Our focus was on high-quality evidence, including randomized controlled trials, systematic reviews, and meta-analyses. We also reviewed guidelines published by prominent urological associations.
Key findings and limitations
Active surveillance, chemoablation, and office fulguration are valid treatment options for recurrent LG Ta NMIBC. These deintensified approaches offer several advantages over TURBT: lower complication rates, less morbidity, lower health care costs, and better quality of life for patients. Importantly, these benefits are achieved without compromising oncological safety.
Conclusions and clinical implications
Our review demonstrates that less intensive treatment strategies for recurrent LG Ta NMIBC are both feasible and valuable. The IBCG recommends use of these approaches for carefully selected patients to help lower health care costs and enhance patients’ quality of life.
Patient summary
We reviewed studies on less invasive management options for low-grade noninvasive bladder cancer, including active surveillance, chemical ablation, and heat treatment. Recent results confirm that these less intense treatment options can reduce the treatment burden and costs for patients and preserve their quality of life without negatively affecting cancer control outcomes.
背景和目的：低级别（LG）尿路黏膜封闭型（Ta 期）非肌浸润性膀胱癌（NMIBC）的治疗是一项独特的治疗挑战。经尿道膀胱肿瘤切除术（TURBT）是标准治疗方法，但由于肿瘤复发率高，经常需要重复进行。这给患者和医疗基础设施都造成了相当大的压力，凸显了对替代治疗方法的需求。在此，IBCG（国际膀胱癌组织）进行了一项综述，以探讨针对复发性 LG Ta NMIBC 的去强化治疗策略的有效性和安全性：我们对 PubMed/MEDLINE 和 Cochrane CENTRAL 数据库中的相关文献进行了合作性综述。我们的重点是高质量的证据，包括随机对照试验、系统综述和荟萃分析。我们还查阅了著名泌尿外科协会发布的指南：积极监测、化疗消融和手术切除是治疗复发性 LG Ta NMIBC 的有效方法。与 TURBT 相比，这些非强化治疗方法具有以下优势：并发症发生率低、发病率低、医疗费用低、患者生活质量高。重要的是，这些优势是在不影响肿瘤安全性的前提下实现的：我们的综述表明，针对复发性 LG Ta NMIBC 的低强度治疗策略既可行又有价值。患者总结：我们回顾了有关低级别非侵袭性膀胱癌微创治疗方案的研究，包括主动监测、化学消融和热疗。最近的研究结果证实，这些强度较低的治疗方案可以减轻患者的治疗负担和费用，并在不对癌症控制结果产生负面影响的情况下保持患者的生活质量。
{"title":"Deintensification of Treatment for Low-grade Bladder Tumors: A Collaborative Review by the International Bladder Cancer Group (IBCG)","authors":"Roberto Contieri , Mark S. Soloway , Paolo Gontero , Harry Herr , Wassim Kassouf , Laura S. Mertens , Marco Moschini , Michael O’Donnell , Joan Palou , Sarah P. Psutka , Morgan Rouprêt , Jeremy Y.C. Teoh , Ashish M. Kamat","doi":"10.1016/j.euo.2024.08.001","DOIUrl":"10.1016/j.euo.2024.08.001","url":null,"abstract":"<div><h3>Background and objective</h3><div>Management of low-grade (LG) urothelium-confined (Ta stage) non–muscle-invasive bladder cancer (NMIBC) poses a distinct therapeutic challenge. Transurethral resection of bladder tumor (TURBT), the standard treatment, frequently has to be repeated because of high tumor recurrence rates. This places a considerable strain on both patients and health care infrastructure, underscoring the need for alternative management approaches. Herein, the IBCG (International Bladder Cancer Group), conducted a review to explore the efficacy and safety of deintensified treatment strategies for recurrent LG Ta NMIBC.</div></div><div><h3>Methods</h3><div>We conducted a collaborative review of relevant literature in the PubMed/MEDLINE and Cochrane CENTRAL databases. Our focus was on high-quality evidence, including randomized controlled trials, systematic reviews, and meta-analyses. We also reviewed guidelines published by prominent urological associations.</div></div><div><h3>Key findings and limitations</h3><div>Active surveillance, chemoablation, and office fulguration are valid treatment options for recurrent LG Ta NMIBC. These deintensified approaches offer several advantages over TURBT: lower complication rates, less morbidity, lower health care costs, and better quality of life for patients. Importantly, these benefits are achieved without compromising oncological safety.</div></div><div><h3>Conclusions and clinical implications</h3><div>Our review demonstrates that less intensive treatment strategies for recurrent LG Ta NMIBC are both feasible and valuable. The IBCG recommends use of these approaches for carefully selected patients to help lower health care costs and enhance patients’ quality of life.</div></div><div><h3>Patient summary</h3><div>We reviewed studies on less invasive management options for low-grade noninvasive bladder cancer, including active surveillance, chemical ablation, and heat treatment. Recent results confirm that these less intense treatment options can reduce the treatment burden and costs for patients and preserve their quality of life without negatively affecting cancer control outcomes.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 1","pages":"Pages 179-189"},"PeriodicalIF":8.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105926","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}
Pub Date : 2025-02-01DOI: 10.1016/j.euo.2024.08.004
Lia D. Oliveira , Jiayun Lu , Eric Erak , Adrianna A. Mendes , Oluwademilade Dairo , Onur Ertunc , Ibrahim Kulac , Javier A. Baena-Del Valle , Tracy Jones , Jessica L. Hicks , Stephanie Glavaris , Gunes Guner , Igor D. Vidal , Bruce J. Trock , Uttara Joshi , Chaith Kondragunta , Saikiran Bonthu , Corinne Joshu , Nitin Singhal , Angelo M. De Marzo , Tamara L. Lotan
Gleason grade group (GG) is the most powerful prognostic variable in localized prostate cancer; however, interobserver variability remains a challenge. Artificial intelligence algorithms applied to histopathologic images standardize grading, but most have been tested only for agreement with pathologist GG, without assessment of performance with respect to oncologic outcomes. We compared deep learning–based and pathologist-based GGs for an association with metastatic outcome in three surgical cohorts comprising 777 unique patients. A digitized whole slide image of the representative hematoxylin and eosin–stained slide of the dominant tumor nodule was assigned a GG by an artificial intelligence–based grading algorithm and was compared with the GG assigned by a contemporary pathologist or the original pathologist-assigned GG for the entire prostatectomy. Harrell’s C-indices based on Cox models for time to metastasis were compared. In a combined analysis of all cohorts, the C-index for the artificial intelligence–assigned GG was 0.77 (95% confidence interval [CI]: 0.73–0.81), compared with 0.77 (95% CI: 0.73–0.81) for the pathologist-assigned GG. By comparison, the original pathologist-assigned GG for the entire case had a C-index of 0.78 (95% CI: 0.73–0.82).
Patient summary
Artificial intelligence–enabled prostate cancer grading on a single slide was comparable with pathologist grading for predicting metastatic outcome in men treated by radical prostatectomy, enabling equal access to expert grading in lower resource settings.
格里森分级组（GG）是局部前列腺癌最有力的预后变量；然而，观察者之间的差异仍然是一个挑战。应用于组织病理学图像的人工智能算法可以实现分级标准化，但大多数算法只测试了与病理学家 GG 的一致性，而没有评估与肿瘤结果相关的性能。我们在由 777 名患者组成的三个手术队列中比较了基于深度学习的 GG 和基于病理学家的 GG 与转移性结果的关联性。基于人工智能的分级算法为主要肿瘤结节的苏木精和伊红染色玻片的数字化全片图像分配了一个 GG，并与当代病理学家分配的 GG 或病理学家为整个前列腺切除术分配的原始 GG 进行了比较。同时还比较了基于 Cox 模型的哈雷尔 C 指数对转移时间的影响。在对所有队列进行的综合分析中，人工智能分配的 GG 的 C 指数为 0.77（95% 置信区间 [CI]：0.73-0.81），而病理学家分配的 GG 的 C 指数为 0.77（95% 置信区间 [CI]：0.73-0.81）。相比之下，病理学家最初为整个病例指定的 GG 的 C 指数为 0.78（95% CI：0.73-0.82）。患者总结：在预测根治性前列腺切除术男性患者的转移预后方面，人工智能支持的单张切片前列腺癌分级与病理学家分级结果相当，这使得在资源较少的情况下也能平等地获得专家分级结果。
{"title":"Comparison of Pathologist and Artificial Intelligence–based Grading for Prediction of Metastatic Outcomes After Radical Prostatectomy","authors":"Lia D. Oliveira , Jiayun Lu , Eric Erak , Adrianna A. Mendes , Oluwademilade Dairo , Onur Ertunc , Ibrahim Kulac , Javier A. Baena-Del Valle , Tracy Jones , Jessica L. Hicks , Stephanie Glavaris , Gunes Guner , Igor D. Vidal , Bruce J. Trock , Uttara Joshi , Chaith Kondragunta , Saikiran Bonthu , Corinne Joshu , Nitin Singhal , Angelo M. De Marzo , Tamara L. Lotan","doi":"10.1016/j.euo.2024.08.004","DOIUrl":"10.1016/j.euo.2024.08.004","url":null,"abstract":"<div><div>Gleason grade group (GG) is the most powerful prognostic variable in localized prostate cancer; however, interobserver variability remains a challenge. Artificial intelligence algorithms applied to histopathologic images standardize grading, but most have been tested only for agreement with pathologist GG, without assessment of performance with respect to oncologic outcomes. We compared deep learning–based and pathologist-based GGs for an association with metastatic outcome in three surgical cohorts comprising 777 unique patients. A digitized whole slide image of the representative hematoxylin and eosin–stained slide of the dominant tumor nodule was assigned a GG by an artificial intelligence–based grading algorithm and was compared with the GG assigned by a contemporary pathologist or the original pathologist-assigned GG for the entire prostatectomy. Harrell’s C-indices based on Cox models for time to metastasis were compared. In a combined analysis of all cohorts, the C-index for the artificial intelligence–assigned GG was 0.77 (95% confidence interval [CI]: 0.73–0.81), compared with 0.77 (95% CI: 0.73–0.81) for the pathologist-assigned GG. By comparison, the original pathologist-assigned GG for the entire case had a C-index of 0.78 (95% CI: 0.73–0.82).</div></div><div><h3>Patient summary</h3><div>Artificial intelligence–enabled prostate cancer grading on a single slide was comparable with pathologist grading for predicting metastatic outcome in men treated by radical prostatectomy, enabling equal access to expert grading in lower resource settings.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 1","pages":"Pages 9-13"},"PeriodicalIF":8.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132266","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}
Pub Date : 2025-02-01DOI: 10.1016/j.euo.2024.07.008
Fredrik Liedberg , Truls Gårdmark , Oskar Hagberg , Firas Aljabery , Viveka Ströck , Abolfazl Hosseini , Per-Uno Malmström , Karin Söderkvist , Anders Ullén , Tomas Jerlström , Staffan Jahnson , Lars Holmberg , Christel Häggström
Background and objective
It has been suggested that urinary tract infections (UTIs) are associated with delayed diagnosis of bladder cancer (BC). Our aim was to investigate prediagnostic treatments related to UTI and the relation to BC diagnostic delay, reflected by advanced disease at diagnosis.
Methods
We used data from the BladderBaSe 2.0 with data of treatments related to UTI up to 3 yr before BC diagnosis (2008–2019) for BC patients in comparison to a matched reference population. We investigated the association between UTI treatments and more advanced disease at diagnosis in the BC cohort. We used generalized ordered logistic regression to calculate odds ratios (ORs) for more advanced disease as an ordered outcome: non–muscle-invasive BC (NMIBC), muscle-invasive BC (MIBC), and metastatic BC (MBC).
Key findings and limitations
The study population included 29 921 BC patients and 149 467 matched reference subjects. The proportions of individuals receiving UTI treatment were higher in the patient groups than in the corresponding reference groups, with the greatest differences observed for the MIBC and MBC subgroups. The OR for the risk of more advanced disease (MIBC or MBC) with at least one UTI treatment versus none was 1.28 (95% confidence interval [CI] 1.19–1.37) for men and 1.42 (95 % CI 1.27–1.58) for women. The association to risk of more advanced disease increased with the number of UTI treatments for both sexes.
Conclusions and clinical implications
Further studies on the effects of treatments related to UTI in combination with other factors are needed to identify reasons for possible delays in the BC diagnostic pathway.
Patient summary
We found that for patients with bladder cancer, previous antibiotic treatment for a urinary tract infection was linked to more advanced disease at diagnosis. Further studies are needed to identify reasons for possible delays in the diagnosis of bladder cancer.
背景和目的：有研究表明，尿路感染（UTI）与膀胱癌（BC）的延迟诊断有关。我们的目的是调查与UTI相关的诊断前治疗以及UTI与膀胱癌诊断延迟的关系，诊断时的晚期疾病反映了这一点：我们使用了来自 BladderBaSe 2.0 的数据，其中包括 BC 患者在 BC 诊断前 3 年（2008-2019 年）接受的 UTI 相关治疗的数据，并与匹配的参照人群进行了比较。我们研究了 BC 队列中UTI 治疗与确诊时疾病晚期之间的关联。我们使用广义有序逻辑回归计算了作为有序结果的晚期疾病的几率比（ORs）：非肌浸润性BC（NMIBC）、肌浸润性BC（MIBC）和转移性BC（MBC）：研究对象包括 29 921 名 BC 患者和 149 467 名匹配参照对象。患者组中接受UTI治疗的比例高于相应的参照组，其中MIBC和MBC亚组的差异最大。至少接受过一次UTI治疗与未接受UTI治疗相比，男性晚期疾病（MIBC或MBC）风险的OR值为1.28（95% 置信区间[CI] 1.19-1.37），女性为1.42（95 % CI 1.27-1.58）。男女患者罹患晚期疾病的风险随着UTI治疗次数的增加而增加：患者小结：我们发现，对于膀胱癌患者而言，既往接受过尿路感染抗生素治疗与确诊时病情更晚期有关。需要进一步研究以确定膀胱癌诊断可能出现延误的原因。
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Pub Date : 2025-02-01DOI: 10.1016/j.euo.2024.04.010
Daniel Sentana-Lledo , Xiangying Chu , David F. Jarrard , Michael A. Carducci , Robert S. DiPaola , Lynn I. Wagner , David Cella , Christopher J. Sweeney , Alicia K. Morgans
Background
Chemohormonal therapy with androgen deprivation therapy and docetaxel (ADT + D) improves overall survival (OS) and quality of life (QOL) at 12 mo versus androgen deprivation therapy (ADT) alone in men with metastatic hormone-sensitive prostate cancer (mHSPC). However, the prognostic role of QOL is unknown in this population.
Objective
To study the relationship between QOL, disease characteristics, and OS in men with mHSPC.
Design, setting, and participants
In this exploratory post hoc analysis, 790 patients with mHSPC completed the QOL instruments Functional Assessment of Cancer Therapy—Prostate (FACT-P), Functional Assessment of Chronic Illness Therapy—Fatigue (FACIT-F), and Brief Pain Inventory (BPI).
Outcome measurements and statistical analysis
Log-rank test and Cox proportional hazard models tested the association between QOL and OS by clinical and disease characteristics.
Results and limitations
Baseline higher FACT-P trended toward improved survival after accounting for clinical variables (hazard ratio [HR] 0.80 [0.62, 1.04], p = 0.09), while higher 3-mo FACT-P was independently associated with better survival (HR 0.76 [0.58, 1.0], p = 0.05). Patients with the poorest QOL (bottom quartile) at baseline and 3 mo had longer survival if they received ADT + D rather than ADT alone (median OS 45.2 vs 34.4 mo, HR 0.75 [0.53, 1.05], p = 0.09, and 48.3 vs 29.3 mo, HR 0.69 [0.48, 0.99], p = 0.05 respectively). In contrast, patients with the best QOL (top quartile) at baseline and 3 mo had comparable survival irrespective of whether or not docetaxel was added (median OS 72.1 vs 51.7 mo, HR 0.92 [0.63, 1.36], p = 0.69, and 69.9 vs 68.9 mo, HR 1.11 [0.73, 1.67], p = 0.63, respectively). Survival was linked with baseline FACIT-F (HR 0.76 [0.57, 1.0], p = 0.05), but not BPI (HR 0.98 [0.75, 1.28], p = 0.90).
Conclusions
Three-month QOL had a stronger independent association with survival. The most symptomatic patients had longer survival with the addition of docetaxel; conversely, the least symptomatic patients did not appear to benefit. Consideration of QOL may enhance decision-making and patient selection when choosing chemohormonal treatment in mHSPC.
Patient summary
Quality of life independently forecasted the survival of men with metastatic hormone-sensitive prostate cancer in the CHAARTED study. Close tracking of quality of life could help patients and clinicians make decisions about the appropriate treatment in this setting.
背景：在转移性激素敏感性前列腺癌（mHSPC）男性患者中，化疗激素联合雄激素剥夺疗法和多西他赛（ADT + D）与单纯雄激素剥夺疗法（ADT）相比，可提高患者12个月后的总生存期（OS）和生活质量（QOL）。然而，QOL在这一人群中的预后作用尚不清楚：研究男性转移性前列腺癌患者的 QOL、疾病特征和 OS 之间的关系：在这项探索性事后分析中，790名mHSPC患者填写了QOL工具：前列腺癌治疗功能评估（FACT-P）、慢性疾病治疗功能评估-疲劳（FACIT-F）和简明疼痛量表（BPI）：结果测量和统计分析：对数秩检验和 Cox 比例危险模型按临床和疾病特征检验了 QOL 与 OS 之间的关系：在考虑临床变量后，基线较高的 FACT-P 有改善生存率的趋势（危险比 [HR] 0.80 [0.62, 1.04]，P = 0.09），而较高的 3 个月 FACT-P 与较好的生存率独立相关（HR 0.76 [0.58, 1.0]，P = 0.05）。基线和 3 个月时 QOL 最差（最低四分位数）的患者如果接受 ADT + D 而不是单独 ADT，则生存期更长（中位 OS 分别为 45.2 月 vs 34.4 月，HR 0.75 [0.53, 1.05]，p = 0.09；48.3 月 vs 29.3 月，HR 0.69 [0.48, 0.99]，p = 0.05）。相比之下，无论是否加用多西他赛，基线和3个月时QOL最好（前四分之一）的患者生存率相当（中位OS分别为72.1个月 vs 51.7个月，HR 0.92 [0.63，1.36]，p = 0.69；69.9个月 vs 68.9个月，HR 1.11 [0.73，1.67]，p = 0.63）。存活率与基线 FACIT-F 有关（HR 0.76 [0.57, 1.0]，P = 0.05），但与 BPI 无关（HR 0.98 [0.75, 1.28]，P = 0.90）：结论：三个月的 QOL 与存活率有更密切的关系。症状最严重的患者在加用多西他赛后生存期更长；反之，症状最轻微的患者似乎并没有获益。在mHSPC患者选择化疗激素治疗时，对生活质量的考虑可能会促进决策和患者选择：在CHAARTED研究中，生活质量可独立预测转移性激素敏感性前列腺癌男性患者的生存期。密切跟踪生活质量有助于患者和临床医生在这种情况下做出适当治疗的决定。
{"title":"Patient-reported Quality of Life and Survival Outcomes in Prostate Cancer: Analysis of the ECOG-ACRIN E3805 Chemohormonal Androgen Ablation Randomized Trial (CHAARTED)","authors":"Daniel Sentana-Lledo , Xiangying Chu , David F. Jarrard , Michael A. Carducci , Robert S. DiPaola , Lynn I. Wagner , David Cella , Christopher J. Sweeney , Alicia K. Morgans","doi":"10.1016/j.euo.2024.04.010","DOIUrl":"10.1016/j.euo.2024.04.010","url":null,"abstract":"<div><h3>Background</h3><div>Chemohormonal therapy with androgen deprivation therapy and docetaxel (ADT + D) improves overall survival (OS) and quality of life (QOL) at 12 mo versus androgen deprivation therapy (ADT) alone in men with metastatic hormone-sensitive prostate cancer (mHSPC). However, the prognostic role of QOL is unknown in this population.</div></div><div><h3>Objective</h3><div>To study the relationship between QOL, disease characteristics, and OS in men with mHSPC.</div></div><div><h3>Design, setting, and participants</h3><div>In this exploratory post hoc analysis, 790 patients with mHSPC completed the QOL instruments Functional Assessment of Cancer Therapy—Prostate (FACT-P), Functional Assessment of Chronic Illness Therapy—Fatigue (FACIT-F), and Brief Pain Inventory (BPI).</div></div><div><h3>Outcome measurements and statistical analysis</h3><div>Log-rank test and Cox proportional hazard models tested the association between QOL and OS by clinical and disease characteristics.</div></div><div><h3>Results and limitations</h3><div>Baseline higher FACT-P trended toward improved survival after accounting for clinical variables (hazard ratio [HR] 0.80 [0.62, 1.04], <em>p</em> = 0.09), while higher 3-mo FACT-P was independently associated with better survival (HR 0.76 [0.58, 1.0], <em>p</em> = 0.05). Patients with the poorest QOL (bottom quartile) at baseline and 3 mo had longer survival if they received ADT + D rather than ADT alone (median OS 45.2 vs 34.4 mo, HR 0.75 [0.53, 1.05], <em>p</em> = 0.09, and 48.3 vs 29.3 mo, HR 0.69 [0.48, 0.99], <em>p</em> = 0.05 respectively). In contrast, patients with the best QOL (top quartile) at baseline and 3 mo had comparable survival irrespective of whether or not docetaxel was added (median OS 72.1 vs 51.7 mo, HR 0.92 [0.63, 1.36], <em>p</em> = 0.69, and 69.9 vs 68.9 mo, HR 1.11 [0.73, 1.67], <em>p</em> = 0.63, respectively). Survival was linked with baseline FACIT-F (HR 0.76 [0.57, 1.0], <em>p</em> = 0.05), but not BPI (HR 0.98 [0.75, 1.28], <em>p</em> = 0.90).</div></div><div><h3>Conclusions</h3><div>Three-month QOL had a stronger independent association with survival. The most symptomatic patients had longer survival with the addition of docetaxel; conversely, the least symptomatic patients did not appear to benefit. Consideration of QOL may enhance decision-making and patient selection when choosing chemohormonal treatment in mHSPC.</div></div><div><h3>Patient summary</h3><div>Quality of life independently forecasted the survival of men with metastatic hormone-sensitive prostate cancer in the CHAARTED study. Close tracking of quality of life could help patients and clinicians make decisions about the appropriate treatment in this setting.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 1","pages":"Pages 29-37"},"PeriodicalIF":8.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140859836","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}
Pub Date : 2025-02-01DOI: 10.1016/j.euo.2024.04.017
Randy A. Vince Jr , Helen Sun , Udit Singhal , Fredrick R. Schumacher , Erika Trapl , Johnie Rose , Jennifer Cullen , Nicholas Zaorsky , Jonathan Shoag , Holly Hartman , Angela Y. Jia , Daniel E. Spratt , Lars G. Fritsche , Todd M. Morgan
Background and objective
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.
Methods
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.
Key findings and limitations
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.
Conclusions and clinical implications
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.
Patient summary
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.
{"title":"Assessing the Clinical Utility of Published Prostate Cancer Polygenic Risk Scores in a Large Biobank Data Set","authors":"Randy A. Vince Jr , Helen Sun , Udit Singhal , Fredrick R. Schumacher , Erika Trapl , Johnie Rose , Jennifer Cullen , Nicholas Zaorsky , Jonathan Shoag , Holly Hartman , Angela Y. Jia , Daniel E. Spratt , Lars G. Fritsche , Todd M. Morgan","doi":"10.1016/j.euo.2024.04.017","DOIUrl":"10.1016/j.euo.2024.04.017","url":null,"abstract":"<div><h3>Background and objective</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Key findings and limitations</h3><div>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.</div></div><div><h3>Conclusions and clinical implications</h3><div>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.</div></div><div><h3>Patient summary</h3><div>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.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 1","pages":"Pages 47-55"},"PeriodicalIF":8.3,"publicationDate":"2025-02-01","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}
Pub Date : 2025-02-01DOI: 10.1016/j.euo.2024.05.011
Philip Sutera , Yang Song , Amol C. Shetty , Keara English , Kim Van der Eecken , Ozan Cem Guler , Jarey Wang , Yufeng Cao , Soha Bazyar , Sofie Verbeke , Jo Van Dorpe , Valérie Fonteyne , Bram De Laere , Mark Mishra , Zaker Rana , Jason Molitoris , Matthew Ferris , Ana Kiess , Daniel Y. Song , Theodore DeWeese , Matthew P. Deek
<div><h3>Background and objective</h3><div>Oligometastatic castration-sensitive prostate cancer (omCSPC) represents an early state in the progression of metastatic disease for which patients experience better outcomes in comparison to those with higher disease burden. Despite the generally more indolent nature, there is still much heterogeneity, with some patients experiencing a more aggressive clinical course unexplained by clinical features alone. Our aim was to investigate correlation of tumor genomics with the mode of progression (MOP) and pattern of failure (POF) following first treatment (metastasis-directed and/or systemic therapy) for omCSPC.</div></div><div><h3>Methods</h3><div>We performed an international multi-institutional retrospective study of men treated for metachronous omCSPC who underwent tumor next-generation sequencing with at least 1 yr of follow-up after their first treatment. Descriptive MOP and POF results are reported with respect to the presence of genomic alterations in pathways of interest. MOP was defined as class I, long-term control (LTC; no radiographic progression at last follow-up), class II, oligoprogression (1–3 lesions), or class III, polyprogression (≥4 lesions). POF included the location of lesions at first failure. Genomic pathways of interest included <em>TP53</em>, <em>ATM, RB1, BRCA1/2, SPOP</em>, and WNT (<em>APC, CTNNB1, RNF43)</em>. Genomic associations with MOP/POF were compared using χ<sup>2</sup> tests. Exploratory analyses revealed that the COSMIC mutational signature and differential gene expression were also correlated with MOP/POF. Overall survival (OS) was calculated via the Kaplan-Meier method from the time of first failure.</div></div><div><h3>Key findings and clinical implications</h3><div>We included 267 patients in our analysis; the majority had either one (47%) or two (30%) metastatic lesions at oligometastasis. The 3-yr OS rate was significantly associated with MOP (71% for polyprogression vs 91% for oligoprogression; <em>p</em> = 0.005). <em>TP53</em> mutation was associated with a significantly lower LTC rate (27.6% vs 42.3%; <em>p</em> = 0.04) and <em>RB1</em> mutation was associated with a high rate of polyprogression (50% vs 19.9%; <em>p</em> = 0.022). Regarding POF, bone failure was significantly more common with tumors harboring <em>TP53</em> mutations (44.8% vs25.9%; <em>p</em> = 0.005) and less common with <em>SPOP</em> mutations (7.1% vs 31.4%; <em>p</em> = 0.007). Visceral failure was more common with tumors harboring either WNT pathway mutations (17.2% vs 6.8%, <em>p</em> = 0.05) or <em>SPOP</em> mutations (17.9% vs 6.3%; <em>p</em> = 0.04). Finally, visceral and bone failures were associated with distinct gene-expression profiles.</div></div><div><h3>Conclusions and clinical implications</h3><div>Tumor genomics provides novel insight into MOP and POF following treatment for metachronous omCSPC. Patients with <em>TP53</em> and <em>RB1</em> mutations have a higher likelihood
背景和目的：低转移性阉割敏感性前列腺癌（omCSPC）是转移性疾病进展的早期状态，与疾病负担较重的患者相比，患者的预后较好。尽管前列腺癌一般较为隐匿，但仍存在很大的异质性，一些患者的临床病程更具侵袭性，而临床特征本身无法解释其原因。我们的目的是研究肿瘤基因组学与omCSPC首次治疗（转移导向和/或全身治疗）后的进展模式（MOP）和失败模式（POF）的相关性：我们开展了一项国际多机构回顾性研究，研究对象是接受过转移性omCSPC治疗的男性患者，他们在首次治疗后至少随访1年，并接受了肿瘤新一代测序。报告了相关通路基因组改变的描述性澳门巴黎人娱乐官网和 POF 结果。MOP定义为I级，长期控制（LTC；最后一次随访时无放射学进展）；II级，少进展（1-3个病灶）；或III级，多进展（≥4个病灶）。POF包括首次失败时病变的位置。受关注的基因组通路包括 TP53、ATM、RB1、BRCA1/2、SPOP 和 WNT（APC、CTNNB1、RNF43）。使用χ2检验比较了基因组与MOP/POF的相关性。探索性分析表明，COSMIC突变特征和差异基因表达也与MOP/POF相关。总生存期（OS）采用卡普兰-梅耶法计算，从首次失败时算起：我们在分析中纳入了267名患者；大多数患者在少转移灶有一个（47%）或两个（30%）转移病灶。3年的OS率与MOP显著相关（多发转移为71%，少发转移为91%；P = 0.005）。TP53突变与明显较低的长期生存率相关（27.6% vs 42.3%; p = 0.04），RB1突变与较高的多发性进展率相关（50% vs 19.9%; p = 0.022）。关于POF，骨衰竭在TP53突变的肿瘤中更常见（44.8% vs 25.9%；p = 0.005），而在SPOP突变的肿瘤中较少见（7.1% vs 31.4%；p = 0.007）。内脏衰竭在WNT通路突变（17.2% vs 6.8%，p = 0.05）或SPOP突变（17.9% vs 6.3%；p = 0.04）的肿瘤中更为常见。最后，内脏和骨骼衰竭与不同的基因表达谱有关：结论和临床意义：肿瘤基因组学提供了治疗远期omCSPC后MOP和POF的新见解。TP53和RB1基因突变的患者病情进展的可能性更高，TP53、SPOP和WNT通路突变可能在转移性有机体中发挥作用。患者摘要：我们评估了转移性前列腺癌首次治疗后的癌症进展情况，转移灶多达5个。我们发现，某些基因的突变与这些患者进一步转移的位置和程度有关。
{"title":"Genomic Determinants Associated with Modes of Progression and Patterns of Failure in Metachronous Oligometastatic Castration-sensitive Prostate Cancer","authors":"Philip Sutera , Yang Song , Amol C. Shetty , Keara English , Kim Van der Eecken , Ozan Cem Guler , Jarey Wang , Yufeng Cao , Soha Bazyar , Sofie Verbeke , Jo Van Dorpe , Valérie Fonteyne , Bram De Laere , Mark Mishra , Zaker Rana , Jason Molitoris , Matthew Ferris , Ana Kiess , Daniel Y. Song , Theodore DeWeese , Matthew P. Deek","doi":"10.1016/j.euo.2024.05.011","DOIUrl":"10.1016/j.euo.2024.05.011","url":null,"abstract":"<div><h3>Background and objective</h3><div>Oligometastatic castration-sensitive prostate cancer (omCSPC) represents an early state in the progression of metastatic disease for which patients experience better outcomes in comparison to those with higher disease burden. Despite the generally more indolent nature, there is still much heterogeneity, with some patients experiencing a more aggressive clinical course unexplained by clinical features alone. Our aim was to investigate correlation of tumor genomics with the mode of progression (MOP) and pattern of failure (POF) following first treatment (metastasis-directed and/or systemic therapy) for omCSPC.</div></div><div><h3>Methods</h3><div>We performed an international multi-institutional retrospective study of men treated for metachronous omCSPC who underwent tumor next-generation sequencing with at least 1 yr of follow-up after their first treatment. Descriptive MOP and POF results are reported with respect to the presence of genomic alterations in pathways of interest. MOP was defined as class I, long-term control (LTC; no radiographic progression at last follow-up), class II, oligoprogression (1–3 lesions), or class III, polyprogression (≥4 lesions). POF included the location of lesions at first failure. Genomic pathways of interest included <em>TP53</em>, <em>ATM, RB1, BRCA1/2, SPOP</em>, and WNT (<em>APC, CTNNB1, RNF43)</em>. Genomic associations with MOP/POF were compared using χ<sup>2</sup> tests. Exploratory analyses revealed that the COSMIC mutational signature and differential gene expression were also correlated with MOP/POF. Overall survival (OS) was calculated via the Kaplan-Meier method from the time of first failure.</div></div><div><h3>Key findings and clinical implications</h3><div>We included 267 patients in our analysis; the majority had either one (47%) or two (30%) metastatic lesions at oligometastasis. The 3-yr OS rate was significantly associated with MOP (71% for polyprogression vs 91% for oligoprogression; <em>p</em> = 0.005). <em>TP53</em> mutation was associated with a significantly lower LTC rate (27.6% vs 42.3%; <em>p</em> = 0.04) and <em>RB1</em> mutation was associated with a high rate of polyprogression (50% vs 19.9%; <em>p</em> = 0.022). Regarding POF, bone failure was significantly more common with tumors harboring <em>TP53</em> mutations (44.8% vs25.9%; <em>p</em> = 0.005) and less common with <em>SPOP</em> mutations (7.1% vs 31.4%; <em>p</em> = 0.007). Visceral failure was more common with tumors harboring either WNT pathway mutations (17.2% vs 6.8%, <em>p</em> = 0.05) or <em>SPOP</em> mutations (17.9% vs 6.3%; <em>p</em> = 0.04). Finally, visceral and bone failures were associated with distinct gene-expression profiles.</div></div><div><h3>Conclusions and clinical implications</h3><div>Tumor genomics provides novel insight into MOP and POF following treatment for metachronous omCSPC. Patients with <em>TP53</em> and <em>RB1</em> mutations have a higher likelihood","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 1","pages":"Pages 111-118"},"PeriodicalIF":8.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.euo.2024.05.009
Neal D. Shore , Michael S. Broder , Pedro C. Barata , Tony Crispino , André P. Fay , Jennifer Lloyd , Begoña Mellado , Nobuaki Matsubara , Nicklas Pfanzelter , Katrin Schlack , Paul Sieber , Andrey Soares , Hannah Dalglish , Alexander Niyazov , Saif Shaman , Michael A. Zielinski , Jane Chang , Neeraj Agarwal
Background and objective
Recent clinical trials have shown improvement in progression-free survival in men with metastatic prostate cancer (mPC) treated with combination poly-ADP ribose polymerase (PARP) inhibitors (PARPi) and novel hormonal therapy (NHT). Regulatory bodies in the USA, Canada, Europe, and Japan have recently approved this combination therapy for mPC. Common adverse events (AEs) include fatigue, nausea and vomiting, and anemia. Nuanced AE management guidance for these combinations is lacking. The panel objective was to develop expert consensus on AE management in patients with mPC treated with the combination PARPi + NHT.
Methods
The RAND/University of California Los Angeles modified Delphi Panel method was used. AEs were defined using the Common Terminology Criteria for Adverse Events. Twelve experts (seven medical oncologists, one advanced practice registered nurse, three urologists, and one patient advocate) reviewed the relevant literature; independently rated initial AE management options for the agent suspected of causing the AE for 419 patient scenarios on a 1–9 scale; discussed areas of agreement (AoAs) and disagreement (AoDs) at a March 2023 meeting; and repeated these ratings following the meeting. Second-round ratings formed the basis of guidelines.
Key findings and limitations
AoDs decreased from 41% to 21% between the first and second round ratings, with agreement on at least one management strategy for every AE. AoAs included the following: (1) continue therapy with symptomatic treatment for patients with mild AEs; (2) for moderate fatigue, recommend nonpharmacologic treatment, hold treatment temporarily, and restart at a reduced dose when symptoms resolve; (3) for severe nausea or any degree of vomiting where symptomatic treatment fails, hold treatment temporarily and restart at a reduced dose when symptoms resolve; and (4) for hemoglobin 7.1–8.0 g/dl and symptoms of anemia, hold treatment temporarily and restart at a reduced dose after red blood cell transfusion.
Conclusions and clinical implications
This expert guidance can support management of AEs in patients with mPC receiving combination PARPi + NHT therapy.
Patient summary
A panel of experts developed guidelines for adverse event (AE) management in patients with metastatic prostate cancer treated with a combination of poly-ADP ribose polymerase inhibitors and novel hormonal therapy. For mild AEs, continuation of cancer therapy along with symptomatic treatment is recommended. For moderate or severe AEs, cancer therapy should be stopped temporarily and restarted at the same or a reduced dose when AE resolves.
{"title":"Expert Consensus Recommendations on the Management of Treatment-emergent Adverse Events Among Men with Prostate Cancer Taking Poly-ADP Ribose Polymerase Inhibitor + Novel Hormonal Therapy Combination Therapy","authors":"Neal D. Shore , Michael S. Broder , Pedro C. Barata , Tony Crispino , André P. Fay , Jennifer Lloyd , Begoña Mellado , Nobuaki Matsubara , Nicklas Pfanzelter , Katrin Schlack , Paul Sieber , Andrey Soares , Hannah Dalglish , Alexander Niyazov , Saif Shaman , Michael A. Zielinski , Jane Chang , Neeraj Agarwal","doi":"10.1016/j.euo.2024.05.009","DOIUrl":"10.1016/j.euo.2024.05.009","url":null,"abstract":"<div><h3>Background and objective</h3><div>Recent clinical trials have shown improvement in progression-free survival in men with metastatic prostate cancer (mPC) treated with combination poly-ADP ribose polymerase (PARP) inhibitors (PARPi) and novel hormonal therapy (NHT). Regulatory bodies in the USA, Canada, Europe, and Japan have recently approved this combination therapy for mPC. Common adverse events (AEs) include fatigue, nausea and vomiting, and anemia. Nuanced AE management guidance for these combinations is lacking. The panel objective was to develop expert consensus on AE management in patients with mPC treated with the combination PARPi + NHT.</div></div><div><h3>Methods</h3><div>The RAND/University of California Los Angeles modified Delphi Panel method was used. AEs were defined using the Common Terminology Criteria for Adverse Events. Twelve experts (seven medical oncologists, one advanced practice registered nurse, three urologists, and one patient advocate) reviewed the relevant literature; independently rated initial AE management options for the agent suspected of causing the AE for 419 patient scenarios on a 1–9 scale; discussed areas of agreement (AoAs) and disagreement (AoDs) at a March 2023 meeting; and repeated these ratings following the meeting. Second-round ratings formed the basis of guidelines.</div></div><div><h3>Key findings and limitations</h3><div>AoDs decreased from 41% to 21% between the first and second round ratings, with agreement on at least one management strategy for every AE. AoAs included the following: (1) continue therapy with symptomatic treatment for patients with mild AEs; (2) for moderate fatigue, recommend nonpharmacologic treatment, hold treatment temporarily, and restart at a reduced dose when symptoms resolve; (3) for severe nausea or any degree of vomiting where symptomatic treatment fails, hold treatment temporarily and restart at a reduced dose when symptoms resolve; and (4) for hemoglobin 7.1–8.0 g/dl and symptoms of anemia, hold treatment temporarily and restart at a reduced dose after red blood cell transfusion.</div></div><div><h3>Conclusions and clinical implications</h3><div>This expert guidance can support management of AEs in patients with mPC receiving combination PARPi + NHT therapy.</div></div><div><h3>Patient summary</h3><div>A panel of experts developed guidelines for adverse event (AE) management in patients with metastatic prostate cancer treated with a combination of poly-ADP ribose polymerase inhibitors and novel hormonal therapy. For mild AEs, continuation of cancer therapy along with symptomatic treatment is recommended. For moderate or severe AEs, cancer therapy should be stopped temporarily and restarted at the same or a reduced dose when AE resolves.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 1","pages":"Pages 94-104"},"PeriodicalIF":8.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.euo.2024.08.006
Maria Ruiz-Vico , Daniel Wetterskog , Francesco Orlando , Suparna Thakali , Anna Wingate , Anuradha Jayaram , Paolo Cremaschi , Osvaldas Vainauskas , Nicole Brighi , Daniel Castellano-Gauna , Lennart Åström , Vsevolod B. Matveev , Sergio Bracarda , Adil Esen , Susan Feyerabend , Elżbieta Senkus , Marta López-Brea Piqueras , Santosh Gupta , Rick Wenstrup , Gunther Boysen , Gerhardt Attard
<div><h3>Background and objective</h3><div>The PRESIDE (NCT02288247) randomized trial demonstrated prolonged progression-free survival (PFS) with continuing enzalutamide beyond progression in metastatic castration-resistant prostate cancer (mCRPC) patients starting docetaxel. This study aims to test the associations of PFS and circulating tumor DNA (ctDNA) prior to and after one cycle (cycle 2 day 1 [C2D1]) of docetaxel and with a liquid biopsy resistance biomarker (LBRB; plasma androgen receptor [<em>AR</em>] gain and/or circulating tumor cells [CTCs] expressing AR splice variant 7 [CTC-AR-V7]) prior to continuation of enzalutamide/placebo.</div></div><div><h3>Methods</h3><div>Patients consenting to the biomarker substudy and donating blood before starting docetaxel with enzalutamide/placebo (<em>N</em> = 157) were included. Sequential plasma DNA samples were characterized with a prostate-cancer bespoke next-generation-sequencing capture panel (PCF_SELECT), and CTCs were assessed for AR-V7 (Epic Sciences, San Diego, CA, USA). Cox models, Kaplan-Meier, and restricted mean survival time (RMST) at 18 mo were calculated.</div></div><div><h3>Key findings and limitations</h3><div>There was a significant association of worse PFS with pre-docetaxel ctDNA detection (<em>N</em> = 86 (55%), 8.1 vs 10.8 mo hazard ratio [HR] = 1.78, <em>p</em> = 0.004) or persistence/rise of ctDNA at C2D1 (<em>N</em> = 35/134, 5.5 vs 10.9 mo, HR = 1.95, 95% confidence interval [CI] = 1.15–3.30, <em>p</em> = 0.019). LBRB-positive patients (<em>N</em> = 62) had no benefit from continuing enzalutamide with docetaxel (HR = 0.78, 95% CI = 0.41–1.48, <em>p</em> = 0.44; RMST: 7.9 vs 7.1 mo, <em>p</em> = 0.50). Conversely, resistance biomarker–negative patients (<em>N</em> = 87) had significantly prolonged PFS (HR = 0.49, 95% CI = 0.29–0.82, <em>p</em> = 0.006; RMST: 11.5 vs 8.9 mo, <em>p</em> = 0.005). Eight patients were unevaluable. An exploratory analysis identified increased copy-number gains (<em>CDK6</em>/<em>CDK4</em>) at progression on docetaxel. Limitations included relatively low detection of CTC-AR-V7. Validation of impact on overall survival is required.</div></div><div><h3>Conclusions and clinical implications</h3><div>Liquid biopsy gives an early indication of docetaxel futility, could guide patient selection for continuing enzalutamide, and identifies cell cycle gene alterations as a potential cause of docetaxel resistance in mCRPC.</div></div><div><h3>Patient summary</h3><div>In the PRESIDE biomarker study, we found that detecting circulating tumor DNA in plasma after starting treatment with docetaxel (chemotherapy) for metastatic prostate cancer resistant to androgen deprivation therapy can predict early how long patients will take to respond to treatment. Patients negative for a liquid biopsy resistance biomarker (based on the status of androgen receptor (<em>AR</em>) gene and AR splice variant 7 in circulating tumor cells) benefit from continuing enzalutamide in
背景和目的：PRESIDE（NCT02288247）随机试验证明，对于开始接受多西他赛治疗的转移性耐药前列腺癌（mCRPC）患者，在病情进展后继续服用恩杂鲁胺可延长无进展生存期（PFS）。本研究旨在检验多西他赛一个周期（第2周期第1天[C2D1]）之前和之后的PFS与循环肿瘤DNA（ctDNA）的关系，以及在继续服用恩杂鲁胺/安慰剂之前与液体活检抗性生物标记物（LBRB；血浆雄激素受体[AR]增量和/或表达AR剪接变体7[CTC-AR-V7]的循环肿瘤细胞[CTC]）的关系：纳入同意生物标志物子研究并在开始多西他赛与恩杂鲁胺/安慰剂治疗前献血的患者（N = 157）。使用前列腺癌定制的新一代测序捕获面板（PCF_SELECT）对连续血浆 DNA 样品进行定性，并对 CTC 进行 AR-V7 评估（Epic Sciences，San Diego，CA，USA）。计算了Cox模型、Kaplan-Meier和18个月时的限制性平均生存时间（RMST）：多西他赛前检测到ctDNA（86例（55%），8.1个月 vs 10.8个月，危险比[HR] = 1.78，P = 0.004）或C2D1时ctDNA持续/上升（35/134例，5.5个月 vs 10.9个月，HR = 1.95，95%置信区间[CI] = 1.15-3.30，P = 0.019）会导致PFS恶化。LBRB阳性患者（N = 62）继续服用恩杂鲁胺与多西他赛无益（HR = 0.78，95% CI = 0.41-1.48，p = 0.44；RMST：7.9 月 vs 7.1 月，p = 0.50）。相反，耐药性生物标志物阴性患者（N = 87）的 PFS 明显延长（HR = 0.49，95% CI = 0.29-0.82，p = 0.006；RMST：11.5 月 vs 8.9 月，p = 0.005）。有八名患者无法进行评估。一项探索性分析发现，多西他赛治疗进展期拷贝数增殖（CDK6/CDK4）增加。局限性包括CTC-AR-V7的检出率相对较低。结论和临床意义：患者总结：在PRESIDE生物标志物研究中，我们发现在开始使用多西他赛（化疗）治疗对雄激素剥夺疗法耐药的转移性前列腺癌后，检测血浆中的循环肿瘤DNA可以及早预测患者对治疗的反应时间。液体活检耐药性生物标志物（基于循环肿瘤细胞中雄激素受体（AR）基因和AR剪接变体7的状态）阴性的患者可从继续恩杂鲁胺联合多西他赛中获益，而耐药性生物标志物阳性的患者则不能获益。此外，我们还发现细胞周期基因CDK6和CDK4的改变是导致多西他赛耐药的潜在遗传学原因，这可能有助于测试针对这些改变的特定药物。
{"title":"Liquid Biopsy in Progressing Prostate Cancer Patients Starting Docetaxel with or Without Enzalutamide: A Biomarker Study of the PRESIDE Phase 3b Trial","authors":"Maria Ruiz-Vico , Daniel Wetterskog , Francesco Orlando , Suparna Thakali , Anna Wingate , Anuradha Jayaram , Paolo Cremaschi , Osvaldas Vainauskas , Nicole Brighi , Daniel Castellano-Gauna , Lennart Åström , Vsevolod B. Matveev , Sergio Bracarda , Adil Esen , Susan Feyerabend , Elżbieta Senkus , Marta López-Brea Piqueras , Santosh Gupta , Rick Wenstrup , Gunther Boysen , Gerhardt Attard","doi":"10.1016/j.euo.2024.08.006","DOIUrl":"10.1016/j.euo.2024.08.006","url":null,"abstract":"<div><h3>Background and objective</h3><div>The PRESIDE (NCT02288247) randomized trial demonstrated prolonged progression-free survival (PFS) with continuing enzalutamide beyond progression in metastatic castration-resistant prostate cancer (mCRPC) patients starting docetaxel. This study aims to test the associations of PFS and circulating tumor DNA (ctDNA) prior to and after one cycle (cycle 2 day 1 [C2D1]) of docetaxel and with a liquid biopsy resistance biomarker (LBRB; plasma androgen receptor [<em>AR</em>] gain and/or circulating tumor cells [CTCs] expressing AR splice variant 7 [CTC-AR-V7]) prior to continuation of enzalutamide/placebo.</div></div><div><h3>Methods</h3><div>Patients consenting to the biomarker substudy and donating blood before starting docetaxel with enzalutamide/placebo (<em>N</em> = 157) were included. Sequential plasma DNA samples were characterized with a prostate-cancer bespoke next-generation-sequencing capture panel (PCF_SELECT), and CTCs were assessed for AR-V7 (Epic Sciences, San Diego, CA, USA). Cox models, Kaplan-Meier, and restricted mean survival time (RMST) at 18 mo were calculated.</div></div><div><h3>Key findings and limitations</h3><div>There was a significant association of worse PFS with pre-docetaxel ctDNA detection (<em>N</em> = 86 (55%), 8.1 vs 10.8 mo hazard ratio [HR] = 1.78, <em>p</em> = 0.004) or persistence/rise of ctDNA at C2D1 (<em>N</em> = 35/134, 5.5 vs 10.9 mo, HR = 1.95, 95% confidence interval [CI] = 1.15–3.30, <em>p</em> = 0.019). LBRB-positive patients (<em>N</em> = 62) had no benefit from continuing enzalutamide with docetaxel (HR = 0.78, 95% CI = 0.41–1.48, <em>p</em> = 0.44; RMST: 7.9 vs 7.1 mo, <em>p</em> = 0.50). Conversely, resistance biomarker–negative patients (<em>N</em> = 87) had significantly prolonged PFS (HR = 0.49, 95% CI = 0.29–0.82, <em>p</em> = 0.006; RMST: 11.5 vs 8.9 mo, <em>p</em> = 0.005). Eight patients were unevaluable. An exploratory analysis identified increased copy-number gains (<em>CDK6</em>/<em>CDK4</em>) at progression on docetaxel. Limitations included relatively low detection of CTC-AR-V7. Validation of impact on overall survival is required.</div></div><div><h3>Conclusions and clinical implications</h3><div>Liquid biopsy gives an early indication of docetaxel futility, could guide patient selection for continuing enzalutamide, and identifies cell cycle gene alterations as a potential cause of docetaxel resistance in mCRPC.</div></div><div><h3>Patient summary</h3><div>In the PRESIDE biomarker study, we found that detecting circulating tumor DNA in plasma after starting treatment with docetaxel (chemotherapy) for metastatic prostate cancer resistant to androgen deprivation therapy can predict early how long patients will take to respond to treatment. Patients negative for a liquid biopsy resistance biomarker (based on the status of androgen receptor (<em>AR</em>) gene and AR splice variant 7 in circulating tumor cells) benefit from continuing enzalutamide in ","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 1","pages":"Pages 135-144"},"PeriodicalIF":8.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.euo.2024.09.001
Alessio Pecoraro , Giuseppe Dario Testa , Laura Marandino , Laurence Albiges , Axel Bex , Umberto Capitanio , Ilaria Cappiello , Lorenzo Masieri , Carme Mir , Morgan Roupret , Sergio Serni , Andrea Ungar , Giulia Rivasi , Riccardo Campi
Context
Frailty, a geriatric syndrome characterized by decreased resilience and physiological reserve, impacts the prognosis and management of older adults significantly, particularly in the context of surgical and oncological care.
Objective
To provide an overview of frailty assessment in the management of older patients with a renal mass/renal cell carcinoma (RCC), focusing on its implications for diagnostic workup, treatment decisions, and clinical outcomes.
Evidence acquisition
A narrative review of the literature was conducted, focusing on frailty definitions, assessment tools, and their application in geriatric oncology, applied to the field of RCC. Relevant studies addressing the prognostic value of frailty, its impact on treatment outcomes, and potential interventions were summarized.
Evidence synthesis
Frailty is a poor prognostic factor and can influence decision-making in the management of both localized and metastatic RCC. Screening tools such as the Geriatric Screening Tool 8 (G8) and the Mini-COG test can aid clinicians to select older patients (ie, aged ≥65 yr) for a further comprehensive geriatric assessment (CGA) performed by dedicated geriatricians. The CGA provides insights to risk stratify patients and guide subsequent treatment pathways. As such, the involvement of geriatricians in multidisciplinary tumor boards emerges as an essential priority to address the complex needs of frail patients and optimize clinical outcomes. Herein, we propose a dedicated care pathway as a first key step to implement frailty assessment in clinical practice and research for RCC.
Conclusions
Frailty has emerged as a crucial factor influencing the management and outcomes of older patients with RCC. Involvement of geriatricians in diagnostic and therapeutic pathways represents a pragmatic approach to screen and assess frailty, fostering individualized treatment decisions according to holistic patient risk stratification.
Patient summary
Frailty, a decline in resilience and physiological reserve, influences treatment decisions and outcomes in elderly patients with renal cell carcinoma, guiding personalized care. In this review, we focused on pragmatic strategies to screen patients with a renal mass suspected for renal cell carcinoma, who are older than 65 yr, for frailty and on personalized management algorithms integrating geriatric input beyond patient- and tumor-related factors.
{"title":"Frailty and Renal Cell Carcinoma: Integration of Comprehensive Geriatric Assessment into Shared Decision-making","authors":"Alessio Pecoraro , Giuseppe Dario Testa , Laura Marandino , Laurence Albiges , Axel Bex , Umberto Capitanio , Ilaria Cappiello , Lorenzo Masieri , Carme Mir , Morgan Roupret , Sergio Serni , Andrea Ungar , Giulia Rivasi , Riccardo Campi","doi":"10.1016/j.euo.2024.09.001","DOIUrl":"10.1016/j.euo.2024.09.001","url":null,"abstract":"<div><h3>Context</h3><div>Frailty, a geriatric syndrome characterized by decreased resilience and physiological reserve, impacts the prognosis and management of older adults significantly, particularly in the context of surgical and oncological care.</div></div><div><h3>Objective</h3><div>To provide an overview of frailty assessment in the management of older patients with a renal mass/renal cell carcinoma (RCC), focusing on its implications for diagnostic workup, treatment decisions, and clinical outcomes.</div></div><div><h3>Evidence acquisition</h3><div>A narrative review of the literature was conducted, focusing on frailty definitions, assessment tools, and their application in geriatric oncology, applied to the field of RCC. Relevant studies addressing the prognostic value of frailty, its impact on treatment outcomes, and potential interventions were summarized.</div></div><div><h3>Evidence synthesis</h3><div>Frailty is a poor prognostic factor and can influence decision-making in the management of both localized and metastatic RCC. Screening tools such as the Geriatric Screening Tool 8 (G8) and the Mini-COG test can aid clinicians to select older patients (ie, aged ≥65 yr) for a further comprehensive geriatric assessment (CGA) performed by dedicated geriatricians. The CGA provides insights to risk stratify patients and guide subsequent treatment pathways. As such, the involvement of geriatricians in multidisciplinary tumor boards emerges as an essential priority to address the complex needs of frail patients and optimize clinical outcomes. Herein, we propose a dedicated care pathway as a first key step to implement frailty assessment in clinical practice and research for RCC.</div></div><div><h3>Conclusions</h3><div>Frailty has emerged as a crucial factor influencing the management and outcomes of older patients with RCC. Involvement of geriatricians in diagnostic and therapeutic pathways represents a pragmatic approach to screen and assess frailty, fostering individualized treatment decisions according to holistic patient risk stratification.</div></div><div><h3>Patient summary</h3><div>Frailty, a decline in resilience and physiological reserve, influences treatment decisions and outcomes in elderly patients with renal cell carcinoma, guiding personalized care. In this review, we focused on pragmatic strategies to screen patients with a renal mass suspected for renal cell carcinoma, who are older than 65 yr, for frailty and on personalized management algorithms integrating geriatric input beyond patient- and tumor-related factors.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 1","pages":"Pages 190-200"},"PeriodicalIF":8.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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