Active surveillance (AS) is a widely accepted strategy for low-risk prostate cancer, but its application to intermediate-risk disease remains controversial. Given the potential to reduce overtreatment without compromising survival, this review evaluates the safety and clinical outcomes of AS in intermediate-risk prostate cancer (IR-PCa), with a focus on favorable intermediate-risk (FIR) subsets. The objective is to synthesize current evidence on AS utilization, selection criteria, oncologic outcomes, and predictors of disease progression.We conducted a narrative review of 85 studies published between 2009 and 2025 identified through PubMed, Embase, and Web of Science. Search terms included “AS,” “intermediate-risk prostate cancer,” “Gleason 3 + 4,” and “watchful waiting.” Eligible studies included prospective and retrospective cohorts, registry-based analyses, and comparative observational studies evaluating AS in IR-PCa. Data were extracted regarding inclusion criteria, follow-up protocols, progression rates, survival outcomes, and use of imaging and genomic tools for risk stratification. AS is increasingly used in FIR patients with low-volume Gleason 3 + 4 disease, low PSA density, and favorable imaging/genomic profiles. In these patients, 5-10 year metastasis-free survival exceeds 95%. However, AS in unfavorable IR disease is associated with higher risks of disease progression and prostate cancer–specific mortality. Limitations include heterogeneity in AS protocols, lack of randomized trials, and variable definitions of FIR. AS is a viable option for well-selected FIR-PCa patients. Incorporating PSA density, mpMRI, and genomic testing enhances risk stratification. Clinical guidelines should support tailored AS approaches with standardized follow-up and timely intervention triggers.
主动监测(AS)是一种被广泛接受的低危前列腺癌治疗策略,但其在中危前列腺癌中的应用仍存在争议。鉴于在不影响生存的情况下减少过度治疗的潜力,本综述评估了AS治疗中危前列腺癌(IR-PCa)的安全性和临床结果,重点关注有利的中危(FIR)亚群。目的是综合目前关于AS使用、选择标准、肿瘤预后和疾病进展预测因素的证据。我们通过PubMed、Embase和Web of Science对2009年至2025年间发表的85项研究进行了叙述性回顾。搜索词包括“AS”、“中等风险前列腺癌”、“Gleason 3 + 4”和“观察等待”。符合条件的研究包括前瞻性和回顾性队列,基于登记的分析,以及评估IR-PCa中AS的比较观察性研究。提取有关纳入标准、随访方案、进展率、生存结果以及使用成像和基因组工具进行风险分层的数据。AS越来越多地用于低体积Gleason 3 + 4疾病、低PSA密度和有利的影像学/基因组谱的FIR患者。在这些患者中,5-10年无转移生存率超过95%。然而,不利IR疾病的AS与疾病进展和前列腺癌特异性死亡率的高风险相关。局限性包括AS协议的异质性、缺乏随机试验和FIR的可变定义。对于精心挑选的FIR-PCa患者,AS是一种可行的选择。结合PSA密度,mpMRI和基因组检测增强了风险分层。临床指南应支持量身定制的AS方法,采用标准化的随访和及时的干预触发器。
{"title":"Active Surveillance in Intermediate-Risk Prostate Cancer: A Contemporary Synthesis of Evidence","authors":"Fausto Petrelli , Lorenzo Dottorini , Giada Parsani , Francesca Ceresoli , Domenico Taglialatela , Margherita Pampado , Alessandro Serino , Agostina De Stefani , Francesca Trevisan , Valentina Riboldi , Lorenza Bruschieri , Ivano Vavassori","doi":"10.1016/j.clgc.2025.102407","DOIUrl":"10.1016/j.clgc.2025.102407","url":null,"abstract":"<div><div>Active surveillance (AS) is a widely accepted strategy for low-risk prostate cancer, but its application to intermediate-risk disease remains controversial. Given the potential to reduce overtreatment without compromising survival, this review evaluates the safety and clinical outcomes of AS in intermediate-risk prostate cancer (IR-PCa), with a focus on favorable intermediate-risk (FIR) subsets. The objective is to synthesize current evidence on AS utilization, selection criteria, oncologic outcomes, and predictors of disease progression.We conducted a narrative review of 85 studies published between 2009 and 2025 identified through PubMed, Embase, and Web of Science. Search terms included “AS,” “intermediate-risk prostate cancer,” “Gleason 3 + 4,” and “watchful waiting.” Eligible studies included prospective and retrospective cohorts, registry-based analyses, and comparative observational studies evaluating AS in IR-PCa. Data were extracted regarding inclusion criteria, follow-up protocols, progression rates, survival outcomes, and use of imaging and genomic tools for risk stratification. AS is increasingly used in FIR patients with low-volume Gleason 3 + 4 disease, low PSA density, and favorable imaging/genomic profiles. In these patients, 5-10 year metastasis-free survival exceeds 95%. However, AS in unfavorable IR disease is associated with higher risks of disease progression and prostate cancer–specific mortality. Limitations include heterogeneity in AS protocols, lack of randomized trials, and variable definitions of FIR. AS is a viable option for well-selected FIR-PCa patients. Incorporating PSA density, mpMRI, and genomic testing enhances risk stratification. Clinical guidelines should support tailored AS approaches with standardized follow-up and timely intervention triggers.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 5","pages":"Article 102407"},"PeriodicalIF":2.7,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144890035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-05DOI: 10.1016/j.clgc.2025.102412
Giacomo Musso , Giuseppe Garofano , Mai Dabbas , Margaret F. Meagher , Kit L. Yuen , Natalie Birouty , Benjamin Baker , Cesare Saitta , Melis Guer , Francesco Montorsi , Alberto Briganti , Umberto Capitanio , Alessandro Larcher , Andrea Salonia , Ithaar H. Derweesh
Introduction
Lymphovascular invasion (LVI) is a recognized adverse pathological feature in renal cell carcinoma (RCC). However, its impact on staging and prognosis remains poorly defined, especially across T-stage subcategories.
Patients and Methods
We analyzed surgically treated RCC patients from the National Cancer Database (NCDB), including clear cell, papillary and chromophobe RCCs. Data on pathological T-stage and LVI status were retrieved, with overall survival (OS) as the primary outcome. Kaplan-Meier curves (KMA) and log-rank test evaluated survival differences between T-stages with and without LVI. Univariable and multivariable Cox Proportional Hazard Model (CoxPH) were fitted to test the association between LVI and All-cause Mortality (ACM) and the interaction term between LVI and T-stage. Forest plots and regression lines from the CoxPH interaction hazard ratios (HR) illustrated the impact of LVI across T-stages.
Results
Among 159,387 RCC patients, 11.3% showed LVI. LVI was associated with larger and higher‐grade tumors, and increased rates of nodal and metastatic disease (P < .001). KMA showed significantly lower 5‐year OS among LVI‐positive versus LVI‐negative patients (61% vs. 85%; P < .001). Across T stages, LVI conferred a “functional upstaging” with survival of T1a+LVI approximating T1b, T1b+LVI resembling T2, T2+LVI approximating T3, and T3a+LVI mirroring T3b outcomes. At univariable and multivariable CoxPH, LVI was an independent predictor of ACM (P < .001), with forest plots indicating its highest relative impact in earlier T-stages.
Conclusion
LVI is an aggressive pathological feature in RCC that impairs survival, especially in lower‐stage tumors. Incorporating LVI status into RCC staging may refine risk stratification and guide more intensive surveillance and adjuvant management, particularly for patients with early T-stage disease.
{"title":"The Influence of Lymphovascular Invasion on T Stage Upstaging and Overall Survival in Renal Cell Carcinoma: A Population-Based Study","authors":"Giacomo Musso , Giuseppe Garofano , Mai Dabbas , Margaret F. Meagher , Kit L. Yuen , Natalie Birouty , Benjamin Baker , Cesare Saitta , Melis Guer , Francesco Montorsi , Alberto Briganti , Umberto Capitanio , Alessandro Larcher , Andrea Salonia , Ithaar H. Derweesh","doi":"10.1016/j.clgc.2025.102412","DOIUrl":"10.1016/j.clgc.2025.102412","url":null,"abstract":"<div><h3>Introduction</h3><div>Lymphovascular invasion (LVI) is a recognized adverse pathological feature in renal cell carcinoma (RCC). However, its impact on staging and prognosis remains poorly defined, especially across T-stage subcategories.</div></div><div><h3>Patients and Methods</h3><div>We analyzed surgically treated RCC patients from the National Cancer Database (NCDB), including clear cell, papillary and chromophobe RCCs. Data on pathological T-stage and LVI status were retrieved, with overall survival (OS) as the primary outcome. Kaplan-Meier curves (KMA) and log-rank test evaluated survival differences between T-stages with and without LVI. Univariable and multivariable Cox Proportional Hazard Model (CoxPH) were fitted to test the association between LVI and All-cause Mortality (ACM) and the interaction term between LVI and T-stage. Forest plots and regression lines from the CoxPH interaction hazard ratios (HR) illustrated the impact of LVI across T-stages.</div></div><div><h3>Results</h3><div>Among 159,387 RCC patients, 11.3% showed LVI. LVI was associated with larger and higher‐grade tumors, and increased rates of nodal and metastatic disease (<em>P</em> < .001). KMA showed significantly lower 5‐year OS among LVI‐positive versus LVI‐negative patients (61% vs. 85%; <em>P</em> < .001). Across T stages, LVI conferred a “functional upstaging” with survival of T1a+LVI approximating T1b, T1b+LVI resembling T2, T2+LVI approximating T3, and T3a+LVI mirroring T3b outcomes. At univariable and multivariable CoxPH, LVI was an independent predictor of ACM (<em>P</em> < .001), with forest plots indicating its highest relative impact in earlier T-stages.</div></div><div><h3>Conclusion</h3><div>LVI is an aggressive pathological feature in RCC that impairs survival, especially in lower‐stage tumors. Incorporating LVI status into RCC staging may refine risk stratification and guide more intensive surveillance and adjuvant management, particularly for patients with early T-stage disease.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 5","pages":"Article 102412"},"PeriodicalIF":2.7,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-05DOI: 10.1016/j.clgc.2025.102410
Lorenzo Dottorini , Italo Sarno , Alessandro Iaculli , Giandomenico Di Menna , Yasser Hussein , Ivano Vavassori , Mauro Rossitto , Andrea Luciani , Fausto Petrelli
To assess the comparative efficacy of intensified systemic treatments in older patients (≥ 65 years) with metastatic hormone-sensitive prostate cancer (mHSPC) through a network meta-analysis (NMA), and evaluate whether routine use of intensified regimens is justified in this population. A systematic literature search of MEDLINE, Embase, and Cochrane Library databases identified randomized controlled trials published between 2000 and 2024 evaluating first-line systemic therapies in mHSPC. Eligible studies combined androgen deprivation therapy (ADT) with docetaxel, abiraterone, enzalutamide, apalutamide, darolutamide, or antiandrogens. The primary endpoint was overall survival (OS). Bayesian NMA was conducted using a consistency model and Markov chain Monte Carlo simulations. SUCRA values were used to estimate treatment rankings. Subgroup data for older patients were extracted where available. Eleven were included in the analysis. Compared to ADT alone, none of the intensified regimens showed statistically significant superiority in OS in older subgroups. ADT + docetaxel + darolutamide had the highest probability of being the most effective treatment (SUCRA 87.8%), followed by ADT + abiraterone + enzalutamide (SUCRA 80.9%). In older patients with mHSPC, intensified systemic regimens demonstrate trends toward improved OS but fail to achieve clear statistical superiority over ADT alone. The substantial heterogeneity across studies and absence of older-specific subgroup data limit definitive conclusions. Treatment decisions in this population should be individualized using geriatric assessment, considering patient fitness, comorbidities, life expectancy, and treatment goals. Further dedicated trials in older and frail patients are warranted to guide optimal therapeutic strategies.
{"title":"Reassessing the Evidence: Is Intensified Therapy Justified in Older Patients with Metastatic Hormone-Sensitive Prostate Cancer?","authors":"Lorenzo Dottorini , Italo Sarno , Alessandro Iaculli , Giandomenico Di Menna , Yasser Hussein , Ivano Vavassori , Mauro Rossitto , Andrea Luciani , Fausto Petrelli","doi":"10.1016/j.clgc.2025.102410","DOIUrl":"10.1016/j.clgc.2025.102410","url":null,"abstract":"<div><div>To assess the comparative efficacy of intensified systemic treatments in older patients (≥ 65 years) with metastatic hormone-sensitive prostate cancer (mHSPC) through a network meta-analysis (NMA), and evaluate whether routine use of intensified regimens is justified in this population. A systematic literature search of MEDLINE, Embase, and Cochrane Library databases identified randomized controlled trials published between 2000 and 2024 evaluating first-line systemic therapies in mHSPC. Eligible studies combined androgen deprivation therapy (ADT) with docetaxel, abiraterone, enzalutamide, apalutamide, darolutamide, or antiandrogens. The primary endpoint was overall survival (OS). Bayesian NMA was conducted using a consistency model and Markov chain Monte Carlo simulations. SUCRA values were used to estimate treatment rankings. Subgroup data for older patients were extracted where available. Eleven were included in the analysis. Compared to ADT alone, none of the intensified regimens showed statistically significant superiority in OS in older subgroups. ADT + docetaxel + darolutamide had the highest probability of being the most effective treatment (SUCRA 87.8%), followed by ADT + abiraterone + enzalutamide (SUCRA 80.9%). In older patients with mHSPC, intensified systemic regimens demonstrate trends toward improved OS but fail to achieve clear statistical superiority over ADT alone. The substantial heterogeneity across studies and absence of older-specific subgroup data limit definitive conclusions. Treatment decisions in this population should be individualized using geriatric assessment, considering patient fitness, comorbidities, life expectancy, and treatment goals. Further dedicated trials in older and frail patients are warranted to guide optimal therapeutic strategies.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 5","pages":"Article 102410"},"PeriodicalIF":2.7,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144908294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-05DOI: 10.1016/j.clgc.2025.102401
Aditi Chaurasia , Shiva Singh , Noah Pinson , Nikhil Gopal , Jessica Hsueh , Daniel Nethala , Rabindra Gautam , Christopher J. Ricketts , Cathy D. Vocke , Laura S. Schmidt , Maria J. Merino , Ashkan A. Malayeri , W. Marston Linehan , Mark W. Ball
Objectives
To investigate the clinical characteristics, tumor growth rate, oncologic and renal function outcomes in patients with bilateral, multifocal renal oncocytoma managed with active surveillance and/or surgery.
Materials and Methods
Bilateral, multifocal renal oncocytoma patients were evaluated using clinical, cross-sectional imaging and pathologic records. The cohort was divided into 3 groups: those under active surveillance only, those who underwent surgery in combination with active surveillance, and those who underwent multiple interventions. Growth rate, metastases and renal function outcomes were compared between the 3 groups.
Results
Sixty-two patients (median age 64 years (IQR 57.5-69), 49 men) were identified with 10 patients (16.1%) having a known family history of bilateral, multifocal oncocytoma. Overall, the combined median growth rate of primary tumors across all 3 groups was 0.25 cm/year (IQR 0.1-0.4). Comparing between all 3 groups identified a statistically significant difference in age of diagnosis (P = .01), whereas no difference was noted for age at death. No distant metastasis was observed. A statistically significant difference in median tumor size at the time of last follow-up (P = .02) was reported among the 3 groups. No statistically significant differences were seen in primary tumor growth rate (P = .50), initial eGFR (P = .35), final eGFR (P = .26) and change in eGFR levels over time (P = .10) among all 3 groups.
Conclusion
Disease-specific outcomes and renal function outcomes do not differ significantly among the patients managed with active surveillance and/or surgery.
{"title":"Is Active Surveillance a Suitable Approach for Bilateral Multifocal Renal Oncocytomas? The 20-Year National Cancer Institute Experience","authors":"Aditi Chaurasia , Shiva Singh , Noah Pinson , Nikhil Gopal , Jessica Hsueh , Daniel Nethala , Rabindra Gautam , Christopher J. Ricketts , Cathy D. Vocke , Laura S. Schmidt , Maria J. Merino , Ashkan A. Malayeri , W. Marston Linehan , Mark W. Ball","doi":"10.1016/j.clgc.2025.102401","DOIUrl":"10.1016/j.clgc.2025.102401","url":null,"abstract":"<div><h3>Objectives</h3><div>To investigate the clinical characteristics, tumor growth rate, oncologic and renal function outcomes in patients with bilateral, multifocal renal oncocytoma managed with active surveillance and/or surgery.</div></div><div><h3>Materials and Methods</h3><div>Bilateral, multifocal renal oncocytoma patients were evaluated using clinical, cross-sectional imaging and pathologic records. The cohort was divided into 3 groups: those under active surveillance only, those who underwent surgery in combination with active surveillance, and those who underwent multiple interventions. Growth rate, metastases and renal function outcomes were compared between the 3 groups.</div></div><div><h3>Results</h3><div>Sixty-two patients (median age 64 years (IQR 57.5-69), 49 men) were identified with 10 patients (16.1%) having a known family history of bilateral, multifocal oncocytoma. Overall, the combined median growth rate of primary tumors across all 3 groups was 0.25 cm/year (IQR 0.1-0.4). Comparing between all 3 groups identified a statistically significant difference in age of diagnosis (<em>P</em> = .01), whereas no difference was noted for age at death. No distant metastasis was observed. A statistically significant difference in median tumor size at the time of last follow-up (<em>P</em> = .02) was reported among the 3 groups. No statistically significant differences were seen in primary tumor growth rate (<em>P</em> = .50), initial eGFR (<em>P</em> = .35), final eGFR (<em>P</em> = .26) and change in eGFR levels over time (<em>P</em> = .10) among all 3 groups.</div></div><div><h3>Conclusion</h3><div>Disease-specific outcomes and renal function outcomes do not differ significantly among the patients managed with active surveillance and/or surgery.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 5","pages":"Article 102401"},"PeriodicalIF":2.7,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-05DOI: 10.1016/j.clgc.2025.102411
George Dimitrov , Elenko Popov
Objective
This retrospective study evaluates the clinical significance of mutations in effector genes (BRCA1, BRCA2, PALB2, RAD51, FANCD2) versus sensor genes (ATM, ATR, CHEK1, CHEK2, NBS1) in patients with metastatic castration-resistant prostate cancer (mCRPC) classified as homologous recombination deficiency (HRD)-positive. The study assesses their predictive value for response to poly(ADP-ribose) polymerase inhibitors (PARPi) combined with androgen receptor signaling inhibitors (ARSi).
Design
A multicenter, retrospective real-world study conducted across 6 oncology hospitals in Bulgaria. Patient data were obtained through a formal request to the Ministry of Health’s United Information Portal, an electronic health records repository. The analysis included mCRPC patients treated with olaparib plus abiraterone who underwent next-generation sequencing (NGS) between January 1, 2022, and January 1, 2025, conducted in a certified national reference laboratory, with a median follow-up of 16 months. The primary endpoints were overall survival (OS) and progression-free survival (PFS).
Results
Of the 210 mCRPC patients screened via NGS, 28% (n = 58) harbored mutations in at least one HRR gene, classified as sensor (n = 27) or effector (n = 31). Patients with effector mutations demonstrated a statistically significant improvement in PFS compared to those with sensor mutations (median PFS: 20 vs. 14 months, HR = 0.48, 95% CI: 0.252–0.914, P = .0294). Similarly, overall survival (OS) was significantly prolonged in the effector group. While the median OS for the sensor group was 19 months, the effector group had not yet reached median OS at the time of analysis (HR = 0.38, 95% CI, 0.154-0.945, P = .0373). Logistic regression analysis and PSM supported findings.
Conclusion
Patients with mCRPC harboring effector HRR mutations derive greater clinical benefit from PARPi plus ARSi than those with sensor mutations. These findings highlight the heterogeneous predictive value of HRR gene alterations and suggest that mutation sub-class should guide treatment decisions in HRD-positive mCRPC.
{"title":"Impact of HRR Gene Subclass on Clinical Outcomes of PARP Inhibitors in Metastatic Castration-Resistant Prostate Cancer","authors":"George Dimitrov , Elenko Popov","doi":"10.1016/j.clgc.2025.102411","DOIUrl":"10.1016/j.clgc.2025.102411","url":null,"abstract":"<div><h3>Objective</h3><div>This retrospective study evaluates the clinical significance of mutations in effector genes (<em>BRCA1, BRCA2, PALB2, RAD51, FANCD2</em>) versus sensor genes (<em>ATM, ATR, CHEK1, CHEK2, NBS1</em>) in patients with metastatic castration-resistant prostate cancer (mCRPC) classified as homologous recombination deficiency (HRD)-positive. The study assesses their predictive value for response to poly(ADP-ribose) polymerase inhibitors (PARPi) combined with androgen receptor signaling inhibitors (ARSi).</div></div><div><h3>Design</h3><div>A multicenter, retrospective real-world study conducted across 6 oncology hospitals in Bulgaria. Patient data were obtained through a formal request to the Ministry of Health’s United Information Portal, an electronic health records repository. The analysis included mCRPC patients treated with olaparib plus abiraterone who underwent next-generation sequencing (NGS) between January 1, 2022, and January 1, 2025, conducted in a certified national reference laboratory, with a median follow-up of 16 months. The primary endpoints were overall survival (OS) and progression-free survival (PFS).</div></div><div><h3>Results</h3><div>Of the 210 mCRPC patients screened via NGS, 28% (<em>n</em> = 58) harbored mutations in at least one HRR gene, classified as sensor (<em>n</em> = 27) or effector (<em>n</em> = 31). Patients with effector mutations demonstrated a statistically significant improvement in PFS compared to those with sensor mutations (median PFS: 20 vs. 14 months, HR = 0.48, 95% CI: 0.252–0.914, <em>P</em> = .0294). Similarly, overall survival (OS) was significantly prolonged in the effector group. While the median OS for the sensor group was 19 months, the effector group had not yet reached median OS at the time of analysis (HR = 0.38, 95% CI, 0.154-0.945, <em>P</em> = .0373). Logistic regression analysis and PSM supported findings.</div></div><div><h3>Conclusion</h3><div>Patients with mCRPC harboring effector HRR mutations derive greater clinical benefit from PARPi plus ARSi than those with sensor mutations. These findings highlight the heterogeneous predictive value of HRR gene alterations and suggest that mutation sub-class should guide treatment decisions in HRD-positive mCRPC.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 5","pages":"Article 102411"},"PeriodicalIF":2.7,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-05DOI: 10.1016/j.clgc.2025.102413
Andrea Piccolini , Stephan M. Korn , Zhiyu Qian , Pietro Brin , Klara Pohl , Hanna Zurl , Boyuan Xiao , Giovanni Lughezzani , Nicolò M. Buffi , Paul L. Nguyen , Mutlay Sayan , Quoc-Dien Trinh , Alexander P. Cole
Introduction
Lymph node involvement after radical prostatectomy (pN1) is associated with worse oncologic outcomes, yet its optimal management remains controversial. We evaluated oncologic outcomes and treatment patterns in pN1 prostate cancer.
Patients and Methods
We analyzed data from the National Cancer Database (NCDB) on men undergoing radical pN1 between 2010 and 2020. Exclusion criteria included distant metastases and delayed androgen-deprivation therapy (ADT) or adjuvant radiotherapy (aRT) beyond 1 year from surgery. The primary outcome was overall survival (OS). Multinomial logistic regression identified demographic and clinical predictors of treatment selection. Inverse probability of treatment weighting (IPTW) was applied to adjust baseline characteristics and perform weighted survival analysis across treatment groups.
Results
Among 13,454 patients with pN1 disease, 51.2% were managed with observation, 17.8% received ADT alone, 26.9% ADT plus aRT, and 4.1% aRT alone. Median follow-up was 56.3 months (IQR:36-83). ISUP grade 4-5, pT3-4 disease, and increased nodal burden were associated with treatment intensification. Compared to Non-Hispanic Whites, Non-Hispanic Black patients had lower odds of receiving ADT plus aRT (aOR: 0.79, 95% CI, 0.69-0.91, P < .001). ADT alone or aRT alone did not improve OS; ADT combined with aRT was significantly associated with improved OS (HR: 0.78, 95% CI, 0.68-0.89, P < .001).
Conclusion
This national analysis revealed variability in postsurgical management for pN1 disease. Only less than a third of men received aRT, despite this treatment being associated with improved OS. Given the observed variability in treatment use and outcomes, our findings support the value of individualized management strategies and multidisciplinary decision-making.
导言:根治性前列腺切除术(pN1)后淋巴结累及与较差的肿瘤预后相关,但其最佳管理仍存在争议。我们评估了pN1前列腺癌的肿瘤预后和治疗模式。患者和方法:我们分析了国家癌症数据库(NCDB)中2010年至2020年间接受根治性pN1的男性的数据。排除标准包括远处转移和延迟雄激素剥夺治疗(ADT)或辅助放疗(aRT)手术后1年以上。主要终点是总生存期(OS)。多项逻辑回归确定了治疗选择的人口学和临床预测因素。应用治疗加权逆概率(IPTW)调整基线特征,并对各治疗组进行加权生存分析。结果:13454例pN1患者中,51.2%接受观察治疗,17.8%单独接受ADT治疗,26.9% ADT联合aRT治疗,4.1%单独接受aRT治疗。中位随访时间为56.3个月(IQR:36-83)。ISUP分级4-5级、pT3-4级疾病和淋巴结负担增加与强化治疗相关。与非西班牙裔白人相比,非西班牙裔黑人患者接受ADT + aRT的几率较低(aOR: 0.79, 95% CI: 0.69-0.91, P < 0.001)。单独ADT或单独aRT不能改善OS;ADT联合aRT与改善OS显著相关(HR: 0.78, 95% CI: 0.68-0.89, P < 0.001)。结论:这项全国性的分析揭示了pN1疾病的术后处理的可变性。只有不到三分之一的男性接受了aRT治疗,尽管这种治疗与改善OS有关。鉴于观察到的治疗使用和结果的可变性,我们的研究结果支持个性化管理策略和多学科决策的价值。
{"title":"Treatment Patterns and Outcomes in Lymph-Node-Positive (pN1) Prostate Cancer: A National Cancer Database Study","authors":"Andrea Piccolini , Stephan M. Korn , Zhiyu Qian , Pietro Brin , Klara Pohl , Hanna Zurl , Boyuan Xiao , Giovanni Lughezzani , Nicolò M. Buffi , Paul L. Nguyen , Mutlay Sayan , Quoc-Dien Trinh , Alexander P. Cole","doi":"10.1016/j.clgc.2025.102413","DOIUrl":"10.1016/j.clgc.2025.102413","url":null,"abstract":"<div><h3>Introduction</h3><div>Lymph node involvement after radical prostatectomy (pN1) is associated with worse oncologic outcomes, yet its optimal management remains controversial. We evaluated oncologic outcomes and treatment patterns in pN1 prostate cancer.</div></div><div><h3>Patients and Methods</h3><div>We analyzed data from the National Cancer Database (NCDB) on men undergoing radical pN1 between 2010 and 2020. Exclusion criteria included distant metastases and delayed androgen-deprivation therapy (ADT) or adjuvant radiotherapy (aRT) beyond 1 year from surgery. The primary outcome was overall survival (OS). Multinomial logistic regression identified demographic and clinical predictors of treatment selection. Inverse probability of treatment weighting (IPTW) was applied to adjust baseline characteristics and perform weighted survival analysis across treatment groups.</div></div><div><h3>Results</h3><div>Among 13,454 patients with pN1 disease, 51.2% were managed with observation, 17.8% received ADT alone, 26.9% ADT plus aRT, and 4.1% aRT alone. Median follow-up was 56.3 months (IQR:36-83). ISUP grade 4-5, pT3-4 disease, and increased nodal burden were associated with treatment intensification. Compared to Non-Hispanic Whites, Non-Hispanic Black patients had lower odds of receiving ADT plus aRT (aOR: 0.79, 95% CI, 0.69-0.91, <em>P</em> < .001). ADT alone or aRT alone did not improve OS; ADT combined with aRT was significantly associated with improved OS (HR: 0.78, 95% CI, 0.68-0.89, <em>P</em> < .001).</div></div><div><h3>Conclusion</h3><div>This national analysis revealed variability in postsurgical management for pN1 disease. Only less than a third of men received aRT, despite this treatment being associated with improved OS. Given the observed variability in treatment use and outcomes, our findings support the value of individualized management strategies and multidisciplinary decision-making.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 5","pages":"Article 102413"},"PeriodicalIF":2.7,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-29DOI: 10.1016/j.clgc.2025.102408
Lian Hu , Jia-Wei Hu , Chang-Quan Wang , Rui-Ying Li , Song Li
Neoadjuvant immune checkpoint inhibitors have emerged as a potential treatment option for muscle-invasive bladder cancer (MIBC), but their comparative efficacy and safety remain unclear. This meta-analysis evaluated pathological outcomes and adverse events of neoadjuvant PD-(L)1 inhibitors across different therapeutic approaches. A systematic search was conducted across multiple databases (PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases), from their inception to December 21, 2024, for studies investigating neoadjuvant PD-(L)1 inhibitors in patients with MIBC. Primary outcomes included pathological complete response (pCR), pathological partial response (pPR), downstaging (DS), and grade ≥3 immune-related adverse events (irAEs). Random-effects models were used to calculate pooled estimates, with subgroup analyses performed based on treatment strategy and inhibitor type. Twenty-nine studies were finally included, involving 33 treatment arms. The overall pooled pCR rate was 32.7% (95% confidence interval [CI]: 27.7%-37.7%), with PD-(L)1 inhibitors plus chemotherapy showing the highest rate (39.2%, 95% CI: 32.1%-46.3%), followed by dual checkpoint inhibition (27.6%, 95% CI: 15.5%-39.6%), and monotherapy (24.6%, 95% CI: 16.9%-32.3%). The overall pooled pPR was 45.3% (95% CI: 38.4%-52.2%), and DS rate was 62.9% (95% CI: 53.1%-72.8%). Grade ≥3 irAEs varied significantly by approach: 9.4% (95% CI: 6.0%-12.7%) for monotherapy, 24.9% (95% CI: 9.6%-40.2%) for dual checkpoint inhibition, and 14.2% (95% CI: 6.9%-21.5%) for combination with chemotherapy. Sensitivity analyses confirmed the robustness of these findings. Neoadjuvant PD-(L)1 inhibitors demonstrate promising efficacy in MIBC with acceptable toxicity profiles. Combination with chemotherapy provides the highest pathological response rates with moderate toxicity, while monotherapy offers a favorable safety profile that may benefit cisplatin-ineligible patients. These findings support the continued investigation of these approaches in ongoing Phase III trials.
{"title":"Neoadjuvant PD-1/PD-L1 Inhibitors for Muscle-Invasive Bladder Cancer: A Meta-Analysis","authors":"Lian Hu , Jia-Wei Hu , Chang-Quan Wang , Rui-Ying Li , Song Li","doi":"10.1016/j.clgc.2025.102408","DOIUrl":"10.1016/j.clgc.2025.102408","url":null,"abstract":"<div><div>Neoadjuvant immune checkpoint inhibitors have emerged as a potential treatment option for muscle-invasive bladder cancer (MIBC), but their comparative efficacy and safety remain unclear. This meta-analysis evaluated pathological outcomes and adverse events of neoadjuvant PD-(L)1 inhibitors across different therapeutic approaches. A systematic search was conducted across multiple databases (PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases), from their inception to December 21, 2024, for studies investigating neoadjuvant PD-(L)1 inhibitors in patients with MIBC. Primary outcomes included pathological complete response (pCR), pathological partial response (pPR), downstaging (DS), and grade ≥3 immune-related adverse events (irAEs). Random-effects models were used to calculate pooled estimates, with subgroup analyses performed based on treatment strategy and inhibitor type. Twenty-nine studies were finally included, involving 33 treatment arms. The overall pooled pCR rate was 32.7% (95% confidence interval [CI]: 27.7%-37.7%), with PD-(L)1 inhibitors plus chemotherapy showing the highest rate (39.2%, 95% CI: 32.1%-46.3%), followed by dual checkpoint inhibition (27.6%, 95% CI: 15.5%-39.6%), and monotherapy (24.6%, 95% CI: 16.9%-32.3%). The overall pooled pPR was 45.3% (95% CI: 38.4%-52.2%), and DS rate was 62.9% (95% CI: 53.1%-72.8%). Grade ≥3 irAEs varied significantly by approach: 9.4% (95% CI: 6.0%-12.7%) for monotherapy, 24.9% (95% CI: 9.6%-40.2%) for dual checkpoint inhibition, and 14.2% (95% CI: 6.9%-21.5%) for combination with chemotherapy. Sensitivity analyses confirmed the robustness of these findings. Neoadjuvant PD-(L)1 inhibitors demonstrate promising efficacy in MIBC with acceptable toxicity profiles. Combination with chemotherapy provides the highest pathological response rates with moderate toxicity, while monotherapy offers a favorable safety profile that may benefit cisplatin-ineligible patients. These findings support the continued investigation of these approaches in ongoing Phase III trials.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 5","pages":"Article 102408"},"PeriodicalIF":2.7,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144920357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-29DOI: 10.1016/j.clgc.2025.102406
Andrea Marchetti , Veronica Mollica , Andrea Farolfi , Gianfilippo Bianciardi , Matteo Rosellini , Elisa Tassinari , Linda Danielli , Lorenzo Bianchi , Riccardo Schiavina , Stefano Fanti , Francesco Massari
Background and objective
In metastatic hormone-sensitive prostate cancer (mHSPC), to evaluate therapy response is currently used conventional imaging and PSA levels. Positron emission tomography with 68Gallium Prostate-specific membrane antigen (68Ga-PSMA-PET/CT) could be useful, although it is not recommended by international guidelines. Its prognostic utility has been already investigated in several works in the castration-resistant setting, but no sufficient efforts have been made to better define it in mHSPC.
Methods
Retrospective monocentric study to preliminary explore the value of 68Ga-PSMA-PET/CT in this setting. We enrolled metastatic patients at the baseline 68Ga-PSMA-PET/CT, treated with androgen deprivation therapy plus docetaxel or androgen receptor signaling inhibitors (ARSI) or both as first-line.
Key findings and limitations
The survival analysis indicated that a Major SUVmax exceeding the cut-off (P = .037) and a SUVmean above the cut-off (P = .025) were linked to improved progression-free survival (PFS) as compared to values ≤ cut-off. While several parameters were associated with undetectable PSA levels at any point after the initiation of first-line therapy, only low-volume disease (HR 7.64, P .002), MTV ≤ cut-off 3-months PSA (HR 5.36, P = .012) and SUVmean ≤ cut-off 3-months PSA (HR 38.6, P < .001) were associated with a higher probability of reaching an undetectable value of PSA in the multivariate analysis. Limitations: retrospective nature, short follow-up time and lack of comparison with conventional imaging.
Conclusion and clinical implications
Lower values of 68Ga-PSMA-PET/CT derived-parameters at baseline are negative prognostic factor, in view of the correlation with lower PFS. This study could help oncologists in the management of mHSPC patients, although further investigations are needed to better understand the prognostic and predictive 68Ga-PSMA-PET/CT role in this setting.
背景和目的:在转移性激素敏感性前列腺癌(mHSPC)中,评估治疗反应目前使用常规影像学和PSA水平。正电子发射断层扫描68镓前列腺特异性膜抗原(68Ga-PSMA-PET/CT)可能是有用的,尽管国际指南不推荐。它的预后效用已经在一些阉割抵抗设置的工作中进行了调查,但没有做出足够的努力来更好地定义mHSPC。方法:回顾性单中心研究,初步探讨68Ga-PSMA-PET/CT在这种情况下的价值。我们招募了68Ga-PSMA-PET/CT基线转移性患者,接受雄激素剥夺治疗加多西紫杉醇或雄激素受体信号抑制剂(ARSI)或两者作为一线治疗。主要发现和局限性:生存分析表明,与≤临界值相比,超过临界值的主要SUVmax (P = 0.037)和高于临界值的SUVmean (P = 0.025)与改善的无进展生存(PFS)相关。虽然在一线治疗开始后的任何时间点,有几个参数与无法检测到的PSA水平相关,但只有小体积疾病(HR 7.64, P。002)、MTV≤截止3个月PSA (HR 5.36, P = 0.012)和SUVmean≤截止3个月PSA (HR 38.6, P < 0.001)与多因素分析中PSA达到不可检测值的概率较高相关。局限性:回顾性,随访时间短,缺乏与常规影像学的比较。结论及临床意义:68Ga-PSMA-PET/CT衍生参数基线值较低与PFS较低相关,是影响预后的不利因素。这项研究可以帮助肿瘤学家管理mHSPC患者,尽管需要进一步的研究来更好地了解68Ga-PSMA-PET/CT在这种情况下的预后和预测作用。
{"title":"The Prognostic Role of 68GA-PSMA-PET/CT in Metastatic Hormone-Sensitive Prostate Cancer: A Preliminary Analysis","authors":"Andrea Marchetti , Veronica Mollica , Andrea Farolfi , Gianfilippo Bianciardi , Matteo Rosellini , Elisa Tassinari , Linda Danielli , Lorenzo Bianchi , Riccardo Schiavina , Stefano Fanti , Francesco Massari","doi":"10.1016/j.clgc.2025.102406","DOIUrl":"10.1016/j.clgc.2025.102406","url":null,"abstract":"<div><h3>Background and objective</h3><div>In metastatic hormone-sensitive prostate cancer (mHSPC), to evaluate therapy response is currently used conventional imaging and PSA levels. Positron emission tomography with <sup>68</sup>Gallium Prostate-specific membrane antigen (<sup>68</sup>Ga-PSMA-PET/CT) could be useful, although it is not recommended by international guidelines. Its prognostic utility has been already investigated in several works in the castration-resistant setting, but no sufficient efforts have been made to better define it in mHSPC.</div></div><div><h3>Methods</h3><div>Retrospective monocentric study to preliminary explore the value of <sup>68</sup>Ga-PSMA-PET/CT in this setting. We enrolled metastatic patients at the baseline <sup>68</sup>Ga-PSMA-PET/CT, treated with androgen deprivation therapy plus docetaxel or androgen receptor signaling inhibitors (ARSI) or both as first-line.</div></div><div><h3>Key findings and limitations</h3><div>The survival analysis indicated that a Major SUVmax exceeding the cut-off (<em>P</em> = .037) and a SUVmean above the cut-off (<em>P</em> = .025) were linked to improved progression-free survival (PFS) as compared to values ≤ cut-off. While several parameters were associated with undetectable PSA levels at any point after the initiation of first-line therapy, only low-volume disease (HR 7.64, <em>P</em> .002), MTV ≤ cut-off 3-months PSA (HR 5.36, <em>P</em> = .012) and SUVmean ≤ cut-off 3-months PSA (HR 38.6, <em>P</em> < .001) were associated with a higher probability of reaching an undetectable value of PSA in the multivariate analysis. Limitations: retrospective nature, short follow-up time and lack of comparison with conventional imaging.</div></div><div><h3>Conclusion and clinical implications</h3><div>Lower values of <sup>68</sup>Ga-PSMA-PET/CT derived-parameters at baseline are negative prognostic factor, in view of the correlation with lower PFS. This study could help oncologists in the management of mHSPC patients, although further investigations are needed to better understand the prognostic and predictive <sup>68</sup>Ga-PSMA-PET/CT role in this setting.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 5","pages":"Article 102406"},"PeriodicalIF":2.7,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-23DOI: 10.1016/j.clgc.2025.102405
Salvador Jaime-Casas , Miguel Zugman , Regina Barragan-Carrillo , Hedyeh Ebrahimi , Koral Shah , Wesley Yip , Cory M. Hugen , Kevin G. Chan , Clayton S. Lau , Bertram E. Yuh , Benjamin Mercier , Nicholas J. Salgia , Daniela V. Castro , Xiaochen Li , JoAnn Hsu , Charles B. Nguyen , Alexander Chehrazi-Raffle , Sumanta K Pal , Abhishek Tripathi
Background
Occult pathological lymph node involvement in patients with clinical node-negative (cN0) bladder cancer (BC) remains a diagnostic challenge. We evaluate predictors of lymph node positivity (pN+) in patients with cT1-4N0M0 BC undergoing radical cystectomy and pelvic lymph node dissection (RC-PLND).
Methods
We included patients with cT1-4N0M0 BC undergoing RC-PLND from February 2004 through October 2020. Patients were classified as pN+ vs. pN0. Baseline characteristics were summarized using descriptive statistics. Logistic regression models and multivariable analysis estimated odds ratios (OR) for pN+ status. Kaplan Meier analysis and multivariable Cox proportional hazards models analyzed recurrence-free survival (RFS) and overall survival (OS).
Results
440 patients were evaluated, of which 81% (n = 359) had pN0 and 17% (n = 74) had pN+ disease. Most were male (80%), white (88%), and had a median age of 71 years. Most had clinical T2 (55%) and T1 (25%) disease. Lymphovascular invasion (LVI) on TURBT (OR 2.62, P = .04), positive surgical margins (OR 16.77, P < .001), and ≥ cT2 disease (OR 1.89, P = .04) had higher odds of pN+ status. pN+ patients were more likely to suffer recurrence (HR 7.67, P < .001) or death (HR 3.26, P < .001) compared to pN0 patients. Preoperative hydronephrosis predicted worse RFS (HR 1.76, P = .011) and OS (HR 1.55, P = .007). Positive surgical margins (HR 2.34, P = .008) and preoperative renal function (HR 1.50, P = .004) predicted worse OS.
Conclusion
Positive surgical margins, LVI, and ≥ cT2 disease strongly predict pN+ findings in patients with cT1-4N0M0 BC. Preoperative variables can inform treatment for patients with a higher risk for positive lymph node findings at surgery.
背景:临床淋巴结阴性(cN0)膀胱癌(BC)患者的隐匿病理淋巴结累及仍然是一个诊断挑战。我们评估cT1-4N0M0 BC患者接受根治性膀胱切除术和盆腔淋巴结清扫(RC-PLND)时淋巴结阳性(pN+)的预测因素。方法:我们纳入了2004年2月至2020年10月期间接受RC-PLND的cT1-4N0M0 BC患者。将患者分为pN+和pN0。使用描述性统计总结基线特征。Logistic回归模型和多变量分析估计了pN+状态的比值比(OR)。Kaplan Meier分析和多变量Cox比例风险模型分析了无复发生存期(RFS)和总生存期(OS)。结果:440例患者被评估,其中81% (n = 359)为pN0, 17% (n = 74)为pN+。大多数为男性(80%),白人(88%),中位年龄为71岁。大多数临床T2(55%)和T1(25%)病变。TURBT淋巴血管侵犯(LVI) (OR 2.62, P = 0.04)、手术切缘阳性(OR 16.77, P < 0.001)和≥cT2疾病(OR 1.89, P = 0.04)出现pN+的几率较高。与pN0患者相比,pN+患者更容易出现复发(HR 7.67, P < 0.001)或死亡(HR 3.26, P < 0.001)。术前肾积水预示较差的RFS (HR 1.76, P = 0.011)和OS (HR 1.55, P = 0.07)。阳性手术切缘(HR 2.34, P = 0.008)和术前肾功能(HR 1.50, P = 0.004)预示较差的OS。结论:阳性手术切缘、LVI和≥cT2疾病强烈预测cT1-4N0M0 BC患者的pN+表现。术前变量可以为手术中淋巴结阳性发现风险较高的患者提供治疗信息。
{"title":"Clinical and Pathological Predictors for Occult Lymph Node Involvement in Patients With Clinical Node-Negative Bladder Cancer Undergoing Radical Cystectomy","authors":"Salvador Jaime-Casas , Miguel Zugman , Regina Barragan-Carrillo , Hedyeh Ebrahimi , Koral Shah , Wesley Yip , Cory M. Hugen , Kevin G. Chan , Clayton S. Lau , Bertram E. Yuh , Benjamin Mercier , Nicholas J. Salgia , Daniela V. Castro , Xiaochen Li , JoAnn Hsu , Charles B. Nguyen , Alexander Chehrazi-Raffle , Sumanta K Pal , Abhishek Tripathi","doi":"10.1016/j.clgc.2025.102405","DOIUrl":"10.1016/j.clgc.2025.102405","url":null,"abstract":"<div><h3>Background</h3><div>Occult pathological lymph node involvement in patients with clinical node-negative (cN0) bladder cancer (BC) remains a diagnostic challenge. We evaluate predictors of lymph node positivity (pN+) in patients with cT1-4N0M0 BC undergoing radical cystectomy and pelvic lymph node dissection (RC-PLND).</div></div><div><h3>Methods</h3><div>We included patients with cT1-4N0M0 BC undergoing RC-PLND from February 2004 through October 2020. Patients were classified as pN+ vs. pN0. Baseline characteristics were summarized using descriptive statistics. Logistic regression models and multivariable analysis estimated odds ratios (OR) for pN+ status. Kaplan Meier analysis and multivariable Cox proportional hazards models analyzed recurrence-free survival (RFS) and overall survival (OS).</div></div><div><h3>Results</h3><div>440 patients were evaluated, of which 81% (<em>n</em> = 359) had pN0 and 17% (<em>n</em> = 74) had pN+ disease. Most were male (80%), white (88%), and had a median age of 71 years. Most had clinical T2 (55%) and T1 (25%) disease. Lymphovascular invasion (LVI) on TURBT (OR 2.62, <em>P</em> = .04), positive surgical margins (OR 16.77, <em>P</em> < .001), and ≥ cT2 disease (OR 1.89, <em>P</em> = .04) had higher odds of pN+ status. pN+ patients were more likely to suffer recurrence (HR 7.67, <em>P</em> < .001) or death (HR 3.26, <em>P</em> < .001) compared to pN0 patients. Preoperative hydronephrosis predicted worse RFS (HR 1.76, <em>P</em> = .011) and OS (HR 1.55, <em>P</em> = .007). Positive surgical margins (HR 2.34, <em>P</em> = .008) and preoperative renal function (HR 1.50, <em>P</em> = .004) predicted worse OS.</div></div><div><h3>Conclusion</h3><div>Positive surgical margins, LVI, and ≥ cT2 disease strongly predict pN+ findings in patients with cT1-4N0M0 BC. Preoperative variables can inform treatment for patients with a higher risk for positive lymph node findings at surgery.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 5","pages":"Article 102405"},"PeriodicalIF":2.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-07-23DOI: 10.1016/j.clgc.2025.102402
Cristina Suárez , Òscar Reig Torras , Rafael Morales Barrera , Ángel Rodríguez Sánchez , Georgia Anguera Palacios , André Miguel Branco Manshino , Natalia Fernández Núñez , María José Méndez Vidal , Icíar García Carbonero , Ovidio Fernández Calvo , Regina Gironés Sarrió , Guillermo Crespo Herrero , Javier Afonso Afonso , María José Juan Fita , Josep Gumà Padró , Martín Lázaro Quintela , Alejo Rodriguez-Vida , Carolina Hernández Pérez , Ana Medina Colmenero , Ricardo Collado Martín , Enrique Gallardo
Background
The SPRWEC study investigated cabozantinib effectiveness and safety in patients with advanced renal cell carcinoma (RCC) in real-world Spanish and Portuguese settings.
Patients and methods
Observational, ambispective, multicenter study including adult patients with advanced RCC receiving cabozantinib between October 2016 and May 2020 as second or subsequent treatment line. Primary endpoint was progression-free survival (PFS).
Results
About 258 patients (mean [SD] age 62.5 [11.0] years, 75.6% male) were included, 55.8% with prior immunotherapy. Median follow-up was 34.3 months. Median PFS was 7.63 months (95% CI, 6.64-8.72). Median overall survival (OS) was 15.36 months (95% CI, 11.58-19.11); objective response rate (ORR), 29.5% (95% CI, 24.0-35.4); median time to first response, 3.27 months (95% CI, 3.03-3.68); median duration of response, 9.77 months (95% CI, 7.24-12.63); median time to discontinuation, 6.97 months (95% CI, 5.79-8.42). Prior immunotherapy increased ORR (OR 2.132) and decreased OS (HR 1.529). ECOG 0-1 and dose reductions were associated with increased PFS (HR 0.470 and 0.558); poor and intermediate MSKCC (HR 3.861 and 1.681) and IMDC risks (HR 2.558 and 1.537) with decreased PFS. Most common AEs were diarrhea (41.9%), asthenia (34.9%), and anorexia (18.2%).
Conclusion
Cabozantinib’s effectiveness and safety as second or subsequent treatment line for advanced RCC in real-world settings are similar to those observed in clinical trials. This treatment after prior immunotherapy, the front-line standard of care, resulted in increased ORR and decreased OS, without changes in PFS.
{"title":"Effectiveness and Safety of Cabozantinib Treatment in Patients with Advanced Renal Cell Carcinoma in Spanish and Portuguese Real-world Practice: The SOGUG-SPRWEC Study","authors":"Cristina Suárez , Òscar Reig Torras , Rafael Morales Barrera , Ángel Rodríguez Sánchez , Georgia Anguera Palacios , André Miguel Branco Manshino , Natalia Fernández Núñez , María José Méndez Vidal , Icíar García Carbonero , Ovidio Fernández Calvo , Regina Gironés Sarrió , Guillermo Crespo Herrero , Javier Afonso Afonso , María José Juan Fita , Josep Gumà Padró , Martín Lázaro Quintela , Alejo Rodriguez-Vida , Carolina Hernández Pérez , Ana Medina Colmenero , Ricardo Collado Martín , Enrique Gallardo","doi":"10.1016/j.clgc.2025.102402","DOIUrl":"10.1016/j.clgc.2025.102402","url":null,"abstract":"<div><h3>Background</h3><div>The SPRWEC study investigated cabozantinib effectiveness and safety in patients with advanced renal cell carcinoma (RCC) in real-world Spanish and Portuguese settings.</div></div><div><h3>Patients and methods</h3><div>Observational, ambispective, multicenter study including adult patients with advanced RCC receiving cabozantinib between October 2016 and May 2020 as second or subsequent treatment line. Primary endpoint was progression-free survival (PFS).</div></div><div><h3>Results</h3><div>About 258 patients (mean [SD] age 62.5 [11.0] years, 75.6% male) were included, 55.8% with prior immunotherapy. Median follow-up was 34.3 months. Median PFS was 7.63 months (95% CI, 6.64-8.72). Median overall survival (OS) was 15.36 months (95% CI, 11.58-19.11); objective response rate (ORR), 29.5% (95% CI, 24.0-35.4); median time to first response, 3.27 months (95% CI, 3.03-3.68); median duration of response, 9.77 months (95% CI, 7.24-12.63); median time to discontinuation, 6.97 months (95% CI, 5.79-8.42). Prior immunotherapy increased ORR (OR 2.132) and decreased OS (HR 1.529). ECOG 0-1 and dose reductions were associated with increased PFS (HR 0.470 and 0.558); poor and intermediate MSKCC (HR 3.861 and 1.681) and IMDC risks (HR 2.558 and 1.537) with decreased PFS. Most common AEs were diarrhea (41.9%), asthenia (34.9%), and anorexia (18.2%).</div></div><div><h3>Conclusion</h3><div>Cabozantinib’s effectiveness and safety as second or subsequent treatment line for advanced RCC in real-world settings are similar to those observed in clinical trials. This treatment after prior immunotherapy, the front-line standard of care, resulted in increased ORR and decreased OS, without changes in PFS.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 5","pages":"Article 102402"},"PeriodicalIF":2.7,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144884456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}