Urologic Oncology-seminars and Original Investigations最新文献

{"title":"Impact of neoadjuvant therapy on prognosis in renal cell carcinoma with inferior vena cava thrombus.","authors":"Takuto Hara, Kotaro Suzuki, Yasuyoshi Okamura, Hideto Ueki, Yukari Bando, Keisuke Okada, Tomoaki Terakawa, Yoji Hyodo, Koji Chiba, Jun Teishima, Hideaki Miyake","doi":"10.1016/j.urolonc.2024.10.017","DOIUrl":"https://doi.org/10.1016/j.urolonc.2024.10.017","url":null,"abstract":"<p><strong>Background: </strong>The standard treatment for non-metastatic renal cell carcinoma (RCC) with inferior vena cava (IVC) thrombus is complete surgical resection; however, this procedure is complex and carries high complication rates and perioperative mortality. Previous studies have explored preoperative multimodal therapy to reduce surgical difficulty, but limited evidence prevents guideline recommendations. This study aimed to investigate the impact of neoadjuvant therapy on the prognosis of patients with RCC and IVC thrombus without distant metastasis.</p><p><strong>Methods: </strong>Data from 2006 to 2024 on RCC patients with IVC thrombus undergoing radical nephrectomy plus IVC thrombus resection were collected. Patients received neoadjuvant therapy, including tyrosine kinase inhibitors or immune checkpoint inhibitors, followed by surgery. Tumor size and thrombus height were assessed by computed tomography. Disease-free survival (DFS) and overall survival (OS) were calculated using Kaplan-Meier curves. Multivariate analysis was used to identify factors predicting DFS.</p><p><strong>Results: </strong>Thirty-one patients who did not receive neoadjuvant chemotherapy therapy (NAC-Naive group) and 19 patients who received neoadjuvant chemotherapy therapy (NAC group) were analyzed. The NAC group showed significant reductions in primary renal tumor size and neutrophil-to-lymphocyte ratio compared to the NAC-Naive group just before nephrectomy. The NAC group had significantly improved DFS and OS. Median DFS and OS were not reached in the NAC group compared to 26.3 months and 73.5 months, respectively, in the NAC-Naive group. The NAC group had a 2-year recurrence-free survival rate of 70.9% compared to 50.6% in the NAC-Naive group. Multivariate analysis identified a preoperative tumor size of 10 cm or larger and lack of neoadjuvant therapy as poor prognostic factors for DFS.</p><p><strong>Conclusion: </strong>Neoadjuvant therapy significantly improves the prognosis of RCC patients with IVC thrombus. This therapy reduces surgical invasiveness and has a mid- to long-term preventive effect on recurrence. These findings support the potential benefit of neoadjuvant systemic therapy in improving outcomes for this patient population.</p>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628945","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}

{"title":"Comparative prognostic value of tumor volume in IOIO and IOTKI treatment for metastatic renal cancer.","authors":"Takuto Hara, Hideto Ueki, Yasuyoshi Okamura, Yukari Bando, Kotaro Suzuki, Tomoaki Terakawa, Koji Chiba, Yoji Hyodo, Jun Teishima, Hideaki Miyake","doi":"10.1016/j.urolonc.2024.10.015","DOIUrl":"https://doi.org/10.1016/j.urolonc.2024.10.015","url":null,"abstract":"<p><strong>Objectives: </strong>We aimed to investigate the prognostic significance of tumor size in metastatic renal cell carcinoma (mRCC) by comparing the effectiveness of dual immune checkpoint inhibitor (IOIO) and immune checkpoint inhibitor combined with tyrosine kinase inhibitor (IOTKI) therapies.</p><p><strong>Methods: </strong>This retrospective observational study included patients with mRCC diagnosed between October 2014 and February 2024 who received IOIO or IOTKI treatment at Kobe University Hospital and 5 affiliated hospitals. Clinical and imaging data were collected, and target lesions were measured according to RECIST v.1.1 criteria. Time-dependent ROC curve analysis was performed to evaluate the prognostic value of tumor size, nephrectomy status, and IMDC risk criteria for progression-free survival (PFS) and overall survival (OS).</p><p><strong>Results: </strong>The study included 180 mRCC patients, consisting of 99 receiving IOIO therapy and 81 receiving IOTKI therapy. Time-dependent AUC analysis showed that tumor size had a higher predictive ability for PFS and OS in the IOIO group than the IOTKI group. In multivariate analysis, tumor size was a significant independent prognostic factor for PFS (HR: 1.010, 95% CI: 1.004-1.016, P < 0.001) in the IOIO group. Moreover, the AUC for tumor size was consistently superior in predicting outcomes compared to nephrectomy status and IMDC risk classification in the IOIO group. Kaplan-Meier curves indicated that tumor size effectively stratified PFS in both nephrectomized and non-nephrectomized cases.</p><p><strong>Conclusion: </strong>Tumor size significantly impacts the prognosis of mRCC patients treated with IOIO therapy, demonstrating greater predictive ability than nephrectomy status and IMDC risk classification. These findings suggest that tumor volume should be considered a critical factor in treatment decision-making for renal cancer, particularly in patients undergoing IOIO therapy.</p>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629037","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}

{"title":"Pathologic prostate cancer grade concordance among high-resolution micro-ultrasound, systematic transrectal ultrasound and MRI fusion biopsy.","authors":"Soum D Lokeshwar, Ankur U Choksi, Shayan Smani, Victoria Kong, Vinaik Sundaresan, Ryan Sutherland, Joseph Brito, Joseph F Renzulli, Preston C Sprenkle, Michael S Leapman","doi":"10.1016/j.urolonc.2024.10.018","DOIUrl":"https://doi.org/10.1016/j.urolonc.2024.10.018","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objective: &lt;/strong&gt;Comparative studies among biopsy strategies have not been conducted evaluating pathologic concordance at radical prostatectomy(RP), especially with novel micro-ultrasound (micro-US) image-guided biopsy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A retrospective study among patients with PCa who underwent RP following TRUS, MRI-TRUS fusion, microUS, or MRI-microUS fusion biopsy in a multi-site single institution. We compared GG-upgrade from biopsy to RP based on highest GG in any biopsy core and examined clinical/pathologic factors associated with pathologic upgrading using descriptive statistics, and multivariable logistic-regression analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;429 patients between 1/2021 and 6/2023 including 10 (25.6%) who underwent systematic TRUS, 237 (55.2%) MRI-TRUS, 67 (15.6%) MRI-microUS and 15 (3.5%) micoUS-alone biopsy prior to RP. 78 (18.2%) were upgraded on final pathology (TRUS 31 (28.2%), MRI-TRUS 31 (13.1%), MRI-microUS 10 (14.9%), microUS: 6 (40%)) and 99 downgraded. 14 (3.5%) experienced a major upgrade (≥2 GG increase). On multivariable-analysis both MRI-TRUS (odds ratio, OR: 0.31,95% CI:0.17-0.56, P &lt; 0.001) and MRI-microUS (OR: 0.43,95%CI: 0.19-0.98, P = 0.044) were associated with lower odds pathological-upgrade compared with TRUS biopsy alone. No significant differences in the odds of upgrade between TRUS and microUS alone (P &gt; 0.05), or between MRI-microUS and MRI-TRUS(P = 0.696) on pairwise comparisons. MRI-microUS was associated with lower upgrade compared with microUS (OR: 0.26,95% CI:0.08-0.90, P = 0.034). No difference among the biopsy strategies in pathologic downgrading or overall GG concordance. Limitations include retrospective analysis, inter-clinician experience and lesion selection in varying biopsy techniques.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Both MRI-microUS and MRI-TRUS fusion were associated with similarly improved GG concordance compared with TRUS biopsy. No significant differences between microUS-alone and TRUS or between MRI-microUS and MRI-TRUS fusion approaches, may suggest similar accuracy performance for disease sampling.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What does the study add: &lt;/strong&gt;To our knowledge, this is the first study to investigate GG concordance based on type of biopsy, especially microUS related GG upgrading after RP. In a moderately sized cohort this is the first to investigate pathologic concordance in MRI-microUS fusion compared to MRI-TRUS fusion biopsy. Our study may help urologists in counseling patients after biopsy and choosing the ideal image guided biopsy technique, however randomized controlled trials are needed to validate our results.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Patient summary: &lt;/strong&gt;We performed a study to see if the type of prostate biopsy, including use of MRI assistance as well as a new image-guided biopsy using a more advanced ultrasound, was better able to identify the aggressiveness of prostate cancer patients had. We found that the new biopsy typ","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629080","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}

{"title":"A machine learning-based analysis for the definition of an optimal renal biopsy for kidney cancer.","authors":"F Belladelli, F De Cobelli, C Piccolo, F Cei, C Re, G Musso, G Rosiello, D Cignoli, A Santangelo, G Fallara, R Matloob, R Bertini, S Gusmini, G Brembilla, R Lucianò, N Tenace, A Salonia, A Briganti, F Montorsi, A Larcher, U Capitanio","doi":"10.1016/j.urolonc.2024.10.020","DOIUrl":"https://doi.org/10.1016/j.urolonc.2024.10.020","url":null,"abstract":"<p><strong>Objective: </strong>Renal Tumor biopsy (RTB) can assist clinicians in determining the most suitable approach for treatment of renal cancer. However, RTB's limitations in accurately determining histology and grading have hindered its broader adoption and data on the concordance rate between RTB results and final pathology after surgery are unavailable. Therefore, we aimed to develop a machine learning algorithm to optimize RTB technique and to investigate the degree of concordance between RTB and surgical pathology reports.</p><p><strong>Materials and methods: </strong>Within a prospectively maintained database, patients with indeterminate renal masses who underwent RTB at a single tertiary center were identified. We recorded and analyzed the approach (US vs. CT), the number of biopsy cores (NoC), and total core tissue length (LoC) to evaluate their impact on diagnostic outcomes. The K-Nearest Neighbors (KNN), a non-parametric supervised machine learning model, predicted the probability of obtaining pathological characterization and grading. In surgical patients, final pathology reports were compared with RTB results.</p><p><strong>Results: </strong>Overall, 197 patients underwent RTB. Overall, 89.8% (n=177) and 44.7% (n=88) of biopsies were informative in terms of histology and grading, respectively. The discrepancy rate between the pathology results from renal tissue biopsy (RTB) and the final pathology report following surgery was 3.6% (n=7) for histology and 5.0% (n=10) for grading. According to the machine learning model, a minimum of 2 cores providing at least 0.8 cm of total tissue should be obtained to achieve the best accuracy in characterizing the cancer. Alternatively, in cases of RTB with more than two cores, no specific minimum tissue threshold is required.</p><p><strong>Conclusions: </strong>The discordance rates between RTB pathology and final surgical pathology are notably minimal. We defined an optimal renal biopsy strategy based on at least 2 cores and at least 0.8 cm of tissue or at least 3 cores and no minimum tissue threshold.</p><p><strong>Patients summary: </strong>RTB is a useful test for kidney cancer, but it's not always perfect. Our study shows that it usually matches up well with what doctors find during surgery. Using machine learning can make RTB even better by helping doctors know how many samples to take. This helps doctors treat kidney cancer more accurately.</p>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629034","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}

{"title":"The clinical relevance of cut-off percentage for high-grade urothelial carcinoma within low-grade urothelial carcinoma: A determining factor?","authors":"Gozde Kir, Gozde Ecem Cecikoglu, Abdullah Aydin, Asif Yildirim","doi":"10.1016/j.urolonc.2024.10.016","DOIUrl":"https://doi.org/10.1016/j.urolonc.2024.10.016","url":null,"abstract":"<p><strong>Aims: </strong>The aim of the study was to analyze the cut-off value for the percentage of the high-grade (HG) component that has clinical significance in urothelial carcinoma (UC).</p><p><strong>Material and methods: </strong>The study included a total of 362 patients, mixed-grade UC (MGUC) patients were classified as Combine Group (CG) 1 based on the presence of less than 5% HG areas. High-grade papillary UC (HGPUC) patients were grouped based on HG component proportions: CG2 (≥5%-<50% HG), CG3 (≥50%-<100% HG), and pure HGPUC (PHGPUC) for 100% HG components.</p><p><strong>Results: </strong>There was a statistically significant difference between low-grade papillary UC (LGPUC) and CG1, CG2, or CG3, as well as LGPUC and PHGPUC, in terms of cancer-specific survival (CSS) (hazard ratio (HR) = 19.85, 95% confidence interval (CI) = 2.30-171.10 P = 0.007, HR = 28.38, 95% CI = 3.50-229.97 P = 0.002, HR = 18.64, 95% CI = 2.26-153.64 P = 0.007, and HR = 35.41, 95% CI = 4.61-271.72 P < 0.001, respectively). There was no statistically significant difference between PHGPUC and CG1, CG2, or CG3 in terms of CSS.</p><p><strong>Conclusions: </strong>These findings suggest that even the presence of less than 5% HGPUC within LGPUC significantly impacts CSS. Furthermore, the increase in the percentage of HGPUC beyond 5% does not substantially influence the CSS. Based on these findings, disclosing the percentage of the high-grade component may be crucial for future patient management and treatment.</p>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591301","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}

{"title":"Impact of postprogression therapies on overall survival: Recommendations from the 2023 kidney cancer association think tank meeting.","authors":"Stephanie A Berg, Salvatore La Rosa, Tian Zhang, Phillip M Pierorazio, Laurence Albiges, Kathryn E Beckermann, Matthew T Campbell, Maria I Carlo, Katie Coleman, Daniel J George, Daniel M Geynisman, Ritchie Johnson, Eric Jonasch, Jodi K Maranchie, Bradley A McGregor, Daniel D Shapiro, Eric A Singer, Brian M Shuch, Walter M Stadler, Nizar M Tannir, Yousef Zakharia, Ulka N Vaishampayan, Peter F Thall, Pavlos Msaouel","doi":"10.1016/j.urolonc.2024.10.022","DOIUrl":"https://doi.org/10.1016/j.urolonc.2024.10.022","url":null,"abstract":"<p><p>Modern advances in systemic and localized therapies for patients with renal cell carcinoma (RCC) have significantly improved patients' outcomes. If disease progression occurs after initial treatment, clinicians often have multiple options for a first salvage therapy. Because salvage and initial treatments both may affect overall survival time, and they may interact in unanticipated ways, there is a growing need to determine sequences of initial therapy and first salvage therapy that maximize overall survival while maintaining quality of life. The complexity of this problem grows if a second salvage therapy must be chosen for patients with treatment-resistant disease or a second progression occurs following first salvage. On November 9, 2023, a think tank was convened during the International Kidney Cancer Symposium (IKCS) North America to discuss challenges in accounting for postprogression therapies when estimating overall survival (OS) time based on randomized controlled trial (RCT) data. The present manuscript summarizes the topics discussed, with the aim to encourage adoption of statistical methods that account for salvage therapy effects to obtain scientifically valid OS estimation. We highlight limitations of traditional methods for estimating OS that account for initial treatments while ignoring salvage therapy effects and discuss advantages of applying more sophisticated statistical methods for estimation and trial design. These include identifying multistage treatment strategies, correcting for confounding due to salvage therapy effects, and conducting Sequentially Multiple Assignment Randomized Trials (SMARTs) to obtain unbiased comparisons between multistage strategies. We emphasize the critical role of patient input in trial design, and the potential for information technology (IT) advances to support complex trial designs and real-time data analyses. By addressing these challenges, future RCTs can better inform clinical decision-making and improve patient outcomes in RCC.</p>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584400","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}

{"title":"Causal relationship between bladder cancer and gut microbiota contributes to the gut-bladder axis: A two-sample Mendelian randomization study.","authors":"Han Yang, Chen Jin, Jie Li, Zongliang Zhang, Kai Zhao, Xinbao Yin, Zhenlin Wang, Guanqun Zhu, Xuechuan Yan, Zaiqing Jiang, Yixin Qi, Xuezhen Ma, Ke Wang","doi":"10.1016/j.urolonc.2024.10.014","DOIUrl":"https://doi.org/10.1016/j.urolonc.2024.10.014","url":null,"abstract":"<p><strong>Background: </strong>Recent studies have underscored a potential link between gut microbiota and urological tumors, yet the causal relationship with bladder cancer (BCa) and the role of metabolic pathways remain unclear.</p><p><strong>Methods: </strong>Instrumental variables (IVs) for gut microbiota were obtained from genome-wide association studies (GWAS) conducted by the MiBioGen consortium (n = 18,340). GWAS data for BCa were sourced from a comprehensive genome-wide meta-analysis encompassing 23 cohorts. Mendelian randomization (MR) was employed to investigate the causal relationship between gut microbiota and BCa, utilizing inverse variance weighted (IVW) as the primary MR method. Additionally, metabolic pathways associated with these microbiota were analyzed to understand their functional roles in BCa pathogenesis. Sensitivity analyses were conducted to validate all MR results.</p><p><strong>Results: </strong>The MR analysis identified five gut microbiota taxa with a causal association with BCa, with the genus Bilophila notably promoting BCa. Metabolic pathway analysis revealed significant associations between specific pathways and BCa, suggesting that changes in amino acid and NAD metabolism might influence BCa development. Sensitivity analyses indicated no significant heterogeneity or horizontal pleiotropy among the IVs.</p><p><strong>Conclusion: </strong>This study revealed the significant causal relationship between gut microbiota and BCa, particularly identifying Bilophila as a key pathogenic initiator. These findings elucidated the potential impact of metabolic pathways, especially amino acid and NAD metabolism, on the pathogenesis of BCa. They not only laid the foundation for innovative therapeutic strategies but also highlighted the immense potential of microbiota-based interventions in the prevention and treatment of BCa, paving the way for new directions in precision medicine.</p>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569638","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}

{"title":"Germline genetic testing for prostate cancer: Ordering trends in the era of expanded hereditary cancer screening recommendations.","authors":"Jacob L Roberts, Luke Luchen Wang, Brent Rose, Tyler M Seibert, Lisa Madlensky, Sarah M Nielsen, Amir Salmasi, A Karim Kader, Christopher J Kane, E David Crawford, Juan Javier-Desloges, Rana R McKay, Aditya Bagrodia","doi":"10.1016/j.urolonc.2024.10.010","DOIUrl":"https://doi.org/10.1016/j.urolonc.2024.10.010","url":null,"abstract":"<p><strong>Purpose: </strong>The availability of targeted therapies for advanced prostate cancer led to the expansion of national guidelines recommending germline genetic testing. The aim of this study was to describe recent trends in germline test ordering patterns for patients with prostate cancer.</p><p><strong>Materials and methods: </strong>A retrospective cohort analysis of patients with prostate cancer who underwent germline testing through a single commercial laboratory (Invitae Corporation) between 2015-2020 was performed. Ordering trends between provider medical specialties were compared. Our primary hypothesis was that the proportion of tests ordered by urologists would increase over time.</p><p><strong>Results: </strong>In total, 17,256 prostate cancer patients underwent germline genetic testing; 14,400 patients had an ordering provider with an associated medical specialty and were included in the final comparison cohort. Total prostate cancer patients undergoing germline testing increased quarterly from 21 in Q2 of 2015 to 1,509 in Q3 of 2020. The proportion of tests ordered by urologists increased from 0% in Q2 2015 to 8.3% in Q3 2020 (P < 0.001). Compared to medical genetics, medical oncology, and other specialties, urology ordered more tests for patients under 70 years old (66% vs 51%-55%, P <0.004) and for patients who reported negative family history (25% vs 12%-20%, P = 0.012).</p><p><strong>Conclusions: </strong>As awareness and indications for germline testing continue to expand, aggregate ordering volume is increasing, and urologists are becoming more involved in facilitating testing. This highlights the continued importance of educating urologists on the indications for and implications of germline genetic testing, as well as providing tools to support implementation.</p>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558882","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}

{"title":"Statin use and oncological outcomes in a propensity-matched cohort of nonmetastatic castration resistant prostate cancer patients of the ARAMIS trial.","authors":"Julian Chavarriaga, Katherine Lajkosz, Nishant Sangole, Linda Z Penn, Najia Khurram, Robert J Hamilton","doi":"10.1016/j.urolonc.2024.08.023","DOIUrl":"https://doi.org/10.1016/j.urolonc.2024.08.023","url":null,"abstract":"<p><strong>Introduction: </strong>While observational studies suggest favorable associations between statin use and prostate cancer (CaP) outcomes, data from randomized-controlled trials remain inconclusive. Our study explores the relationship between statin use and survival outcomes in the context of the phase III ARAMIS study, a trial of darolutamide in the treatment of nonmetastatic castration-resistant prostate cancer.</p><p><strong>Methods: </strong>We reviewed all 1,509 patients in the ARAMIS trial. Statin use was identified at baseline. Statin users were matched 1:2 with nonusers using a propensity score matching model. The primary endpoint was metastasis-free survival (MFS). Kaplan-Meier curves were plotted for MFS comparing statin users and nonusers across ARAMIS trial arms. A multivariate Cox proportional hazards model was fitted using the propensity-matched cohort and incorporating statin use and all covariates.</p><p><strong>Results: </strong>Of the 1,509 patients in ARAMIS, 334 (22.1%) were statin users. We matched 297 statin users to 550 nonusers. Characteristics appeared well balanced. Among nonusers, 331 (60.3%) and 219 (39.7%) were in the ARAMIS darolutamide and placebo arms, respectively. Among statin users, 179 (60.3%) and 118 (39.7%) were in the ARAMIS darolutamide and placebo arms, respectively. Overall, we found no significant difference in MFS between statin users and nonusers (HR 1.05, 95% CI 0.80-1.38 P = .72). However, we found significant interaction between statin use and ARAMIS trial arm. Specifically, statin use had a stronger association with MFS in the placebo arm (P = 0.024). However, this is likely coincidental and due to the statin-placebo patients having higher nodal positivity than the nonusers-placebo patients (14.3% vs. 5.5%). Statin use was similarly not associated with the secondary outcomes of PSA progression-free survival (P = 0.42), time-to-pain progression (P = 0.85), or overall survival (P = 0.15).</p><p><strong>Conclusions: </strong>In our secondary analysis of the ARAMIS trial, statin users had similar MFS and secondary outcomes compared to nonusers. These results suggest pursuing further statin synergies with amide-based androgen receptor axis target agents may not be fruitful.</p>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547749","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}

{"title":"Bempegaldesleukin plus nivolumab in first-line advanced/metastatic urothelial carcinoma: Results from a phase II single-arm study (PIVOT-10).","authors":"Arlene O Siefker-Radtke, Robert A Huddart, Mehmet A Bilen, Arjun Balar, Daniel Castellano, Srikala S Sridhar, Ugo De Giorgi, Konstantin Penkov, Aleksandr Vasiliev, Avivit Peer, Riikka Järvinen, Hakan Harputluoğlu, Vadim S Koshkin, Shermeen Poushnejad, Tianhua Wang, Anila Qureshi, Mary A Tagliaferri, Jonathan Zalevsky, Yohann Loriot","doi":"10.1016/j.urolonc.2024.09.030","DOIUrl":"https://doi.org/10.1016/j.urolonc.2024.09.030","url":null,"abstract":"<p><strong>Background: </strong>In PIVOT-02, bempegaldesleukin (BEMPEG), a pegylated interleukin-2 cytokine prodrug, in combination with nivolumab (NIVO), a Programmed cell death protein 1 inhibitor, demonstrated the potential to provide additional benefits over immune checkpoint inhibitor monotherapy in patients with urothelial carcinoma, warranting further investigation. We evaluated BEMPEG plus NIVO in cisplatin-ineligible patients with previously untreated locally advanced or metastatic urothelial carcinoma.</p><p><strong>Methods: </strong>This open-label, multicenter, single-arm, phase II study enrolled patients with locally advanced/surgically unresectable or metastatic urothelial carcinoma and who were ineligible for cisplatin-based treatment. Patients received BEMPEG plus NIVO were administered intravenously every 3 weeks for ≤2 years or until progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by blinded independent central review (BICR) in patients with low programmed death ligand-1 (PD-L1) expression. Secondary endpoints included ORR and duration of response in the overall population. Progression-free survival (PFS) and overall survival (OS) were exploratory endpoints.</p><p><strong>Results: </strong>One hundred and eighty-eight patients were enrolled; 123 patients were PD-L1 low (combined positive score [CPS] <10; 65.4%), 59 were PD-L1 high (31.4%; CPS ≥10), and 6 had PD-L1 status unknown (3.2%). ORR per blinded independent central review in patients with PD-L1-low tumors was 17.9% (95% confidence interval [CI] 11.6-25.8) while in all treated patients was 19.7% (95% CI 14.3-26.1). Median PFS and OS in the overall population were 3.0 months and 12.6 months, respectively. BEMPEG plus NIVO combination was well tolerated, with a safety profile similar to previously reported trials; no new or unexpected safety signals were reported.</p><p><strong>Conclusions: </strong>BEMPEG plus NIVO did not meet the efficacy threshold for ORR in patients with previously untreated locally advanced or metastatic urothelial carcinoma and low PD-L1 expression.</p>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547748","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}