As therapeutics in renal cell carcinoma (RCC) continues to advance with approval of novel treatments and recently, adjuvant therapy, the need for highly sensitive tests that go beyond traditional methods to measure disease is becoming more crucial. Tumor informed high sensitivity circulating tumor DNA (ctDNA) assays originally developed for detection of minimal residual disease (MRD) theoretically could be utilized for initial detection of occult disease but also potentially for risk and response assessment in the management of advanced RCC. There are concerns related to the sensitivity of ctDNA based assays in RCC. This article aims to summarize the available evidence for high sensitivity MRD assays in RCC. We included studies with both localized and metastatic stages of RCC. The studies show a varying sensitivity depending on disease settings but a high specificity (∼100%) regardless. Detectable ctDNA appeared to be a significant negative prognostic risk factor for subsequent progressive disease. ctDNA may provide significant lead time allowing physicians to adapt therapy. Several high sensitivity assays with novel analytic approaches are in development for solid tumors including RCC.
{"title":"High Sensitivity Circulating Tumor-DNA Assays in Renal Cell Carcinoma–Are we there yet?","authors":"Fady Sidhom , Shefali Patel , Arpita Desai , Arnab Basu","doi":"10.1016/j.clgc.2024.102235","DOIUrl":"10.1016/j.clgc.2024.102235","url":null,"abstract":"<div><div>As therapeutics in renal cell carcinoma (RCC) continues to advance with approval of novel treatments and recently, adjuvant therapy, the need for highly sensitive tests that go beyond traditional methods to measure disease is becoming more crucial. Tumor informed high sensitivity circulating tumor DNA (ctDNA) assays originally developed for detection of minimal residual disease (MRD) theoretically could be utilized for initial detection of occult disease but also potentially for risk and response assessment in the management of advanced RCC. There are concerns related to the sensitivity of ctDNA based assays in RCC. This article aims to summarize the available evidence for high sensitivity MRD assays in RCC. We included studies with both localized and metastatic stages of RCC. The studies show a varying sensitivity depending on disease settings but a high specificity (∼100%) regardless. Detectable ctDNA appeared to be a significant negative prognostic risk factor for subsequent progressive disease. ctDNA may provide significant lead time allowing physicians to adapt therapy. Several high sensitivity assays with novel analytic approaches are in development for solid tumors including RCC.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"22 6","pages":"Article 102235"},"PeriodicalIF":2.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634594","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 : 2024-10-09DOI: 10.1016/j.clgc.2024.102236
Takuto Hara, Jun Teishima, Yasuyoshi Okamura, Kotaro Suzuki, Yukari Bando, Tomoaki Terakawa, Koji Chiba, Yoji Hyodo, Yuzo Nakano, Hideaki Miyake
Objectives
This study investigated the variations in response patterns, including target lesion enlargement and the emergence of new lesions, in patients with urothelial carcinoma receiving pembrolizumab therapy and assessed the impact of new lesions on patient outcomes.
Methods
This retrospective analysis included patients with urothelial carcinoma treated with pembrolizumab following platinum failure. Response Evaluation Criteria in Solid Tumors criteria were used to assess the target lesion size and appearance of new lesions. Patients were categorized into 2 groups: the primary progressive disease (PD) group, consisting of patients who progressed within 28 to 84 days of treatment initiation, and the secondary PD group, consisting of patients who progressed more than 84 days after treatment initiation. Survival analyses were performed to evaluate the impact of new lesions on patient outcomes.
Results
In this study, 42 patients experienced primary PD, and 37 experienced secondary PD. Among patients with primary PD, 64.3%, 73.8%, 45.2% had an increase of 20% or more in target lesion size, newly emerged lesions, and both an increase in target lesion size and new lesions, respectively. Kaplan–Meier analysis revealed that patients with primary PD and new lesions had significantly shorter overall survival after PD than those with only target lesion growth and those with secondary PD (both P < .001).
Conclusion
This study revealed the heterogeneity of response patterns during pembrolizumab therapy in patients with urothelial carcinoma and primary pembrolizumab resistance and the presence of new lesions early in treatment. Earlier imaging evaluation should be performed to assess for the appearance of new lesions, leading to sequential treatment.
{"title":"Appearance of New Lesions Associate With Poor Prognosis in Pembrolizumab-Treated Urothelial Carcinoma","authors":"Takuto Hara, Jun Teishima, Yasuyoshi Okamura, Kotaro Suzuki, Yukari Bando, Tomoaki Terakawa, Koji Chiba, Yoji Hyodo, Yuzo Nakano, Hideaki Miyake","doi":"10.1016/j.clgc.2024.102236","DOIUrl":"10.1016/j.clgc.2024.102236","url":null,"abstract":"<div><h3>Objectives</h3><div>This study investigated the variations in response patterns, including target lesion enlargement and the emergence of new lesions, in patients with urothelial carcinoma receiving pembrolizumab therapy and assessed the impact of new lesions on patient outcomes.</div></div><div><h3>Methods</h3><div>This retrospective analysis included patients with urothelial carcinoma treated with pembrolizumab following platinum failure. Response Evaluation Criteria in Solid Tumors criteria were used to assess the target lesion size and appearance of new lesions. Patients were categorized into 2 groups: the primary progressive disease (PD) group, consisting of patients who progressed within 28 to 84 days of treatment initiation, and the secondary PD group, consisting of patients who progressed more than 84 days after treatment initiation. Survival analyses were performed to evaluate the impact of new lesions on patient outcomes.</div></div><div><h3>Results</h3><div>In this study, 42 patients experienced primary PD, and 37 experienced secondary PD. Among patients with primary PD, 64.3%, 73.8%, 45.2% had an increase of 20% or more in target lesion size, newly emerged lesions, and both an increase in target lesion size and new lesions, respectively. Kaplan–Meier analysis revealed that patients with primary PD and new lesions had significantly shorter overall survival after PD than those with only target lesion growth and those with secondary PD (both <em>P</em> < .001).</div></div><div><h3>Conclusion</h3><div>This study revealed the heterogeneity of response patterns during pembrolizumab therapy in patients with urothelial carcinoma and primary pembrolizumab resistance and the presence of new lesions early in treatment. Earlier imaging evaluation should be performed to assess for the appearance of new lesions, leading to sequential treatment.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"22 6","pages":"Article 102236"},"PeriodicalIF":2.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549466","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 : 2024-10-05DOI: 10.1016/j.clgc.2024.102233
Nahuel Paesano , María José Gutiérrez Vallecillo , Violeta Catalá , Larisa Tcholakian , Xavier Alomar , Miguel Barranco , Abel González-Huete , Jonathan Hernández Mancera , Enric Trilla , Juan Morote
Purpose
Prostate-magnetic resonance imaging (MRI) interpretation is challenging, with expertise playing a crucial role. Biparametric MRI (bpMRI) is gaining popularity in experienced centers due to its time and cost advantages over multiparametric MRI (mpMRI). We aim to analyze concordance between nonexpert radiologist PI-RADS from mpMRI and expert radiologist PI-RADS from bpMRI, and its clinical implications.
Material and Methods
222 men suspected of having prostate cancer (PCa) and mpMRI reported by nonexpert radiologists were referred to a reference center for transperineal MRI-TRUS fusion biopsy where an expert radiologist reported bpMRI PI-RADS 2.1 and segmentation, blinded to external mpMRI. Mapping targeted suspected lesions and 12-core systematic biopsies were performed. Clinically significant PCa (csPCa) was diagnosed when ISUP-grade group was ≥2.
Results
Concordance between both PI-RADS existed in 49.1% of cases (Kappa index 0.288). In 102 cases (45.9%), expert reclassification to lower PI-RADS existed, while an increase existed in 11 cases (5.0%), P < .001. Agreement existed in 30.8% of nonexpert PI-RADS 3, 43.6% of PI-RADS 4, and 83.7% of PI-RADS 5, P < .001. Potential clinical implications included 27% reduction in prostate biopsies when using expert bpMRI readings compared to nonexpert mpMRI readings (P < 0.001), while undetected csPCa were 4.2% and 3.4%, respectively, P = .669. Over-detection reduction of insignificant PCa was 29.4% and 0%, respectively, P = .034.
Conclusions
Concordance between nonexpert PI-RADS mpMRI and expert PI-RADS bpMRI was low, increasing with nonexpert PI-RADS. Expert reclassification would reduce prostate biopsies by more than one quarter and over-detection of iPCa, while csPCa detection remained similar.
{"title":"Concordance Between the Expert Reading of Biparametric-MRI and the Nonexpert Multiparametric-MRI for the Detection of Clinically Significant Prostate Cancer: Clinical Implications","authors":"Nahuel Paesano , María José Gutiérrez Vallecillo , Violeta Catalá , Larisa Tcholakian , Xavier Alomar , Miguel Barranco , Abel González-Huete , Jonathan Hernández Mancera , Enric Trilla , Juan Morote","doi":"10.1016/j.clgc.2024.102233","DOIUrl":"10.1016/j.clgc.2024.102233","url":null,"abstract":"<div><h3>Purpose</h3><div>Prostate-magnetic resonance imaging (MRI) interpretation is challenging, with expertise playing a crucial role. Biparametric MRI (bpMRI) is gaining popularity in experienced centers due to its time and cost advantages over multiparametric MRI (mpMRI). We aim to analyze concordance between nonexpert radiologist PI-RADS from mpMRI and expert radiologist PI-RADS from bpMRI, and its clinical implications.</div></div><div><h3>Material and Methods</h3><div>222 men suspected of having prostate cancer (PCa) and mpMRI reported by nonexpert radiologists were referred to a reference center for transperineal MRI-TRUS fusion biopsy where an expert radiologist reported bpMRI PI-RADS 2.1 and segmentation, blinded to external mpMRI. Mapping targeted suspected lesions and 12-core systematic biopsies were performed. Clinically significant PCa (csPCa) was diagnosed when ISUP-grade group was ≥2.</div></div><div><h3>Results</h3><div>Concordance between both PI-RADS existed in 49.1% of cases (Kappa index 0.288). In 102 cases (45.9%), expert reclassification to lower PI-RADS existed, while an increase existed in 11 cases (5.0%), <em>P</em> < .001. Agreement existed in 30.8% of nonexpert PI-RADS 3, 43.6% of PI-RADS 4, and 83.7% of PI-RADS 5, <em>P</em> < .001. Potential clinical implications included 27% reduction in prostate biopsies when using expert bpMRI readings compared to nonexpert mpMRI readings (<em>P</em> < 0.001), while undetected csPCa were 4.2% and 3.4%, respectively, <em>P</em> = .669. Over-detection reduction of insignificant PCa was 29.4% and 0%, respectively, <em>P</em> = .034.</div></div><div><h3>Conclusions</h3><div>Concordance between nonexpert PI-RADS mpMRI and expert PI-RADS bpMRI was low, increasing with nonexpert PI-RADS. Expert reclassification would reduce prostate biopsies by more than one quarter and over-detection of iPCa, while csPCa detection remained similar.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"22 6","pages":"Article 102233"},"PeriodicalIF":2.3,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514699","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 : 2024-10-05DOI: 10.1016/j.clgc.2024.102230
Anna Patrikidou , Calogero Saieva , Richard Lee-Ying , Pier Vitale Nuzzo , Talal El Zarif , Heather McClure , Matthew Davidsohn , Marc Eid , Gian Paolo Spinelli , Fabio Catalano , Malvina Cremante , Giuseppe Fotia , Sabrina Rossetti , Loana Valenca , Charles Vauchier , Carlotta Ottanelli , Livia Andrade , Vincenzo Gennusa , Ricardo Pereira Mestre , Giuseppe Fornarini , Edoardo Francini
Background
Androgen receptor signalling inhibitors (ARSIs) abiraterone acetate (AA) enzalutamide (Enza), are currently the standard first-line (L1) treatments for metastatic castration-resistant prostate cancer (mCRPC), and docetaxel (D) is reserved as second-line (L2) after ARSI failure. Nonetheless, D use in men ≥ 75 years old is restricted owing to treatment toxicities and patient comorbidities, and a L2 alternative ARSI is frequently used. We aimed to evaluate real-life survival and toxicity outcomes of these elderly patients after failure of L1 ARSI treatment.
Material and Methods
We retrospectively evaluated efficacy and safety in a real-world international cohort of consecutive patients ≥ 75 years old when starting L1 ARSI for mCRPC according to the choice of L2 treatment (D versus alternative ARSI).
Results
Of the 122 identified patients, 57 (46.7%) had received L2 ARSI and 65 (53.3%) L2 D. No difference was found in the L1 overall survival (OS) for the ARSI and D groups (32.8 vs. 30.0 months, respectively; Hazard ratio [HR] = 1.22; 95% CI, 0.77-1.95; P = .40) or in the L2 OS (18.5 vs. 17.8 months, respectively; HR = 1.09; 95% CI, 0.69-1.74; P = .71). No difference was observed for rPFS from L2 (P = .12), although a trend was observed for a numerically improved rPFS on D.
Conclusion
Within the limitations of a retrospective design and small population, our study suggests that D or ARSI after failure of L1 alternative ARSI are clinically comparable L2 options for elderly patients with mCRPC.
{"title":"Docetaxel Versus Androgen-Receptor Signaling Inhibitors (ARSI) as Second-Line Therapy After Failure of First-Line Alternative ARSI for the Elderly ≥ 75 Years Old With Metastatic Castration-Resistant Prostate Cancer (mCRPC): A SPARTACUSS—Meet-URO 26 Real-World Study","authors":"Anna Patrikidou , Calogero Saieva , Richard Lee-Ying , Pier Vitale Nuzzo , Talal El Zarif , Heather McClure , Matthew Davidsohn , Marc Eid , Gian Paolo Spinelli , Fabio Catalano , Malvina Cremante , Giuseppe Fotia , Sabrina Rossetti , Loana Valenca , Charles Vauchier , Carlotta Ottanelli , Livia Andrade , Vincenzo Gennusa , Ricardo Pereira Mestre , Giuseppe Fornarini , Edoardo Francini","doi":"10.1016/j.clgc.2024.102230","DOIUrl":"10.1016/j.clgc.2024.102230","url":null,"abstract":"<div><h3>Background</h3><div>Androgen receptor signalling inhibitors (ARSIs) abiraterone acetate (AA) enzalutamide (Enza), are currently the standard first-line (L1) treatments for metastatic castration-resistant prostate cancer (mCRPC), and docetaxel (D) is reserved as second-line (L2) after ARSI failure. Nonetheless, D use in men ≥ 75 years old is restricted owing to treatment toxicities and patient comorbidities, and a L2 alternative ARSI is frequently used. We aimed to evaluate real-life survival and toxicity outcomes of these elderly patients after failure of L1 ARSI treatment.</div></div><div><h3>Material and Methods</h3><div>We retrospectively evaluated efficacy and safety in a real-world international cohort of consecutive patients ≥ 75 years old when starting L1 ARSI for mCRPC according to the choice of L2 treatment (D versus alternative ARSI).</div></div><div><h3>Results</h3><div>Of the 122 identified patients, 57 (46.7%) had received L2 ARSI and 65 (53.3%) L2 D. No difference was found in the L1 overall survival (OS) for the ARSI and D groups (32.8 vs. 30.0 months, respectively; Hazard ratio [HR] = 1.22; 95% CI, 0.77-1.95; <em>P</em> = .40) or in the L2 OS (18.5 vs. 17.8 months, respectively; HR = 1.09; 95% CI, 0.69-1.74; <em>P</em> = .71). No difference was observed for rPFS from L2 (<em>P</em> = .12), although a trend was observed for a numerically improved rPFS on D.</div></div><div><h3>Conclusion</h3><div>Within the limitations of a retrospective design and small population, our study suggests that D or ARSI after failure of L1 alternative ARSI are clinically comparable L2 options for elderly patients with mCRPC.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"22 6","pages":"Article 102230"},"PeriodicalIF":2.3,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-04DOI: 10.1016/j.clgc.2024.102228
Deniz Tural , Cagatay Arslan , Fatih Selcukbiricik , Omer Fatih Olmez , Emre Akar , Mustafa Erman , Yüksel Ürün , Dilek Erdem , Saadettin Kilickap
Background
In this study, we reported the real-life results of data from impaired renal patients with urothelial carcinoma who were treated with ICTs.
Methods
The patients were categorized into 3 different groups GFR ≥60mL/min (normal), 60mL/min-30mL/min (low), and less than 30 mL/min (very low) based on GFR. The primary endpoints were the overall response rate (ORR), overall survival (OS), duration of response with ICT, and safety. Median follow-up and OS were estimated by using the Kaplan-Meier method.
Results
One hundred-five (60.3%) of patients were GFR normal, 26.4% were GFR low with 30mL/min-60mL/min, and 13.2% were very low group. ORR for GFR normal, low and very low groups were 36% (n = 38), 26% (n = 12) and %31 (7); P = .2, respectively. The median duration of response for GFR normal, low and very low groups were 47.2 months (95% CI, 24.5-51.4), 33.1 months (95% CI, 26.9-47), and 23.5 months (95% CI, 12.2-43.7); P = .01, respectively. The Median OS rate for GFR normal, low and very low groups were 11.9 (7.2-16.5) months, 4.7 (1.8-7.7) and 6.8 (1.1-13.6) months, P = .015, respectively. In addition, GFR <60 ml/min HR = 1.6; 95% CI 1.12-1.80; P = .02, maintained a significant association with OS in multivariate analysis.
Conclusions
Long-term follow-up of real-world data confirms that the overall survival rate and durable response rate with ICT were higher in patients with GFR >60mL/min. On the other hand, we demonstrated that ICT was effective and a durable response seen in a group of patients with renal inpairement who did not have an effective systemic treatment option.
背景在这项研究中，我们报告了肾功能受损的尿路上皮癌患者接受信息通信技术治疗的实际结果：根据 GFR 将患者分为 GFR ≥60mL/min（正常）、60mL/min-30mL/min（低）和小于 30 mL/min（极低）三组。主要终点是总反应率（ORR）、总生存期（OS）、ICT反应持续时间和安全性。中位随访时间和OS采用Kaplan-Meier法估算：结果：15 名患者（60.3%）的 GFR 正常，26.4% 的患者 GFR 较低，在 30mL/min-60mL/min 之间，13.2% 的患者 GFR 很低。GFR正常组、低组和极低组的ORR分别为36%（38人）、26%（12人）和%31（7人）；P = .2。GFR正常组、低组和极低组的中位反应持续时间分别为47.2个月（95% CI，24.5-51.4）、33.1个月（95% CI，26.9-47）和23.5个月（95% CI，12.2-43.7）；P = .01。GFR正常组、低组和极低组的中位OS率分别为11.9（7.2-16.5）个月、4.7（1.8-7.7）个月和6.8（1.1-13.6）个月，P = .015。此外，GFR对真实世界数据的长期随访证实，GFR>60mL/min的患者使用ICT的总生存率和持久应答率更高。另一方面，我们也证明了 ICT 的疗效，并在一组没有有效全身治疗方案的肾功能不全患者中看到了持久的反应。
{"title":"Immune Checkpoint Blockade Therapies Efficacy and Toxicity in Patients With Impaired Renal Function in Metastatic Bladder Cancer","authors":"Deniz Tural , Cagatay Arslan , Fatih Selcukbiricik , Omer Fatih Olmez , Emre Akar , Mustafa Erman , Yüksel Ürün , Dilek Erdem , Saadettin Kilickap","doi":"10.1016/j.clgc.2024.102228","DOIUrl":"10.1016/j.clgc.2024.102228","url":null,"abstract":"<div><h3>Background</h3><div>In this study, we reported the real-life results of data from impaired renal patients with urothelial carcinoma who were treated with ICTs.</div></div><div><h3>Methods</h3><div>The patients were categorized into 3 different groups GFR ≥60mL/min (normal), 60mL/min-30mL/min (low), and less than 30 mL/min (very low) based on GFR. The primary endpoints were the overall response rate (ORR), overall survival (OS), duration of response with ICT, and safety. Median follow-up and OS were estimated by using the Kaplan-Meier method.</div></div><div><h3>Results</h3><div>One hundred-five (60.3%) of patients were GFR normal, 26.4% were GFR low with 30mL/min-60mL/min, and 13.2% were very low group. ORR for GFR normal, low and very low groups were 36% (<em>n</em> = 38), 26% (<em>n</em> = 12) and %31 (7); <em>P</em> = .2, respectively. The median duration of response for GFR normal, low and very low groups were 47.2 months (95% CI, 24.5-51.4), 33.1 months (95% CI, 26.9-47), and 23.5 months (95% CI, 12.2-43.7); <em>P</em> = .01, respectively. The Median OS rate for GFR normal, low and very low groups were 11.9 (7.2-16.5) months, 4.7 (1.8-7.7) and 6.8 (1.1-13.6) months, <em>P</em> = .015, respectively. In addition, GFR <60 ml/min HR = 1.6; 95% CI 1.12-1.80; <em>P</em> = .02, maintained a significant association with OS in multivariate analysis.</div></div><div><h3>Conclusions</h3><div>Long-term follow-up of real-world data confirms that the overall survival rate and durable response rate with ICT were higher in patients with GFR >60mL/min. On the other hand, we demonstrated that ICT was effective and a durable response seen in a group of patients with renal inpairement who did not have an effective systemic treatment option.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"22 6","pages":"Article 102228"},"PeriodicalIF":2.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514711","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 : 2024-10-04DOI: 10.1016/j.clgc.2024.102234
Jane McKenzie , Ciara Conduit , Melissa Ng Liet Hing , Kristina Zlatic , Kerrie Stokes , Sharlea Disney , Amit Khot , Simon J. Harrison , Jeremy Lewin , Ben Tran
•
At relapse, testicular germ cell tumors may be treated with high-dose chemotherapy and autologous stem cell transplant.
•
Traditional chemomobilisation protocols for autologous stem cell transplant may be unsuitable for pretreated patients.
•
Gemcitabine and Oxaliplatin provides satisfactory stem cell mobilization and treatment outcomes for this high-risk group.
{"title":"Chemomobilisation Using Gemcitabine-Oxaliplatin for Salvage High Dose Chemotherapy and Autologous Stem Cell Transplant in Advanced Testicular Germ Cell Cancer","authors":"Jane McKenzie , Ciara Conduit , Melissa Ng Liet Hing , Kristina Zlatic , Kerrie Stokes , Sharlea Disney , Amit Khot , Simon J. Harrison , Jeremy Lewin , Ben Tran","doi":"10.1016/j.clgc.2024.102234","DOIUrl":"10.1016/j.clgc.2024.102234","url":null,"abstract":"<div><div><ul><li><span>•</span><span><div>At relapse, testicular germ cell tumors may be treated with high-dose chemotherapy and autologous stem cell transplant.</div></span></li><li><span>•</span><span><div>Traditional chemomobilisation protocols for autologous stem cell transplant may be unsuitable for pretreated patients.</div></span></li><li><span>•</span><span><div>Gemcitabine and Oxaliplatin provides satisfactory stem cell mobilization and treatment outcomes for this high-risk group.</div></span></li></ul></div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"22 6","pages":"Article 102234"},"PeriodicalIF":2.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142535138","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 : 2024-10-03DOI: 10.1016/j.clgc.2024.102231
Younjuong Kim , Jun Gyo Gwon , Hyun Young Lee , Bumjin Lim , Jung Kwon Kim , Cheryn Song , Dalsan You , In Gab Jeong , Jun Hyuk Hong , Bumsik Hong , Hanjong Ahn , Jungyo Suh
Objective
To assess the impact of age on cancer-specific mortality (CSM) and other-cause mortality (OCM) in patients undergoing radical nephrectomy with thrombectomy (RNTx) for renal cell carcinoma (RCC) with venous thrombus.
Patients and Methods
We retrospectively analyzed 196 patients who underwent RNTx for RCC with venous thrombus between 1990 and 2018 at a single tertiary referral center. Patients were categorized into three age groups: <60, 60-69, and ≥70 years. The cumulative incidence function (CIF) for CSM and OCM was calculated using the Aalen-Johansen estimator, and hazard ratios (HR) from sub-distributional hazard (SDH) and cause-specific hazard (CSH) models were employed to assess the impact of age on mortality.
Results
The median follow-up was 40.5 months. Of the 196 patients, 105 experienced disease progression, 125 had cancerrelated deaths, and 155 died from any cause. Perioperative outcomes, including ICU admission, 90-day readmission, and 90-day mortality, were similar across age groups. The CIF for 5-year CSM differed significantly among age groups (p = 0.032), though this difference was not observed at 10 years. OCM increased significantly with age, particularly in the ≥70 group at 10 years (p = 0.045). Multivariable SDH and CSH models showed no significant differences in CSM between age groups.
Conclusion
While age was associated with increased OCM, it did not significantly impact the hazard of CSM. Older age alone should not be considered a contraindication for surgical intervention in RCC with venous thrombus.
{"title":"Age Does Not Impact Cancer Specific Mortality: From Sub-Distributional and Cause-Specific Hazard Analysis in RCC Patients Undergoing Radical Nephrectomy and Thrombectomy","authors":"Younjuong Kim , Jun Gyo Gwon , Hyun Young Lee , Bumjin Lim , Jung Kwon Kim , Cheryn Song , Dalsan You , In Gab Jeong , Jun Hyuk Hong , Bumsik Hong , Hanjong Ahn , Jungyo Suh","doi":"10.1016/j.clgc.2024.102231","DOIUrl":"10.1016/j.clgc.2024.102231","url":null,"abstract":"<div><h3>Objective</h3><div>To assess the impact of age on cancer-specific mortality (CSM) and other-cause mortality (OCM) in patients undergoing radical nephrectomy with thrombectomy (RNTx) for renal cell carcinoma (RCC) with venous thrombus.</div></div><div><h3>Patients and Methods</h3><div>We retrospectively analyzed 196 patients who underwent RNTx for RCC with venous thrombus between 1990 and 2018 at a single tertiary referral center. Patients were categorized into three age groups: <60, 60-69, and ≥70 years. The cumulative incidence function (CIF) for CSM and OCM was calculated using the Aalen-Johansen estimator, and hazard ratios (HR) from sub-distributional hazard (SDH) and cause-specific hazard (CSH) models were employed to assess the impact of age on mortality.</div></div><div><h3>Results</h3><div>The median follow-up was 40.5 months. Of the 196 patients, 105 experienced disease progression, 125 had cancerrelated deaths, and 155 died from any cause. Perioperative outcomes, including ICU admission, 90-day readmission, and 90-day mortality, were similar across age groups. The CIF for 5-year CSM differed significantly among age groups (<em>p</em> = 0.032), though this difference was not observed at 10 years. OCM increased significantly with age, particularly in the ≥70 group at 10 years (<em>p</em> = 0.045). Multivariable SDH and CSH models showed no significant differences in CSM between age groups.</div></div><div><h3>Conclusion</h3><div>While age was associated with increased OCM, it did not significantly impact the hazard of CSM. Older age alone should not be considered a contraindication for surgical intervention in RCC with venous thrombus.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"22 6","pages":"Article 102231"},"PeriodicalIF":2.3,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549465","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 : 2024-09-24DOI: 10.1016/j.clgc.2024.102227
Zakaria Chakrani , Mann Patel , George Mellgard , Stephen McCroskery , Nathaniel Saffran , Nicole Taylor , Bobby C. Liaw , Matthew Galsky , William Oh , Che-Kai Tsao , Teja Ganta , Vaibhav Patel
Background
Statins may provide a compounded effect on ART by decreasing cholesterol levels thus decreasing de novo androgen synthesis and tumor cell viability. We investigated the clinical efficacy of concurrent statin use on outcomes of patients with mCRPC taking ART.
Methods
A single-institution retrospective analysis of patients with mCRPC receiving ART from 2010 to 2021 was performed. Our primary outcome was PSA progression free survival (PFS), and our secondary outcomes were overall survival (OS). Patient characteristics were collected in addition to ART treatment course, statin treatment, and survival outcomes. Cox proportional hazards regression model was used to estimate hazard ratios (HR) for OS and PSA PFS and multivariable logistic regression to determine risk factors.
Results
153 patients with mCRPC treated with ART were included. A total of 67 patients (43.8%) received concurrent statins. Median PSA PFS was 20.4 months for patients that received statins versus 15.3 months for patients who did not receive statins. Median OS was 45.1 months for patients who received concurrent statins versus 29.7 months for patients who did not. On univariate and multivariate survival analyses, there was no statistically significant difference between groups for PSA PFS (HR 0.7; CI 0.44-1.1; P = .123) and OS (HR 0.67; CI 0.42-1.06; P = .089).
Conclusions
Our analysis suggests that statins do not significantly improve clinical outcomes in patients with mCRPC. Ultimately, current understanding remains limited, and prospective studies are needed, but here we provide a cost-effective, timely, and selective preliminary analysis.
{"title":"The Association of Statin Use With Survival Outcomes in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treated With Androgen Receptor Targeted Therapies (ART)","authors":"Zakaria Chakrani , Mann Patel , George Mellgard , Stephen McCroskery , Nathaniel Saffran , Nicole Taylor , Bobby C. Liaw , Matthew Galsky , William Oh , Che-Kai Tsao , Teja Ganta , Vaibhav Patel","doi":"10.1016/j.clgc.2024.102227","DOIUrl":"10.1016/j.clgc.2024.102227","url":null,"abstract":"<div><h3>Background</h3><div>Statins may provide a compounded effect on ART by decreasing cholesterol levels thus decreasing de novo androgen synthesis and tumor cell viability. We investigated the clinical efficacy of concurrent statin use on outcomes of patients with mCRPC taking ART.</div></div><div><h3>Methods</h3><div>A single-institution retrospective analysis of patients with mCRPC receiving ART from 2010 to 2021 was performed. Our primary outcome was PSA progression free survival (PFS), and our secondary outcomes were overall survival (OS). Patient characteristics were collected in addition to ART treatment course, statin treatment, and survival outcomes. Cox proportional hazards regression model was used to estimate hazard ratios (HR) for OS and PSA PFS and multivariable logistic regression to determine risk factors.</div></div><div><h3>Results</h3><div>153 patients with mCRPC treated with ART were included. A total of 67 patients (43.8%) received concurrent statins. Median PSA PFS was 20.4 months for patients that received statins versus 15.3 months for patients who did not receive statins. Median OS was 45.1 months for patients who received concurrent statins versus 29.7 months for patients who did not. On univariate and multivariate survival analyses, there was no statistically significant difference between groups for PSA PFS (HR 0.7; CI 0.44-1.1; <em>P</em> = .123) and OS (HR 0.67; CI 0.42-1.06; <em>P</em> = .089).</div></div><div><h3>Conclusions</h3><div>Our analysis suggests that statins do not significantly improve clinical outcomes in patients with mCRPC. Ultimately, current understanding remains limited, and prospective studies are needed, but here we provide a cost-effective, timely, and selective preliminary analysis.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"22 6","pages":"Article 102227"},"PeriodicalIF":2.3,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514712","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 : 2024-09-20DOI: 10.1016/j.clgc.2024.102214
Moritz J. Reike , Daniele Raggi , Chiara Mercinelli , Antonio Cigliola , Valentina Tateo , Damiano Alfio Patanè , Emanuele Crupi , Tiago Costa de Padua , Peter C. Black , Ewan A. Gibb , Andrea Necchi
Purpose
The PURE-01 clinical trial reported the use of neoadjuvant treatment with pembrolizumab prior to radical cystectomy (RC) in patients with muscle-invasive bladder. Specific molecular subtypes and immune signatures were reported to be associated with a favorable survival. However, reports on the detailed tumor biology of patients relapsing after neoadjuvant pembrolizumab are lacking.
Materials and Methods
Microarray data from transurethral resection of the bladder tumor (TURBT; n = 102) and matched RC (N = 25) tissue from patients in PURE-01 who experience a disease relapse were analyzed, with gene expression signatures and molecular subtypes. The Kaplan–Meier method was used to estimate differences in patient outcomes. Immune-signatures were split by median for survival analysis. All significance testing used a two-sided t-test at a threshold of P < .05.
Results
The study cohort consisted of 102 patients, of whom N = 19 (19%) experienced relapse. Molecular subtyping revealed that neuroendocrine-like tumors had the worst outcomes, while tumors classified as Claudin-low did show only one recurrence event. Differential gene expression analysis identified genes associated with relapse, including KRT20, H19, and immune-associated genes such as CXCL9 and CXCL11.
Conclusion
This study provides a detailed characterization of patients who relapsed after neoadjuvant pembrolizumab and RC and identifies distinct gene expression patterns associated with relapse. These findings may have implications for predicting patient response and guiding treatment decisions in the neoadjuvant setting.
目的：PURE-01 临床试验报告了在对肌肉浸润性膀胱患者进行根治性膀胱切除术（RC）前使用 pembrolizumab 进行新辅助治疗的情况。据报道，特定的分子亚型和免疫特征与良好的生存率有关。然而，关于新辅助治疗后复发的患者的详细肿瘤生物学情况还缺乏报道：分析了 PURE-01 中复发患者经尿道膀胱肿瘤切除术（TURBT；n = 102）和匹配的 RC（n = 25）组织的微阵列数据，以及基因表达特征和分子亚型。采用 Kaplan-Meier 法估计患者预后的差异。免疫特征按中位数分割，用于生存分析。所有显著性检验均采用双侧 t 检验，阈值为 P <.05：研究队列由102名患者组成，其中19人（19%）复发。分子亚型分析显示，神经内分泌样肿瘤的预后最差，而被归类为Claudin-low的肿瘤仅有一次复发。差异基因表达分析确定了与复发相关的基因，包括KRT20、H19和免疫相关基因，如CXCL9和CXCL11：这项研究详细描述了新辅助治疗彭博利珠单抗和RC后复发患者的特征，并确定了与复发相关的不同基因表达模式。这些发现可能会对预测患者反应和指导新辅助治疗决策产生影响。
{"title":"Distinct Gene Expression Patterns Identify Patients who Relapse After Neoadjuvant Pembrolizumab and Radical Cystectomy in the PURE-01 Study","authors":"Moritz J. Reike , Daniele Raggi , Chiara Mercinelli , Antonio Cigliola , Valentina Tateo , Damiano Alfio Patanè , Emanuele Crupi , Tiago Costa de Padua , Peter C. Black , Ewan A. Gibb , Andrea Necchi","doi":"10.1016/j.clgc.2024.102214","DOIUrl":"10.1016/j.clgc.2024.102214","url":null,"abstract":"<div><h3>Purpose</h3><div>The PURE-01 clinical trial reported the use of neoadjuvant treatment with pembrolizumab prior to radical cystectomy (RC) in patients with muscle-invasive bladder. Specific molecular subtypes and immune signatures were reported to be associated with a favorable survival. However, reports on the detailed tumor biology of patients relapsing after neoadjuvant pembrolizumab are lacking.</div></div><div><h3>Materials and Methods</h3><div>Microarray data from transurethral resection of the bladder tumor (TURBT; n = 102) and matched RC (N = 25) tissue from patients in PURE-01 who experience a disease relapse were analyzed, with gene expression signatures and molecular subtypes. The Kaplan–Meier method was used to estimate differences in patient outcomes. Immune-signatures were split by median for survival analysis. All significance testing used a two-sided t-test at a threshold of <em>P</em> < .05.</div></div><div><h3>Results</h3><div>The study cohort consisted of 102 patients, of whom N = 19 (19%) experienced relapse. Molecular subtyping revealed that neuroendocrine-like tumors had the worst outcomes, while tumors classified as Claudin-low did show only one recurrence event. Differential gene expression analysis identified genes associated with relapse, including KRT20, H19, and immune-associated genes such as CXCL9 and CXCL11.</div></div><div><h3>Conclusion</h3><div>This study provides a detailed characterization of patients who relapsed after neoadjuvant pembrolizumab and RC and identifies distinct gene expression patterns associated with relapse. These findings may have implications for predicting patient response and guiding treatment decisions in the neoadjuvant setting.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"22 6","pages":"Article 102214"},"PeriodicalIF":2.3,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514698","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 : 2024-09-17DOI: 10.1016/j.clgc.2024.102224
Vincent E. Xu , Oluwafolajimi Adesanya , Sarah Azari , Samita Islam , Matthew Klein , Arthur Drouaud , Ryan M. Antar , Phat Chang , Armine Smith , Michael J Whalen
Introduction
Upper tract urothelial carcinoma (UTUC) is a rare malignancy with poor prognosis. Radical nephroureterectomy (RNU) remains the standard treatment for high-risk UTUC. Considering the decline in renal function with RNU and results from prospective trials, NAC has emerged as a favored perioperative treatment for chemo-eligible patients with UTUC. However, strong evidence of the efficacy of NAC and predictors for its use are scarce. We aimed to assess trends in NAC utilization and pathologic outcomes and survival with NAC use.
Methods
The National Cancer Database was queried for patients with high-grade cTanyNanyM0 UTUC treated with RNU from 2004 to 2019. Outcomes included overall survival (OS), pathologic response (pR) and pathologic complete response (pCR), defined as ≤pT1pN0/X and pT0pN0/X, respectively.
Results
Of 6,645 patients treated with RNU, 209 received RNU NAC. Greater distance from treatment facility decreased the likelihood of receiving NAC. Higher cT stages (OR 1.72, P = .028), cN+ status (OR 7.40, P < .001) and treatment at an academic facility (OR 2.02, P < .001) predicted NAC treatment. NAC was associated with 34.0% pR and 5.3% pCR. In multivariable analysis, patients with pR and pCR had improved OS (HR = 0.176, P < .014).
Conclusion
We report significant response rates with NAC and improved OS in patients who experienced pR or pCR. Over a 15-year study period, NAC was underutilized, especially in nonacademic settings and among patients living farther from care facilities, underscoring the need for improved regionalization and multidisciplinary approaches in UTUC management.
{"title":"Analysis of Neoadjuvant Chemotherapy Utilization, Pathologic Response, and Overall Survival in Upper Tract Urothelial Carcinoma","authors":"Vincent E. Xu , Oluwafolajimi Adesanya , Sarah Azari , Samita Islam , Matthew Klein , Arthur Drouaud , Ryan M. Antar , Phat Chang , Armine Smith , Michael J Whalen","doi":"10.1016/j.clgc.2024.102224","DOIUrl":"10.1016/j.clgc.2024.102224","url":null,"abstract":"<div><h3>Introduction</h3><div>Upper tract urothelial carcinoma (UTUC) is a rare malignancy with poor prognosis. Radical nephroureterectomy (RNU) remains the standard treatment for high-risk UTUC. Considering the decline in renal function with RNU and results from prospective trials, NAC has emerged as a favored perioperative treatment for chemo-eligible patients with UTUC. However, strong evidence of the efficacy of NAC and predictors for its use are scarce. We aimed to assess trends in NAC utilization and pathologic outcomes and survival with NAC use.</div></div><div><h3>Methods</h3><div>The National Cancer Database was queried for patients with high-grade cTanyNanyM0 UTUC treated with RNU from 2004 to 2019. Outcomes included overall survival (OS), pathologic response (pR) and pathologic complete response (pCR), defined as ≤pT1pN0/X and pT0pN0/X, respectively.</div></div><div><h3>Results</h3><div>Of 6,645 patients treated with RNU, 209 received RNU NAC. Greater distance from treatment facility decreased the likelihood of receiving NAC. Higher cT stages (OR 1.72, <em>P</em> = .028), cN+ status (OR 7.40, <em>P</em> < .001) and treatment at an academic facility (OR 2.02, <em>P</em> < .001) predicted NAC treatment. NAC was associated with 34.0% pR and 5.3% pCR. In multivariable analysis, patients with pR and pCR had improved OS (HR = 0.176, <em>P</em> < .014).</div></div><div><h3>Conclusion</h3><div>We report significant response rates with NAC and improved OS in patients who experienced pR or pCR. Over a 15-year study period, NAC was underutilized, especially in nonacademic settings and among patients living farther from care facilities, underscoring the need for improved regionalization and multidisciplinary approaches in UTUC management.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"22 6","pages":"Article 102224"},"PeriodicalIF":2.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441172","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}
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