Pub Date : 2025-03-01DOI: 10.1016/j.urolonc.2024.12.049
Spyridon P Basourakos, Grant Henning, Reza Nabavizadeh, Maddy Dorr, John Cheville John Cheville, Brian A. Costello, Stephen A Boorjian, Bradley C Leibovich, Vidit Sharma
<div><h3>Introduction</h3><div>The likelihood of recurrence after surgery for non-metastatic renal cell carcinoma (RCC) with venous tumor thrombus (VTT) remains considerable and previously developed predictive models remain underutilized in clinical practice. Adjuvant pembrolizumab was recently FDA approved and all RCC patients with VTT technically fall under the FDA approval guidance. However, we have previously conducted a cost-effectiveness analysis to demonstrate that the 3% survival benefit of adjuvant pembrolizumab outweighs its costs and risks when the 5-year risk of metastasis is at least 60%. As such, many patients with RCC and VTT may not benefit from adjuvant pembrolizumab treatment. The purpose of this study was to develop and internally validate an easy-to-use metastasis risk calculator after radical nephrectomy for non-metastatic RCC with VTT.</div></div><div><h3>Methods</h3><div>We performed a single-institution retrospective analysis of all adult patients who underwent radical nephrectomy with thrombectomy for non-metastatic RCC with VTT between 2000 and 2021. Demographic, clinicopathologic, and procedural characteristics were examined for association with the primary outcome of metastasis-free survival (MFS). A 70%-30% split was used to divide the cohort into a development/training and validation cohort, respectively. A least absolute shrinkage and selection operation (LASSO) Cox regression model was used to select variable combinations that best correlated with RCC metastasis. These variables were used to develop an MFS nomogram for which the area under the curve (AUC) was measured at 5 years. Decision curve analysis was performed to compare the net benefit of a nomogram-based strategy vs a treat-all strategy.</div></div><div><h3>Results</h3><div>Of the 532 M0 patients, 278 (52.3%), 66 (12.4%), 116 (21.8%), 35 (6.6%), and 37 (7.0%) had a level 0, I, II, III, and IV thrombus, respectively. Baseline characteristics are found in <strong>Table 1</strong>. The 5-year MFS for VTT level 0, I, II, III, IV was 51.2%, 34.7%, 28.5%, and 33.7%, respectively (p<0.01). Using LASSO feature selection, an MFS nomogram (<strong>Figure 1A</strong>) was built using four pathologic variables: thrombus level, necrosis, sarcomatoid, and positive nodes. The nomogram separated patients into low (36% of cohort), medium, and high-risk groups for metastasis (<strong>Figure 1B</strong>) with a 5-year risk of metastasis of approximately 30%, 60%, and 80%, respectively (p<0.001). The AUC at 5-years was 0.74 for both the development and validation cohorts (<strong>Figure 1C</strong>). Decision curve analysis found a significant net benefit favoring the nomogram over a treat-all strategy when adjuvant therapy treatment thresholds were over 30% metastasis risk (<strong>Figure 1D</strong>).</div></div><div><h3>Conclusions</h3><div>Identifying VTT patients who are at increased risk of recurrence is important in determining post-operative follow-up and potent
{"title":"ONCOLOGICAL OUTCOMES OF RADICAL NEPHRECTOMY WITH VENOUS THROMBECTOMY FOR RENAL CELL CARCINOMA AND DEVELOPMENT OF A RECURRENCE RISK CALCULATOR","authors":"Spyridon P Basourakos, Grant Henning, Reza Nabavizadeh, Maddy Dorr, John Cheville John Cheville, Brian A. Costello, Stephen A Boorjian, Bradley C Leibovich, Vidit Sharma","doi":"10.1016/j.urolonc.2024.12.049","DOIUrl":"10.1016/j.urolonc.2024.12.049","url":null,"abstract":"<div><h3>Introduction</h3><div>The likelihood of recurrence after surgery for non-metastatic renal cell carcinoma (RCC) with venous tumor thrombus (VTT) remains considerable and previously developed predictive models remain underutilized in clinical practice. Adjuvant pembrolizumab was recently FDA approved and all RCC patients with VTT technically fall under the FDA approval guidance. However, we have previously conducted a cost-effectiveness analysis to demonstrate that the 3% survival benefit of adjuvant pembrolizumab outweighs its costs and risks when the 5-year risk of metastasis is at least 60%. As such, many patients with RCC and VTT may not benefit from adjuvant pembrolizumab treatment. The purpose of this study was to develop and internally validate an easy-to-use metastasis risk calculator after radical nephrectomy for non-metastatic RCC with VTT.</div></div><div><h3>Methods</h3><div>We performed a single-institution retrospective analysis of all adult patients who underwent radical nephrectomy with thrombectomy for non-metastatic RCC with VTT between 2000 and 2021. Demographic, clinicopathologic, and procedural characteristics were examined for association with the primary outcome of metastasis-free survival (MFS). A 70%-30% split was used to divide the cohort into a development/training and validation cohort, respectively. A least absolute shrinkage and selection operation (LASSO) Cox regression model was used to select variable combinations that best correlated with RCC metastasis. These variables were used to develop an MFS nomogram for which the area under the curve (AUC) was measured at 5 years. Decision curve analysis was performed to compare the net benefit of a nomogram-based strategy vs a treat-all strategy.</div></div><div><h3>Results</h3><div>Of the 532 M0 patients, 278 (52.3%), 66 (12.4%), 116 (21.8%), 35 (6.6%), and 37 (7.0%) had a level 0, I, II, III, and IV thrombus, respectively. Baseline characteristics are found in <strong>Table 1</strong>. The 5-year MFS for VTT level 0, I, II, III, IV was 51.2%, 34.7%, 28.5%, and 33.7%, respectively (p<0.01). Using LASSO feature selection, an MFS nomogram (<strong>Figure 1A</strong>) was built using four pathologic variables: thrombus level, necrosis, sarcomatoid, and positive nodes. The nomogram separated patients into low (36% of cohort), medium, and high-risk groups for metastasis (<strong>Figure 1B</strong>) with a 5-year risk of metastasis of approximately 30%, 60%, and 80%, respectively (p<0.001). The AUC at 5-years was 0.74 for both the development and validation cohorts (<strong>Figure 1C</strong>). Decision curve analysis found a significant net benefit favoring the nomogram over a treat-all strategy when adjuvant therapy treatment thresholds were over 30% metastasis risk (<strong>Figure 1D</strong>).</div></div><div><h3>Conclusions</h3><div>Identifying VTT patients who are at increased risk of recurrence is important in determining post-operative follow-up and potent","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"43 3","pages":"Pages 19-20"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509869","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 : 2025-03-01DOI: 10.1016/j.urolonc.2024.12.050
Eric Jonasch, Pooja Ghatalia, Guillermo de Velasco, Laurence Albiges, Mauricio Burotto, Cristina Suarez, James Brugarolas, Roberto Iacovelli, Katriina Jalkanen, Elaine T. Lam, Ramaprasad Srinivasan, Jaime Merchan, Neeraj Agarwal, Ane B. Iversen, Brian Rini, Todd M. Bauer, Howard Gurney, Othon Iliopoulos, Jianxin Lin, Liis Starkopf, Toni K. Choueiri
<div><h3>Introduction</h3><div>The first-in-class hypoxia-inducible factor-2α (HIF-2α) inhibitor belzutifan is approved in the United States for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors not requiring immediate surgery and for adult patients with advanced RCC following a PD-(L)1 inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor. Belzutifan has a unique mechanism of action and a distinct adverse event profile that includes anemia and hypoxia. We characterized the safety profile of belzutifan monotherapy and associated adverse events (AE) management strategies in a post hoc pooled analysis of patients with previously treated advanced clear cell RCC who participated in the phase 1 LITESPARK-001 (NCT02974738), phase 3 LITESPARK-005 (NCT04195750), and phase 2 LITESPARK-013 (NCT04489771) trials and patients with VHL disease-associated RCC enrolled in the phase 2 LITESPARK-004 trial (NCT03401788).</div></div><div><h3>Methods</h3><div>All patients who received ≥1 dose of belzutifan 120 mg by mouth once daily across the 4 trials were included in the pooled population. AE severity was graded per the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03 or 5.0, and was descriptively summarized.</div></div><div><h3>Results</h3><div>Overall, 576 patients were included (LITESPARK-001, n=58 [3 patients had non-RCC advanced solid tumors]; LITESPARK-005, n=381; LITESPARK-013, n=76; and LITESPARK-004, n=61). Of 576 patients, 99.3% experienced ≥1 all-cause AE and 61.6% experienced ≥1 grade 3-5 AE. AEs led to dose modification (reduction/interruption/discontinuation) in 50.0% of patients; 6.4% discontinued treatment due to AEs. The most common AEs were anemia (including decreased hemoglobin; 84.2%; grade 3 or 4, 28.8%) and fatigue (42.7%; grade 3, 2.8%). Hypoxia occurred in 16.3% of patients (grade 3 or 4, 12.2%). Adverse drug reactions (AEs considered associated with belzutifan) are summarized in the table. Among patients with anemia or decreased hemoglobin, 22.9% were treated with erythropoiesis-stimulating agents (ESA) only, 17.5% with blood transfusions only, and 12.8% with ESA and blood transfusions. Among patients with hypoxia, 70.2% received supplemental oxygen. Grade 3-5 treatment-related AEs occurred in 37.7% of patients (grade 5, n=1 [multiple organ dysfunction syndrome]).</div></div><div><h3>Conclusions</h3><div>This post hoc pooled analysis showed that belzutifan monotherapy had a generally manageable safety profile in patients with advanced RCC; few patients discontinued treatment due to AEs. Median time to first onset occurred within the first 3 months of treatment. As expected, anemia and hypoxia were among the most frequent AEs and were generally manageable with dose modification and/or treatment with ESA/blood transfusions fo
{"title":"IN-DEPTH CHARACTERIZATION OF THE SAFETY PROFILE OF BELZUTIFAN MONOTHERAPY IN PATIENTS WITH RENAL CELL CARCINOMA: A POOLED ANALYSIS OF FOUR CLINICAL TRIALS","authors":"Eric Jonasch, Pooja Ghatalia, Guillermo de Velasco, Laurence Albiges, Mauricio Burotto, Cristina Suarez, James Brugarolas, Roberto Iacovelli, Katriina Jalkanen, Elaine T. Lam, Ramaprasad Srinivasan, Jaime Merchan, Neeraj Agarwal, Ane B. Iversen, Brian Rini, Todd M. Bauer, Howard Gurney, Othon Iliopoulos, Jianxin Lin, Liis Starkopf, Toni K. Choueiri","doi":"10.1016/j.urolonc.2024.12.050","DOIUrl":"10.1016/j.urolonc.2024.12.050","url":null,"abstract":"<div><h3>Introduction</h3><div>The first-in-class hypoxia-inducible factor-2α (HIF-2α) inhibitor belzutifan is approved in the United States for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors not requiring immediate surgery and for adult patients with advanced RCC following a PD-(L)1 inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor. Belzutifan has a unique mechanism of action and a distinct adverse event profile that includes anemia and hypoxia. We characterized the safety profile of belzutifan monotherapy and associated adverse events (AE) management strategies in a post hoc pooled analysis of patients with previously treated advanced clear cell RCC who participated in the phase 1 LITESPARK-001 (NCT02974738), phase 3 LITESPARK-005 (NCT04195750), and phase 2 LITESPARK-013 (NCT04489771) trials and patients with VHL disease-associated RCC enrolled in the phase 2 LITESPARK-004 trial (NCT03401788).</div></div><div><h3>Methods</h3><div>All patients who received ≥1 dose of belzutifan 120 mg by mouth once daily across the 4 trials were included in the pooled population. AE severity was graded per the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03 or 5.0, and was descriptively summarized.</div></div><div><h3>Results</h3><div>Overall, 576 patients were included (LITESPARK-001, n=58 [3 patients had non-RCC advanced solid tumors]; LITESPARK-005, n=381; LITESPARK-013, n=76; and LITESPARK-004, n=61). Of 576 patients, 99.3% experienced ≥1 all-cause AE and 61.6% experienced ≥1 grade 3-5 AE. AEs led to dose modification (reduction/interruption/discontinuation) in 50.0% of patients; 6.4% discontinued treatment due to AEs. The most common AEs were anemia (including decreased hemoglobin; 84.2%; grade 3 or 4, 28.8%) and fatigue (42.7%; grade 3, 2.8%). Hypoxia occurred in 16.3% of patients (grade 3 or 4, 12.2%). Adverse drug reactions (AEs considered associated with belzutifan) are summarized in the table. Among patients with anemia or decreased hemoglobin, 22.9% were treated with erythropoiesis-stimulating agents (ESA) only, 17.5% with blood transfusions only, and 12.8% with ESA and blood transfusions. Among patients with hypoxia, 70.2% received supplemental oxygen. Grade 3-5 treatment-related AEs occurred in 37.7% of patients (grade 5, n=1 [multiple organ dysfunction syndrome]).</div></div><div><h3>Conclusions</h3><div>This post hoc pooled analysis showed that belzutifan monotherapy had a generally manageable safety profile in patients with advanced RCC; few patients discontinued treatment due to AEs. Median time to first onset occurred within the first 3 months of treatment. As expected, anemia and hypoxia were among the most frequent AEs and were generally manageable with dose modification and/or treatment with ESA/blood transfusions fo","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"43 3","pages":"Page 20"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509927","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 : 2025-03-01DOI: 10.1016/j.urolonc.2024.12.067
Christian Gratzke, Donald Vile, Zheng Hong Chen, Chris Garratt, Christian Poehlein, Jelena Todoric, Karim Fizazi, John Murray
Introduction
Androgen receptor (AR) somatic mutation activation is a resistance mechanism to AR-directed therapies (ADT) in metastatic castration-resistant prostate cancer (mCRPC). Upstream targeting of androgen biosynthesis may provide a therapeutic advantage over available AR-directed therapies in patients with mCRPC. Opevesostat (MK-5684; ODM-208) is an oral, nonsteroidal inhibitor of cytochrome P450 11A1 (CYP11A1), a catalyst of the first and rate-limiting step of steroid biosynthesis. By blocking the first step of the enzymatic pathway, opevesostat has the potential to inhibit all steroid hormones involved in AR signaling activation. In the phase 1/2 CYPIDES study, opevesostat had antitumor activity in patients with heavily pretreated mCRPC, especially in those with AR ligand binding domain (AR-LBD) mutations. The randomized, open-label, phase 3 MK-5684-004 trial (NCT06136650) will evaluate the efficacy and safety of opevesostat versus abiraterone or enzalutamide in patients with molecularly unselected mCRPC previously treated with 1 prior NHA.
Methods
Eligible patients have mCRPC that progressed during ADT ≤6 months before screening and during/after 1 NHA for hormone-sensitive prostate cancer or non-mCRPC. Approximately 1500 patients (375 with, 1125 without AR-LBD mutations) will be randomly assigned 1:1 to receive opevesostat 5 mg PO BID + dexamethasone 1.5 mg and fludrocortisone 0.1 mg PO QD or abiraterone acetate 1000 mg PO QD (if prior enzalutamide/darolutamide/apalutamide) or enzalutamide 160 mg PO QD (if prior abiraterone). Primary end points are radiographic PFS per PCWG3-modified RECIST v1.1 by BICR and OS in AR-LBD mutation–positive and –negative disease, separately. Secondary end points include time to initiation of first subsequent anticancer therapy or death; ORR and DOR per PCWG3-modified RECIST v1.1 by BICR; and safety. Recruitment is ongoing.
Pub Date : 2025-03-01DOI: 10.1016/j.urolonc.2024.12.091
Danly Omil-Lima, Laura Davis, Michael Lesgart, Shivaram Cumarasamy, Marc Smaldone
Introduction
Adjuvant treatment of stage II nonseminomatous germ cell tumors (NSGCT) following retroperitoneal lymph node dissection (RPLND) requires careful consideration of the risks and benefits of adjuvant versus salvage systemic therapy. While early adjuvant chemotherapy improves recurrence-free survival, its impact on overall survival compared to treatment in the salvage setting is disputed.
Methods
Patients with tumor marker-negative clinical stage II NSGCT (TANYN1-3M0S0) were identified within the NCDB testis cancer dataset from 2004 to 2021. Inclusion criteria were patients who underwent RPLND, had confirmed nodal disease on final pathological staging, and received postoperative chemotherapy. Mean time to chemotherapy by pathological nodal stage was compared using an analysis of variance (ANOVA) with post-hoc pairwise t-tests. A multivariable Cox proportional hazards regression model, incorporating patient comorbidities, tumor characteristics, and an interaction term for chemotherapy receipt at any time, was used to assess overall survival stratified by pathologic nodal stage.
Results
A total of 186 patients with marker-negative clinical stage II disease who underwent RPLND with pathologically confirmed nodal disease were identified. Patient demographics, presented in Table 1, show nominal differences in patient characteristics and general concordance between clinical and pathological nodal staging. Figure 1A indicates a trend towards earlier chemotherapy for patients with pN3 disease (median 7.5 weeks) compared to those with pN1 (11.2 weeks) and pN2 disease (10.2 weeks), although this did not reach statistical significance (p=0.056). With a median follow-up of 86 months, mortality was rare, occurring in only 7 patients (3 pN1, 2 pN2, 2 pN3). The 10-year overall survival curves showed no significant difference (Figure 1B), and early chemotherapy timing did not predict survival (HR 0.99, 95% CI 0.87-1.135) when accounting for chemotherapy receipt at any time.
Conclusions
The timing of chemotherapy does not appear to impact overall survival in patients when controlling for chemotherapy receipt at any time. Therefore, a delay in administration of systemic therapy following RPLND, in this patient population at high risk for developing chemotherapy-associated adverse effects, should be considered. Further research is needed to determine the impact on specific high-risk populations, such as patients with pN3 disease, who were underrepresented in this study.
{"title":"RETHINKING CHEMOTHERAPY TIMING IN STAGE II NSGCT: BALANCING SURVIVAL AND MINIMIZING TOXICITY","authors":"Danly Omil-Lima, Laura Davis, Michael Lesgart, Shivaram Cumarasamy, Marc Smaldone","doi":"10.1016/j.urolonc.2024.12.091","DOIUrl":"10.1016/j.urolonc.2024.12.091","url":null,"abstract":"<div><h3>Introduction</h3><div>Adjuvant treatment of stage II nonseminomatous germ cell tumors (NSGCT) following retroperitoneal lymph node dissection (RPLND) requires careful consideration of the risks and benefits of adjuvant versus salvage systemic therapy. While early adjuvant chemotherapy improves recurrence-free survival, its impact on overall survival compared to treatment in the salvage setting is disputed.</div></div><div><h3>Methods</h3><div>Patients with tumor marker-negative clinical stage II NSGCT (T<sub>ANY</sub>N<sub>1-3</sub>M<sub>0</sub>S<sub>0</sub>) were identified within the NCDB testis cancer dataset from 2004 to 2021. Inclusion criteria were patients who underwent RPLND, had confirmed nodal disease on final pathological staging, and received postoperative chemotherapy. Mean time to chemotherapy by pathological nodal stage was compared using an analysis of variance (ANOVA) with post-hoc pairwise t-tests. A multivariable Cox proportional hazards regression model, incorporating patient comorbidities, tumor characteristics, and an interaction term for chemotherapy receipt at any time, was used to assess overall survival stratified by pathologic nodal stage.</div></div><div><h3>Results</h3><div>A total of 186 patients with marker-negative clinical stage II disease who underwent RPLND with pathologically confirmed nodal disease were identified. Patient demographics, presented in <strong>Table 1</strong>, show nominal differences in patient characteristics and general concordance between clinical and pathological nodal staging. <strong>Figure 1A</strong> indicates a trend towards earlier chemotherapy for patients with pN3 disease (median 7.5 weeks) compared to those with pN1 (11.2 weeks) and pN2 disease (10.2 weeks), although this did not reach statistical significance (p=0.056). With a median follow-up of 86 months, mortality was rare, occurring in only 7 patients (3 pN1, 2 pN2, 2 pN3). The 10-year overall survival curves showed no significant difference (<strong>Figure 1B</strong>), and early chemotherapy timing did not predict survival (HR 0.99, 95% CI 0.87-1.135) when accounting for chemotherapy receipt at any time.</div></div><div><h3>Conclusions</h3><div>The timing of chemotherapy does not appear to impact overall survival in patients when controlling for chemotherapy receipt at any time. Therefore, a delay in administration of systemic therapy following RPLND, in this patient population at high risk for developing chemotherapy-associated adverse effects, should be considered. Further research is needed to determine the impact on specific high-risk populations, such as patients with pN3 disease, who were underrepresented in this study.</div></div>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"43 3","pages":"Page 36"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509946","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 : 2025-03-01DOI: 10.1016/j.urolonc.2024.12.062
Maxwell Sandberg, Mary Namugosa, Rory Ritts, Claudia Marie-Costa, Mitchell Hayes, Wyatt Whitman, Emily Ye, Justin Refugia, Reuben Ben-David, Parissa Alerasool, Rafael Zanotti, Thiago Camelo Mourão, Jung Kwon Kim, Patricio Garcia Marchiñena, Seok-Soo Byun, Diego Abreu, Reza Mehrazin, Philippe Spiess, Stendo de Cassio Zequi, Alejandro Rodriguez
<div><h3>Introduction</h3><div>The gold standard treatment for renal cell carcinoma (RCC) with a tumor thrombus is radical nephrectomy with tumor thrombectomy. This operation carries a high morbidity and mortality rate for patients. Operative approaches to this vary across the world and can be done open, laparoscopic, and robotic, with open being the most common. Most studies on radical nephrectomy and tumor thrombectomy are small case series and lack patient diversity from different regions across the world. The purpose of this is to compare peri- and post-operative outcomes to radical nephrectomy with tumor thrombectomy between open, laparoscopic, and robotic approaches using the Intercontinental Collaboration on Renal Cell Carcinoma (ICORCC) database.</div></div><div><h3>Methods</h3><div>Patient records were reviewed from the ICORCC database, which is a multi-institutional database that pulls cases from the United States of America, Central/South America, Europe, and South Korea. All patients included in the study underwent radical nephrectomy and tumor thrombectomy for RCC from 2006-present. Tumor thrombus level was graded using the Neves classification system. Tumors were graded using the International Society of Urologic Pathology classification system. Statistical analysis was carried out using analysis of variance, chi-squared test, and Kaplan-Meier survival curves with log-rank test to compare a variety of pre, peri-, and post-operative variables based on surgical approach.</div></div><div><h3>Results</h3><div>A total of 366 patients were included (Table 1; 278 male and 88 female). Of all operations, 28 were robotic, 72 laparoscopic, and 266 open. Charlson comorbidity index was lowest in laparoscopic cases (p=0.018). Age at surgery was similar across all approaches (p=0.968). Female patients were more likely to undergo robotic surgery compared to males (p=0.032). Operative time (p=0.153) and length of stay were not different by operative choice (p=0.514). The rate of cytoreductive surgery was similar across all approaches (p=0.594). Thrombus level differed by approach, with open and laparoscopic surgery utilized more as thrombus level increased (p=0.013). Preoperative tumor size on computerized tomography scan was not different (p=0.464). Final tumor stage (p=0.396), grade (p=0.060), and subtype (p=0.971) were similar across all operative approaches. Soft tissue margin positivity did not differ (p=0.541), but renal vein margin positivity was more likely to be seen with laparoscopic surgery (p<0.001). Incidence of cancer-specific death was most likely in the robotic approach (p<0.001) but overall survival (p=0.242), metastasis-free survival (p=0.833), and time to die after a metastatic RCC diagnosis (p=0.231) was not different. Figure 1 compares overall survival (p=0.275), metastasis-free survival (p=0.988), and time to die after metastatic diagnosis (p=0.957) with log-rank tests using a Kaplan-Meier survival curve.</div></div><div>
{"title":"A COMPARISON OF OPEN, LAPAROSCOPIC, AND ROBOTIC RADICAL NEPHRECTOMY WITH TUMOR THROMBECTOMY FROM THE INTERCONTINENTAL COLLABORATION ON RENA CELL CARCINOMA (ICORCC) DATABASE","authors":"Maxwell Sandberg, Mary Namugosa, Rory Ritts, Claudia Marie-Costa, Mitchell Hayes, Wyatt Whitman, Emily Ye, Justin Refugia, Reuben Ben-David, Parissa Alerasool, Rafael Zanotti, Thiago Camelo Mourão, Jung Kwon Kim, Patricio Garcia Marchiñena, Seok-Soo Byun, Diego Abreu, Reza Mehrazin, Philippe Spiess, Stendo de Cassio Zequi, Alejandro Rodriguez","doi":"10.1016/j.urolonc.2024.12.062","DOIUrl":"10.1016/j.urolonc.2024.12.062","url":null,"abstract":"<div><h3>Introduction</h3><div>The gold standard treatment for renal cell carcinoma (RCC) with a tumor thrombus is radical nephrectomy with tumor thrombectomy. This operation carries a high morbidity and mortality rate for patients. Operative approaches to this vary across the world and can be done open, laparoscopic, and robotic, with open being the most common. Most studies on radical nephrectomy and tumor thrombectomy are small case series and lack patient diversity from different regions across the world. The purpose of this is to compare peri- and post-operative outcomes to radical nephrectomy with tumor thrombectomy between open, laparoscopic, and robotic approaches using the Intercontinental Collaboration on Renal Cell Carcinoma (ICORCC) database.</div></div><div><h3>Methods</h3><div>Patient records were reviewed from the ICORCC database, which is a multi-institutional database that pulls cases from the United States of America, Central/South America, Europe, and South Korea. All patients included in the study underwent radical nephrectomy and tumor thrombectomy for RCC from 2006-present. Tumor thrombus level was graded using the Neves classification system. Tumors were graded using the International Society of Urologic Pathology classification system. Statistical analysis was carried out using analysis of variance, chi-squared test, and Kaplan-Meier survival curves with log-rank test to compare a variety of pre, peri-, and post-operative variables based on surgical approach.</div></div><div><h3>Results</h3><div>A total of 366 patients were included (Table 1; 278 male and 88 female). Of all operations, 28 were robotic, 72 laparoscopic, and 266 open. Charlson comorbidity index was lowest in laparoscopic cases (p=0.018). Age at surgery was similar across all approaches (p=0.968). Female patients were more likely to undergo robotic surgery compared to males (p=0.032). Operative time (p=0.153) and length of stay were not different by operative choice (p=0.514). The rate of cytoreductive surgery was similar across all approaches (p=0.594). Thrombus level differed by approach, with open and laparoscopic surgery utilized more as thrombus level increased (p=0.013). Preoperative tumor size on computerized tomography scan was not different (p=0.464). Final tumor stage (p=0.396), grade (p=0.060), and subtype (p=0.971) were similar across all operative approaches. Soft tissue margin positivity did not differ (p=0.541), but renal vein margin positivity was more likely to be seen with laparoscopic surgery (p<0.001). Incidence of cancer-specific death was most likely in the robotic approach (p<0.001) but overall survival (p=0.242), metastasis-free survival (p=0.833), and time to die after a metastatic RCC diagnosis (p=0.231) was not different. Figure 1 compares overall survival (p=0.275), metastasis-free survival (p=0.988), and time to die after metastatic diagnosis (p=0.957) with log-rank tests using a Kaplan-Meier survival curve.</div></div><div>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"43 3","pages":"Pages 24-25"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509959","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 : 2025-03-01DOI: 10.1016/j.urolonc.2024.12.068
Giuseppe Reitano, Mohamed Ahmed, Jamie O'Byrne, Daniel Roberson, Umar Ghaffar, Spyridon Basourakos, Julian Diaz-Cobo, Stephen Boorjian, Igor Frank, Matthew Gettman, Matthew Tollefson, R. Jeffrey Karnes
<div><h3>Introduction</h3><div>Recent advancements in prostate cancer diagnostics and the strategic use of advanced imaging have enhanced our ability to accurately stage patients. The 8<sup>th</sup> edition of the American Joint Committee on Cancer (AJCC) classification system indicates that the extent of lymph node involvement is associated with more advanced disease stages. This study aims to compare cancer specific survival (CSS) and distant metastasis free survival (MFS) for patients with PCa staged as cN1 or cM1a according to the AJCC classification and treated at a single institution.</div></div><div><h3>Methods</h3><div>A total of 207 Patients diagnosed with PCa and clinically suspicious lymphadenopathy treated with radical prostatectomy and extended lymph node dissection (eLND) with or without neoadjuvant androgen deprivation therapy (NADT) between October 2007 and September 2022 were retrospectively identified. Patients were classified as either cN1 or cM1a based on the initial staging. The true positivity of the suspected nodes was confirmed either clinically, through pre-operative re-staging after NADT, or through the final pathological examination. The exact extent of the eLND was based on the location of the positive nodes. Exclusion criteria were the presence of bone and/or visceral metastases, salvage prostatectomy, the use of chemotherapy prior to surgery, and false positive cN1 or cM1a patients. Kaplan-Meyer curves and Cox proportional hazard ratios were estimated to compare CSS and MFS. The date of surgery was considered the time 0 for all the endpoints. Distant metastases were defined as the detection of at least one metastasis outside the pelvic lymph nodes and/or the prostate bed.</div></div><div><h3>Results</h3><div>150 men were classified as cN1, and 57 had at least one retroperitoneal node involved (cM1a). The median age at surgery was 63 years (IQR 58-67). There were no differences between ASA score (p 0.61). Median initial PSA was comparable between the two groups (15.6 ng/ml, IQR 8.35-34.3, p 0.07). Patients in the cM1a group had a higher number of clinically positive nodes (p < 0.001), with a larger median diameter (15 versus 11 mm, p 0.01). Among the cM1a PCa, 26 presented with involvement of common iliac nodes only, while 31 had also other positive retroperitoneal nodes. Most of the patients had a pT ≥ 3b (65.6%), there were no differences in terms of pT stage (p 0.08), pN stage (p 0.79) and final Gleason score (p 0.09) between the two groups. On Cox regression analysis, clinical nodal status was not a statistically significant predictor of MFS even after adjusting for pathological T-stage (HR 1.07, 95%CI 0.66, 1.72, p 0.78). Nodal stage was not a statistically significant predictor of CSS after adjusting for statistically significant predictors (HR1.06, 95%CI 0.46, 2.45, p 0.90).</div></div><div><h3>Conclusions</h3><div>Radical prostatectomy remains a viable primary treatment option for patients with positive lym
{"title":"SURVIVAL PATTERNS AMONG CLINICALLY NODE POSITIVE PROSTATE CANCER TREATED WITH RADICAL PROSTATECTOMY","authors":"Giuseppe Reitano, Mohamed Ahmed, Jamie O'Byrne, Daniel Roberson, Umar Ghaffar, Spyridon Basourakos, Julian Diaz-Cobo, Stephen Boorjian, Igor Frank, Matthew Gettman, Matthew Tollefson, R. Jeffrey Karnes","doi":"10.1016/j.urolonc.2024.12.068","DOIUrl":"10.1016/j.urolonc.2024.12.068","url":null,"abstract":"<div><h3>Introduction</h3><div>Recent advancements in prostate cancer diagnostics and the strategic use of advanced imaging have enhanced our ability to accurately stage patients. The 8<sup>th</sup> edition of the American Joint Committee on Cancer (AJCC) classification system indicates that the extent of lymph node involvement is associated with more advanced disease stages. This study aims to compare cancer specific survival (CSS) and distant metastasis free survival (MFS) for patients with PCa staged as cN1 or cM1a according to the AJCC classification and treated at a single institution.</div></div><div><h3>Methods</h3><div>A total of 207 Patients diagnosed with PCa and clinically suspicious lymphadenopathy treated with radical prostatectomy and extended lymph node dissection (eLND) with or without neoadjuvant androgen deprivation therapy (NADT) between October 2007 and September 2022 were retrospectively identified. Patients were classified as either cN1 or cM1a based on the initial staging. The true positivity of the suspected nodes was confirmed either clinically, through pre-operative re-staging after NADT, or through the final pathological examination. The exact extent of the eLND was based on the location of the positive nodes. Exclusion criteria were the presence of bone and/or visceral metastases, salvage prostatectomy, the use of chemotherapy prior to surgery, and false positive cN1 or cM1a patients. Kaplan-Meyer curves and Cox proportional hazard ratios were estimated to compare CSS and MFS. The date of surgery was considered the time 0 for all the endpoints. Distant metastases were defined as the detection of at least one metastasis outside the pelvic lymph nodes and/or the prostate bed.</div></div><div><h3>Results</h3><div>150 men were classified as cN1, and 57 had at least one retroperitoneal node involved (cM1a). The median age at surgery was 63 years (IQR 58-67). There were no differences between ASA score (p 0.61). Median initial PSA was comparable between the two groups (15.6 ng/ml, IQR 8.35-34.3, p 0.07). Patients in the cM1a group had a higher number of clinically positive nodes (p < 0.001), with a larger median diameter (15 versus 11 mm, p 0.01). Among the cM1a PCa, 26 presented with involvement of common iliac nodes only, while 31 had also other positive retroperitoneal nodes. Most of the patients had a pT ≥ 3b (65.6%), there were no differences in terms of pT stage (p 0.08), pN stage (p 0.79) and final Gleason score (p 0.09) between the two groups. On Cox regression analysis, clinical nodal status was not a statistically significant predictor of MFS even after adjusting for pathological T-stage (HR 1.07, 95%CI 0.66, 1.72, p 0.78). Nodal stage was not a statistically significant predictor of CSS after adjusting for statistically significant predictors (HR1.06, 95%CI 0.46, 2.45, p 0.90).</div></div><div><h3>Conclusions</h3><div>Radical prostatectomy remains a viable primary treatment option for patients with positive lym","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"43 3","pages":"Page 27"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509999","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 : 2025-03-01DOI: 10.1016/j.urolonc.2024.12.055
Giacomo Musso, Margaret Meagher, Kit Yuen, Aaron Ahdoot, Dhruv Puri, Julian Cortes, Cesare Saitta, Dattatraya Patil, Hajime Tanaka, Melis Guer, Masaki Kobayashi, Shohei Fukuda, Francesco Montorsi, Alberto Briganti, Andrea Salonia, Umberto Capitanio, Alessandro Larcher, Yasuhisa Fujii, Viraj Master, Ithaar Derweesh
Introduction
Administration of adjuvant immunotherapy for high-risk (T3) Renal Cell Carcinoma (RCC) has recently become a standard of care with publication of KEYNOTE-564 demonstrating survival benefit in this patient group. Presence of high tumor grade is increasingly understood as marker for adverse oncological outcomes in T1 and T2 RCC. We sought to compare survival outcomes of T1-T2 high-grade disease and T3 RCC.
Methods
Prospectively collected data from a multicenter database involving University of California San Diego Health (USA), IRCCS San Raffaele Hospital (Italy), Emory University Hospital (USA) and Tokyo Medical and Dental University (Japan) were retrospectively analyzed, collecting a total of 5452 non metastatic patients treated with radical or partial nephrectomy. Baseline patient [age, sex, Body Mass Index (BMI), Charlson Comorbidity Index (CCI)] and tumoral characteristics (histology, RENAL score, tumor size, pathological N stage] were evaluated. Kaplan-Meier survival analysis was used to compare cancer-specific survival (CSS) and overall survival (OS) in T1-T2 high-grade and T3 RCC. Cox regression was utilized to evaluate for predictors for CSM and ACM while controlling for demographic and pathological factors.
Results
Median follow-up was 61 months. A total of 5007 patients with a T1-T2 High Grade (HG) tumor and 445 patients with a T3 any Grade tumor were analyzed. Kaplan-Meier analysis revealed that the 5-year CSS for T1-T2 high-grade tumors was 87%, while for T3 tumors it was 86%, indicating comparable survival rates between the two groups (p=0.08). 5-year OS was similar, being 78% for T1-T2 HG and 78% for T3 any Grade (p=0.11). Cox regression analyses showed that stage (T1-T2-HG vs T3a stage) was not predictive of differences in CSM (HR 1.24, p=0.15), or in ACM (HR 1.25, p=0.06).
Conclusions
Cancer-specific mortality is comparable between T1-T2 high-grade tumors and T3 tumors while overall mortality is similar between T1-T2 HG and T3a any grade tumors. Hence, caution must be exercised when managing localized RCC with adverse pathological features, as its prognosis may be as severe as that of a locally advanced disease. Our findings suggest the need to reevaluate the inclusion criteria for adjuvant clinical therapy trials to consider T1-T2 high-grade renal cell carcinoma in future studies.
{"title":"CANCER-SPECIFIC SURVIVAL AND OVERALL SURVIVAL IN LOCALIZED T1-T2 HIGH GRADE VERSUS T3 RENAL CELL CARCINOMA: A MULTICENTER ANALYSIS","authors":"Giacomo Musso, Margaret Meagher, Kit Yuen, Aaron Ahdoot, Dhruv Puri, Julian Cortes, Cesare Saitta, Dattatraya Patil, Hajime Tanaka, Melis Guer, Masaki Kobayashi, Shohei Fukuda, Francesco Montorsi, Alberto Briganti, Andrea Salonia, Umberto Capitanio, Alessandro Larcher, Yasuhisa Fujii, Viraj Master, Ithaar Derweesh","doi":"10.1016/j.urolonc.2024.12.055","DOIUrl":"10.1016/j.urolonc.2024.12.055","url":null,"abstract":"<div><h3>Introduction</h3><div>Administration of adjuvant immunotherapy for high-risk (T3) Renal Cell Carcinoma (RCC) has recently become a standard of care with publication of KEYNOTE-564 demonstrating survival benefit in this patient group. Presence of high tumor grade is increasingly understood as marker for adverse oncological outcomes in T1 and T2 RCC. We sought to compare survival outcomes of T1-T2 high-grade disease and T3 RCC.</div></div><div><h3>Methods</h3><div>Prospectively collected data from a multicenter database involving University of California San Diego Health (USA), IRCCS San Raffaele Hospital (Italy), Emory University Hospital (USA) and Tokyo Medical and Dental University (Japan) were retrospectively analyzed, collecting a total of 5452 non metastatic patients treated with radical or partial nephrectomy. Baseline patient [age, sex, Body Mass Index (BMI), Charlson Comorbidity Index (CCI)] and tumoral characteristics (histology, RENAL score, tumor size, pathological N stage] were evaluated. Kaplan-Meier survival analysis was used to compare cancer-specific survival (CSS) and overall survival (OS) in T1-T2 high-grade and T3 RCC. Cox regression was utilized to evaluate for predictors for CSM and ACM while controlling for demographic and pathological factors.</div></div><div><h3>Results</h3><div>Median follow-up was 61 months. A total of 5007 patients with a T1-T2 High Grade (HG) tumor and 445 patients with a T3 any Grade tumor were analyzed. Kaplan-Meier analysis revealed that the 5-year CSS for T1-T2 high-grade tumors was 87%, while for T3 tumors it was 86%, indicating comparable survival rates between the two groups (p=0.08). 5-year OS was similar, being 78% for T1-T2 HG and 78% for T3 any Grade (p=0.11). Cox regression analyses showed that stage (T1-T2-HG vs T3a stage) was not predictive of differences in CSM (HR 1.24, p=0.15), or in ACM (HR 1.25, p=0.06).</div></div><div><h3>Conclusions</h3><div>Cancer-specific mortality is comparable between T1-T2 high-grade tumors and T3 tumors while overall mortality is similar between T1-T2 HG and T3a any grade tumors. Hence, caution must be exercised when managing localized RCC with adverse pathological features, as its prognosis may be as severe as that of a locally advanced disease. Our findings suggest the need to reevaluate the inclusion criteria for adjuvant clinical therapy trials to consider T1-T2 high-grade renal cell carcinoma in future studies.</div></div>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"43 3","pages":"Page 22"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510051","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 : 2025-03-01DOI: 10.1016/j.urolonc.2024.06.018
Daniel D. Shapiro , Pavlos Msaouel
{"title":"Adjuvant therapy for renal cell carcinoma: Finding the signal in the noise","authors":"Daniel D. Shapiro , Pavlos Msaouel","doi":"10.1016/j.urolonc.2024.06.018","DOIUrl":"10.1016/j.urolonc.2024.06.018","url":null,"abstract":"","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"43 3","pages":"Pages 147-149"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141604217","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 : 2025-03-01DOI: 10.1016/j.urolonc.2024.10.013
Sari Khaleel , Marlon Perera , Nathan Papa , Fengshen Kuo , Mahdi Golkaram , Phillip Rappold , Ritesh R. Kotecha , Jonathan Coleman , Paul Russo , Robert Motzer , Ed Reznik , A. Ari Hakimi
Purpose
Combination systemic therapies (CSTs) of immuno-oncologic (IO) and VEGF-inhibiting agents (VEGFi) have become the standard of care for management of metastatic clear cell renal cell carcinoma (m-ccRCC). However, treatment outcomes vary between patients, with no established biomarkers to determine optimal CST regimens (IO/IO or IO/VEGFi). Prostate Specific Membrane Antigen (PSMA), encoded by the FOLH1 gene, is a marker of tumor neovasculature in ccRCC, the downstream target of VEGFi. We evaluated the relation between FOLH1 expression and angiogenesis, as well as clinical outcomes, in 5 m-ccRCC ST trials.
Materials and Methods
using Spearman's rank correlation (SPRC) test, we assessed the correlation between FOLH1 expression and gene expression signature (GES) scores corresponding to angiogenic and immunologic features of the tumor microenvironment (TME) of m-ccRCC in our trial cohorts. Using Cox proportional hazard regression (Cox-PHR), we assessed the association between FOLH1 expression level, summarized by within-study quantiles (qFOLH1), and progression-free and overall survival (PFS, OS).
Results
Increased FOLH1 expression was significantly associated with higher TME angiogenesis GES scores (SPRC +0.5, P < 0.001), but did not consistently correlate with immune feature GES scores. Meta-analysis of PFS in the sunitinib TKI arm of trial cohorts showed an overall positive association with qFOLH1 (HR = 0.89; 95% CI = 0.85-0.94, P < 0.0001). qFOLH1 was not significantly associated with OS in the sunitinib arms of the two trials with OS data (COMPARZ, HR 0.87, 95% CI 0.71–1.07, P = 0.17; and Checkmate-214, HR 0.89, 95% CI 0.67–1.17, P = 0.70).
Conclusions
PSMA-encoding FOLH1 gene expression correlates with neoangiogenesis and predicts PFS in m-ccRCC patients treated with sunitinib TKI, suggesting that PSMA PET could be explored as a noninvasive biomarker for guiding CST choice (IO/IO or IO/VEGFi) as well as prediction of treatment response to VEGFi in m-ccRCC patients.
{"title":"Gene expression of prostate-specific membrane antigen (FOLH1) in clear cell renal cell carcinoma predicts angiogenesis and response to tyrosine kinase inhibitors","authors":"Sari Khaleel , Marlon Perera , Nathan Papa , Fengshen Kuo , Mahdi Golkaram , Phillip Rappold , Ritesh R. Kotecha , Jonathan Coleman , Paul Russo , Robert Motzer , Ed Reznik , A. Ari Hakimi","doi":"10.1016/j.urolonc.2024.10.013","DOIUrl":"10.1016/j.urolonc.2024.10.013","url":null,"abstract":"<div><h3>Purpose</h3><div>Combination systemic therapies (CSTs) of immuno-oncologic (IO) and VEGF-inhibiting agents (VEGFi) have become the standard of care for management of metastatic clear cell renal cell carcinoma (m-ccRCC). However, treatment outcomes vary between patients, with no established biomarkers to determine optimal CST regimens (IO/IO or IO/VEGFi). Prostate Specific Membrane Antigen (PSMA), encoded by the <em>FOLH1</em> gene, is a marker of tumor neovasculature in ccRCC, the downstream target of VEGFi. We evaluated the relation between <em>FOLH1</em> expression and angiogenesis, as well as clinical outcomes, in 5 m-ccRCC ST trials.</div></div><div><h3>Materials and Methods</h3><div>using Spearman's rank correlation (SPRC) test, we assessed the correlation between <em>FOLH1</em> expression and gene expression signature (GES) scores corresponding to angiogenic and immunologic features of the tumor microenvironment (TME) of m-ccRCC in our trial cohorts. Using Cox proportional hazard regression (Cox-PHR), we assessed the association between <em>FOLH1</em> expression level, summarized by within-study quantiles (qFOLH1), and progression-free and overall survival (PFS, OS).</div></div><div><h3>Results</h3><div>Increased <em>FOLH1</em> expression was significantly associated with higher TME angiogenesis GES scores (SPRC +0.5, <em>P</em> < 0.001), but did not consistently correlate with immune feature GES scores. Meta-analysis of PFS in the sunitinib TKI arm of trial cohorts showed an overall positive association with qFOLH1 (HR = 0.89; 95% CI = 0.85-0.94, <em>P</em> < 0.0001). qFOLH1 was not significantly associated with OS in the sunitinib arms of the two trials with OS data (COMPARZ, HR 0.87, 95% CI 0.71–1.07, <em>P</em> = 0.17; and Checkmate-214, HR 0.89, 95% CI 0.67–1.17, <em>P</em> = 0.70).</div></div><div><h3>Conclusions</h3><div>PSMA<em>-</em>encoding <em>FOLH1</em> gene expression correlates with neoangiogenesis and predicts PFS in m-ccRCC patients treated with sunitinib TKI, suggesting that PSMA PET could be explored as a noninvasive biomarker for guiding CST choice (IO/IO or IO/VEGFi) as well as prediction of treatment response to VEGFi in m-ccRCC patients.</div></div>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"43 3","pages":"Pages 192.e21-192.e28"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628941","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 : 2025-03-01DOI: 10.1016/j.urolonc.2024.10.017
Takuto Hara Ph.D., Kotaro Suzuki Ph.D., Yasuyoshi Okamura Ph.D., Hideto Ueki Ph.D., Yukari Bando Ph.D., Keisuke Okada Ph.D., Tomoaki Terakawa Ph.D., Yoji Hyodo Ph.D., Koji Chiba Ph.D., Jun Teishima Ph.D., Hideaki Miyake Ph.D., Prof.
Background
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.
Methods
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.
Results
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.
Conclusion
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.
{"title":"Impact of neoadjuvant therapy on prognosis in renal cell carcinoma with inferior vena cava thrombus","authors":"Takuto Hara Ph.D., Kotaro Suzuki Ph.D., Yasuyoshi Okamura Ph.D., Hideto Ueki Ph.D., Yukari Bando Ph.D., Keisuke Okada Ph.D., Tomoaki Terakawa Ph.D., Yoji Hyodo Ph.D., Koji Chiba Ph.D., Jun Teishima Ph.D., Hideaki Miyake Ph.D., Prof.","doi":"10.1016/j.urolonc.2024.10.017","DOIUrl":"10.1016/j.urolonc.2024.10.017","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"43 3","pages":"Pages 178-185"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","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}
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