Resection Of Renal Cell Carcinoma Research Articles

Plasma Kidney Injury Molecule-1 for Preoperative Prediction of Renal Cell Carcinoma Versus Benign Renal Masses, and Association With Clinical Outcomes.

Both clear cell and papillary renal cell carcinomas (RCCs) overexpress kidney injury molecule-1 (KIM-1). We investigated whether plasma KIM-1 (pKIM-1) may be a useful risk stratification tool among patients with suspicious renal masses. Prenephrectomy pKIM-1 was measured in two independent cohorts of patients with renal masses. Cohort 1, from the prospective K2 trial, included 162 patients found to have clear cell RCC (cases) and 162 patients with benign renal masses (controls). Cohort 2 included 247 patients with small (cT1a) renal masses from an academic biorepository, of whom 184 had RCC. We assessed the relationship between pKIM-1, surgical pathology, and clinical outcomes. In Cohort 1, pKIM-1 distinguished RCC versus benign masses with area under the receiver operating curve (AUC-ROC, 0.81 [95% CI, 0.76 to 0.86]). In Cohort 2 (cT1a only), pKIM-1 distinguished RCC versus benign masses (AUC-ROC, 0.74 [95% CI, 0.67 to 0.80]) and the addition of pKIM-1 to an established nomogram for predicting malignancy improved the model AUC-ROC (0.65 [95% CI, 0.57 to 0.74] v 0.78 [95% CI, 0.72 to 0.85]). A pKIM-1 cutpoint identified using Cohort 2 demonstrated sensitivity of 92.5% and specificity of 60% for identifying RCC in Cohort 1. In long-term follow-up of RCC cases (Cohort 1), higher prenephrectomy pKIM-1 was associated with worse metastasis-free survival (multivariable MFS hazard ratio [HR] 1.29 per unit increase in log pKIM-1, 95% CI, 1.10 to 1.53) and overall survival (multivariable OS HR 1.31 per unit increase in log pKIM-1, 95% CI, 1.10 to 1.54). In long-term follow-up of Cohort 2, no metastatic events occurred, consistent with the favorable prognosis of resected cT1a RCC. Among patients with renal masses, pKIM-1 is associated with malignant pathology, worse MFS, and risk of death. pKIM-1 may be useful for selecting patients with renal masses for intervention versus surveillance.

Evaluation of tumor response to immune checkpoint inhibitors by a 3D immunotumoroid model.

Only 20 percent of renal and bladder cancer patients will show a significant response to immune checkpoint inhibitor (ICI) therapy, and no test currently available accurately predicts ICI response. We developed an "immunotumoroid" cell model system that recapitulates the tumor, its microenvironment, and necessary immune system components in patient-derived spheroids to enable ex vivo assessment of tumor response to ICI therapy. Immunotumoroids were developed from surgically resected renal cell carcinomas and bladder carcinomas selected for high tumor-infiltrating lymphocytes (TILs) and survived more than a month without media exchange. Immunohistochemistry was used to detect immune and non-immune cells in cryopreserved source tumors and the resulting immunotumoroids. Immunotumoroid response to ICIs (nivolumab, pembrolizumab, and durvalumab) and chemotherapy (cisplatin, gemcitabine, and paclitaxel) was monitored in real-time with Cytotox Red staining in an Incucyte device, and the immunotumoroid response was compared to retrospective clinical drug responses. Six of the 13 cases tested grew viable immunotumoroid models, with failed cases attributed to extensive tumor tissue necrosis or excess lymphocytes preventing spheroid formation. One successfully cultured case was excluded from the study due to low TIL infiltration (<5%) in the primary tumor sample. The five remaining models contained immune cells (CD4+ and CD8+ T cells, and macrophages), non-immune cells (fibroblasts), and tumor cells. Chemotherapy and ICI drugs were tested in immunotumoroids from 5 cases and compared to clinical outcomes where data was available. Four/five models showed cell killing in response to chemotherapy and two/five showed sensitivity to ICI. In three cases, the immunotumoroid model accurately predicted the patient's clinical response or non-response to ICIs or chemotherapy. Our immunotumoroid model replicated the multicellular nature of the tumor microenvironment sufficiently for preclinical ICI screening. This model could enable valuable insights into the complex interactions between cancer cells, the immune system, and the microenvironment. This is a feasibility study on a small number of cases, and additional studies with larger case numbers are required including correlation with clinical response.

Abstract 3843: Role of CD4/CD8 double positive T cells in modulating response to anti-PD-1 treatment in renal cell carcinoma

Abstract Presence of CD4+CD8+ Double Positive T (DPT) cells in the tumor microenvironment has been correlated with good prognosis1. Renal cell carcinoma (RCC) is reported to have relatively much higher DPT cell sub-populations as compared to other cancer types1,2. DPT cells in RCC were reported to express high programmed cell death protein-1(PD-1) and therefore is considered a potential target for checkpoint based immunotherapy2. However, the clinical relevance of these DPT cells in determining response to anti-PD-1 has not yet been studied. Using the near native FarcastTM TruTumor RCC histoculture platform, we attempted to elucidate the role of DPT in anti-PD1 response modulation. Fresh surgically resected RCC samples (n=18) along with matched blood were collected from consented patients. Explants were generated and distributed into arms. These arms were treated in culture with nivolumab (anti-PD1:132µg/ml) for 72 hours. The response was evaluated using histopathology and flow cytometry read-outs. DPT cells were gated and expressed as percentage of CD3 using flowcytometry. We observed a significantly higher proportion of DPT cells in RCC (Mean±SEM: 8.2±2.8) compared to head and neck squamous cell carcinoma (Mean±SEM: 1.2±0.4) and ovarian cancer (Mean±SEM: 0.7±0.1). DPT cell population was found to be well preserved on the TruTumor RCC platform post-culture. We stratified samples as high and low DPT cell sub cohorts based on 5% cut-off. Out of 18, 6 samples (33%) showed high DPT cells (with a range of 7-41%). Eighty-three percent (5 out of 6) of high DPT samples elicited a tumor cytotoxicity on treatment with Nivolumab treatment as compared to only 50% (6 out of 12) in low DPT samples. A significant decrease (p&amp;lt;0.05) in DPT cells was observed in the high DPT sub cohort upon Nivolumab treatment, with a concomitant increase in activated (Granzyme B+) DPT and cytotoxic T cells (CD8+) sub-populations was observed upon nivolumab treatment. However, total CD8+ proportions remained unchanged. In addition, an increase in effector (CD4+ FoxP3-) and decrease in Treg (CD4+FoxP3+) population was also observed. Only one out of six high DPT samples exhibited no cytotoxicity in response to nivolumab treatment. Interestingly in this non-responder sample there was a 3.1-fold increase in M2-like (CD68+CD206+) macrophages, as compared to a M1-like macrophage polarization observed in the remaining high DPT samples. In summary, our data suggests that presence of high percentage of DPT cells could favour better response to anti-PD1 therapy in RCC patients. The FarcastTM TruTumor platform thus provides powerful insights into the role of various immune cell sub-populations in modulating response to treatment with immune-oncology therapies.

Utilization of Patient-Specific Characteristics and Competing Risks to Tailor the Duration of Surveillance Imaging After Surgery for Renal Cell Carcinoma

Purpose: The appropriate duration of follow-up after surgical resection of renal cell carcinoma (RCC) remains incompletely defined. To better inform on this time line, we investigate when an individual's risk of RCC recurrence becomes less significant than their risk of non-RCC death. Materials and Methods: We identified 1672 patients who underwent surgery for M0 RCC between 1999 and 2018. Patients were stratified by pathologic stage, histology, age, and Eastern Cooperative Oncology Group (ECOG) performance status. Cumulative incidence functions were estimated for RCC recurrence and non-RCC death using Fine and Gray models. Follow-up durations were estimated as the time point at which the cumulative incidence of non-RCC death exceeded that of RCC recurrence. Results: At a median follow-up of 2.1 years (IQR 0.6-5.1 years), a total of 272 recurrences (16.3%) and 234 non-RCC deaths (14.0%) occurred. The fitted model showed significant associations of stage with RCC recurrence and of age and ECOG with non-RCC death. For 50-year-old patients with pT1aN0-x clear cell and ECOG 0, the incidence of non-RCC death exceeded that of recurrence after 4.4 years. However, if such patients had an ECOG status of 1 or 2 to 4, the incidence of non-RCC death exceeded that of recurrence at 30 days, suggesting that routine oncologic surveillance may not be necessary. Alternatively, regardless of ECOG status, the incidence of non-RCC death failed to exceed that of recurrence for &gt;13.9 years in all patients age 50 with &gt; pT3aN0-x clear cell thereby suggesting longer surveillance than currently recommended. Conclusion: Modeling competing risks of RCC recurrence and non-RCC death provide patient-specific estimates when follow-up may be reasonably discontinued.

Bilateral Resection of Renal Cell Carcinoma with Postoperative Urinary Ascites

Bilateral Resection of Renal Cell Carcinoma with Postoperative Urinary Ascites

Tubular damage marker as a predictive factor for pathologically upstaged renal cell carcinoma.

To investigate if increased tubular damage biomarker can predict pathologically upstaged renal cell carcinoma (RCC), which may possess sub-radiologic invasive behavior, leading to surrounding tubular damage. We examined 1563 patients with surgically resected RCC between March 2016 and June 2021 from the prospective database SUPER-RCC-Nx. Exclusion criteria were cancer not originating from the kidneys, benign renal tumor, and end-stage renal disease. Of 1297 patients, 131 had a clinically high T stage (T3-4), whereas 1166 had a low one. Patients with a clinically low T stage were subgrouped into identical-stage (n = 1041) and upstaged (n = 125) groups, who were confirmed as a pathologically high T stage. The upstaged group had older age (p = 0.003), larger tumor size (5.72 ± 3.24 vs. 3.12 ± 2.08, p < 0.001), higher Fuhrman grade (grades 3-4) (57.3% vs. 47.1%, p = 0.032), and higher urine N-acetyl-beta-D-glucosaminidase/creatinine (NAG/Cr) (5.13 ± 4.78 vs. 4.05 ± 2.84, p = 0.026). Tumor size (> 4cm; odds ratio = 10.2, p < 0.001) and urine NAG/Cr (odds ratio = 1.16, p = 0.003) were independently associated with pathological upstaging in patients with normal renal function, while age and tumor size were significant risk factors in those with decreased renal function. The receiver operating characteristic curve analysis showed that the model using tumor size and urine NAG/Cr strongly predicted pathological upstaging (area under the curve, 0.84). Urine NAG/Cr may be a useful biomarker predicting pathologically upstaged RCC. Clinicians should be prudent in making management decisions when a large RCC is accompanied by an increased urine NAG/Cr.

A novel technique for avoidance of sternotomy, diaphragmic incision and cardiopulmonary bypass during cavoatrial tumor thrombectomy for renal cell carcinoma with intraatrial tumor thrombus: a case series at a single center.

Radical nephrectomy with thrombectomy in patients with renal cell carcinoma (RCC) and level IV thrombus extending to the right atrium (RA) offers improved survival. However, this procedure is associated with significant perioperative morbidity and mortality. In this report, we describe a novel milking technique for patients with RA tumor thrombus using abdominal access, which does not require diaphragmic incision, sternotomy, right atriotomy, or cardiopulmonary bypass (CPB). Between January 2019 and January 2022, four patients underwent resection of renal cell carcinoma extending into RA by a milking technique developed to avoid diaphragmic incision, sternotomy, or CPB. Patient characteristics, perioperative data, pathological features, and survival were evaluated. Complete resection was successful through pure transabdominal access without diaphragmic incision, sternotomy, or CPB in all patients. We conclude that radical nephrectomy and thrombectomy in optimized cases with renal cell carcinoma extending into RA can be safely and effectively performed without diaphragmic incision, sternotomy, or CPB, avoiding serious perioperative complications while providing acceptable oncological outcomes.

Clinical Outcome of Surgical Resection for Renal Cell Carcinoma with Inferior Vena Cava Tumor Thrombus

We analyzed 45 patients who were diagnosed with renal cell carcinoma with inferior vena cava tumor thrombus (IVC) and underwent surgical resection at Nagasaki University Hospital during the 17 years from March 2003 to November 2020. The median overall survival (OS) was 68.5, 53.5, 45.7, and 20.4 months, respectively, according to the tumor thrombus level (Lv) of I, II, III and IV, with a median level of (P＝0.025). In multivariate analysis, pathological sarcomatoid changes were associated with risk of tumor recurrence in the postoperative complete remission group, and IVC thrombus level above Lv III was associated with poor prognosis in the postoperative incomplete remission group. On postoperative systemic treatment for the postoperative recurrence group and the incomplete remission group, overall survival was significantly prolonged in cases using immune checkpoint inhibitors. The results of surgical treatment of renal cell carcinoma with IVC tumor embolization were analyzed. Patients who underwent surgical resection and achieved postoperative complete remission had a relatively long prognosis with a median OS of more than 6 years. In contrast, patients with metastases, especially those with postoperative incomplete remission group, had a poor prognosis despite surgical resection, depending on the patient's situation.

Adjuvant everolimus after surgery for renal cell carcinoma (EVEREST): a double-blind, placebo-controlled, randomised, phase 3 trial

Patients undergoing resection of renal cell carcinoma are at risk of disease relapse. We evaluated the effectiveness of the mammalian target of rapamycin inhibitor everolimus administered after surgery. In this randomised, double-blind, phase 3 trial, we enrolled adults with histologically confirmed renal cell carcinoma who had undergone a full surgical resection and were at intermediate-high or very high risk of recurrence at 398 academic and community institution centres in the USA. After nephrectomy, patients were randomly assigned (1:1) via a central web-based application using a dynamic balancing algorithm to receive 10 mg oral everolimus daily or placebo for 54 weeks. The primary endpoint was recurrence-free survival. Efficacy analyses included all eligible, randomly assigned patients; safety analysis included all patients who received treatment. This trial is registered with ClinicalTrials.gov, NCT01120249 and is closed to new participants. Between April 1, 2011, and Sept 15, 2016, a total of 1545 patients were randomly assigned to receive everolimus (n=775) or placebo (n=770), of whom 755 assigned to everolimus and 744 assigned to placebo were eligible for inclusion in the efficacy analysis. With a median follow-up of 76 months (IQR 61-92), recurrence-free survival was longer with everolimus than with placebo (5-year recurrence-free survival 67% [95% CI 63-70] vs 63% [60-67]; stratified log-rank p=0·050; stratified hazard ratio [HR] 0·85, 95% CI 0·72-1·00; p=0·051) but did not meet the prespecified p value for statistical significance of 0·044. Recurrence-free survival was longer with everolimus than with placebo in the very-high-risk group (HR 0·79, 95% CI 0·65-0·97; p=0·022) but not in the intermediate-high-risk group (0·99, 0·73-1·35; p=0·96). Grade 3 or higher adverse events occurred in 343 (46%) of 740 patients who received everolimus and 79 (11%) of 723 who received placebo. Postoperative everolimus did not improve recurrence-free survival compared with placebo among patients with renal cell carcinoma at high risk of recurrence after nephrectomy. These results do not support the adjuvant use of everolimus for renal cell carcinoma after surgery. US National Institutes of Health, National Cancer Institute, National Clinical Trials Network, Novartis Pharmaceuticals Corporation, and The Hope Foundation.

Comparison of patients with renal cell carcinoma in adjuvant therapy trials to a real-world population.

To compare characteristics and outcomes of patients included versus those not in adjuvant therapy trials post complete resection of renal cell carcinoma (RCC). Adult patients following complete resection for clear cell RCC between January 1, 2011, and March 31, 2021, were included. Patients had intermediate high, high risk nonmetastatic disease (modified UCLA Integrated Staging System) or fully resected metastatic (M1) disease as per the inclusion criteria of adjuvant studies. Demographic, clinical, and outcomes between trial and nontrial patients were compared. Of 1,459 eligible patients, 63 (4.3%) participated in an adjuvant trial. Disease characteristics were similar between groups. Trial patients were younger (mean age 58.1 vs. 63.6 years; P < 0.0001) and had lower Charlson Comorbidity Index scores (mean 4.2 vs. 4.9; P = 0.009). Unadjusted disease-free survival (DFS) at 5 years for trial patients was 48.6% and 39.2% for nontrial patients (HR 0.71, 0.48-1.05, P = 0.08). Median DFS was higher for trial patients in comparison to nontrial patients (4.4 years, IQR 1.7- not reached; vs. 3.0 years, IQR 0.8-8.6; P = 0.08). Cancer specific survival (CSS) at 5 years for trial patients was 85.2% in comparison to 78.6% for nontrial patients (HR 0.45, 0.22-0.92, P = 0.03). Unadjusted estimated overall survival (OS) at 5 years was 80.8% for trial patients and 74.8% (HR 0.42, 0.18-0.94; P = 0.04) for nontrial patients. Patients in adjuvant trials were younger and healthier with longer CSS and OS in comparison to those not included in adjuvant trials. These findings may have implications when we generalize trial results to real world patients.

Comparison of peri- and intraoperative outcomes of open vs robotic-assisted partial nephrectomy for renal cell carcinoma: a propensity-matched analysis

BackgroundPartial nephrectomy (PN) is the gold standard surgical treatment for resectable renal cell carcinoma (RCC) tumors. However, the decision whether a robotic (RAPN) or open PN (OPN) approach is chosen is often based on the surgeon’s individual experience and preference. To overcome the inherent selection bias when comparing peri- and postoperative outcomes of RAPN vs. OPN, a strict statistical methodology is needed.Materials and methodsWe relied on an institutional tertiary-care database to identify RCC patients treated with RAPN and OPN between January 2003 and January 2021. Study endpoints were estimated blood loss (EBL), length of stay (LOS), rate of intraoperative and postoperative complications, and trifecta. In the first step of analyses, descriptive statistics and multivariable regression models (MVA) were applied. In the second step of analyses, to validate initial findings, MVA were applied after 2:1 propensity-score matching (PSM).ResultsOf 615 RCC patients, 481 (78%) underwent OPN vs 134 (22%) RAPN. RAPN patients were younger and presented with a smaller tumor diameter and lower RENAL-Score sum, respectively. Median EBL was comparable, whereas LOS was shorter in RAPN vs. OPN. Both intraoperative (27 vs 6%) and Clavien-Dindo > 2 complications (11 vs 3%) were higher in OPN (both < 0.05), whereas achievement of trifecta was higher in RAPN (65 vs 54%; p = 0.028). In MVA, RAPN was a significant predictor for shorter LOS, lower rates of intraoperative and postoperative complications as well as higher trifecta rates. After 2:1 PSM with subsequent MVA, RAPN remained a statistical and clinical predictor for lower rates of intraoperative and postoperative complications and higher rates of trifecta achievement but not LOS.ConclusionsDifferences in baseline and outcome characteristics exist between RAPN vs. OPN, probably due to selection bias. However, after applying two sets of statistical analyses, RAPN seems to be associated with more favorable outcomes regarding complications and trifecta rates.

The role of immune checkpoint inhibitors (ICI) as adjuvant treatment in renal cell carcinoma (RCC): A systematic review and meta-analysis.

Pembrolizumab, a PD-1 ICI is approved for the adjuvant treatment of postnephrectomy patients with clear cell RCC in some countries worldwide. However, recent negative data from randomized clinical trials (RCT) with another ICIs makes the benefit of this treatment uncertain. A systematic review and study-level meta-analysis was performed to evaluate the benefit of disease-free survival (DFS) with adjuvant ICI treatment for patients with localized and/or metastatic resected RCC. Using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement, a systematic search was performed in PUBMED/MEDLINE, Scopus and EMBASE up to September 15, 2022. The statistical analysis was performed by ProMeta 3 software in intention-to-treat (ITT) population and in predetermined subgroups. Four RCT totalizing 3407 patients were included in this analysis. Systemic immunotherapy was pembrolizumab, atezolizumab, nivolumab, and ipilimumab plus nivolumab in 496, 390, 404, and 405 patients, respectively. In the ITT population there was a nonstatistically significant DFS benefit with adjuvant ICI (HR: 0.85, 95% CI: 0.69-1.04). Regarding the subgroups, there was a DFS benefit for PD-L1 positive (HR: 0.72; 95% CI: 0.55-0.94), intermediate-high risk patients (HR: 0.77; 95% CI: 0.63-0.94), and patients with sarcomatoid component (HR: 0.66; 95% CI: 0.43-0.99). This meta-analysis did not demonstrate a statistically significant DFS benefit in overall population, however considering the heterogeneity between the RCTs the use of adjuvant ICI should be individualized.

Efficacy of Therapy vs Surveillance in Patients with Resected Early-Stage Intermediate to High-Risk Renal Cell Carcinoma

BACKGROUND: The historical standard of care for locally advanced renal cell carcinoma (RCC) is nephrectomy + active surveillance. Despite a high recurrence rate ( 40%), adjuvant therapy was previously not included in the standard of care. This review of adjuvant pharmacotherapy reflects conflicting results from multiple trials. OBJECTIVE: The objective of this review is to summarize the efficacy of therapy vs surveillance in resected early-stage intermediate to high-risk renal cell carcinoma. METHODS: We performed a systematic literature search using PubMed, EMBASE, and SCOPUS. Keywords such as “renal cell carcinoma”, “adjuvant therapy” and “nephrectomy” were used. In the literature search, 2,711 studies were identified and screened. RESULTS: We included a total of 21 publications. The most common histology seen in trials was clear cell carcinoma. A variety of interventions were reviewed including immunotherapy, medroxyprogesterone acetate, interferon alfa, and tyrosine kinase inhibitors. Most trials did not demonstrate a benefit in relapse-free survival (RPS) or overall survival (OS). Pembrolizumab demonstrated a significant difference in disease recurrence in the KEYNOTE-564 trial although median data was not reached. Blinded independent reviewers identified a benefit in disease-free survival (DFS) with Sunitinib in the S-TRAC trial. CONCLUSION: There was not a clear benefit in using adjuvant therapy broadly for resected locoregional RCC; however, further investigation should be done in the highest-risk group to elucidate potential benefit.

MP41-09 ARTIFICIAL INTELLIGENCE TO PREDICT RECURRENCE AFTER SURGICAL RESECTION OF NON-METASTATIC RENAL CELL CARCINOMA

You have accessJournal of UrologyCME1 Apr 2023MP41-09 ARTIFICIAL INTELLIGENCE TO PREDICT RECURRENCE AFTER SURGICAL RESECTION OF NON-METASTATIC RENAL CELL CARCINOMA Zine-Eddine Khene and Karim Bensalah Zine-Eddine KheneZine-Eddine Khene More articles by this author and Karim BensalahKarim Bensalah More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003279.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Predictive tools can be useful to adapt surveillance or include patients in adjuvant trials after surgical resection of non-metastatic renal cell carcinoma (RCC). Current models have been built using traditional statistical modelling and prespecified variables, which limits their performance.Our aim was To investigate the performance of machine learning (ML) framework to predict recurrence after RCC surgery and compare them with current validated models. METHODS: In this observational study, we derived and tested a ensembles of machine learning-based models (Random Survival Forests [RSF], Survival Support Vector Machines [S-SVM], and Extreme Gradient Boosting [XG boost]) of patients who underwent radical or partial nephrectomy for a non-metastatic RCC, between 2013 and 2020, at 21 French medical centres using standard clinicopathological variables.The primary end point of prediction was disease-free survival. Model discrimination was assessed using the concordance index (c-index), and calibration was assessed using the Brier score. ML models were compared with four conventional prognostic models, using decision curve analysis (DCA). RESULTS: 4067 patients were included in this study. ML models obtained higher c-index values than conventional models. The RSF yielded the highest c-index values (0.794) followed by S-SVM (c-index 0.784) and XG boost (c-index 0.782). In addition, all models showed good calibration with low integrated Brier scores (all integrated brier scores <0.1). However, we found calibration drift over time for all models, albeit with a smaller magnitude for ML models. Finally, DCA showed an incremental net benefit from all ML models compared to conventional models currently used in practice. CONCLUSIONS: Applying ML approaches to predict recurrence following surgical resection of RCC resulted in better prediction than that of current validated models available in clinical practice. However, there is still room for improvement that may come from the integration of novel biological and/or imaging biomarkers. Source of Funding: none © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e557 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Zine-Eddine Khene More articles by this author Karim Bensalah More articles by this author Expand All Advertisement PDF downloadLoading ...

MP47-18 OUTCOMES OF PERCUTANEOUS RENAL CRYOABLATION IN A LARGE COHORT OVER 15 YEARS

You have accessJournal of UrologyCME1 Apr 2023MP47-18 OUTCOMES OF PERCUTANEOUS RENAL CRYOABLATION IN A LARGE COHORT OVER 15 YEARS Zachary A. Valley, Evan Allarie, Steven Lu, Richard Cormack, Michael Welsh, Bryan J. Donnelly, and Kamaljot S. Kaler Zachary A. ValleyZachary A. Valley More articles by this author , Evan AllarieEvan Allarie More articles by this author , Steven LuSteven Lu More articles by this author , Richard CormackRichard Cormack More articles by this author , Michael WelshMichael Welsh More articles by this author , Bryan J. DonnellyBryan J. Donnelly More articles by this author , and Kamaljot S. KalerKamaljot S. Kaler More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003293.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Historically, the standard of care for renal cell carcinoma (RCC) has been partial nephrectomy (PN) or radical nephrectomy (RN). Image-guided percutaneous cryoablation (PCA) of renal masses has emerged as a nephron-sparing, minimally invasive alternative. In this study, we aim to assess outcomes of percutaneous renal cryoablation at a single centre over 15 years. METHODS: Patients who underwent PCA of renal masses from 2006 to 2022 were included with no exclusions. All patients had cross-sectional imaging prior to the procedure and most underwent biopsy at the time of procedure. Cryoprobe placement and ice-ball formation was monitored via computed tomography (CT) imaging during the procedure. Data were collected via electronic medical record review, as well as pre-, intra-, and post-procedure imaging review. Data included demographics, tumor characteristics, pathology, local recurrence and metastatic disease rates, complications, pre- and post-procedure renal function and blood counts, co-morbidities, and mortality rate of patients in follow-up. RESULTS: This study included 598 patients in the analysis with a median age of 65.1 years and median follow-up of 39 months (Table 1). The average size of tumor was 2.7 cm. Overall local recurrence rate was 4.8% including surgically resected and hereditary RCC. Average nephrometry score was 6.1. Median time to local recurrence was 2.0 years. Five percent of patients made up 52% of the recurrences. Overall survival rate was 82.3% at time of analysis. Cancer-specific survival overall was 97.3%. Average length of time to discharge was 28.2 hours. The Clavien-Dindo 3+ complication rate was 2.3%. Overall metastatic rate was 1.8% and 0.7% in patients with no recurrence. CONCLUSIONS: PCA outcomes in this large cohort with no exclusions and long-term follow-up revealed an overall low recurrence rate, low complication rate, and an acceptable metastatic rate. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e651 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Zachary A. Valley More articles by this author Evan Allarie More articles by this author Steven Lu More articles by this author Richard Cormack More articles by this author Michael Welsh More articles by this author Bryan J. Donnelly More articles by this author Kamaljot S. Kaler More articles by this author Expand All Advertisement PDF downloadLoading ...

V05-07 ROBOTIC-ASSISTED LEFT RADICAL NEPHRECTOMY AND IVC THROMBECTOMY IN CROSS-FUSED RENAL ECTOPIA

You have accessJournal of UrologyCME1 Apr 2023V05-07 ROBOTIC-ASSISTED LEFT RADICAL NEPHRECTOMY AND IVC THROMBECTOMY IN CROSS-FUSED RENAL ECTOPIA Hannah Pham, Raj Satkunasivam, Brian Miles, Wesley Ekeruo, Mark Sultenfuss, Michael Brooks, and Monty Aghazadeh Hannah PhamHannah Pham More articles by this author , Raj SatkunasivamRaj Satkunasivam More articles by this author , Brian MilesBrian Miles More articles by this author , Wesley EkeruoWesley Ekeruo More articles by this author , Mark SultenfussMark Sultenfuss More articles by this author , Michael BrooksMichael Brooks More articles by this author , and Monty AghazadehMonty Aghazadeh More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003263.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Crossed fused renal ectopia is a relatively rare entity with an estimated prevalence of 1 in 2000 births (Tsuboi et al). Renal cell carcinoma (RCC) in this setting is even more rare and there are no previous reports of associated inferior vena cava (IVC) tumor thrombi. Renal malignancy involving crossed fused ectopia presents a unique, complex surgical challenge and, therefore, there a few reports of minimally invasive surgical management. Herein, we describe a successful robotic resection of a large left renal mass with IVC thrombus involving a crossed fused ectopic right kidney. METHODS: We performed a transperitoneal robotic nephrectomy and caval thrombectomy on a 68-year-old male with an 11cm left renal mass and level 1 IVC thrombus, in the setting of a crossed fused ectopic right kidney. A two-position approach - modified left flank, followed by modified right flank - was employed to safely complete the procedure. Critical procedure steps included: 1) Pre-operative left renal artery embolization, 2) IVC control, cavotomy, and thrombectomy, 3) Left radical nephrectomy, and 4) Partial nephrectomy of the ectopic right kidney. The use of intraoperative ultrasound, Firefly technology, and indocyanine green were also fundamental adjuncts to the procedure. Perioperative outcomes are reported along with associated contemporary comparisons. RESULTS: The total operative time was five hours and thirty-one minutes, which included re-positioning and re-docking time. Estimated blood loss was 300cc without the need for perioperative transfusion. The postoperative course was uncomplicated, and the patient was discharged on postoperative day 4. There were no major perioperative complications. Pre- and postoperative estimated glomerular filtration rate was 86 and 52, respectively. Final pathology showed pT3b, N1, and clear cell RCC. Margins were negative. CONCLUSIONS: We demonstrate robotic resection of RCC with IVC thrombus in the setting of crossed fused renal ectopia, which is, to our knowledge, the first reported description of this entity and this approach. Success was predicated on strict adherence to standard oncologic and operative principles for minimally invasive IVC thrombectomy, radical nephrectomy, and partial nephrectomy. Source of Funding: None. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e426 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hannah Pham More articles by this author Raj Satkunasivam More articles by this author Brian Miles More articles by this author Wesley Ekeruo More articles by this author Mark Sultenfuss More articles by this author Michael Brooks More articles by this author Monty Aghazadeh More articles by this author Expand All Advertisement PDF downloadLoading ...

Immune checkpoint inhibitors in the peri-operative setting in renal cell carcinoma: A meta-analysis of the randomized clinical trials.

682 Background: Localized and oligometastatic resectable renal cell carcinoma (RCC) have moderate to high rates of relapse after surgery and evidence regarding the efficacy of perioperative treatments is conflicting. The risk of relapse varies across studies and there is a need to define the benefit/risk of immune checkpoint inhibitors (ICI) in this setting to optimize their use. Methods: A meta-analysis of the randomized phase 3 trials of peri-operative treatment with anti-PD-1/PD-L1 agents or anti-PD1/antiCTL4 in combination was conducted. The primary outcomes of interest were disease-free survival (DFS) and overall survival (OS). Secondary outcomes of interest were the proportion of grade 3-4 adverse events (AE) according to CTCAE 5.0. Subgroup analyses were performed according to clinically relevant characteristics. Statistical heterogeneity assumption was evaluated by the χ²-based Cochran’s Q test and quantified with the I² statistic. All statistical analyses were performed using Stata software (StataCorp LLC), version 16. Results: Published results of 4 phase 3 trials were included, involving 3393 patients. 1695 patients received ICI (anti-PD1: 900 patients; anti-PD-L1 390 patients, antiPD1/anti-CTLA4 405 patients) while 1712 received no active treatment (1297 placebo, 415 observation). ICI did not show to increase DFS (Hazard ratio (HR) 0.84 95% CI 0.69-1.03 p 0.10) or OS (HR 0.73 95% CI 0.40-1.34 p 0.31). High-grade AEs were 2.6 times more frequent in the immunotherapy arm (OR 2.64 95% CI 1.54 – 4.68 p &lt; 0.001) while high grade treatment-related AEs were 8 times more frequent in the experimental arm (OR 8.60 95% CI 3.23-22.91 p &lt; 0.001). Interestingly, subgroup analyses showed statistically significant differences favoring the experimental arm in females (HR 0.72 95% CI 0.55-0.93 p 0.01), in patients with sarcomatoid differentiation (HR 0.59 95% CI 0.403-0.88 p 0.010) and PD-L1 positive tumors (HR 0.74 95% CI 0.61-0.90 p 0.003). No significant effect was found in patients according to age, type of nephrectomy (radical vs. partial), and stage (M1 without evidence of disease vs M0 patients). Conclusions: The introduction of anti-PD-(L)1 +/- anti-CTLA-4 agents in the adjuvant setting of RCC might benefit selected RCC patients, although with increased toxicity. Longer follow-up of the conducted studies is needed to establish a potential benefit in long-term survival.

Mapping distribution of brain metastases in renal cell carcinoma (RCC) and association with clinical features.

727 Background: Brain metastases (BM) are frequently observed in metastatic RCC (mRCC) with a tendency to present with hemorrhagic BM. Distribution patterns of BM in RCC and associations with clinical outcomes are not well understood. Here we present a detailed distribution analysis in a surgically resected BM RCC cohort with a focus on clinically relevant associations. Methods: A retrospective analysis was performed on patients (pts) with mRCC who underwent craniotomy for BM at our institution. We reviewed gadolinium-enhanced MRI brain and CT head (if available) at the time of BM diagnosis. We assessed the presence of hemosiderin on MRI or hemorrhage on CT in the BM lesion and marked each at their corresponding anatomic location. Public brain atlases were used for distribution analysis. Overall survival (OS) from the date of BM diagnosis and CNS progression free survival (CNS-PFS) from the date of craniotomy were calculated. Results: A total of 67 BM were analyzed from 46 pts. 23 with synchronous BM, 9 with two and 6 with 3 concurrent BM. Most patients were male (n=35, 76%) with a median age at diagnosis of 63 years. Primary histology was clear cell in 42 pts (91%) and 10 pts (22%) had renal vein thrombosis (RVT) at primary diagnosis. IMDC scores at time of BM diagnosis were favorable in 20%, intermediate in 60% and poor in 20%. Hemosiderin (MRI) or hemorrhage (CT) was seen in 82% and 80% of BM, respectively. 55% of lesions were left sided, 45% frontal, 21% parietal, 18% occipital, 7% temporal and 6% cerebellar. Posterior circulation and posterior cerebral artery territories contained 42% and 34% of BM despite supplying only 30% and 16% of the brain volume, respectively. Patients with solitary BM had higher Karnofsky performance status (p=0.006) and lower disease burden (p=0.004) than those with multiple BM. Shorter CNS-PFS was seen in association with hemosiderin on MRI (log-rank p=0.04) and RVT in primary specimen (log-rank p=0.002). IMDC risk scores (log-rank p&lt;0.001) predicted OS. On multivariable OS analysis, BM lateralized to the right (HR 2.6, p=0.06), hemosiderin in BM (HR 6.5, p=0.02) and IMDC risk groups (intermediate HR 2.9, poor risk HR 25.6, p&lt;0.04) were independent prognostic factors for shorter OS. Conclusions: The above-presented lesion mapping method shows clinically relevant findings in RCC BM. Tumoral hemosiderin deposits appear a potential parameter to predict outcomes in RCC BM which deserve further study and validation.

Preoperative c-reactive protein and risk of major complications and mortality outcomes in patients undergoing surgery for renal cell carcinoma.

723 Background: C-reactive protein (CRP) has been demonstrated to be an independent predictor of survival outcomes in renal cell carcinoma (RCC). The use of biomarkers to predict post-surgical complications is not well studied. We sought to investigate predictive factors for major complications following surgery for RCC and delineate their impact on mortality outcomes. Methods: We performed a two-center retrospective analysis of patients who underwent partial (PN) and radical nephrectomy (RN) for RCC. Patients who had complications within 30 days after surgery were identified and the complications were scored using the Clavien-Dindo classification system. Patients were grouped based on whether they experienced 30-day major (Clavien ≥3) complications and whether they had elevated preoperative CRP defined as &gt;5mg/L. Primary outcome was non-cancer mortality (NCM), with secondary outcomes being all-cause (ACM) and cancer-specific (CSM) mortality. Multivariable analyses (MVA) were conducted to evaluate predictors for Clavien ≥3 complications, NCM, CSM, and ACM. Kaplan-Meier analyses (KMA) were performed to compare overall survival (OS), noncancer-specific survival (NCS), and cancer-specific survival (CSS) between patients with non-elevated and elevated preoperative CRP and between patients without and with 30-day Clavien ≥3 complications. Results: A total of 2,234 patients were analyzed [116 (5.2%) experienced Clavien ≥3 complications; median follow up 44 months]. MVA revealed that coronary artery disease (OR 2.37, p=0.005), elevated CRP (OR 2.25, p=0.004), PN (OR 2.79, p&lt;0.001), and open surgical approach (OR 1.74, p=0.049) were predictive of Clavien ≥3 complications. Additionally, MVA demonstrated that elevated CRP was an independent predictor of NCM (HR 2.50, p=0.009), CSM (HR 5.51, p&lt;0.001) and ACM (HR 4.04, p&lt;0.001), while presence of 30-day Clavien ≥3 complications was independently associated with worsened NCM (HR 3.05, p=0.042) but not CSM or ACM. KMA comparing non-elevated and elevated preoperative CRP revealed significant differences for 5-year OS (96.0% vs. 66.8%, p&lt;0.001), 5-year CSS (98.2% vs. 75.6%, p&lt;0.001), and 5-year NCS (97.6% vs. 87.7%, p&lt;0.001). KMA comparing patients without and with 30-day Clavien ≥3 complications revealed significant differences for 5-year OS (87.3% vs. 80.7%, p=0.015) and 5-year NCS (95.6% vs. 87.0%, p&lt;0.001), but not 5-year CSS (91.3% vs. 88.9%, p=0.601). Conclusions: In patients undergoing surgical resection for RCC, elevated preoperative CRP was an independent risk factor for development of 30-day Clavien ≥3 complications, while elevated CRP and development of Clavien ≥3 complications were associated with worsened NCM. Our findings suggest an interplay between major complications and NCM in patients who undergo surgery for RCC, with elevated preoperative CRP being a predictor for both.

CXCR3 Expression Is Associated with Advanced Tumor Stage and Grade Influencing Survival after Surgery of Localised Renal Cell Carcinoma

Surgery is the standard treatment in localized renal cell carcinoma (RCC). Pembrolizumab is now approved for adjuvant therapy in high-risk patients. However, inhomogeneity of studies gives ambiguity which patient benefit most from adjuvant therapy. A high infiltration of CD8+ T cells is known to be linked with poor prognosis in RCC. CXCR3 is a key player of CD8+ T cell differentiation and infiltration. We aimed to evaluate CXCR3 as a potential marker for predicting recurrence. CXCR3 and immune cell subsets (CD4, CD8, CD68 and FoXP3) were measured on RCC samples by multiplex immunofluorescence (mIF) staining. Cellular localization of CXCR3 was evaluated using single-cell RNA analysis on a publicly available dataset. Tumor samples of 42 RCC patients were analyzed, from which 59.5% were classified as clear-cell RCC and of which 20 had recurrence. Single-cell RNA analysis revealed that CXCR3 was predominantly expressed in intratumoral T cells and dendritic cells. CXCR3 expression was higher in advanced tumors stages (p = 0.0044) and grade (p = 0.0518), correlating significantly with a higher CD8+ T cell expression (p < 0.001). Patients with CXCR3high RCCs had also a significant shorter RFS compared to CXCR3low (median: 78 vs. 147 months, p = 0.0213). In addition, also tumor stage pT3/4 (p < 0.0001) as well as grade G3/4 (p = 0.0008) negatively influenced RFS. CXCR3high cell density was associated with high T cell infiltration and advanced tumor stage, worsening RFS in surgically resected RCC patients. Beside its prognostic value, CXCR3 might be a predictive biomarker to guide therapy decision for adjuvant therapy in localized RCC.