Percutaneous Microwave Ablation for Treatment of Retroperitoneal Tumors.

Purpose To determine if microwave ablation (MWA) of retroperitoneal tumors can safely provide high rates of local tumor control. Materials and Methods This retrospective study included 19 patients (median age, 65 years [range = 46-78 years]; 13 [68.4%] men and six [31.6%] women) with 29 retroperitoneal tumors treated over 22 MWA procedures. Hydrodissection (0.9% saline with 2% iohexol) was injected in 17 of 22 (77.3%) procedures to protect nontarget anatomy. The primary outcomes evaluated were local tumor progression (LTP) and complication rates. Oncologic outcomes, including overall survival (OS), progression-free survival (PFS), and treatment-free interval (TFI), were examined as secondary outcome measures. Results Median follow-up was 18 months (range = 0.5-113). Hydrodissection was successful in displacing nontarget anatomy in 16 of 17 (94.1%) procedures. The LTP rate was 3.4% (one of 29; 95% CI: 0.1, 17.8) per tumor and 5.3% (one of 19; 95% CI: 0.1, 26.0) per patient. The overall complication rate per patient was 15.8% (three of 19), including two minor complications and one major complication. The OS rate at 1, 2, and 3 years was 81.8%, 81.8%, and 72.7%, respectively, with a median OS estimated at greater than 7 years. There was no evidence of a difference in OS (P = .34) and PFS (P = .56) between patients with renal cell carcinoma (six of 19 [31.6%]) versus other tumors (13 of 19 [68.4%]) and patients treated with no evidence of disease (15 of 22 [68.2%]) versus patients with residual tumors (seven of 22 [31.8%]). Median TFI was 18 months (range = 0.5-108). Conclusion Treatment of retroperitoneal tumors with MWA combined with hydrodissection provided high rates of local control, prolonged systemic therapy-free intervals, and few serious complications. Keywords: Ablation Techniques (ie, Radiofrequency, Thermal, Chemical), Retroperitoneum, Microwave Ablation, Hydrodissection © RSNA, 2024.

The Selection for Cytoreductive Nephrectomy (SCREEN) Score: Improving Surgical Risk Stratification by Integrating Common Radiographic Features.

BACKGROUND: Careful patient selection is critical when considering cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) but few studies have investigated the prognostic value of radiologic features that measure tumor burden. OBJECTIVE: To develop a prognostic model to improve CN selection with integration of common radiologic features with known prognostic factors associated with mortality in the first year following surgery. DESIGN, SETTINGS, AND PARTICIPANTS: Data were analyzed for consecutive patients with mRCC treated with upfront CN at five institutions from 2006 to 2017. Univariable and multivariable models were used to evaluate radiographic features and known risk factors for associations with overall survival. Relevant factors were used to create the SCREEN model and compared to the International mRCC Database Consortium (IMDC) model for predictive accuracy and clinical usefulness. RESULTS AND LIMITATIONS: A total of 914 patients with mRCC were treated with upfront CN during the study period. Seven independently predictive variables were used in the SCREEN score: three or more metastatic sites, total metastatic tumor burden ≥5 cm, bone metastasis, systemic symptoms, low serum hemoglobin, low serum albumin, and neutrophil/lymphocyte ratio ≥4. Predictive accuracy measured as the area under the receiver operating characteristic curves was 0.76 for the SCREEN score and 0.55 for the IMDC model. Decision curve analysis showed that the SCREEN model was useful beyond the IMDC classifier for threshold first-year mortality probabilities between 15% and 70%. CONCLUSIONS: The SCREEN score had higher predictive accuracy for first-year mortality compared to the IMDC scheme in a multi-institutional cohort and may be used to improve CN selection. PATIENT SUMMARY: This study provides a model to improve selection of patients with metastatic kidney cancer who may benefit from surgical removal of the primary kidney tumor. We found that radiographic measurements of the tumor burden predicted the risk of death in the first year after surgery. The model can be used to improve decision-making by these patients and their physicians.

A Comparison of Histotripsy and Percutaneous Cryoablation in a Chronic Healthy Swine Kidney Model.

PURPOSE: To compare the safety and efficacy of histotripsy with cryoablation in a chronic human-scale normal porcine kidney model. MATERIALS AND METHODS: Eighteen female domestic swine were divided evenly into histotripsy and cryoablation treatment arms. A planned 2-3 cm diameter treatment was performed under ultrasound (histotripsy) or ultrasound and computed tomography (CT) guidance (cryoablation). Contrast-enhanced CT and serum blood analysis were performed immediately postprocedure and on day 7, with either immediate killing (n = 3) or continued survival to day 30 (n = 6), at which time contrast-enhanced CT, serum blood analysis, and necropsy were performed. Animal welfare, treatment zone appearance, procedure-related adverse events, and histopathology of the treatment zones and surrounding tissues were assessed. RESULTS: Histotripsy treatment zones (mean ±standard deviation diameters, 2.7 ± 0.12 × 2.4 ± 0.19 × 2.4 ± 0.26 cm; volume, 8.3 ± 1.9 cm3) were larger than cryoablation zones (mean diameters, 2.2 ± 0.19 × 1.9 ± 0.13 × 1.7 ± 0.19 cm; volume, 3.9 ± 0.8 cm3; P < .001). At 30 days, histotripsy and cryoablation treatment zone volumes decreased by 96% and 83% on CT, respectively (P < .001). Perirenal hematomas were present after 8 of 9 (89%) cryoablation (mean volume, 22.2 cm3) and 1 of 9 (11%, P < .001) histotripsy (volume, 0.4 cm3) procedures, with active arterial extravasation in 4 of 9 (44%) cryoablation and no histotripsy animals (P = .206). All 9 histotripsy animals and 5 of 9 (56%) cryoablation animals had collecting system debris (P = .042). Changes in serum creatinine were similar between the groups (P = .321). CONCLUSIONS: Other than a higher rate of bleeding after cryoablation, the safety and early efficacy of histotripsy and cryoablation were comparable for creating treatment zones in a chronic normal porcine kidney model.

Understanding and integrating cytoreductive nephrectomy with immune checkpoint inhibitors in the management of metastatic RCC.

Cytoreductive nephrectomy became accepted as standard of care for selected patients with metastatic renal cell carcinoma (mRCC) because of improved survival observed in patients treated with cytoreductive nephrectomy in combination with interferon-α in two randomized clinical trials published in 2001. Over the past two decades, novel systemic therapies have shown higher treatment response rates and improved survival outcomes compared with interferon-α. During this rapid evolution of mRCC treatments, systemic therapies have been the primary focus of clinical trials. Results from multiple retrospective studies continue to suggest an overall survival benefit for selected patients treated with nephrectomy in combination with systemic mRCC treatments, with the notable exception of one debated clinical trial. The optimal timing for surgery is unknown, and proper patient selection remains crucial to improving surgical outcomes. As systemic therapies continue to evolve, clinicians have an increasing need to understand how to incorporate cytoreductive nephrectomy into the management of mRCC.

Cytoreductive Nephrectomy Following Immune Checkpoint Inhibitor Therapy Is Safe and Facilitates Treatment-free Intervals.

Patients with metastatic renal cell cancer (mRCC) who respond to upfront immune checkpoint inhibitor (ICI) combination therapies may be treated with cytoreductive nephrectomy (CN) to remove radiographically viable primary tumors. Early data for post-ICI CN suggested that ICI therapies induce desmoplastic reactions in some patients, increasing the risk of surgical complications and perioperative mortality. We evaluated perioperative outcomes for 75 consecutive patients treated with post-ICI CN at four institutions from 2017 to 2022. Our cohort of 75 patients had minimal or no residual metastatic disease but radiographically enhancing primary tumors after ICI and were treated with CN. Intraoperative complications were identified in 3/75 patients (4%) and 90-d postoperative complications in 19/75 (25%), including two patients (3%) with high-grade (Clavien ≥III) complications. One patient was readmitted within 30 d. No patients died within 90 d after surgery. Viable tumor was present in all but one specimen. Approximately half of the patients (36/75, 48%) remained off systemic therapy at last follow-up. These data suggest that CN following ICI therapy is safe and associated with low rates of major postoperative complications in appropriately selected patients at experienced centers. Post-ICI CN may facilitate observation without additional systemic therapy in patients without significant residual metastatic disease. Patient summary: Current first-line treatment for patients with kidney cancer that has spread to other sites (metastatic cancer) is immunotherapy. For cases in which metastatic sites respond to this therapy but primary tumor is still detected in the kidney, surgical treatment of the tumor is feasible and has a low rate of complications, and may delay the need for further chemotherapy.

Hepatic and Renal Histotripsy in an Anticoagulated Porcine Model.

PURPOSE: To determine the risk of mechanical vessel wall damage resulting in hemorrhage during and after hepatic and renal histotripsy in an anticoagulated in vivo porcine model. MATERIALS AND METHODS: Non-tumor-bearing pigs (n = 8; mean weight, 52.5 kg) were anticoagulated with warfarin (initial dose, 0.08 mg/kg) to a target prothrombin time (PT) of 30%-50% above baseline. A total of 15 histotripsy procedures were performed (kidney: n = 8, 2.0-cm sphere; liver: n = 7, 2.5-cm sphere). Treatments were immediately followed by computed tomography (CT) imaging. Animals were observed for 7 days while continuing anticoagulation, followed by repeat CT and necropsy. RESULTS: All animals survived to complete the entire protocol with no signs of disability or distress. Three animals had hematuria (pink urine without clots). Baseline PT values (mean, 16.0 seconds) were elevated to 22.0 seconds (37.5% above baseline, P = .003) on the day of treatment and to 28.8 seconds (77.8% above baseline, P < .001) on the day of necropsy. At the time of treatment, 5 of 8 (63%) animals were at a therapeutic anticoagulation level, and all 8 animals (100%) reached therapeutic levels by the time of necropsy. There were no cases of intraparenchymal, peritoneal, or retroperitoneal hemorrhage associated with any treatments despite 5 of 7 (71%) liver and all 8 (100%) kidney treatments extending to the organ surface. CONCLUSIONS: Liver and kidney histotripsy seems safe with no elevated bleeding risk in this anticoagulated animal model, supporting the possibility of histotripsy treatments in patients on anticoagulation.

The SUMO protease SENP1 promotes aggressive behaviors of high HIF2α expressing renal cell carcinoma cells.

While an important role for the SUMO protease SENP1 is recognized in multiple solid cancers, its role in renal cell carcinoma (RCC) pathogenesis, particularly the most dominant subtype, clear cell RCC (ccRCC), is poorly understood. Here we show that a combination of high HIF2α and SENP1 expression in ccRCC samples predicts poor patient survival. Using ccRCC cell models that express high HIF2α but low SENP1, we show that overexpression of SENP1 reduces sumoylation and ubiquitination of HIF2α, increases HIF2α transcriptional activity, and enhances expression of genes associated with cancer cell invasion, stemness and epithelial-mesenchymal transition. Accordingly, ccRCC cells with high HIF2α and SENP1 showed increased invasion and sphere formation in vitro, and local invasion and metastasis in vivo. Finally, SENP1 overexpression caused high HIF2α ccRCC cells to acquire resistance to a clinical mTOR inhibitor, everolimus. These results reveal a combination of high SENP1 and HIF2α expression gives particularly poor prognosis for ccRCC patients and suggest that SENP1 may be an attractive new target for treating metastatic RCC (mRCC).

Differentiation of benign from malignant solid renal lesions with MRI-based radiomics and machine learning.

BACKGROUND: Solid renal masses are often indeterminate for benignity versus malignancy on magnetic resonance imaging. Such masses are typically evaluated with either percutaneous biopsy or surgical resection. Percutaneous biopsy can be non-diagnostic and some surgically resected lesions are inadvertently benign. PURPOSE: To assess the performance of ten machine learning (ML) algorithms trained with MRI-based radiomics features in distinguishing benign from malignant solid renal masses. METHODS: Patients with solid renal masses identified on pre-intervention MRI were curated from our institutional database. Masses with a definitive diagnosis via imaging (for angiomyolipomas) or via biopsy or surgical resection (for oncocytomas or renal cell carcinomas) were selected. Each mass was segmented for both T2- and post-contrast T1-weighted images. Radiomics features were derived from the segmented masses for each imaging sequence. Ten ML algorithms were trained with the radiomics features gleaned from each MR sequence, as well as the combination of MR sequences. RESULTS: In total, 182 renal masses in 160 patients were included in the study. The support vector machine algorithm trained on radiomics features from T2-weighted images performed superiorly, with an accuracy of 0.80 and an area under the curve (AUC) of 0.79. Linear discriminant analysis (accuracy = 0.84 and AUC = 0.77) and logistic regression (accuracy = 0.78 and AUC = 0.78) algorithms trained on T2-based radiomics features performed similarly. ML algorithms trained on radiomics features from post-contrast T1-weighted images or the combination of radiomics features from T2- and post-contrast T1-weighted images yielded lower performance. CONCLUSION: Machine learning models trained with radiomics features derived from T2-weighted images can provide high accuracy for distinguishing benign from malignant solid renal masses. CLINICAL IMPACT: Machine learning models derived from MRI-based radiomics features may improve the clinical management of solid renal masses and have the potential to reduce the frequency with which benign solid renal masses are biopsied or surgically resected.

Models of Renal Cell Carcinoma Used to Investigate Molecular Mechanisms and Develop New Therapeutics.

Modeling renal cell carcinoma is critical to investigating tumor biology and therapeutic mechanisms. Multiple systems have been developed to represent critical components of the tumor and its surrounding microenvironment. Prominent in vitro models include traditional cell cultures, 3D organoid models, and microphysiological devices. In vivo models consist of murine patient derived xenografts or genetically engineered mice. Each system has unique advantages as well as limitations and researchers must thoroughly understand each model to properly investigate research questions. This review addresses common model systems for renal cell carcinoma and critically evaluates their performance and ability to measure tumor characteristics.

Contrast-enhanced CT immediately following percutaneous microwave ablation of cT1a renal cell carcinoma: Optimizing cancer outcomes.

OBJECTIVE: To evaluate the effect of intra-procedural contrast-enhanced CT (CECT) and same-session repeat ablation (SSRA) on primary efficacy, the complete eradication of tumor after the first ablation session as confirmed on first imaging follow-up, of clinically localized T1a (cT1a) renal cell carcinoma (RCC). METHODS: 398 consecutive patients with cT1a RCC were treated with cryoablation between 10/2003 and 12/2017, radiofrequency (RFA) or microwave ablation (MWA) between 1/2010 and 12/2017. SSRA was performed for residual tumor identified on intra-procedural CECT. Kruskal-Wallis and Pearson's chi-squared tests were performed to assess differences in continuous and categorical variables, respectively. Multivariate linear regression was used to determine predictors for primary efficacy and decline in estimated glomerular filtration rate. RESULTS: 347 consecutive patients (231 M, mean age 67.5 ± 9.1 years) were included. Median tumor diameter was smaller [2.5 vs 2.7 vs 2.6 (p = 0.03)] and RENAL Nephrometry Score (NS) was lower [6 vs 7 vs 7 (p = 0.009] for MWA compared to the RFA and cryoablation cohorts, respectively. Primary efficacy was higher in the MWA cohort [99.4% (170/171)] compared to the RFA [91.4% (85/93)] and cryoablation [92.8% (77/83)] cohorts (p = 0.001). Microwave ablation and SSRA was associated with higher primary efficacy on multivariate linear regression (p = 0.01-0.03). CONCLUSION: MWA augmented by SSRA, when residual tumor is identified on intra-procedural CECT, may improve primary efficacy for cT1a RCC.

Microphysiological model of renal cell carcinoma to inform anti-angiogenic therapy.

Renal cell carcinomas are common genitourinary tumors characterized by high vascularization and strong reliance on glycolysis. Despite the many available therapies for renal cell carcinomas, first-line targeted therapies, such as cabozantinib, and durable reaponses are seen in only a small percentage of patients. Yet, little is known about the mechanisms that drive response (or lack thereof). This dearth of knowledge can be explained by the dynamic and complex microenvironment of renal carcinoma, which remains challenging to recapitulate in vitro. Here, we present a microphysiological model of renal cell carcinoma, including a tubular blood vessel model of induced pluripotent stem cell-derived endothelial cells and an adjacent 3D carcinoma model. Our model recapitulated hypoxia, glycolic metabolism, and sprouting angiogenesis. Using our model, we showed that cabozantinib altered cancer cell metabolism and decreased sprouting angiogenesis but did not restore barrier function. This microphysiological model could be helpful to elucidate, through multiple endpoints, the contributions of the relevant environmental components in eliciting a functional response or resistance to therapy in renal cell carcinoma.

Natural history of simple renal cysts: longitudinal CT-based evaluation.

PURPOSE: Simple renal cysts are common benign lesions that arise from the renal parenchyma. Cyst growth can lead to confusion as well as concern from patients and referring providers about the need for imaging follow-up or additional evaluation. The purpose of this study was to evaluate the natural history of simple renal cysts and determine the best metric to characterize cyst evolution. METHODS: 222 simple renal cysts in 182 adults (age = 58.4 ± 6.0 years) were longitudinally evaluated on non-contrast CT examinations over a mean interval of 7.5 ± 2.8 years. Axial long axis, surface area, and volume were evaluated at baseline and follow-up CT examinations. Absolute and percent annualized growth rates were computed between CT studies for each parameter. RESULTS: At baseline CT examinations, mean (± SD) axial long axis, surface area, and volume measurements were 2.5 ± 1.7 cm, 2.5 ± 4.5 cm2, and 17.6 ± 52.5 ml, respectively. On follow-up examinations, measurements were 3.4 ± 2.0 cm, 4.2 ± 5.9 cm2, and 34.4 ± 92.3 ml, respectively. Significant differences (p < 0.01) were found between baseline and follow-up values for each parameter. The absolute growth rate of each parameter was + 0.1 ± 0.1 cm/year, + 2.1 ± 3.4 cm2/year, and + 2.0 ± 5.6 ml/year, respectively. The percent annualized growth rate for each parameter was +6.5 ± 7.3%/year, +18 ± 24%/year, and +46 ± 100%/year, respectively. Overall, 86% (190/222) of cysts increased in size over time; most notably 78% (174/222) increased by ≥ 6% in volume per year. None of the simple cysts developed septations or solid components on follow-up examinations. CONCLUSION: The majority of simple renal cysts increase in size over time, which was not associated with the development of complex features. Surface area and volume are the parameters most indicative of cyst growth or regression over time. In patients with enlarging asymptomatic simple renal cysts, no follow-up imaging is indicated.

Microwave Ablation of Renal Cell Carcinoma.

Management options for small renal masses include active surveillance, partial nephrectomy, radical nephrectomy, and thermal ablation. For tumors typically ≤3 cm in size, thermal ablation is a good option for those desiring an alternative to surgery or active surveillance, especially in patients who are considered high surgical risk. We favor microwave ablation because of the more rapid heating, higher temperatures that overcome the heat sink effect of vessels, reproducible cell kill, and a highly visible ablation zone formed by water vapor that corresponds well to the zone of necrosis. For central tumors, we favor cryoablation because of the slower formation of the ablation zone and less likelihood of damage to the collecting system. With microwaves, it is important to monitor the ablation zone in real time (ultrasound is the best modality for this purpose), avoid direct punctures of the collecting system, and to place probes tangential to the collecting system to avoid burning open a persistent tract between the urothelium and extrarenal spaces or causing strictures. The surgical steps described in this video cover our use of high-frequency jet ventilation with general anesthesia to minimize organ motion, initial imaging and targeting, probe insertion, hydrodissection (a technique that enables displacement of adjacent structures), the ablation itself, and finally our dressing. Postoperative cares typically consist of observation with a same-day discharge or an overnight stay. Follow-up includes a magnetic resonance imaging abdomen with and without contrast, chest X-ray, and laboratories (basic metabolic panel, complete blood count, and C-reactive protein) 6 months postablation. Overall, percutaneous microwave ablation is an effective and safe treatment option for renal cell carcinoma in both T1a and T1b tumors in selected patients with multiple studies showing excellent oncologic outcomes when compared with partial and radical nephrectomy.

Combining Stereotactic Body Radiotherapy and Microwave Ablation Appears Safe and Feasible for Renal Cell Carcinoma in an Early Series.

Microwave (MW) ablation and stereotactic body radiation therapy (SBRT) are both used in treating inoperable renal cell carcinoma (RCC). MW ablation and SBRT have potentially complementary advantages and limitations. Combining SBRT and MW ablation may optimize tumor control and toxicity for patients with larger (> 5 cm) RCCs or those with vascular involvement. Seven patients with RCC were treated at our institution with combination of SBRT and MW ablation, median tumor size of 6.4 cm. Local control was 100% with a median follow-up of 15 months. Four patients experienced grade 2 nausea during SBRT. Three patients experienced toxicities after MW ablation, 2 with grade 1 hematuria and 1 with grade 3 retroperitoneal bleed/collecting system injury. Median eGFR (estimated glomerular filtration rate) preceding and following SBRT and MW ablation was 69 mL/min/1.73 m2 and 68 mL/min/1.73 m2 (P = .19), respectively. In patients who are not surgical candidates, larger RCCs or those with vascular invasion are challenging to treat. Combination treatment with SBRT and MW ablation may balance the risks and benefits of both therapies and demonstrates high local control in our series. MW ablation and SBRT have potentially complementary advantages and limitations.

Evaluation of radiomics and machine learning in identification of aggressive tumor features in renal cell carcinoma (RCC).

PURPOSE: The purpose of this study was to evaluate the use of CT radiomics features and machine learning analysis to identify aggressive tumor features, including high nuclear grade (NG) and sarcomatoid (sarc) features, in large renal cell carcinomas (RCCs). METHODS: CT-based volumetric radiomics analysis was performed on non-contrast (NC) and portal venous (PV) phase multidetector computed tomography images of large (> 7 cm) untreated RCCs in 141 patients (46W/95M, mean age 60 years). Machine learning analysis was applied to the extracted radiomics data to evaluate for association with high NG (grade 3-4), with multichannel analysis for NG performed in a subset of patients (n = 80). A similar analysis was performed in a sarcomatoid rich cohort (n = 43, 31M/12F, mean age 63.7 years) using size-matched non-sarcomatoid controls (n = 49) for identification of sarcomatoid change. RESULTS: The XG Boost Model performed best on the tested data. After manual and machine feature extraction, models consisted of 3, 7, 5, 10 radiomics features for NC sarc, PV sarc, NC NG and PV NG, respectively. The area under the receiver operating characteristic curve (AUC) for these models was 0.59, 0.65, 0.69 and 0.58 respectively. The multichannel NG model extracted 6 radiomic features using the feature selection strategy and showed an AUC of 0.67. CONCLUSIONS: Statistically significant but weak associations between aggressive tumor features (high nuclear grade, sarcomatoid features) in large RCC were identified using 3D radiomics and machine learning analysis.

Comparison of CT Texture Analysis Software Platforms in Renal Cell Carcinoma: Reproducibility of Numerical Values and Association With Histologic Subtype Across Platforms.

OBJECTIVE. The purpose of this article is to evaluate interobserver, intraobserver, and interplatform variability and compare the previously established association between texture metrics and tumor histologic subtype using three commercially available CT texture analysis (CTTA) software platforms on the same dataset of large (> 7 cm) renal cell carcinomas (RCCs). MATERIALS AND METHODS. CT-based texture analysis was performed on contrast-enhanced MDCT images of large (> 7 cm) untreated RCCs in 124 patients (median age, 62 years; 82 men and 42 women) using three different software platforms. Using this previously studied cohort, texture features were compared across platforms. Features were correlated with histologic subtype, and strength of association was compared between platforms. Single-slice and volumetric measures from one platform were compared. Values for interobserver and intraobserver variability on a tumor subset (n = 30) were assessed across platforms. RESULTS. Metrics including mean gray-level intensity, SD, and volume correlated fairly well across platforms (concordance correlation coefficient [CCC], 0.66-0.99; mean relative difference [MRD], 0.17-5.97%). Entropy showed high variability (CCC, 0.04; MRD, 44.5%). Mean, SD, mean of positive pixels (MPP), and entropy were associated with clear cell histologic subtype on almost all platforms (p < .05). Mean, SD, entropy, and MPP were highly reproducible on most platforms on both interobserver and intraobserver analysis. CONCLUSION. Select texture metrics were reproducible across platforms and readers, but other metrics were widely variable. If clinical models are developed that use CTTA for medical decision making, these differences in reproducibility of some features across platforms need to be considered, and standardization is critical for more widespread adaptation and implementation.

Beta-Adrenergic Antagonists and Cancer Specific Survival in Patients With Advanced Prostate Cancer: A Veterans Administration Cohort Study.

OBJECTIVE: To interrogate the National Veterans Health Administration (VA) database to determine if beta-blocker use at time of initiation of androgen therapy deprivation (ADT) would result in improved oncological outcomes in advanced prostate cancer (PCa). METHODS: All men diagnosed with high risk PCa (PSA >20) from 2000-2008 who were on ADT ≥ 6 months were identified. Patients receiving ADT concurrently with primary radiation therapy were excluded. Pharmacy data was interrogated for all beta-blockers, but then focused on the selective beta-1 blocker metoprolol. Cox proportional hazards ratios were calculated for overall survival (OS), PCa specific survival (CSS) and skeletal related events (SREs). RESULTS: In 39,198 patients with high risk PCa on ADT, use of any beta-blocker was not associated with improvement in OS, CSS, or SREs. Further analyses focusing on metoprolol found that 10,224 (31.9%) had used metoprolol while 21,834 had no beta-blocker use. Multivariable analysis with Inverse Propensity Score Weighting, adjusted for factors including PSA, Gleason score, and duration ADT, found that utilization of metoprolol was not associated with improvement in OS (hazard ratio [HR] 0.97, P = .19), CSS (HR 0.94, P = .23) or SREs (HR 0.98, P = .79). CONCLUSION: In this large cohort, metoprolol use in conjunction with ADT in high risk PCa was not associated with improvement in OS, CSS, or risk of SRE. In contrast to a recent smaller clinical study, our data strongly suggests no cancer specific benefit to beta-blocker use in advanced PCa.