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Microwave (MW) ablation and stereotactic body radiation therapy (SBRT) have potentially complementary advantages and limitations for treating inoperable renal cell carcinoma (RCC). Combining SBRT and MWA may optimize tumor control and toxicity for patients with larger (>5 cm) RCCs or those with vascular involvement. We retrospectively reviewed patients at our institution with RCC treated between 2014 – 2018 to identify patients treated with a combination of SBRT and MW ablation. Seven patients with RCC were treated 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, two with grade 1 hematuria and one with grade 3 retroperitoneal bleed/collecting system injury. Median eGFR preceding and following SBRT and MW ablation was 69 mL/min/1.73m2 and 68 mL/min/1.73m2 (p=0.19) 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.

Although therapeutic options for patients with advanced renal cell carcinoma (RCC) have increased in the past decade, no biomarkers are yet available for patient stratification or evaluation of therapy resistance. Given the dynamic and heterogeneous nature of clear cell RCC (ccRCC), tumor biopsies provide limited clinical utility, but liquid biopsies could overcome these limitations. Prior liquid biopsy approaches have lacked clinically relevant detection rates for patients with ccRCC. This study employed ccRCC‐specific markers, CAIX and CAXII, to identify circulating tumor cells (CTC) from patients with metastatic ccRCC. Distinct subtypes of ccRCC CTCs were evaluated for PD‐L1 and HLA‐I expression and correlated with patient response to therapy. CTC enumeration and expression of PD‐L1 and HLA‐I correlated with disease progression and treatment response, respectively. Longitudinal evaluation of a subset of patients demonstrated potential for CTC enumeration to serve as a pharmacodynamic biomarker. Further evaluation of phenotypic heterogeneity among CTCs is needed to better understand the clinical utility of this new biomarker., Circulating tumor cells (CTCs) were evaluated for their expression of programmed death ligand‐1 (PD‐L1) and human leukocyte antigen class I (HLA‐I), so that biomarkers of therapeutic resistance of clear cell renal cell carcinoma can be developed. CTCs were captured with antibody‐conjugated magnetic beads against EpCAM and CAIX then probed for CAXII and CK expression using microfluidic technology.

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.

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.

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). 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. 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. 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

Close to 74,000 cases of renal cell carcinoma (RCC) are diagnosed each year in the United States. The past 2 decades have shown great developments in surgical techniques, targeted therapy and immunotherapy agents, and longer complete response rates. However, without a global cure, there is still room for further advancement in improving patient care in this space. To address some of the gaps restricting this progress, the Kidney Cancer Association brought together a group of 27 specialists across the areas of clinical care, research, industry, and advocacy at the inaugural "Think Tank: Coalition for a Cure" session. Topics addressed included screening, imaging, rarer RCC subtypes, combination drug therapy options, and patient response. This commentary summarizes the discussion of these topics and their respective clinical challenges, along with a proposal of projects for collaboration in overcoming those needs and making a greater impact on care for patients with RCC moving forward.

To evaluate the effect of intravenous iodinated contrast on estimated glomerular filtration rate (eGFR) when administered immediately after thermal ablation of clinically localized T1a (cT1a) renal cell carcinoma (RCC). This HIPAA-compliant, dual-center retrospective study was performed under a waiver of informed consent. Three hundred forty-two consecutive patients with cT1a biopsy-proven RCC were treated with percutaneous ablation between January 2010 and December 2017. Immediate post-ablation contrast-enhanced CT was the routine standard of care at one institution (contrast group), but not the other (control group). One-month pre- and 6-month post-ablation eGFR were compared using the Wilcoxon signed-rank test or the Kruskal-Wallis test. Multivariate linear regression was used to determine the effect of contrast on eGFR. A 1:1 propensity score matching was performed for all patients with a logistic model using patient, tumor, and procedural covariates. In total, 246 patients (158 M; median age 69 years, IQR 62–74) were included. Median tumor diameter (2.4 vs 2.5, p = 0.23) and RENAL nephrometry scores (6 vs 6, p = 0.92), surrogates for ablation zone size, were similar. Baseline kidney function was similar for the control and contrast groups, respectively (median eGFR: 70 vs 74 mL/min/1.73 m2, p = 0.29). There was an expected mild decline in eGFR after ablation (control: 70 vs 60 mL/min/1.73 m2, p < 0.001; contrast: 75 vs 71 mL/min/1.73 m2, p = 0.001). Intravenous iodinated contrast was not associated with a decline in eGFR on multivariate linear regression (1.91, 95% CI - 3.43–7.24, p = 0.46) or 1:1 propensity score-matched model (- 0.33, 95% CI - 6.81–6.15, p = 0.92). Intravenous iodinated contrast administered during ablation of cT1a RCC has no effect on eGFR. • Intravenous iodinated contrast administered during thermal ablation of clinically localized T1a renal cell carcinoma has no effect on kidney function. • Thermal ablation of clinically localized T1a renal cell carcinoma results in a mild decline in kidney function. • A decline in kidney function is similar for radiofrequency and microwave ablation of clinically localized T1a renal cell carcinoma.

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.Non-tumor-bearing pigs (n=8, mean weight=52.5kg) were anticoagulated with warfarin (initial dose 0.08 mg/kg) to a target 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 CT imaging. Animals were observed for 7 days while continuing anticoagulation, followed by repeat CT and necropsy.All animals survived to complete the entire protocol with no signs of disability or distress. Three animals had hematuria (pink urine without clots). Baseline prothrombin time (PT) values (mean 16.0 sec) were elevated to 22.0 sec (37.5% above baseline, p=0.003) on the day of treatment, and 28.8 sec (77.8% above baseline, p0.001) on the day of necropsy. At the time of treatment 63% (5/8) of subjects were at a therapeutic anticoagulation level, and 100% (8/8) reached therapeutic levels by the time of necropsy. There were no cases of intra-parenchymal, peritoneal, or retroperitoneal hemorrhage associated with any treatments despite 71% (5/7) of liver and 100% (8/8) of kidney treatments extending to the organ surface.Liver and kidney histotripsy appears safe with no elevated bleeding risk in this anticoagulated animal model supporting the possibility of histotripsy treatments in patients on anti-coagulation.

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.

Clear cell renal cell carcinoma (ccRCC) is a common genitourinary cancer associated with the development of abnormal tumor angiogenesis. Although multiple anti-angiogenic therapies have been developed, responses to individual treatment are highly variable between patients. Thus, the use of one-patient clinical trials has been suggested as an alternative to standard trials. We used a microfluidic device to generate organotypic primary patient-specific blood vessel models using normal (NEnC) and tumor-associated primary CD31(+) selected cells (TEnC). Our model was able to recapitulate differences in angiogenic sprouting and vessel permeability that characterize normal and tumor-associated vessels. We analyzed the expression profile of vessel models to define vascular normalization in a patient-specific manner. Using this data, we identified actionable targets to normalize TEnC vessel function to a more NEnC-like phenotype. Finally, we tested two of these drugs in our patient-specific models to determine the efficiency in restoring vessel function showing the potential of the model for single-patient clinical trials.

Objective To analyze risk factors and patterns of RCC recurrence following percutaneous ablation for stage 1 tumors and develop risk-stratified follow-up imaging protocols. Method Biopsy-proven sporadic stage 1 RCC patients treated with percutaneous microwave ablation (MWA) or cryoablation (CA) from 2002 to 2017 were included. Kaplan-Meier analysis was used to estimate local and distant recurrence-free survival, cancer-specific survival and metastatic-free survival. Multivariable models were used to identify risk factors associated with recurrence. Results A total of 256 patients with stage 1 RCC (215 T1a, 41 T1b) were treated with percutaneous MWA (178 subjects) or CA (78 subjects). Recurrence was identified in 23 patients (16 local, 7 distant). Clinical T stage (HR 2.46, 95% CI 1.06-5.72, P = .04) and tumor grade (HR 4.17, 95% CI 1.17-14.76, P = .03) were independent predictors of recurrence. Recurrence was not associated with Nephrometry score, cystic tumors, ablation modality (CA vs MWA) or gender. Five-year cancer-specific survival, and metastatic-free survival were 98.6% and 97.4%, respectively. Patients were stratified into 2 groups: reduced risk stage 1 (no risk factors) or elevated risk stage 1 (≥1 risk factor). Recurrence risk was higher in the elevated-risk group (HR = 3.19, 95% CI 1.35-7.53, P = .008). Five-year overall recurrence-free survival (local + distant) was higher in reduced-risk vs elevated-risk cohorts, 88% vs 69%, P = .005. Conclusion High nuclear grade or T1b tumors have increased recurrence risk following percutaneous thermal ablation for stage 1 RCC. Current postablation follow-up protocols may be modified for individual recurrence risk to allow more frequent imaging for elevated-risk patients, while enabling less frequent imaging for reduced-risk patients.

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.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.At baseline CT examinations, mean (± SD) axial long axis, surface area, and volume measurements were 2.5 ± 1.7 cm, 2.5 ± 4.5 cmThe 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.

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.

INTRODUCTION AND OBJECTIVE:The recommended frequency of imaging surveillance following percutaneous ablation of renal cell carcinoma (RCC) is variable among institutions. The purpose of this study ...

INTRODUCTION AND OBJECTIVE:Limited data are available to evaluate the prognostic value of primary tumor and metastatic tumor response to preoperative systemic therapy (PST) for metastatic RCC follo...