Perioperative nivolumab versus observation in patients with renal cell carcinoma undergoing nephrectomy (PROSPER ECOG-ACRIN EA8143): an open-label, randomised, phase 3 study.

BACKGROUND: The standard of care for patients with intermediate-to-high risk renal cell carcinoma is partial or radical nephrectomy followed by surveillance. We aimed to investigate use of nivolumab before nephrectomy followed by adjuvant nivolumab in patients with high-risk renal cell carcinoma to determine recurrence-free survival compared with surgery only. METHODS: In this open-label, randomised, phase 3 trial (PROSPER EA8143), patients were recruited from 183 community and academic sites across the USA and Canada. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-1, with previously untreated clinical stage T2 or greater or Tany N+ renal cell carcinoma of clear cell or non-clear cell histology planned for partial or radical nephrectomy. Selected patients with oligometastatic disease, who were disease free at other disease sites within 12 weeks of surgery, were eligible for inclusion. We randomly assigned (1:1) patients using permuted blocks (block size of 4) within stratum (clinical TNM stage) to either nivolumab plus surgery, or surgery only followed by surveillance. In the nivolumab group, nivolumab 480 mg was administered before surgery, followed by nine adjuvant doses. The primary endpoint was investigator-reviewed recurrence-free survival in patients with renal cell carcinoma assessed in all randomly assigned patients regardless of histology. Safety was assessed in all randomly assigned patients who started the assigned protocol treatment. This trial is registered with ClinicalTrials.gov, NCT03055013, and is closed to accrual. FINDINGS: Between Feb 2, 2017, and June 2, 2021, 819 patients were randomly assigned to nivolumab plus surgery (404 [49%]) or surgery only (415 [51%]). 366 (91%) of 404 patients assigned to nivolumab plus surgery and 387 (93%) of 415 patients assigned to surgery only group started treatment. Median age was 61 years (IQR 53-69), 248 (30%) of 819 patients were female, 571 (70%) were male, 672 (88%) were White, and 77 (10%) were Hispanic or Latino. The Data and Safety Monitoring Committee stopped the trial at a planned interim analysis (March 25, 2022) because of futility. Median follow-up was 30·4 months (IQR 21·5-42·4) in the nivolumab group and 30·1 months (21·9-41·8) in the surgery only group. 381 (94%) of 404 patients in the nivolumab plus surgery group and 399 (96%) of 415 in the surgery only group had renal cell carcinoma and were included in the recurrence-free survival analysis. As of data cutoff (May 24, 2023), recurrence-free survival was not significantly different between nivolumab (125 [33%] of 381 had recurrence-free survival events) versus surgery only (133 [33%] of 399; hazard ratio 0·94 [95% CI 0·74-1·21]; one-sided p=0·32). The most common treatment-related grade 3-4 adverse events were elevated lipase (17 [5%] of 366 patients in the nivolumab plus surgery group vs none in the surgery only group), anaemia (seven [2%] vs nine [2%]), increased alanine aminotransferase (ten [3%] vs one [<1%]), abdominal pain (four [1%] vs six [2%]), and increased serum amylase (nine [2%] vs none). 177 (48%) patients in the nivolumab plus surgery group and 93 (24%) in the surgery only group had grade 3-5 adverse events due to any cause, the most common of which were anaemia (23 [6%] vs 19 [5%]), hypertension (27 [7%] vs nine [2%]), and elevated lipase (18 [5%] vs six [2%]). 48 (12%) of 404 patients in the nivolumab group and 40 (10%) of 415 in the surgery only group died, of which eight (2%) and three (1%), respectively, were determined to be treatment-related. INTERPRETATION: Perioperative nivolumab before nephrectomy followed by adjuvant nivolumab did not improve recurrence-free survival versus surgery only followed by surveillance in patients with high-risk renal cell carcinoma. FUNDING: US National Institutes of Health National Cancer Institute and Bristol Myers Squibb.

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.

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.

Effect of iodinated contrast material on post-operative eGFR when administered during renal mass ablation.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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). CONCLUSION: Intravenous iodinated contrast administered during ablation of cT1a RCC has no effect on eGFR. KEY POINTS: • 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.

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.

Functional penile replantation after traumatic avulsion amputation below the pubis: A case report.

Penile amputation is a rare injury with significant posttraumatic ramifications. We present a case of successful immediate replantation after traumatic penile avulsion in a 52-year-old male patient. The patient reported his penis was caught in machinery during a boating accident, and avulsed at the level of the pubis. Immediate replantation of this proximal avulsion injury with no suitable proximal arterial stumps required transfer of the superficial inferior epigastric artery for arterial inflow. One artery and two veins were repaired. The urethral injury was found to be immediately distal to the urethral sphincter in the membranous portion, and repaired primarily. Urinary diversion was performed with a suprapubic catheter until the repair had healed. The postoperative course was complicated by less than 10% skin necrosis requiring skin grafting. At three years follow up, the patient has a penis with normal urinary function and is able to obtain erections with pharmacologic aids. Avulsion should not preclude penile replantation, which may have acceptable functional and esthetic results.

The Impact of Agent Orange Exposure on Prostate Cancer Outcomes.

PURPOSE: In this study we explored the effect of Agent Orange exposure on prostate cancer survival in VA (Veterans Affairs) patients receiving androgen deprivation therapy for advanced prostate cancer. MATERIALS AND METHODS: We retrospectively examined the association between Agent Orange exposure in men with prostate cancer in national VA databases who were being treated with androgen deprivation therapy. Patients were diagnosed with prostate cancer from 2000 to 2008 with followup through May 2016. Clinical, pathological and demographic variables were compared by Agent Orange exposure. Associations of Agent Orange with overall survival, skeletal related events and cancer specific survival were performed using adjusted Cox proportional hazard models after IPSW (inverse propensity score weighted) adjustment. RESULTS: Overall 87,344 patients were identified. The 3,475 Agent Orange exposed patients were younger (p <0.001), had lower prostate specific antigen (p = 0.002) and were more likely to receive local therapy and chemotherapy (p <0.001) than the 83,869 nonexposed patients. The Charlson comorbidity index was similar in the groups (p = 0.40). After IPSW adjustment Agent Orange exposure was associated with improved overall survival (HR 0.84, 95% CI 0.73-0.97, p = 0.02). However, no difference was observed in the risk of skeletal related events (HR 1.04, 95% CI 0.80-1.35, p = 0.77) or cancer specific survival (HR 0.79, 95% CI 0.60-1.03, p = 0.08). CONCLUSIONS: Agent Orange exposure was associated with a decreased risk of death in men receiving androgen deprivation therapy for advanced prostate cancer. It does not appear to be associated with worse oncologic outcomes.

Risk Factors for Complications and Nondiagnostic Results following 1,155 Consecutive Percutaneous Core Renal Mass Biopsies.

PURPOSE: The purpose of this study was to evaluate patient, tumor and technical factors associated with procedural complications and nondiagnostic findings following percutaneous core renal mass biopsy. MATERIALS AND METHODS: We reviewed core renal mass biopsies from 2000 to 2017. Complications at 30 days or less were graded using the Clavien-Dindo system. Univariate and multivariable analyses were done to evaluate associations between clinical characteristics and the risk of complications or nondiagnostic findings. RESULTS: Of the 1,155 biopsies performed in a total of 965 patients procedural complications were identified in 24 patients (2.2%), including 5 (0.4%) with major complications (Clavien 3a or greater). No patients were identified with tumor seeding of the biopsy tract. Patient age, body mass index, gender, Charlson comorbidity index, smoking, mass diameter, nephrometry score, number of cores and prior biopsy were not associated with complication risk (p = 0.06 to 0.53). Complications were not increased for patients on aspirin or those with low platelets (25,000 to 160,000/µl blood) or a mildly elevated INR (international normalized ratio) (1.2 to 2.0, p = 0.16, 0.07 and 0.50, respectively). The complication risk was not increased during the initial 50 cases of a radiologist or when a trainee was present (p = 0.35 and 0.12, respectively). Nondiagnostic findings were present in 14.6% of biopsies. Independent predictors included cystic features, contrast enhancement, mass diameter and skin-to-mass distance (p <0.001, 0.002, 0.02 and 0.049, respectively). Radiologist experience was not associated with the nondiagnostic rate (p = 0.23). Prior nondiagnostic biopsy was not associated with an increased nondiagnostic rate on subsequent attempts (19.2% vs 14.2%, p = 0.23). CONCLUSIONS: Procedural complications following biopsy are rare even with low serum platelets, a mildly elevated INR or when the patient remains on aspirin. Cystic features, hypo-enhancement on imaging, a smaller mass diameter and a longer skin-to-tumor distance increase the risk of nondiagnostic findings.

Collagen organization of renal cell carcinoma differs between low and high grade tumors.

BACKGROUND: The traditional pathologic grading for human renal cell carcinoma (RCC) has low concordance between biopsy and surgical specimen. There is a need to investigate adjunctive pathology technique that does not rely on the nuclear morphology that defines the traditional grading. Changes in collagen organization in the extracellular matrix have been linked to prognosis or grade in breast, ovarian, and pancreatic cancers, but collagen organization has never been correlated with RCC grade. In this study, we used Second Harmonic Generation (SHG) based imaging to quantify possible differences in collagen organization between high and low grades of human RCC. METHODS: A tissue microarray (TMA) was constructed from RCC tumor specimens. Each TMA core represents an individual patient. A 5 µm section from the TMA tissue was stained with standard hematoxylin and eosin (H&E). Bright field images of the H&E stained TMA were used to annotate representative RCC regions. In this study, 70 grade 1 cores and 51 grade 4 cores were imaged on a custom-built forward SHG microscope, and images were analyzed using established software tools to automatically extract and quantify collagen fibers for alignment and density assessment. A linear mixed-effects model with random intercepts to account for the within-patient correlation was created to compare grade 1 vs. grade 4 measurements and the statistical tests were two-sided. RESULTS: Both collagen density and alignment differed significantly between RCC grade 1 and RCC grade 4. Specifically, collagen fiber density was greater in grade 4 than in grade 1 RCC (p < 0.001). Collagen fibers were also more aligned in grade 4 compared to grade 1 (p < 0.001). CONCLUSIONS: Collagen density and alignment were shown to be significantly higher in RCC grade 4 vs. grade 1. This technique of biopsy sampling by SHG could complement classical tumor grading approaches. Furthermore it might allow biopsies to be more clinically relevant by informing diagnostics. Future studies are required to investigate the functional role of collagen organization in RCC.

Tumor location does not impact oncologic outcomes for percutaneous microwave ablation of clinical T1a renal cell carcinoma.

OBJECTIVE: To evaluate the impact of anterior tumor location on oncologic efficacy, complication rates, and procedure duration for 151 consecutive biopsy-proven clinical T1a renal cell carcinoma (RCC) treated with percutaneous microwave (MW) ablation. METHODS: This single-center retrospective study was performed under a waiver of informed consent. One hundred forty-eight consecutive patients (103 M/45 F; median age 67 years, IQR 61-73) with 151 cT1a biopsy-proven RCC (median diameter 2.4 cm, IQR 1.9-3.0) were treated with percutaneous MW ablation between March 2011 and August 2017. Patient and procedural data collected included Charlson comorbidity index (CCI), RENAL nephrometry score (NS), use of hydrodisplacement, MW antennas/generator output/time, and procedure time (PT). Data were stratified by anterior, posterior, and midline tumor location and compared with the Kruskal-Wallis or chi-squared tests. The Kaplan-Meier method was used for survival analyses. RESULTS: Tumor size, NS, and use/volume of hydrodisplacement were similar for posterior and anterior tumors (p > 0.05). Patients with anterior tumors had a higher CCI (3 vs 4, p = 0.001). Median PT for posterior and anterior tumors was similar (100 vs 108 min, p = 0.26). Single session technical success and primary efficacy were achieved for all 151 tumors including 61 posterior and 67 anterior tumors. The 4 (3%) Clavien III-IV complications and 6 (4%) local recurrences were not associated with tumor location (p > 0.05). Three-year RFS, CSS, and OS were 95% (95% CI 0.87, 0.98), 100% (95% CI 1.0, 1.0), and 96% (95% CI 0.89, 0.98), respectively. CONCLUSIONS: The safety and efficacy of percutaneous microwave ablation for anterior and posterior RCC are similar. KEY POINTS: • The safety profile for percutaneous microwave ablation of anterior and posterior T1a renal cell carcinoma is equivalent. • Percutaneous microwave ablation of T1a renal cell carcinoma provides durable oncologic control regardless of tumor location. • Placement of additional microwave antennas and use of hydrodisplacement are associated with longer procedure times.

Patient selection for cytoreductive nephrectomy in combination with targeted therapies or immune checkpoint inhibitors.

PURPOSE OF REVIEW: Recent cytoreductive nephrectomy studies provide continued evidence of the critical role of patient selection prior to surgery. The purpose of this review is to examine current data regarding patient selection for cytoreductive surgery and evaluate, which metastatic renal cell carcinoma (mRCC) patients are likely to benefit from surgical treatment. RECENT FINDINGS: Individual prognostic factors and risk stratification models can be used to estimate survival for mRCC patients and to aid in patient selection. Recent studies also have demonstrated prognostic value for serum labs or tumor histology.The available data suggests that upfront cytoreductive nephrectomy is associated with benefit for selected mRCC patients with good performance status and favorable or intermediate-risk criteria. Upfront systemic therapy should be considered for patients with poor-risk features and poor surgical candidates after multidisciplinary discussion with surgical and medical oncology teams. SUMMARY: Ideal patient selection for cytoreductive nephrectomy should include individual consideration of poor prognostic risk factors and discussion of the potential risks and benefits for surgery.

Robotically-Assisted Sonic Therapy for Renal Ablation in a Live Porcine Model: Initial Preclinical Results.

PURPOSE: To demonstrate the feasibility of Robotically Assisted Sonic Therapy (RAST)-a noninvasive and nonthermal focused ultrasound therapy based on histotripsy-for renal ablation in a live porcine model. MATERIALS AND METHODS: RAST ablations (n = 11) were performed in 7 female swine: 3 evaluated at 1 week (acute) and 4 evaluated at 4 weeks (chronic). Treatment groups were acute bilateral (3 swine, 6 ablations with immediate computed tomography [CT] and sacrifice); chronic single kidney (3 swine, 3 ablations; CT at day 0, week 1, and week 4 after treatment, followed by sacrifice); and chronic bilateral (1 swine, 2 ablations). Treatments were performed using a prototype system (VortxRx; HistoSonics, Inc) and targeted a 2.5-cm-diameter sphere in the lower pole of each kidney, intentionally including the central collecting system. RESULTS: Mean treatment time was 26.4 minutes. Ablations had a mean diameter of 2.4 ± 0.3 cm, volume of 8.5 ± 2.4 cm3, and sphericity index of 1.00. Median ablation volume decreased by 96.1% over 4 weeks. Histology demonstrated complete lysis with residual blood products inside the ablation zone. Temporary collecting system obstruction by thrombus was observed in 4/11 kidneys (2 acute and 2 chronic) and resolved by 1 week. There were no urinary leaks, main vessel thromboses, or adjacent organ injuries on imaging or necropsy. CONCLUSIONS: In this normal porcine model, renal RAST demonstrated complete histologic destruction of the target renal tissue while sparing the urothelium.

Utility of CT Texture Analysis in Differentiating Low-Attenuation Renal Cell Carcinoma From Cysts: A Bi-Institutional Retrospective Study.

OBJECTIVE. The purpose of this study was to evaluate the utility of CT texture analysis (CTTA) in differentiating low-attenuation renal cell carcinoma (RCC) from renal cysts on unenhanced CT. MATERIALS AND METHODS. Ninety-four patients with low-attenuation RCC on unenhanced CT were compared with a cohort of 192 patients with benign renal cysts. CT characteristics (size and minimum, maximum, and mean attenuation) and CTTA features were recorded using an ROI approximately two-thirds the size of the mass. Masses were subjectively assessed by two expert genitourinary readers and two novice readers using a 5-point Likert scale (1 = definite cyst, 5 = definite renal cell carcinoma). Results of first-order CTTA and subjective evaluation were compared using ROC analysis. RESULTS. The group of 94 patients with low-attenuation RCC included 62 men and 32 women (mean age, 58.0 years). On unenhanced CT, the RCC were larger than 10 mm and of a median size of 50 mm with less than or equal to 20 HU (mean attenuation, 16 ± 4 HU). Of the RCC cohort, 83 were clear cell subtype. The cohort of 192 patients included 134 men and 58 women (mean age, 64.7 years) with benign renal cysts greater than 10 mm and a median size of 27 mm and less than or equal to 20 HU (mean attenuation, 9 ± 6 HU). The mean follow-up time was 6.2 years. Mean entropy in the low-attenuation RCC group (4.1 ± 0.7) was significantly higher than in the cyst group (2.8 ± 1.3, p < 0.0001). Entropy showed an ROC AUC of 0.89, with sensitivity of 84% and specificity of 80% at threshold 3.9. The AUC was better than subjective evaluation by novice readers (AUC, 0.77) and comparable to subjective evaluation by two expert readers (AUC, 0.90). A model combining the three best texture features (unfiltered mean gray-level attenuation, coarse entropy, and kurtosis) showed an improved AUC of 0.92. CONCLUSION. High entropy revealed with CTTA may be used to differentiate low-attenuation RCC from cysts at unenhanced CT; this technique performs as well as expert readers.

Contrast-Enhanced Ultrasound in Renal Imaging and Intervention.

PURPOSE OF REVIEW: In recent years, there has been renewed interest in the use of contrast-enhanced ultrasound (CEUS) in abdominal imaging and intervention. The goal of this article is to review the practical applications of CEUS in the kidney, including renal mass characterization, treatment monitoring during and after percutaneous ablation, and biopsy guidance. RECENT FINDINGS: Current evidence suggests that CEUS allows accurate differentiation of solid and cystic renal masses and is an acceptable alternative to either computed tomography (CT) or magnetic resonance imaging (MRI) for characterization of indeterminate renal masses. CEUS is sensitive and specific for diagnosing residual or recurrent renal cell carcinoma (RCC) following percutaneous ablation. Furthermore, given its excellent spatial and temporal resolution, CEUS is well suited to demonstrate tumoral microvascularity associated with malignant renal masses and is an effective complement to conventional grayscale ultrasound (US) for percutaneous biopsy guidance. Currently underutilized, CEUS is an important problem-solving tool in renal imaging and intervention whose role will continue to expand in coming years.

Impact of bilateral biopsy-detected prostate cancer on an active surveillance population.

BACKGROUND: To assess factors that can predict active surveillance (AS) failure on serial transrectal ultrasound guided biopsies in patients with low-risk prostate cancer. METHODS: We evaluated the records of 144 consecutive patients enrolled in AS between 2007 and 2014 at a single academic institution. Low risk inclusion criteria included PSA < 10 ng/ml, cT1c or cT2a, Grade Group (GG) 1, < 3 positive cores, and < 50% tumor in a single core with the majority having a PSA density of < 0.15. AS reclassification was defined as progression to GG ≥2, 3 or more cores, or core tumor volume ≥ 50%. Univariate and multivariate Cox proportional hazards regression analysis was used to determine predictors of reclassification and a match-pair analysis performed on a control group of patients choosing surgery. RESULTS: Inclusion criteria were met by 130 men with a median follow-up of 52 months. The reclassification or AS failure rate was 38.5%, with the majority 41/50 (82%) finding GG ≥ 2 cancer. Most patients had unilateral disease on diagnostic biopsy (94.6%), but 40.7% had bilateral cancer detected during follow-up. Men with bilateral detected tumor were more likely to ultimately fail AS than patients with unilateral tumors (HR 4.089; P < 0.0001) and failed earlier with a reclassification-free survival of 32 vs 119 months respectively. In a matched-pair analysis using a population of 211 concurrent patients that chose radical prostatectomy rather than AS, 76% of patients with unilateral cancer on biopsy had bilateral cancer on final pathology. CONCLUSIONS: The finding of bilateral prostate cancer on biopsy is associated with earlier AS reclassification. Finding bilateral disease may not represent disease progression, but rather enhanced detection of more extensive disease highlighting the importance of confirmatory biopsy.

Metformin Use is Associated with Improved Survival for Patients with Advanced Prostate Cancer on Androgen Deprivation Therapy.

PURPOSE: Metformin is commonly prescribed for patients with type 2 diabetes mellitus. We hypothesized that metformin plus androgen deprivation therapy may be beneficial in combination. Our objective was to assess this combination in a retrospective cohort of patients with advanced prostate cancer. MATERIALS AND METHODS: Using national Veterans Affairs databases we identified all men diagnosed with prostate cancer between 2000 and 2008 who were treated with androgen deprivation therapy with followup through May 2016. Study exclusions included treatment with androgen deprivation therapy for 6 months or longer, or receipt of androgen deprivation therapy concurrently with localized radiation. Three patient cohorts were developed, including no diabetes mellitus, diabetes mellitus with no metformin and diabetes mellitus with metformin. Cox proportional HRs were calculated for overall survival, skeletal related events and cancer specific survival. RESULTS: After exclusions the cohort consisted of 87,344 patients, including 61% with no diabetes mellitus, 22% with diabetes mellitus and no metformin, and 17% with diabetes mellitus on metformin. Cox proportional hazard analysis of overall survival showed improved survival in men with diabetes mellitus on metformin (HR 0.82, 95% CI 0.78-0.86) compared to those with diabetes mellitus who were not on metformin (HR 1.03, 95% CI 0.99-1.08). The reference group was men with no diabetes mellitus. Cox proportional hazard analysis of predictors of skeletal related events revealed a HR of 0.82 (95% CI 0.72-0.93) in men with diabetes mellitus on metformin. Cox proportional hazard analysis of cancer specific survival showed improved survival in men with diabetes mellitus on metformin (HR 0.70, 95% CI 0.64-0.77) vs those with diabetes mellitus without metformin (HR 0.93, 95% CI 0.85- 1.00). The reference group was men with no diabetes mellitus. CONCLUSIONS: Metformin use in veterans with prostate cancer who receive androgen deprivation therapy is associated with improved oncologic outcomes. This association should be evaluated in a prospective clinical trial.

Effect of Tumor Complexity and Technique on Efficacy and Complications after Percutaneous Microwave Ablation of Stage T1a Renal Cell Carcinoma: A Single-Center, Retrospective Study.

Purpose To evaluate the effects of tumor complexity and technique on early and midterm oncologic efficacy and rate of complications for 100 consecutive biopsy-proved stage T1a renal cell carcinomas (RCCs) treated with percutaneous microwave ablation. Materials and Methods This HIPAA-compliant, single-center retrospective study was approved by the institutional review board. The requirement to obtain informed consent was waived. Ninety-six consecutive patients (68 men, 28 women; mean age, 66 years ± 9.4) with 100 stage T1a N0M0 biopsy-proved RCCs (median diameter, 2.6 cm ± 0.8) underwent percutaneous microwave ablation between March 2011 and June 2015. Patient and procedural data were collected, including body mass index, comorbidities, tumor histologic characteristics and grade, RENAL nephrometry score, number of antennas, generator power, and duration of ablation. Technical success, local tumor progression, and presence of complications were assessed at immediate and follow-up imaging. The Kaplan-Meier method was used for survival analyses. Results Technical success was achieved for all 100 tumors (100%), including 47 moderately and five highly complex RCCs. Median clinical and imaging follow-up was 17 months (range, 0-48 months) and 15 months (range, 0-44 months), respectively. No change in estimated glomerular filtration rate was noted after the procedure (P = .49). There were three (3%) procedure-related complications and six (6%) delayed complications, all urinomas. One case of local tumor progression (1%) was identified 25 months after the procedure. Three-year local progression-free survival, cancer-specific survival, and overall survival were 88% (95% confidence interval: 0.52%, 0.97%), 100% (95% confidence interval: 1.0%, 1.0%), and 91% (95% confidence interval: 0.51%, 0.99%), respectively. Conclusion Percutaneous microwave ablation is an effective and safe treatment option for stage T1a RCC, regardless of tumor complexity. Long-term follow-up is needed to establish durable oncologic efficacy and survival relative to competing ablation modalities and surgery. © RSNA, 2017.

Cytoreductive Nephrectomy for Renal Cell Carcinoma with Venous Tumor Thrombus.

PURPOSE: Careful selection is critical to identify those with metastatic renal cell carcinoma who are most likely to benefit from cytoreductive nephrectomy. Surgery in patients who have metastatic renal cell carcinoma with tumor thrombus is complex and may not benefit some patients with poor overall survival. We evaluated whether preoperative variables or risk stratification systems could predict overall survival following cytoreductive nephrectomy. MATERIALS AND METHODS: Prognostic factors for overall survival after surgery were evaluated in patients who had metastatic renal cell carcinoma with venous tumor thrombus at 5 institutions from 2000 to 2014. Prognostic variables, including metastatic renal cell carcinoma risk models, were evaluated for associations with overall survival. Multivariable analysis was used to determine independent associations of preoperative variables with overall survival. RESULTS: A total of 427 patients with metastatic renal cell carcinoma were identified with tumor thrombus. Patients with inferior vena cava thrombus above the diaphragm had shorter median overall survival vs those with renal vein only thrombus (9.2 months, IQR 4.2-30.8, vs 21.7, IQR 7.7-42.8, p = 0.0165). Individual risk factors from prognostic models were evaluated among other preoperative characteristics for associations with overall survival in 122 patients (32%) who died within 270 days of surgery. Independent predictors of overall survival included lactate dehydrogenase greater than the upper limit of normal (p = 0.003), systemic symptoms (p = 0.003), inferior vena cava thrombus above the diaphragm (p = 0.02) and sarcomatoid features (p = 0.005). CONCLUSIONS: Poor overall survival following cytoreductive nephrectomy in patients with metastatic renal cell carcinoma with tumor thrombus is associated with inferior vena cava thrombus above the diaphragm, poor risk group, systemic symptoms or sarcomatoid dedifferentiation. Patients with expected poor overall survival should be considered for preoperative systemic therapy clinical trials.

Predictive Nomogram for Recurrence following Surgery for Nonmetastatic Renal Cell Cancer with Tumor Thrombus.

PURPOSE: Following surgery for nonmetastatic renal cell carcinoma with tumor thrombus the risk of recurrence is significant but variable among patients. The purpose of this study was to develop and validate a predictive nomogram for individual estimation of recurrence risk following surgery for renal cell carcinoma with venous tumor thrombus. MATERIALS AND METHODS: Comprehensive data were collected on patients with nonmetastatic renal cell carcinoma and thrombus treated at a total of 5 institutions from 2000 to 2013. Independent predictors of recurrent renal cell carcinoma from a competing risks analysis were developed into a nomogram. Predictive accuracy was compared between the development and validation cohorts, and between the nomogram and the UISS (UCLA Integrated Staging System, SSIGN (Stage, Size, Grade and Necrosis) and Sorbellini models. RESULTS: A total of 636 patients were analyzed, including the development cohort of 465 and the validation cohort of 171. Independent predictors, including tumor diameter, body mass index, preoperative hemoglobin less than the lower limit of normal, thrombus level, perinephric fat invasion and nonclear cell histology, were developed into a nomogram. Estimated 5-year recurrence-free survival was 49% overall. Five-year recurrence-free survival in patients with 0, 1, 2 and more than 2 risk factors was 77%, 53%, 47% and 20%, respectively. Predictive accuracy was similar in the development and validation cohorts (AUC 0.726 and 0.724, respectively). Predictive accuracy of the thrombus nomogram was higher than that of the UISS (AUC 0.726 vs 0.595, p = 0.001), SSIGN (AUC 0.713 vs 0.612, p = 0.04) and Sorbellini models (AUC 0.709 vs 0.638, p = 0.02). CONCLUSIONS: We present a predictive nomogram for postoperative recurrence in patients with nonmetastatic renal cell carcinoma with venous thrombus. Improving individual postoperative risk assessment may allow for better design and analysis of future adjuvant clinical trials.

Reduced estimated glomerular filtration rate (eGFR <60 mL/min/1.73 m2 ) at first transurethral resection of bladder tumour is a significant predictor of subsequent recurrence and progression.

OBJECTIVE: To evaluate if moderate chronic kidney disease [CKD; estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 ] is associated with high rates of non-muscle-invasive bladder cancer (NMIBC) recurrence or progression. PATIENTS AND METHODS: A multi-institutional database identified patients with serum creatinine values prior to first transurethral resection of bladder tumour (TURBT). The CKD-epidemiology collaboration formula calculated patient eGFR. Cox proportional hazards models evaluated associations with recurrence-free (RFS) and progression-free survival (PFS). RESULTS: In all, 727 patients were identified with a median (interquartile range [IQR]) patient age of 69.8 (60.1-77.6) years. Data for eGFR were available for 632 patients. During a median (IQR) follow-up of 3.7 (1.5-6.5) years, 400 (55%) patients had recurrence and 145 (19.9%) patients had progression of tumour stage or grade. Moderate or severe CKD was identified in 183 patients according to eGFR. Multivariable analysis identified an eGFR of <60 mL/min/1.73 m2 (hazard ratio [HR] 1.5, 95% confidence interval [CI]: 1.2-1.9; P = 0.002) as a predictor of tumour recurrence. The 5-year RFS rate was 46% for patients with an eGFR of ≥60 mL/min/1.73 m2 and 27% for patients with an eGFR of <60 mL/min/1.73 m2 (P < 0.001). Multivariable analysis showed that an eGFR of <60 mL/min/1.73 m2 (HR 3.7, 95% CI: 1.75-7.94; P = 0.001) was associated with progression to muscle-invasive disease. The 5-year PFS rate was 83% for patients with an eGFR of ≥60 mL/min/1.73 m2 and 71% for patients with an eGFR of <60 mL/min/1.73 m2 (P = 0.01). CONCLUSION: Moderate CKD at first TURBT is associated with reduced RFS and PFS. Patients with reduced renal function should be considered for increased surveillance.