Radiomics Correlation to CD68+ Tumor-Associated Macrophages in Clear Cell Renal Cell Carcinoma.

INTRODUCTION: Renal cell carcinoma (RCC) is the ninth most common cancer worldwide, with clear cell RCC (ccRCC) being the most frequent histological subtype. The tumor immune microenvironment (TIME) of ccRCC is an important factor to guide treatment, but current assessments are tissue-based, which can be time-consuming and resource-intensive. In this study, we used radiomics extracted from clinically performed computed tomography (CT) as a noninvasive surrogate for CD68 tumor-associated macrophages (TAMs), a significant component of ccRCC TIME. METHODS: TAM population was measured by CD68+/PanCK+ ratio and tumor-TAM clustering was measured by normalized K function calculated from multiplex immunofluorescence (mIF). A total of 1,076 regions on mIF slides from 78 patients were included. Radiomic features were extracted from multiphase CT of the ccRCC tumor. Statistical machine learning models, including random forest, Adaptive Boosting, and ElasticNet, were used to predict TAM population and tumor-TAM clustering. RESULTS: The best models achieved an area under the ROC curve of 0.81 (95% CI: [0.69, 0.92]) for TAM population and 0.77 (95% CI: [0.66, 0.88]) for tumor-TAM clustering, respectively. CONCLUSION: Our study demonstrates the potential of using CT radiomics-derived imaging markers as a surrogate for assessment of TAM in ccRCC for real-time treatment response monitoring and patient selection for targeted therapies and immunotherapies.

A nomogram to predict the absence of clinically significant prostate cancer in males with negative MRI

PURPOSE: To create a nomogram to predict the absence of clinically significant prostate cancer (CSPCa) in males with non-suspicion multiparametric magnetic resonance imaging (mpMRI) undergoing prostate biopsy (PBx). MATERIALS AND METHODS: We identified consecutive patients who underwent 3T mpMRI followed by PBx for suspicion of PCa or surveillance follow-up. All patients had Prostate Imaging Reporting and Data System score 1-2 (negative mpMRI). CSPCa was defined as Grade Group ≥2. Multivariate logistic regression analysis was performed via backward elimination. Discrimination was evaluated with area under the receiver operating characteristic (AUROC). Internal validation with 1,000x bootstrapping for estimating the optimism corrected AUROC. RESULTS: Total 327 patients met inclusion criteria. The median (IQR) age and PSA density (PSAD) were 64 years (58-70) and 0.10 ng/mL2 (0.07-0.15), respectively. Biopsy history was as follows: 117 (36%) males were PBx-naive, 130 (40%) had previous negative PBx and 80 (24%) had previous positive PBx. The majority were White (65%); 6% of males self-reported Black. Overall, 44 (13%) patients were diagnosed with CSPCa on PBx. Black race, history of previous negative PBx and PSAD ≥0.15ng/mL2 were independent predictors for CSPCa on PBx and were included in the nomogram. The AUROC of the nomogram was 0.78 and the optimism corrected AUROC was 0.75. CONCLUSIONS: Our nomogram facilitates evaluating individual probability of CSPCa on PBx in males with PIRADS 1-2 mpMRI and may be used to identify those in whom PBx may be safely avoided. Black males have increased risk of CSPCa on PBx, even in the setting of PIRADS 1-2 mpMRI.

Robotic Bladder Autotransplantation: Preclinical Studies in Preparation for First-in-human Bladder Transplant.

PURPOSE: Human urinary bladder transplantation has never been performed. From a technical standpoint, challenges include the complex deep pelvic vascular anatomy, limited intraoperative visualization, and high procedural complexity. In preparation for a first-in-human clinical trial, we report preclinical studies to develop the technique of robotic retrieval and autotransplantation of vascularized composite bladder allograft. MATERIALS AND METHODS: Institutional Animal Care and Use Committee, Institutional Review Board, and UNOS (United Network for Organ Sharing) approvals were obtained, and IDEAL (Idea, Development, Exploration, Assessment, Long-term Study) Reporting Guidelines were followed. Robotic vascularized composite bladder allograft recovery, back-table graft preparation, and robotic autotransplantation were performed in 3 vascularized model settings: living porcine (n=3), pulsatile human cadavers (n=2), and heart-beating brain-dead deceased research human donors (n=5). Our primary objective was to develop a reproducible technique for robotic vascularized composite bladder allograft transplantation. Technical success was defined by adequate, sustained vascularized composite bladder allograft reperfusion. Secondary objectives were intraoperative parameters, including operative time, graft ischemia time, and blood loss. RESULTS: Successful robotic vascularized composite bladder allograft autotransplantation was achieved in 2 porcine, 1 cadaver, and 3 brain-dead research donors. In the heart-beating research donors, console time decreased with successive surgeries, and visual inspection revealed healthy revascularized autografts with prompt, global indocyanine green immunofluorescence uptake. In 1 heart-beating donor who was hemodynamically maintained for 12 hours postoperatively, reinspection confirmed excellent maintained global vascularized composite bladder allograft vascularity and bladder mucosal integrity. CONCLUSIONS: To our knowledge, the first preclinical experience of bladder autotransplantation in vascularized models is reported, including robotic vascularized composite bladder allograft recovery, back-table reconstruction, and autotransplantation. This experience represents the essential preclinical work required to build toward the first-in-human trial of bladder transplantation, performed under a UNOS-approved genitourinary vascularized composite bladder allograft program (NCT No. 05462561).

Radiogenomic Associations Clear Cell Renal Cell Carcinoma: An Exploratory Study.

INTRODUCTION: This study investigates how quantitative texture analysis can be used to non-invasively identify novel radiogenomic correlations with clear cell renal cell carcinoma (ccRCC) biomarkers. METHODS: The Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma open-source database was used to identify 190 sets of patient genomic data that had corresponding multiphase contrast-enhanced CT images in The Cancer Imaging Archive. 2,824 radiomic features spanning fifteen texture families were extracted from CT images using a custom-built MATLAB software package. Robust radiomic features with strong inter-scanner reproducibility were selected. Random forest, AdaBoost, and elastic net machine learning (ML) algorithms evaluated the ability of the selected radiomic features to predict the presence of 12 clinically relevant molecular biomarkers identified from the literature. ML analysis was repeated with cases stratified by stage (I/II vs. III/IV) and grade (1/2 vs. 3/4). 10-fold cross validation was used to evaluate model performance. RESULTS: Before stratification by tumor grade and stage, radiomics predicted the presence of several biomarkers with weak discrimination (AUC 0.60-0.68). Once stratified, radiomics predicted KDM5C, SETD2, PBRM1, and mTOR mutation status with acceptable to excellent predictive discrimination (AUC ranges from 0.70 to 0.86). CONCLUSIONS: Radiomic texture analysis can potentially identify a variety of clinically relevant biomarkers in patients with ccRCC and may have a prognostic implication.

Partial or radical nephrectomy for complex renal mass: a comparative analysis of oncological outcomes and complications from the ROSULA (Robotic Surgery for Large Renal Mass) Collaborative Group.

PURPOSE: To compare outcomes of robotic-assisted partial nephrectomy (RAPN) and minimally invasive radical nephrectomy (MIS-RN) for complex renal masses (CRM). METHODS: We conducted a retrospective multicenter analysis of CRM patients who underwent MIS-RN and RAPN. CRM was defined as RENAL score 10-12. Primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS), recurrence, and complications. Multivariable analysis (MVA) and Kaplan-Meier Analysis (KMA) were used to analyze functional and survival outcomes for RN vs. PN by pathological stage. RESULTS: 926 patients were analyzed (MIS-RN = 437/RAPN = 489; median follow-up 24.0 months). MVA demonstrated lack of transfusion (HR = 1.63, p = 0.005), low-grade (HR = 1.18, p = 0.018) and smaller tumor size (HR = 1.05, p < 0.001) were associated with OS. Younger age (HR = 1.01, p = 0.017), high-grade (HR = 1.18, p = 0.017), smaller tumor size (HR = 1.05, p < 0.001), and lack of transfusion (HR = 1.39, p = 0.038) were associated with CSS. Increasing tumor size (HR = 1.18, p < 0.001), high-grade (HR = 3.21, p < 0.001), and increasing age (HR = 1.02, p = 0.009) were independent risk factors for recurrence. Type of surgery was not associated with major complications (p = 0.094). For KMA of MIS-RN vs. RAPN for pT1, pT2 and pT3, 5-year OS was 85% vs. 88% (p = 0.078); 82% vs. 80% (p = 0.442) and 84% vs. 83% (p = 0.863), respectively. 5-year CSS was 98% for both procedures (p = 0.473); 94% vs. 92% (p = 0.735) and 91% vs. 90% (p = 0.581). 5-year non-CSS was 87% vs. 93% (p = 0.107); 87% for pT2 (p = 0.485) and 92% for pT3 for both procedures (p = 0.403). CONCLUSION: RAPN in CRM is not associated with increased risk of complications or worsened oncological outcomes when compared to MIS-RN and may be preferred when clinically indicated.

Tailored Feedback Based on Clinically Relevant Performance Metrics Expedites the Acquisition of Robotic Suturing Skills-An Unblinded Pilot Randomized Controlled Trial.

PURPOSE: Previously, we identified 8 objective suturing performance metrics highly predictive of urinary continence recovery after robotic-assisted radical prostatectomy. Here, we aimed to test the feasibility of providing tailored feedback based upon these clinically relevant metrics and explore the impact on the acquisition of robotic suturing skills. MATERIALS AND METHODS: Training surgeons were recruited and randomized to a feedback group or a control group. Both groups completed a baseline, midterm and final dry laboratory vesicourethral anastomosis (VUA) and underwent 4 intervening training sessions each, consisting of 3 suturing exercises. Eight performance metrics were recorded during each exercise: 4 automated performance metrics (derived from kinematic and system events data of the da Vinci® Robotic System) representing efficiency and console manipulation competency, and 4 suturing technical skill scores. The feedback group received tailored feedback (a visual diagram+verbal instructions+video examples) based on these metrics after each session. Generalized linear mixed model was used to compare metric improvement (Δ) from baseline to the midterm and final VUA. RESULTS: Twenty-three participants were randomized to the feedback group (11) or the control group (12). Demographic data and baseline VUA metrics were comparable between groups. The feedback group showed greater improvement than the control group in aggregate suturing scores at midterm (mean Δ feedback group 4.5 vs Δ control group 1.1) and final VUA (Δ feedback group 5.3 vs Δ control group 4.9). The feedback group also showed greater improvement in the majority of the included metrics at midterm and final VUA. CONCLUSIONS: Tailored feedback based on specific, clinically relevant performance metrics is feasible and may expedite the acquisition of robotic suturing skills.

CT-based radiomics stratification of tumor grade and TNM stage of clear cell renal cell carcinoma.

OBJECTIVES: To evaluate the utility of CT-based radiomics signatures in discriminating low-grade (grades 1-2) clear cell renal cell carcinomas (ccRCC) from high-grade (grades 3-4) and low TNM stage (stages I-II) ccRCC from high TNM stage (stages III-IV). METHODS: A total of 587 subjects (mean age 60.2 years ± 12.2; range 22-88.7 years) with ccRCC were included. A total of 255 tumors were high grade and 153 were high stage. For each subject, one dominant tumor was delineated as the region of interest (ROI). Our institutional radiomics pipeline was then used to extract 2824 radiomics features across 12 texture families from the manually segmented volumes of interest. Separate iterations of the machine learning models using all extracted features (full model) as well as only a subset of previously identified robust metrics (robust model) were developed. Variable of importance (VOI) analysis was performed using the out-of-bag Gini index to identify the top 10 radiomics metrics driving each classifier. Model performance was reported using area under the receiver operating curve (AUC). RESULTS: The highest AUC to distinguish between low- and high-grade ccRCC was 0.70 (95% CI 0.62-0.78) and the highest AUC to distinguish between low- and high-stage ccRCC was 0.80 (95% CI 0.74-0.86). Comparable AUCs of 0.73 (95% CI 0.65-0.8) and 0.77 (95% CI 0.7-0.84) were reported using the robust model for grade and stage classification, respectively. VOI analysis revealed the importance of neighborhood operation-based methods, including GLCM, GLDM, and GLRLM, in driving the performance of the robust models for both grade and stage classification. CONCLUSION: Post-validation, CT-based radiomics signatures may prove to be useful tools to assess ccRCC grade and stage and could potentially add to current prognostic models. Multiphase CT-based radiomics signatures have potential to serve as a non-invasive stratification schema for distinguishing between low- and high-grade as well as low- and high-stage ccRCC. KEY POINTS: • Radiomics signatures derived from clinical multiphase CT images were able to stratify low- from high-grade ccRCC, with an AUC of 0.70 (95% CI 0.62-0.78). • Radiomics signatures derived from multiphase CT images yielded discriminative power to stratify low from high TNM stage in ccRCC, with an AUC of 0.80 (95% CI 0.74-0.86). • Models created using only robust radiomics features achieved comparable AUCs of 0.73 (95% CI 0.65-0.80) and 0.77 (95% CI 0.70-0.84) to the model with all radiomics features in classifying ccRCC grade and stage, respectively.

A new view of macula densa cell microanatomy.

Although macula densa (MD) cells are chief regulatory cells in the nephron with unique microanatomical features, they have been difficult to study in full detail due to their inaccessibility and limitations in earlier microscopy techniques. The present study used a new mouse model with a comprehensive imaging approach to visualize so far unexplored microanatomical features of MD cells, their regulation, and functional relevance. MD-GFP mice with conditional and partial induction of green fluorescent protein (GFP) expression, which specifically and intensely illuminated only single MD cells, were used with fluorescence microscopy of fixed tissue and live MD cells in vitro and in vivo with complementary electron microscopy of the rat, rabbit, and human kidney. An elaborate network of major and minor cell processes, here named maculapodia, were found at the cell base, projecting toward other MD cells and the glomerular vascular pole. The extent of maculapodia showed upregulation by low dietary salt intake and the female sex. Time-lapse imaging of maculapodia revealed highly dynamic features including rapid outgrowth and an extensive vesicular transport system. Electron microscopy of rat, rabbit, and human kidneys and three-dimensional volume reconstruction in optically cleared whole-mount MD-GFP mouse kidneys further confirmed the presence and projections of maculapodia into the extraglomerular mesangium and afferent and efferent arterioles. The newly identified dynamic and secretory features of MD cells suggest the presence of novel functional and molecular pathways of cell-to-cell communication in the juxtaglomerular apparatus between MD cells and between MD and other target cells.NEW & NOTEWORTHY This study illuminated a physiologically regulated dense network of basal cell major and minor processes (maculapodia) in macula densa (MD) cells. The newly identified dynamic and secretory features of these microanatomical structures suggest the presence of novel functional and molecular pathways of cell-to-cell communication in the juxtaglomerular apparatus between MD and other target cells. Detailed characterization of the function and molecular details of MD cell intercellular communications and their role in physiology and disease warrant further studies.

Systematic Biopsy of the Prostate can Be Omitted in Men with PI-RADS™ 5 and Prostate Specific Antigen Density Greater than 15.

PURPOSE: We evaluated the prostate cancer and clinically significant prostate cancer detection on systematic biopsy (SB), target biopsy (TB) alone and combined SB and TB in men with Prostate Imaging Reporting and Data System™ (PI-RADS™) 5 lesion. MATERIALS AND METHODS: From a prospectively maintained prostate biopsy database, we identified consecutive patients with PI-RADS 5 lesion on multiparametric magnetic resonance imaging. The patients underwent multiparametric magnetic resonance imaging followed by transrectal TB of PI-RADS 5 lesion and 12-core SB. The prostate cancer and clinically significant prostate cancer (Grade Group, GG ≥2) detection on SB, TB and SB+TB were determined for all men and accordingly to prostate specific antigen density. Statistic significant was set a p <0.05. RESULTS: Overall, 112 patients met inclusion criteria. The detection rate of prostate cancer for SB, TB and SB+TB was 89%, 93% and 95%, respectively, and for clinically significant prostate cancer it was 72%, 81% and 85%, respectively. SB added 2% prostate cancer and 4% clinically significant prostate cancer detection to TB. A total of 78 patients had prostate specific antigen density >0.15 ng/ml2, and the detection rate of PCa for SB, TB and SB+TB was 92%, 97% and 97%, respectively, and for clinically significant prostate cancer it was 79%, 91% and 95%, respectively. In this population, if SB was omitted, 0 prostate cancer and only 4% (3) of clinically significant prostate cancer would be missed. The clinically significant prostate cancer detection rate improved with increased prostate specific antigen density for SB (p=0.01), TB (p <0.0001) and combined SB+TB (p=0.002). CONCLUSIONS: In patients with PI-RADS 5 on multiparametric magnetic resonance imaging and prostate specific antigen density >0.15 ng/ml2, SB marginally increases clinically significant prostate cancer detection, but not overall prostate cancer detection in comparison to TB alone. Systematic biopsy did not affect patients' management and can be omitted on this population.

Timing, Patterns and Predictors of 90-Day Readmission Rate after Robotic Radical Cystectomy.

PURPOSE: We examine the timing, patterns and predictors of 90-day readmission after robotic radical cystectomy. MATERIALS AND METHODS: From September 2009 to March 2017, 271 consecutive patients undergoing robotic radical cystectomy with intent to cure bladder cancer (intracorporeal diversion 253, 93%) were identified from our prospectively collated institutional database. Readmission was defined as any subsequent inpatient admission or unplanned visit occurring within 90 days from discharge after the index hospitalization. Multiple readmissions were defined as 2 or more readmissions within a 90-day period. Logistic regression analysis was used to identify independent factors related to single and multiple 90-day readmissions. RESULTS: A total of 78 (28.8%) patients were readmitted at least once within 90 days after discharge, of whom 20 (25.6%) reported multiple readmissions. The cumulative duration of readmission was 6.2 (6.17) days with 6 (7.6%) patients having less than 24 hours readmission. Metabolic, infectious, genitourinary and gastrointestinal complications were identified as the primary cause of readmission in 39.5%, 23.5%, 22.3% and 17%, respectively. Fifty percent of readmissions occurred in the first 2 weeks after hospital discharge. On multivariable logistic regression analysis in-hospital infections (OR 2.85, p=0.001) were independent predictors for overall readmission. Male gender (OR 3.5, p=0.02) and in-hospital infections (OR 4.35, p=0.002) were independent predictors for multiple readmissions. CONCLUSIONS: The 90-day readmission rate following robotic radical cystectomy is significant. In-hospital infections and male gender were independent factors for readmission. Most readmissions occurred in the first 2 weeks following discharge, with metabolic derangements and infections being the most common causes.

Multiparametric magnetic resonance imaging facilitates reclassification during active surveillance for prostate cancer.

OBJECTIVE: To investigate the utility of multiparametric magnetic resonance imaging (mpMRI) in the reassessment and monitoring of patients on active surveillance (AS) for Grade Group (GG) 1 prostate cancer (PCa). PATIENTS AND METHODS: We identified, from our prospectively maintained institutional review board-approved database, 181 consecutive men enrolled on AS for GG 1 PCa who underwent at least one surveillance mpMRI followed by MRI/prostate biopsy (PBx). A subset analysis was performed among 68 patients who underwent serial (at least two) mpMRI/PBx during AS. Pathological progression (PP) was defined as upgrade to GG ≥2 on follow up biopsy. RESULTS: Baseline MRI was performed in 34 patients (19%). At a median follow-up of 2.2 years for the overall cohort, the PP was 12% (6/49) for Prostate Imaging Reporting and Data System (PI-RADS) 1-2 lesions and 37% (48/129) for the PI-RADS ≥3 lesions. The 2-year PP-free survival rate was 84%. Surveillance prostate-specific antigen density (P < 0.001) and surveillance PI-RADS ≥3 (P = 0.002) were independent predictors of PP on reassessment MRI/PBx. In the serial MRI cohort, the 2-year PP-free survival was 95% for the No-MRI-progression group vs 85% for the MRI-progression group (P = 0.02). MRI progression was significantly higher in the PP (62%) than in the No-PP (31%) group (P = 0.04). If serial MRI were used for PCa surveillance and biopsy were triggered based only on MRI progression, 63% of PBx might be postponed at the cost of missing 12% of GG ≥2 PCa in those with stable MRI. Conversely, this strategy would miss 38% of those with upgrading to GG ≥2 PCa on biopsy. Stable serial mpMRI correlates with no reclassification to GG ≥3 PCa during AS. CONCLUSION: On surveillance mpMRI, PI-RADS ≥3 was associated with increased risk of PCa reclassification. Surveillance biopsy based only on MRI progression may avoid a large number of biopsies at the cost of missing many PCa reclassifications.

Five-alpha reductase inhibitors in men undergoing active surveillance for prostate cancer: impact on treatment and reclassification after 6 years follow-up.

OBJECTIVES: To evaluate the impact of 5-alpha reductase inhibitors (5-ARIs) on definitive treatment (DT) and pathological progression (PP) in patients on active surveillance (AS) for prostate cancer. METHODS: We identified 361 consecutive patients, from an IRB-approved database, on AS for prostate cancer with minimum 2 years follow-up. Patients were grouped into two cohorts, those using 5-ARIs (5-ARI; n = 119) or not using 5-ARIs (no 5-ARI; n = 242). Primary and secondary endpoints were treatment-free survival (TFS) and PP-free survival (PPFS), which were evaluated by Kaplan-Meier analysis. Univariate and multivariable cox regression analysis were used to identify predictors for PP and DT. A p value < 0.05 was considered statistically significant. RESULTS: Baseline characteristics and the prostate biopsy rate were similar between the two groups. Median (range) follow-up was 5.7 (2.0-17.2) years. Five-year and 10-year TFS was 92% and 59% for the 5-ARI group versus 80% and 51% for the no 5-ARI group (p = 0.005), respectively. Five-year and 10-year PPFS was 77% and 41% for the 5-ARI group versus 70% and 32% for the no 5-ARI group (p = 0.04), respectively. Independent predictors for treatment and PP were not taking 5-ARIs (p = 0.005; p = 0.02), entry PSA > 2.5 ng/mL (p = 0.03; p = 0.01) and Gleason pattern 4 on initial biopsy (p < 0.001; p < 0.001), respectively. The main limitation is the retrospective study design. CONCLUSIONS: 5-ARIs reduces reclassification and cross-over to treatment in men on active surveillance for prostate cancer. Further, taking 5-ARIs was an independent predictor for prostate cancer progression and definitive treatment.

Shape and texture-based radiomics signature on CT effectively discriminates benign from malignant renal masses.

OBJECTIVES: Using a radiomics framework to quantitatively analyze tumor shape and texture features in three dimensions, we tested its ability to objectively and robustly distinguish between benign and malignant renal masses. We assessed the relative contributions of shape and texture metrics separately and together in the prediction model. MATERIALS AND METHODS: Computed tomography (CT) images of 735 patients with 539 malignant and 196 benign masses were segmented in this retrospective study. Thirty-three shape and 760 texture metrics were calculated per tumor. Tumor classification models using shape, texture, and both metrics were built using random forest and AdaBoost with tenfold cross-validation. Sensitivity analyses on five sub-cohorts with respect to the acquisition phase were conducted. Additional sensitivity analyses after multiple imputation were also conducted. Model performance was assessed using AUC. RESULTS: Random forest classifier showed shape metrics featuring within the top 10% performing metrics regardless of phase, attaining the highest variable importance in the corticomedullary phase. Convex hull perimeter ratio is a consistently high-performing shape feature. Shape metrics alone achieved an AUC ranging 0.64-0.68 across multiple classifiers, compared with 0.67-0.75 and 0.68-0.75 achieved by texture-only and combined models, respectively. CONCLUSION: Shape metrics alone attain high prediction performance and high variable importance in the combined model, while being independent of the acquisition phase (unlike texture). Shape analysis therefore should not be overlooked in its potential to distinguish benign from malignant tumors, and future radiomics platforms powered by machine learning should harness both shape and texture metrics. KEY POINTS: • Current radiomics research is heavily weighted towards texture analysis, but quantitative shape metrics should not be ignored in their potential to distinguish benign from malignant renal tumors. • Shape metrics alone can attain high prediction performance and demonstrate high variable importance in the combined shape and texture radiomics model. • Any future radiomics platform powered by machine learning should harness both shape and texture metrics, especially since tumor shape (unlike texture) is independent of the acquisition phase and more robust from the imaging variations.

Techniques and Outcomes of MRI-TRUS Fusion Prostate Biopsy.

PURPOSE OF REVIEW: The goal of this study is to review recent findings and evaluate the utility of MRI transrectal ultrasound fusion biopsy (FBx) techniques and discuss future directions. RECENT FINDINGS: FBx detects significantly higher rates of clinically significant prostate cancer (csPCa) than ultrasound-guided systematic prostate biopsy (SBx), particularly in repeat biopsy settings. FBx has also been shown to detect significantly lower rates of clinically insignificant prostate cancer. In addition, a dedicated prostate MRI can assist in more accurately predicting the Gleason score and provide further information regarding the index cancer location, prostate volume, and clinical stage. The ability to accurately evaluate specific lesions is vital to both focal therapy and active surveillance, for treatment selection, planning, and adequate follow-up. FBx has been demonstrated in multiple high-quality studies to have improved performance in diagnosis of csPCa compared to SBx. The combination of FBx with novel technologies including radiomics, prostate-specific membrane antigen positron emission tomography (PSMA PET), and high-resolution micro-ultrasound may have the potential to further enhance this performance.

High Intensity Focused Ultrasound Hemigland Ablation for Prostate Cancer: Initial Outcomes of a United States Series.

PURPOSE: We report outcomes of hemigland high intensity focused ultrasound ablation as primary treatment for localized prostate cancer in the United States. MATERIALS AND METHODS: A total of 100 consecutive men underwent hemigland high intensity focused ultrasound (December 2015 to December 2019). Primary end point was treatment failure, defined as Grade Group 2 or greater on followup prostate biopsy, radical treatment, systemic therapy, metastases or prostate cancer specific mortality. IIEF (International Index of Erectile Function), I-PSS (International Prostate Symptom Score) and 90-day complications were reported. RESULTS: At study entry patients had very low (8%), low (20%), intermediate favorable (50%), intermediate unfavorable (17%) and high (5%) risk prostate cancer. Median followup was 20 months. The 2-year survival free from treatment failure, Grade Group 2 or greater recurrence, repeat focal high intensity focused ultrasound and radical treatment was 73%, 76%, 90% and 91%, respectively. Bilateral prostate cancer at diagnosis was the sole predictor for Grade Group 2 or greater recurrence (p=0.03). Of men who underwent posttreatment biopsy (58), 10 had in-field and 8 out-of-field Grade Group 2 or greater positive biopsy. Continence (zero pad) was maintained in 100% of patients. Median IIEF-5 and I-PSS scores before vs after hemigland high intensity focused ultrasound were 22 vs 21 (p=0.99) and 9 vs 6 (p=0.005), respectively. Minor and major complications occurred in 13% and 0% of patients. No patient had rectal fistula or died. CONCLUSIONS: Short-term results of focal high intensity focused ultrasound indicate safety, excellent potency and continence preservation, and adequate short-term prostate cancer control. Radical treatment was avoided in 91% of men at 2 years. Men with bilateral prostate cancer at diagnosis have increased risk for Grade Group 2 or greater recurrence. To our knowledge, this is the initial and largest United States series of focal high intensity focused ultrasound as primary treatment for prostate cancer.

Underestimation of Positron Emission Tomography/Computerized Tomography in Assessing Tumor Burden in Prostate Cancer Nodal Recurrence: Head-to-Head Comparison of 68Ga-PSMA and 11C-Choline in a Large, Multi-Institutional Series of Extended Salvage Lymph Node Dissections.

PURPOSE: We compared the use of 11C-choline and 68Ga-prostate specific membrane antigen in men undergoing salvage lymph node dissection for nodal recurrent prostate cancer. MATERIALS AND METHODS: The study included 641 patients who experienced prostate specific antigen rise and nodal recurrence after radical prostatectomy and underwent salvage lymph node dissection. Lymph node recurrence was documented by positron emission tomography/computerized tomography using 11C-choline (407, 63%) or 68Ga-PSMA ligand (234, 37%). The outcome was underestimation of tumor burden (difference between number of positive nodes on final pathology and number of positive spots at positron emission tomography/computerized tomography). Multivariable analysis tested the association between positron emission tomography/computerized tomography tracer (11C-choline vs 68Ga-PSMA) and tumor burden underestimation. RESULTS: Overall the extent of tumor burden underestimation was significantly higher in the 11C-choline group compared to the 68Ga-PSMA group (p <0.0001), which was confirmed on multivariable analysis (p=0.028). Repeating these analyses according to prostate specific antigen, tumor burden underestimation was lower with 68Ga-PSMA only when prostate specific antigen was 1.5 ng/ml or less. Conversely, the underestimation of the 2 tracers became similar when prostate specific antigen was greater than 1.5 ng/ml. Furthermore, we evaluated the risk of underestimation by number of positive spots on positron emission tomography/computerized tomography. The higher the number of positive spots the higher the underestimation of tumor burden regardless of the tracer used (p=0.2). CONCLUSIONS: Positron emission tomography/computerized tomography significantly underestimates the burden of prostate cancer recurrence, regardless of the tracer used. 68Ga-PSMA was associated with a lower rate of underestimation in patients with a prostate specific antigen below 1.5 ng/ml and a limited nodal tumor load. In all other men there was no benefit from 68Ga-PSMA over 11C-choline in assessing the extent of nodal recurrence.

Radical cystectomy pentafecta: a proposal for standardisation of outcomes reporting following robot-assisted radical cystectomy.

OBJECTIVE: To propose a standardisable composite method for reporting outcomes of radical cystectomy (RC) that incorporates both perioperative morbidity and oncological adequacy. PATIENTS AND METHODS: From July 2010 to December 2017, 277 consecutive patients who underwent robot-assisted RC with intracorporeal urinary diversion (UD) for bladder cancer at our Institution were prospectively analysed. Patients who simultaneously demonstrated negative soft tissue surgical margins (STSMs), ≥16 lymph node (LN) yield, absence of major (grade III-IV) complications at 90 days, absence of UD-related long-term sequelae and absence of clinical recurrence at ≤12 months, were considered as having achieved the RC-pentafecta. A multivariable logistic regression model was assessed to measure predictors for achieving RC-pentafecta. RESULTS AND LIMITATIONS: Since 2010, 270 of 277 patients that had completed at least 12 months of follow-up were included. Over a mean follow-up of 22.3 months, ≥16 LN yield, negative STSMs, absence of major complications at 90 days, and absence of UD-related surgical sequelae and clinical recurrence at ≤12 months were observed in 93.0%, 98.9%, 76.7%, 81.5% and 92.2%, patients, respectively, resulting in a RC-pentafecta rate of 53.3%. Multivariable logistic regression analysis revealed age (odds ratio [OR] 0.95; P = 0.002), type of UD (OR 2.19; P = 0.01) and pN stage (OR 0.48; P = 0.03) as independent predictors for achieving RC-pentafecta. CONCLUSIONS: We present a RC-pentafecta as a standardisable composite endpoint that incorporates perioperative morbidity and oncological adequacy as a potential tool to assess quality of RC. This tool may be useful for assessing the learning curve and calculating cost-effectiveness amongst others but needs to be externally validated in future studies.

Robotic partial nephrectomy vs minimally invasive radical nephrectomy for clinical T2a renal mass: a propensity score-matched comparison from the ROSULA (Robotic Surgery for Large Renal Mass) Collaborative Group.

OBJECTIVE: To compare outcomes of minimally invasive radical nephrectomy (MIS-RN) and robot-assisted partial nephrectomy (RAPN) in clinical T2a renal mass (cT2aRM). PATIENTS AND METHODS: Retrospective, multicentre, propensity score-matched (PSM) comparison of RAPN and MIS-RN for cT2aRM (T2aN0M0). Cohorts were PSM for age, sex, body mass index, American Society of Anesthesiologists (ASA) class, clinical tumour size, and R.E.N.A.L. score using a 2:1 ratio for RN:PN. The primary outcome was disease-free survival (DFS). Secondary outcomes included overall survival (OS), complication rates, and de novo estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2 . Multivariable (MVA) and Kaplan-Meier survival analyses (KMSA) were conducted. RESULTS: In all, 648 patients (216 RAPN/432 MIS-RN) were matched. There were no significant differences in intraoperative complications (P = 0.478), Clavien-Dindo Grade ≥III complications (P = 0.063), and re-admissions (P = 0.238). The MVA revealed high ASA class (hazard ratio [HR] 2.7, P = 0.044) and sarcomatoid (HR 5.3, P = 0.001), but not surgery type (P = 0.601) to be associated with all-cause mortality. Increasing R.E.N.A.L. score (HR 1.31, P = 0.037), high tumour grade (HR 2.5, P = 0.043), and sarcomatoid (HR 2.8, P = 0.02) were associated with recurrence, but not surgery (P = 0.555). Increasing age (HR 1.1, P < 0.001) and RN (HR 3.9, P < 0.001) were predictors of de novo eGFR of <45 mL/min/1.73 m2 . Comparing RAPN and MIS-RN, KMSA revealed no significant differences for 5-year OS (76.3% vs 88.0%, P = 0.221) and 5-year DFS (78.6% vs 85.3%, P = 0.630) for pT2 RCC, and no differences for 3-year OS (P = 0.351) and 3-year DFS (P = 0.117) for pT3a upstaged RCC. The 5-year freedom from de novo eGFR of <45 mL/min/1.73 m2 was 91.6% for RAPN vs 68.9% for MIS-RN (P < 0.001). CONCLUSIONS: RAPN had similar oncological outcomes and morbidity profile as MIS-RN, while conferring functional benefit. RAPN may be considered as a first-line option for cT2aRM.

Using objective robotic automated performance metrics and task-evoked pupillary response to distinguish surgeon expertise.

PURPOSE: In this study, we investigate the ability of automated performance metrics (APMs) and task-evoked pupillary response (TEPR), as objective measures of surgeon performance, to distinguish varying levels of surgeon expertise during generic robotic surgical tasks. Additionally, we evaluate the association between APMs and TEPR. METHODS: Participants completed ten tasks on a da Vinci Xi Surgical System (Intuitive Surgical, Inc.), each representing a surgical skill type: EndoWrist® manipulation, needle targeting, suturing/knot tying, and excision/dissection. Automated performance metrics (instrument motion tracking, EndoWrist® articulation, and system events data) and TEPR were recorded by a systems data recorder (Intuitive Surgical, Inc.) and Tobii Pro Glasses 2 (Tobii Technologies, Inc.), respectively. The Kruskal-Wallis test determined significant differences between groups of varying expertise. Spearman's rank correlation coefficient measured associations between APMs and TEPR. RESULTS: Twenty-six participants were stratified by robotic surgical experience: novice (no prior experience; n = 9), intermediate (< 100 cases; n = 9), and experts (≥ 100 cases; n = 8). Several APMs differentiated surgeon experience including task duration (p < 0.01), time active of instruments (p < 0.03), linear velocity of instruments (p < 0.04), and angular velocity of dominant instrument (p < 0.04). Task-evoked pupillary response distinguished surgeon expertise for three out of four task types (p < 0.04). Correlation trends between APMs and TEPR revealed that expert surgeons move more slowly with high cognitive workload (ρ < - 0.60, p < 0.05), while novices move faster under the same cognitive experiences (ρ > 0.66, p < 0.05). CONCLUSIONS: Automated performance metrics and TEPR can distinguish surgeon expertise levels during robotic surgical tasks. Furthermore, under high cognitive workload, there can be a divergence in robotic movement profiles between expertise levels.