Protective role for kidney TREM2high macrophages in obesity- and diabetes-induced kidney injury.

Diabetic kidney disease (DKD), the most common cause of kidney failure, is a frequent complication of diabetes and obesity, and yet to date, treatments to halt its progression are lacking. We analyze kidney single-cell transcriptomic profiles from DKD patients and two DKD mouse models at multiple time points along disease progression-high-fat diet (HFD)-fed mice aged to 90-100 weeks and BTBR ob/ob mice (a genetic model)-and report an expanding population of macrophages with high expression of triggering receptor expressed on myeloid cells 2 (TREM2) in HFD-fed mice. TREM2high macrophages are enriched in obese and diabetic patients, in contrast to hypertensive patients or healthy controls in an independent validation cohort. Trem2 knockout mice on an HFD have worsening kidney filter damage and increased tubular epithelial cell injury, all signs of worsening DKD. Together, our studies suggest that strategies to enhance kidney TREM2high macrophages may provide therapeutic benefits for DKD.

Postradical prostatectomy prostate-specific antigen outcomes after 6 versus 18 months of perioperative androgen-deprivation therapy in men with localized, unfavorable intermediate-risk or high-risk prostate cancer: Results of part 2 of a randomized phase 2 trial.

BACKGROUND: Patients with localized, unfavorable intermediate-risk and high-risk prostate cancer have an increased risk of relapse after radical prostatectomy (RP). The authors previously reported on part 1 of this phase 2 trial testing neoadjuvant apalutamide, abiraterone, prednisone, plus leuprolide (AAPL) or abiraterone, prednisone, and leuprolide (APL) for 6 months followed by RP. The results demonstrated favorable pathologic responses (tumor <5 mm) in 20.3% of patients (n = 24 of 118). Herein, the authors report the results of part 2. METHODS: For part 2, patients were randomized 1:1 to receive either AAPL for 12 months (arm 2A) or observation (arm 2B), stratified by neoadjuvant therapy and pathologic tumor classification. The primary end point was 3-year biochemical progression-free survival. Secondary end points included safety and testosterone recovery (>200 ng/dL). RESULTS: Overall, 82 of 118 patients (69%) enrolled in part 1 were randomized to part 2. A higher proportion of patients who were not randomized to adjuvant therapy had a favorable prostatectomy pathologic response (32.3% in nonrandomized patients compared with 17.1% in randomized patients). In the intent-to-treat analysis, the 3-year biochemical progression-free survival rate was 81% for arm 2A and 72% for arm 2B (hazard ratio, 0.81; 90% confidence interval, 0.43-1.49). Of the randomized patients, 81% had testosterone recovery in the AAPL group compared with 95% in the observation group, with a median time to recovery of <12 months in both arms. CONCLUSIONS: In this study, because 30% of patients declined adjuvant treatment, part B was underpowered to detect differences between arms. Future perioperative studies should be biomarker-directed and include strategies for investigator and patient engagement to ensure compliance with protocol procedures.

Stereotactic Magnetic Resonance-guided Adaptive Radiation Therapy for Localized Kidney Cancer: Early Outcomes from a Prospective Phase 1 Trial and Supplemental Cohort.

Stereotactic magnetic resonance (MR)-guided adaptive radiotherapy (SMART) for renal cell carcinoma may result in more precise treatment delivery through the capabilities for improved image quality, daily adaptive planning, and accounting for respiratory motion during treatment with real-time MR tracking. In this study, we aimed to characterize the safety and feasibility of SMART for localized kidney cancer. Twenty patients with localized kidney cancer (ten treated in a prospective phase 1 trial and ten in the supplemental cohort) were treated to 40 Gy in five fractions on a 0.35 T MR-guided linear accelerator with daily adaptive planning and a cine MR-guided inspiratory breath hold technique. The median follow-up time was 17 mo (interquartile range: 13-20 months). A single patient developed local failure at 30 mo. No grade ≥3 adverse events were reported. The mean decrease in estimated glomerular filtration rate was -1.8 ml/min/1.73 m2 (95% confidence interval or CI [-6.6 to 3.1 ml/min/1.73 m2]), and the mean decrease in tumor diameter was -0.20 cm (95% CI [-0.6 to 0.2 cm]) at the last follow-up. Anterior location and overlap of the 25 or 28 Gy isodose line with gastrointestinal organs at risk were predictive of the benefit from online adaptive planning. Kidney SMART is feasible and, at the early time point evaluated in this study, was well tolerated with minimal decline in renal function. More studies are warranted to further evaluate the safety and efficacy of this technique. PATIENT SUMMARY: For patients with localized renal cell carcinoma who are not surgical candidates, stereotactic magnetic resonance--guided adaptive radiotherapy is a feasible and safe noninvasive treatment option that results in minimal impact on kidney function.

Anticoagulation prophylaxis patterns following retroperitoneal lymph node dissection for testis cancer.

INTRODUCTION: Retroperitoneal lymph node dissection (RPLND) is the standard of care for testicular cancer in various disease settings. Deep vein thrombosis (DVT) complications have been reported to occur in <1% of primary RPLND cases and up to 3% of postchemotherapy (PC-RPLND) cases. While prophylactic anticoagulation (AC) has been well-documented to reduce DVT rates in patients undergoing surgery in general, the benefit of prophylactic AC in RPLND has not been assessed. In this retrospective cohort study, we seek to address this unmet need by evaluating the rates and associated risk factors of DVT and pulmonary embolism (PE) with a national and institutional database, assess the changing patterns in DVT prophylaxis with postoperative AC following RPLND, and quantify the potential benefit of prophylactic AC in patients who have undergone RPLND using a risk-stratified approach. METHODS: The National Surgical Quality Improvement Program (NSQIP) database was queried for patients who underwent RPLND during the 10-year period from 2011 to 2021. An institutional database was queried for all patients undergoing RPLND from 2013 to 2022. Patient characteristics and operative outcomes were compared between the NSQIP and the institutional database. The institutional database was stratified by prior oncologic treatment (i.e., primary RPLND vs. PC-RPLND) and outcomes were compared. Postoperative AC rate was determined and trended by year. The use of postoperative AC and PE events were stratified by clinical stage. The absolute risk reduction (ARR) of AC prophylaxis on PE events and the number needed to treat (NNT) with AC prophylaxis to prevent a single PE event was determined. RESULTS: In total, the NSQIP database query resulted in 779 patients and our institutional database query resulted in 188 patients. The rate of DVT and PE was 1.2% and 0.5% vs. 2.1% and 1.6% in the NSQIP and institutional cohort, respectively. The rate of postoperative AC following RPLND in patients from the institutional database increased from 5% in 2013 to 43% in 2022 (P = 0.01). There were no statistically significant differences in complication rates, including bleeding events, chyle leaks, or hospital readmissions amongst patients who were prescribed AC at discharge and those who were not. No stage I patients developed PEs and no stage I patients were prescribed AC. The ARR for AC prophylaxis for development of PE was found to be 0.023 for the clinical stage II and stage III cohorts. The NNT to prevent a single PE with AC was 44 and 43 for the stage II and stage III cohorts, respectively. CONCLUSIONS: AC appears beneficial with minimal risk of harm after RPLND, especially in patients with higher risk of developing DVT/PE, highlighting the safety and efficacy of this regimen. There was a significant increase in the rate of AC prophylaxis at discharge amongst patients undergoing RPLND in the institutional database from 2013 to 2022. A risk-stratified protocol of postoperative AC following RPLND appears reasonable, and further prospective trials are warranted to formally confirm this recommendation.

The national utilization of nonoperative management for small renal masses over 10 years.

BACKGROUND: Management of small renal masses often involves a nonoperative approach, but there is a paucity of information about the use and associated predictors of such approaches. This study aimed to determine the trends in and predictors of use of nonoperative management of small renal masses. METHODS: Using data from the National Cancer Database for localized small renal masses (N0/M0, cT1a) diagnosed between 2010 and 2020, we conducted a cross-sectional study. Nonoperative management was defined as expectant management (active surveillance or watchful waiting) or focal ablation. Adjusted odds ratios (AORs) were calculated using multivariable logistic regression models. RESULTS: Of the 156 734 patients included, 10.5% underwent expectant management, and 13.9% underwent focal ablation. Later year of diagnosis was associated with a higher likelihood of nonoperative management. In 2020, the odds of receiving expectant management and focal ablation were 90% (AOR = 1.90, 95% confidence interval [CI] = 1.71 to 2.11) and 44% (AOR = 1.44, 95% CI = 1.31 to 1.57) higher, respectively, than in 2010. Black patients had increased odds of expectant management (AOR = 1.47, 95% CI = 1.39 to 1.55) but decreased odds of focal ablation (AOR = 0.93, 95% CI = 0.88 to 0.99). CONCLUSION: Over the decade, the use nonoperative management of small renal masses increased, with expectant management more frequently used than focal ablation among Black patients. Possible explanations include race-based differences in physicians' risk assessments and resource allocation. Adjusting for Black race in calculations for glomerular filtration rate could influence the differential uptake of these techniques through deflated glomerular filtration rate calculations. These findings highlight the need for research and policies to ensure equitable use of less invasive treatments in small renal masses.

Outcomes of Consolidative Nephrectomy following Primary Immunotherapy in Advanced Renal Cell Carcinoma: A Multicenter Analysis.

BACKGROUND: To evaluate effect and outcomes of combination primary immunotherapy (IO) and nephrectomy for advanced renal cell carcinoma (RCC). METHODS: We conducted a multicenter, retrospective analysis of patients with advanced/metastatic RCC who received IO followed by nephrectomy. Primary outcome was Bifecta (negative surgical margins and no 30-day surgical complications). Secondary outcomes included progression-free survival (PFS) following surgery, reduction in tumor/thrombus size, RENAL score, and clinical/pathologic downstaging. Cox regression multivariable analysis was conducted for predictors of Bifecta and PFS. Kaplan-Meier analysis assessed PFS, comparing Bifecta and non-Bifecta groups. RESULTS: A total of 56 patients were analyzed (median age 63 years; median follow-up 22.5 months). A total of 40 (71.4%) patients were intermediate IMDC risk. Patients were treated with immunotherapy for median duration of 8.1 months. Immunotherapy resulted in reductions in tumor size (P < .001), thrombus size (P = .02), and RENAL score (P < .001); 38 (67.9%) patients were clinically downstaged on imaging (P < .001) and 25 (44.6%) patients were pathologically downstaged following surgery (P < .001). Bifecta was achieved in 38 (67.9%) patients. Predictors for bifecta achievement included decreasing tumor size (HR 1.08, P = .043) and pathological downstaging (HR 2.13, P = .047). Bifecta (HR 5.65, P = .009), pathologic downstaging (HR 5.15, P = .02), and increasing reduction in tumor size (HR 1.2, P = .007) were associated with improved PFS. Bifecta patients demonstrated improved 2-year PFS (84% vs. 71%, P = .019). CONCLUSIONS: Primary immunotherapy reduced tumor/thrombus size and complexity. Pathologically downstaged patients were more likely to achieve bifecta, and these patients displayed improved 2-year PFS. Our study supports further inquiry in the use of CRN following primary immunotherapy for advanced renal cancer.

Institutional trends and safety profile of same-day discharge for robot-assisted laparoscopic radical prostatectomy: A retrospective analysis.

PURPOSE: To report the trends, predictors, and patient outcomes of same-day discharge (SDD) versus non-SDD for robot-assisted laparoscopic radical prostatectomy (RALP). MATERIALS AND METHODS: We queried our centralized data warehouse to identify men with prostate cancer who underwent RALP between January 2020 and May 2022. Patient demographics and clinical characteristics were compared between SDD and non-SDD. Then, we examined the utilization of SDD in a univariable logistic regression. Then, we fitted a logistic regression model to identify the predictors of SDD. To examine the safety profile of SDD, an inverse probability of treatment weighting (IPTW) adjusted logistic regression was fitted to examine the effect of SDD on 30-day postoperative complications and readmissions. RESULTS: Overall, 1,153 patients underwent RALP, of which 224 (19.4%) were SDD. The proportion of SDD increased from 4.4% in the fourth quarter of 2020 to 45% in the second quarter of 2022 (p < 0.01). The predictors of SDD were the facility where the surgery was performed (OR: 1.57; 95%CI [1.08-2.28]; p = 0.02) and whether a high-volume surgeon performed it (OR: 1.96; 95%CI [1.09-3.54]; p = 0.03). After IPTW, SDD compared to non-SDD was not associated with a difference in complications (OR: 1.07; 95%CI [0.38-2.95]; p = 0.90) or readmissions (OR: 1.22; 95%CI [0.40-3.74]; p = 0.72). CONCLUSION: In our health system, the use of SDD is safe and currently composes of half of our RALP volume. With the advent of the hospital-at-home services, we anticipate that almost all our RALP cases will be SDD.

The Promise of Neoadjuvant and Adjuvant Therapies for Renal Cancer.

Because metachronous metastatic disease will develop in 20% to 40% of patients with presumed localized renal cell carcinoma (RCC) treated surgically, research is focused on neoadjuvant and adjuvant systemic therapy, to improve disease-free and overall survival. Neoadjuvant therapies trialed include anti-vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) agents, or combination therapies (immunotherapy with TKI), and aim to improve resectability of locoregional RCC. Adjuvant therapies trialed include cytokines, anti-VEGF TKI agents, or immunotherapy. These therapeutics can facilitate the surgical extirpation of the primary kidney tumor in the neoadjuvant setting and improve disease-free survival in the adjuvant setting.

Reliability and Management Outcomes Following a Percutaneous Biopsy Diagnosis of Oncocytoma: A 15-year Retrospective Analysis.

Background There is uncertainty in the management of renal masses diagnosed as oncocytomas with image-guided percutaneous biopsy. Purpose To assess the reliability of a diagnosis of oncocytoma based on image-guided percutaneous renal mass biopsy and evaluate patient outcomes following different management strategies. Materials and Methods In this retrospective study, image-guided percutaneous biopsy pathology reports from April 2004 to April 2019 were searched for keywords "oncocytoma" and "oncocytic neoplasm" and compared with surgical pathology or repeat biopsy results. Patients with at least 12 months of clinical follow-up and known cause of death were grouped according to management strategies, and disease-specific survival and metastatic renal cell carcinoma (RCC)-free survival were compared. Mass growth rates were calculated with use of a normal linear mixed model. Results The database yielded 160 biopsy reports of 149 renal masses in 139 patients; 149 masses were categorized as oncocytoma (n = 107), likely oncocytoma (n = 12), oncocytic neoplasm (n = 28), and indeterminate with oncocytoma in differential (n = 2). Biopsied masses categorized as oncocytoma or likely oncocytoma were oncocytomas in 16 of 17 masses (94%) based on surgical pathology or repeat biopsy; four of eight masses (50%) categorized as oncocytic neoplasms were low-grade RCCs. Outcome analysis included 121 patients (mean age ± SD, 68 years ± 9.1; 82 men); 80 patients initially underwent active surveillance (11 were later treated), 33 underwent ablation, and eight underwent surgery. Disease-specific survival and metastatic-free survival were 100% after each management strategy (median follow-up, 86.6 months; range, 14.2-207.9 months). Mass growth rate (mean, 1.7 mm per year) showed no evidence of a significant difference among biopsy result categories (P = .37) or initial (P = .84) or final management strategies (P = .11). Conclusion Image-guided percutaneous biopsy diagnosis of renal oncocytoma was reliable. Although some masses diagnosed as oncocytic neoplasms were low-grade renal cell carcinomas (RCCs) at final diagnosis, no patients died of RCC, including those managed with active surveillance. © RSNA, 2023 See also the editorial by Lockhart in this issue.

Promoting the use of the PI-QUAL score for prostate MRI quality: results from the ESOR Nicholas Gourtsoyiannis teaching fellowship.

OBJECTIVES: The Prostate Imaging Quality (PI-QUAL) score is a new metric to evaluate the diagnostic quality of multiparametric magnetic resonance imaging (MRI) of the prostate. This study assesses the impact of an intervention, namely a prostate MRI quality training lecture, on the participant's ability to apply PI-QUAL. METHODS: Sixteen participants (radiologists, urologists, physicists, and computer scientists) of varying experience in reviewing diagnostic prostate MRI all assessed the image quality of ten examinations from different vendors and machines. Then, they attended a dedicated lecture followed by a hands-on workshop on MRI quality assessment using the PI-QUAL score. Five scans assessed by the participants were evaluated in the workshop using the PI-QUAL score for teaching purposes. After the course, the same participants evaluated the image quality of a new set of ten scans applying the PI-QUAL score. Results were assessed using receiver operating characteristic analysis. The reference standard was the PI-QUAL score assessed by one of the developers of PI-QUAL. RESULTS: There was a significant improvement in average area under the curve for the evaluation of image quality from baseline (0.59 [95 % confidence intervals: 0.50-0.66]) to post-teaching (0.96 [0.92-0.98]), an improvement of 0.37 [0.21-0.41] (p < 0.001). CONCLUSIONS: A teaching course (dedicated lecture + hands-on workshop) on PI-QUAL significantly improved the application of this scoring system to assess the quality of prostate MRI examinations. KEY POINTS: • A significant improvement in the application of PI-QUAL for the assessment of prostate MR image quality was observed after an educational intervention. • Appropriate training on image quality can be delivered to those involved in the acquisition and interpretation of prostate MRI. • Further investigation will be needed to understand the impact on improving the acquisition of high-quality diagnostic prostate MR examinations.

Comparison of Long-term Outcomes for Young and Healthy Patients with cT1a and cT3a Renal Cell Carcinoma Treated with Partial Nephrectomy.

Partial nephrectomy (PN) is recommended for renal cell carcinoma (RCC) of <4 cm. We hypothesized that there is no difference in all-cause mortality (ACM) between cT1a, cT1b, and cT3a <4 cm RCC following PN. The National Cancer Database was interrogated to identify patients aged <60 yr with a Charlson comorbidity index ≤1 diagnosed between 2004 and 2017. Cox proportional-hazard models stratified for cT stage were used to predict 10-yr ACM. A total of 30 195 patients (25 121 cT1a, 4884 cT1b, and 190 cT3a <4 cm) who underwent PN with median follow-up of 64.36 mo (interquartile range 42.91-93.77) were included. Cox analysis revealed no significant difference in 10-yr ACM between cT1a and cT3a <4 cm (hazard ratio [HR] 1.05, 95% confidence interval [CI] 0.58-1.90; p = 0.88). However, the cT1b group had higher ACM (HR 1.31, 95% CI 1.15-1.48; p < 0.01). The positive surgical margin (PSM) rate was higher for cT3a <4 cm than for cT1a tumors (14.2% vs 6.3%; p < 0.01). However, there was no difference in 10-yr ACM rate between cT1a and cT3a <4 cm (10.9% vs 9.7%; p = 0.42). Our results suggest that PN is an option for cT3a RCC <4 cm, particularly in cases in which maximum nephron preservation is essential, such as patients with chronic kidney disease or a solitary kidney, although a higher PSM risk should be appreciated. PATIENT SUMMARY: We found that partial removal of the kidney for localized advanced kidney cancer is safe. The rate of surgical margins positive for the presence of tumor is higher in localized advanced kidney cancer than for less advanced cancers, but there was no difference in 10-year predicted mortality.

The Natural History of Renal-Cell Carcinoma with Sarcomatoid Differentiation, a Stage-by-Stage Analysis.

BACKGROUND: Sarcomatoid differentiation in patients diagnosed with renal cell carcinoma (sRCC) imply aggressive behavior and often metastatic disease at the time of diagnosis. We aim to examine the overall survival (OS) in patients with sRCC using the National Cancer Database (NCDB). MATERIALS AND METHODS: We identified patients diagnosed with sRCC between 2010-2015. We employed Kaplan-Meier curves and multivariable Cox proportional hazards regression models to examine the impact of several potential risk factors on OS in patients diagnosed with sRCC. RESULTS: In total, 8582 patients with renal cancer were found to have sarcomatoid differentiation, with 4105 patients (47.8%) being diagnosed with AJCC stage IV disease. The median OS was 17.2 months (IQR 5.4, 68.7 months). Compared to patients who did not undergo surgery, OS was significantly longer in patients undergoing partial or total nephrectomy across all stages. This result remained consistent on multivariable Cox proportional hazards regression adjusting for patient and tumor characteristics (Surgery: Hazard ratio 0.54, 95%Confidence interval 0.43 - 0.68, P < .001). CONCLUSION: In our cohort sRCC was found to have an unfavorable median OS, which was mainly caused by the high number of cases diagnosed with late-stage disease. Additionally, surgery was associated with favorable OS across all stages. This study supports the notion that surgical therapy, even in the setting of cytoreductive surgery, provides a survival benefit in patients with sRCC.

Preoperative anemia is associated with increased radical cystectomy complications.

PURPOSE: The impact of anemia in postoperative complications following radical cystectomy (RC) is not completely elucidated and its association with direct hospital costs has not been characterized in depth. Our goal is to determine the association between anemia, 90-day surgical complications and the expenditure attributed to preoperative anemia in patients undergoing RC. MATERIALS AND METHODS: We captured all patients who underwent RC between 2003 and 2017 using the Premier Hospital Database (Premier Inc, Charlotte, NC). Patient, hospital and surgical characteristics were evaluated. Anemia was defined by a corresponding diagnostic code that was present on admission prior to RC. Unadjusted patients' demographic characteristics with and without anemia, hospital and surgeon characteristics were compared, and multivariable regression models were developed to evaluate 90-day complications and total direct hospital costs. RESULTS: The cohort included 83,470 patients that underwent RC between 2003 and 2017 and 11% were found to be anemic. On multivariable analysis, preoperative anemia more than doubled the odds of having a complication (odds ratio 2.19 (1.89-2.53)) and significantly increased the risk of major complications (odds ratio 1.51 (1.31-1.75)) at 90-days after RC. Anemic patients had significantly higher 90-days total direct costs due to higher laboratory, pharmacologic, radiology and operating room costs. CONCLUSIONS: Anemic cystectomy patients face a 50% increase in the risk of major complications within the first 90-days after surgery. This increased risk persisted after adjusting for patient, hospital and surgical factors. Our study suggests hematocrit level prior to RC may be used as a pre-exisitng condition for increased risk of surgical complications.

The Impact of Venous Thromboembolism on Mortality and Morbidity During Nephrectomy for Renal Mass.

OBJECTIVE: To determine the morbidity, mortality, and costs associated with having concurrent venous thromboembolism (VTE) at the time of surgical resection of a renal mass. PATIENTS AND METHODS: We identified 108,430 patients undergoing elective partial or radical nephrectomy for a renal mass from 2013 to 2017 using the Premier Healthcare database. The association of VTE with 90-day complication rates, mortality, ICU admission, readmission, and direct hospital costs (2019 US dollars) was determined with multivariable logistic regression and quantile regression models, respectively. RESULTS: Of the 108,430 patients who underwent elective partial or radical nephrectomy, 1.2% (n = 1301) of patients were diagnosed with a preoperative VTE. Patients with preoperative VTE have higher rates of minor (odds ratio [OR] 1.47, 95% confidence inteval [CI] 1.34-1.62, P < .0001) and major complications (OR 2.53, 95% CI 2.23-2.86, P < .0001), mortality (OR 2.03, 95% CI 1.6-2.57, P < .0001), and readmissions (OR 1.73, 95% CI 1.57-1.90, P < .0001) compared to patients without preoperative VTE at the time of nephrectomy. Notably, the predicted probability for a major complication was significantly higher among patients with preoperative VTE who underwent either partial or radical nephrectomy, irrespective of the surgical approach utilized. Furthermore, rates of all types of complications except endocrine and soft tissue were significantly increased in patients undergoing nephrectomy with preoperative VTE compared to those without VTE. CONCLUSION: VTE at the time of nephrectomy is associated with significantly higher rates of major complications, increased mortality, and higher overall costs. Taken together, these findings have important implications for the counseling and management of renal masses in presence of VTE.

Obesity in Relation to Renal Cell Carcinoma Incidence and Survival in Three Prospective Studies.

To disentangle the "obesity paradox" in renal cell carcinoma (RCC), we examined associations of body mass index (BMI) and weight change with RCC risk and survival in the Health Professionals Follow-up Study (HPFS) and Nurses' Health Study (NHS) 1 and 2. We estimated cohort-specific and summary covariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for RCC incidence, as well as RCC-specific survival among cases in the pooled HPFS and NHS data. Cumulative average BMI was associated with a higher risk of total RCC (summary HR 2.16, 95% CI 1.77-2.63 for BMI ≥30 vs 18-<25 kg/m2; p trend <0.001) and fatal RCC (HR 2.03, 95% CI 1.37-3.01; p trend <0.001). Prediagnosis BMI was not associated with RCC death. However, first postdiagnosis BMI (HR 0.51, 95% CI 0.29-0.89; p trend 0.006) and prediagnosis to postdiagnosis weight change (HR 0.52, 95% CI 0.29-0.91; p trend 0.001) were significantly inversely associated with RCC death. These results support obesity as a risk factor for total and fatal RCC. They undermine the obesity paradox by suggesting that weight loss around diagnosis, and not low BMI itself, is associated with worse prognosis. PATIENT SUMMARY: We studied obesity in kidney cancer and found that obesity is associated with getting and dying from the disease. Body mass index at diagnosis is not an ideal factor for predicting prognosis, as patients who have lost weight are likely to have more aggressive cancer.

Integrative clinical and molecular characterization of translocation renal cell carcinoma.

Translocation renal cell carcinoma (tRCC) is a poorly characterized subtype of kidney cancer driven by MiT/TFE gene fusions. Here, we define the landmarks of tRCC through an integrative analysis of 152 patients with tRCC identified across genomic, clinical trial, and retrospective cohorts. Most tRCCs harbor few somatic alterations apart from MiT/TFE fusions and homozygous deletions at chromosome 9p21.3 (19.2% of cases). Transcriptionally, tRCCs display a heightened NRF2-driven antioxidant response that is associated with resistance to targeted therapies. Consistently, we find that outcomes for patients with tRCC treated with vascular endothelial growth factor receptor inhibitors (VEGFR-TKIs) are worse than those treated with immune checkpoint inhibitors (ICI). Using multiparametric immunofluorescence, we find that the tumors are infiltrated with CD8+ T cells, though the T cells harbor an exhaustion immunophenotype distinct from that of clear cell RCC. Our findings comprehensively define the clinical and molecular features of tRCC and may inspire new therapeutic hypotheses.

Robotic-assisted radical cystectomy is associated with lower perioperative mortality in octogenarians.

OBJECTIVES: To compare perioperative outcomes between robotic and open radical cystectomy in octogenarians using real-world data SUBJECTS AND METHODS: Using the Premier Healthcare Database, we found 13,127 patients who underwent robotic-assisted radical cystectomy (RARC) between 2008 and 2017, of which 15.1% were ≥80 years old. Perioperative mortality was the primary outcome of interest. Secondary outcomes include complications, hospital length of stay, readmission rates, and disposition after discharge. Multivariable regression analysis was used to adjust for patient and hospital characteristics. RESULTS: In octogenarians, mortality at the index admission was 2.2% in those who underwent RARC, compared to 4.6% in those who underwent open surgery (P = 0.027). On multivariable analysis, robotic surgery was associated with lower in-hospital mortality in octogenarians (OR 0.46, 95% CI 0.22-0.99, P = 0.047) even after controlling for patient, and hospital characteristics. CONCLUSION: RARC is safe and feasible in octogenarians. Elderly patients may derive more benefit from minimally invasive radical cystectomy compared to a younger cohort.

Determining Variable Costs in the Acute Urolithiasis Cycle of Care Through Time-Driven Activity-Based Costing.

OBJECTIVE: To characterize full cycle of care costs for managing an acute ureteral stone using time-driven activity-based costing. METHODS: We defined all phases of care for patients presenting with an acute ureteral stone and built an overarching process map. Maps for sub-processes were constructed through interviews with providers and direct observation of clinical spaces. This facilitated calculation of cost per minute for all aspects of care delivery, which were multiplied by associated process times. These were added to consumable costs to determine cost for each specific step and later aggregated to determine total cost for each sub-process. We compared costs of eight common clinical pathways for acute stone management, defining total cycle of care cost as the sum of all sub-processes that comprised each pathway. RESULTS: Cost per sub-process included $920 for emergency department (ED) care, $1665 for operative stent placement, $2368 for percutaneous nephrostomy tube placement, $106 for urology clinic consultation, $238 for preoperative center visit, $4057 for ureteroscopy with laser lithotripsy (URS), $2923 for extracorporeal shock wave lithotripsy, $169 for clinic stent removal, $197 for abdominal x-ray, and $166 for ultrasound. The lowest cost pathway ($1388) was for medical expulsive therapy, whereas the most expensive pathway ($8002) entailed a repeat ED visit prompting temporizing stent placement and interval URS. CONCLUSION: We found a high degree of cost variation between care pathways common to management of acute ureteral stone episodes. Reliable cost accounting data and an understanding of variability in clinical pathway costs can inform value-based care redesign as payors move away from pure fee-for-service reimbursement.