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Background Postoperative renal function impairment represents a main limitation for delivering adjuvant chemotherapy after radical nephroureterectomy (RNU). Objective To create a model predicting renal function decline after minimally invasive RNU. Design, setting, and participants A total of 490 patients with nonmetastatic UTUC who underwent minimally invasive RNU were identified from a collaborative database including 17 institutions worldwide (February 2006 to March 2020). Renal function insufficiency for cisplatin-based regimen was defined as estimated glomerular filtration rate (eGFR) 50 ml/min/1.73 m2 (n = 361) were geographically divided into a training set (n = 226) and an independent external validation set (n = 135) for further analysis. Outcome measurements and statistical analysis Using transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) guidelines, a nomogram to predict postoperative eGFR Results and limitations The model that incorporated age, body mass index, preoperative eGFR, and hydroureteronephrosis was developed with an area under the curve of 0.771, which was confirmed to be 0.773 in the external validation set. The calibration curve demonstrated good agreement. Besides, the model was converted into a risk score with a cutoff value of 0.583, and the difference between the low- and high-risk groups both in overall death risk (hazard ratio [HR]: 4.59, p Conclusions A nomogram incorporating immediately available clinical variables can accurately predict renal insufficiency for cisplatin-based adjuvant chemotherapy after minimally invasive RNU and may serve as a tool facilitating patient selection. Patient summary We have developed a model for the prediction of renal function loss after radical nephroureterectomy to facilitate patient selection for perioperative chemotherapy.

Introduction:The COVID-19 pandemic starkly affected all aspects of health care, forcing many to divert resources towards emergent patient needs while decreasing emphasis on routine cancer c...

OBJECTIVES To study the effects of adjuvant therapy in patients with sarcomatoid renal cell carcinoma (sRCC) enrolled in the randomised phase III clinical trial E2805. PATIENTS AND METHODS The original trial (E2805) was a randomised, double-blinded phase III clinical trial comparing outcomes in 1943 patients with RCC accrued between 2006 and 2010 and treated with up to 1 year of adjuvant placebo, sunitinib, or sorafenib. The present study analyses the cohort of patients with sRCC that participated in E2805. RESULTS A total of 171 patients (8.8%) had sarcomatoid features. Of these, 52 patients received sunitinib, 58 received sorafenib, and 61 received placebo. Most patients were pT3-4 (71.1%, 63.7%, and 70.5%, respectively); 17.3%, 19.0%, and 27.9% had pathologically positive lymph nodes; and 59.6%, 62.1%, and 62.3% of the patients were University of California Los Angeles (UCLA) Integrated Staging System (UISS) very-high risk. In 49% of patients with subsequent development of metastatic disease, recurrence occurred in the lung, followed by 30% in the lymph nodes, and 13% in the liver. There was a high local recurrence rate in the renal bed (16%, 29%, and 18%, respectively). The 5-year disease-free survival (DFS) rates were 33.6%, 36.0%, and 27.8%, for sunitinib, sorafenib and placebo, respectively (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.45-1.20 for sunitinib vs placebo, and HR 0.82, 95% CI 0.53-1.28 for sorafenib vs placebo). CONCLUSIONS Adjuvant therapy with sunitinib or sorafenib did not show an improvement in DFS or OS in patients with sRCC.

To use data from a large, prospectively- acquired regional collaborative database to compare the risk of infectious complications associated with three American Urologic Association- recommended antibiotic prophylaxis pathways, including culture-directed or augmented antibiotics, following prostate biopsy.Data on prostate biopsies and outcomes were collected from the Pennsylvania Urologic Regional Collaborative, a regional quality collaborative working to improve the diagnosis and treatment of prostate cancer. Patients were categorized as receiving one of three prophylaxis pathways: culture-directed, augmented, or provider-discretion. Infectious complications included fever, urinary tract infections or sepsis within one month of biopsy. Odds ratios of infectious complication by pathway were determined, and univariate and multivariate analyses of patient and biopsy characteristics were performed.11,940 biopsies were included, 120 of which resulted in infectious outcomes. Of the total biopsies, 3246 used "culture-directed", 1446 used "augmented" and 7207 used "provider-discretion" prophylaxis. Compared to provider-discretion, the culture-directed pathway had 84% less chance of any infectious outcome (OR= 0.159, 95% CI = [0.074, 0.344], P0.001). There was no difference in infectious complications between augmented and provider-discretion pathways.The culture-directed pathway for transrectal prostate biopsy resulted in significantly fewer infectious complications compared to other prophylaxis strategies. Tailoring antibiotics addresses antibiotic-resistant bacteria and reduces future risk of resistance. These findings make a strong case for incorporating culture-directed antibiotic prophylaxis into clinical practice guidelines to reduce infection following prostate biopsies.

Intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) has an incidence of approximately 20%-50%. Studies to date have been composed of mixed treatment cohorts-open, laparoscopic and robotic. The objective of this study is to assess clinicopathological risk factors for intravesical recurrence after RNU for UTUC in a completely minimally invasive cohort.We performed a multicenter, retrospective analysis of 485 patients with UTUC without prior or concurrent bladder cancer who underwent robotic or laparoscopic RNU. Patients were selected from an international cohort of 17 institutions across the United States, Europe and Asia. Univariate and multiple Cox regression models were used to identify risk factors for bladder recurrence.A total of 485 (396 robotic, 89 laparoscopic) patients were included in analysis. Overall, 110 (22.7%) of patients developed IVR. The average time to recurrence was 15.2 months (SD 15.5 months). Hypertension was a significant risk factor on multiple regression (HR 1.99, CI 1.06; 3.71, p=0.030). Diagnostic ureteroscopic biopsy incurred a 50% higher chance of developing IVR (HR 1.49, CI 1.00; 2.20, p=0.048). Treatment specific risk factors included positive surgical margins (HR 3.36, CI 1.36; 8.33, p=0.009) and transurethral resection for bladder cuff management (HR 2.73, CI 1.10; 6.76, p=0.031).IVR after minimally invasive RNU for UTUC is a relatively common event. Risk factors include a ureteroscopic biopsy, transurethral resection of the bladder cuff, and positive surgical margins. When possible, avoidance of transurethral resection of the bladder cuff and alternative strategies for obtaining biopsy tissue sample should be considered.

Papillary renal neoplasm with reverse polarity (PRNRP) is a newly proposed entity with distinct histology and frequent KRAS mutations. To date, 93 cases of PRNRPs have been reported. In this study, we present 7 new cases of PRNRP and review the literature. Most of the pathologic features in our 7 cases are similar to those previously reported cases. However, all 7 of our cases showed at least partial cystic changes, which was not stressed in prior studies. Single-nucleotide polymorphism-microarray based chromosomal analysis demonstrated no trisomy or other alteration of chromosomes 7 or 17; and no loss or other alteration of chromosome Y was detected in all 7 cases. Next-generation sequencing detected KRAS missense mutations in 4 of 7 cases. No fusion genes were detected. In summary, PRNRP is a small, well-circumscribed often encapsulated and cystic neoplasm with loose papillary formations. Cuboidal tumor cells always have eosinophilic cytoplasm and nuclei located at the pole opposite the basement membrane with a low World Health Organization (WHO)/International Society of Urologic Pathologists (ISUP) nuclear grade. The fibrovascular cores can be hyalinized or edematous. Macrophage aggregates and intracellular hemosiderin are uncommon, and no psammoma bodies or necrosis should be seen. Immunophenotypically, this tumor is always positive for CK7 and GATA3, and negative for CD117 and vimentin. CD10 and AMACR can be positive, but often weakly and focally. PRNRP often has KRAS mutations, however, only 32% of cases have chromosomal abnormalities in chromosomes 7, 17, and Y. No recurrences, metastases, or tumor-related deaths have been reported following complete resection.

This AUA Guideline focuses on evaluation/counseling/management of adult patients with clinically-localized renal masses suspicious for cancer, including solid-enhancing tumors and Bosniak 3/4 complex-cystic lesions.The Renal Mass and Localized Renal Cancer guideline underwent an update literature review which resulted in the 2021 amendment. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text]).Great progress has been made regarding the evaluation/management of clinically-localized renal masses. These guidelines provide updated, evidence-based recommendations regarding evaluation/counseling including the evolving role of renal-mass-biopsy (RMB). Given great variability of clinical/oncologic/functional characteristics, index patients are not utilized and the panel advocates individualized counseling/management. Options for intervention (partial-nephrectomy (PN), radical-nephrectomy (RN), and thermal-ablation (TA)) are reviewed including recent data about comparative-effectiveness/potential morbidities. Oncologic issues are prioritized while recognizing the importance of functional-outcomes for survivorship. Granular criteria for RN are provided to help reduce overutilization of RN while also avoiding imprudent PN. Priority for PN is recommended for clinical T1a lesions, along with selective utilization of TA, which has good efficacy for tumors≤3.0 cm. Recommendations for genetic-counseling have been revised and considerations for adjuvant-therapies are addressed. Active-surveillance and follow-up after intervention are discussed in an adjunctive article.Several factors require consideration during counseling/management of patients with clinically-localized renal masses including general health/comorbidities, oncologic-considerations, functional-consequences, and relative efficacy/potential morbidities of various management-strategies.

To assess prescribing and refilling trends of narcotics in postoperative urology patients at our institution. Although the opioid epidemic remains a public health threat, no series has assessed prescribing patterns across urologic surgery disciplines following discharge.All urologic surgeries were retrospectively reviewed from May 2017-April 2018. Demographics, comorbidities, and postoperative pain management strategies were analyzed. Narcotics usage following surgery were reported in total morphine equivalents (TME). Opioid refill rate was characterized by medical specialty and stratified by urologic discipline.817 cases were reviewed. Mean age and TME at discharge was 57±15.6 years and 35.43±19.5 mg, respectively. 13.6% (mean age 55±15.9) received a narcotic refill following discharge (mean TME/refill 37.7±28.9 mg). A higher proportion of patients with a pre-operative opioid prescription received a refill compared to opioid naïve patients (38.2% vs 21.6%, P.01). Refill rate did not differ between urologic subspecialties (P = .3). Urologists were only responsible for 20.4% of all refills filled, despite all patients continuing follow-up with their surgeon. Procedures with the highest rates of post-operative refills were in oncology, male reconstruction/trauma and endourology. Patients with a history of chronic pain (OR 1.9, CI 1.1-3.3) preoperative narcotic prescription (OR 1.6, CI 1.0-2.6), and higher ASA score (OR 1.8, CI 1.6-2.8) were more likely to obtain a postoperative opioid prescription refill.Approximately 1 in 7 postoperative urology patients receive a postoperative narcotics refill; however, nearly two-thirds receive refills exclusively from non-urologic providers. Attempts to avoid overprescribing of postoperative narcotics need to account for both surgeon and nonsurgeon sources of opioid refills.

OBJECTIVES To determine whether patients with carcinoma invading bladder muscle (MIBC) and ureteric obstruction can safely receive cisplatin-based neoadjuvant chemotherapy (C-NAC), and to determine whether such patients require relief of obstruction with a ureteric stent or percutaneous nephrostomy prior to beginning C-NAC. PATIENTS AND METHODS We performed a single-institution retrospective analysis of MIBC patients receiving C-NAC and falling into three groups: no ureteric obstruction (NO); relieved ureteric obstruction (RO); and unrelieved ureteric obstruction (URO). To address whether patients with obstruction can safely receive C-NAC, we compared patients with NO to those with RO, with the primary outcome of premature chemotherapy discontinuation. To investigate whether patients with obstruction should have the obstruction relieved prior to NAC, we compared RO to URO patients using a primary composite outcome of grade ≥ 3 adverse events, premature chemotherapy discontinuation, dose reduction, or dose interruption. The primary outcomes were compared using multivariable logistic regression. Sensitivity analyses were performed for the RO vs URO comparison, in which patients with only mild degrees of obstruction were excluded from the URO group. RESULTS A total of 193 patients with NO, 49 with RO, and 35 with URO were analysed. There were no statistically significant differences between those with NO and those with RO in chemotherapy discontinuation (15% vs 22%; P = 0.3) or any secondary outcome. There was no statistically significant difference between those with RO and URO in the primary composite outcome (51% vs 53%; P = 1) or any secondary outcome. CONCLUSION Patients with ureteric obstruction can safely receive C-NAC. Relief of obstruction was not associated with increased safety of C-NAC delivery.

Purpose of review Artificial intelligence holds tremendous potential for disrupting clinical medicine. Here we review the current role of artificial intelligence in the kidney cancer space. Recent findings Machine learning and deep learning algorithms have been developed using information extracted from radiomic, histopathologic, and genomic datasets of patients with renal masses. Summary Although artificial intelligence applications in medicine are still in their infancy, they already hold immediate promise to improve accuracy of renal mass characterization, grade, and prognostication. As algorithms become more robust and generalizable, artificial intelligence is poised to significantly disrupt kidney cancer care.

OBJECTIVE To evaluate existing practice patterns and potential barriers to implementing opioid stewardship protocols after robot-assisted prostatectomies among providers in the Pennsylvania Urology Regional Collaborative. METHODS The Pennsylvania Urology Regional Collaborative (PURC) is a voluntary quality improvement initiative of 11 academic and community urology practices in Pennsylvania and New Jersey representing 97 urologists. PURC distributed a web-based survey of 24 questions, with 74 respondents, including 56 attendings, 11 residents, and 7 advanced practice providers. RESULTS More pills were prescribed if there was a default number of pills from the electronic health record (median 30) then if the number of pills was manually placed (P = .01). Only 8% discussed how to dispose of opioids with their patients, and less than a third of respondents discussed postoperative pain expectations or risks of opioid use. Patient level risk factors were often not reviewed, as 42% did not ask about previous opioid exposure. CONCLUSION This study revealed extensive knowledge disparities among providers about opioid stewardship and significant gaps in the evidence-to-practice continuum of care. In the next year, PURC will be implementing targeted interventions to augment provider education, establish clear pathways for opioid disposal, improve utilization of known resources and implement opioid reduction protocols in all participating sites.

Background Radical nephroureterectomy (RNU) represents the standard of care for high grade upper tract urothelial carcinoma (UTUC). Open and laparoscopic approaches are well-established treatments, but evidence regarding robotic RANU is growing. The introduction of the Xi® system facilitates the implementation of this multi-quadrant procedure. The aim of this video-article is to describe the surgical steps and the outcomes of Xi® robotic RNU. Methods Single stage Xi® robotic RNU without patients repositioning and robot re-docking were done between 2015 and 2019 and collected in a large worldwide multi-institutional study, the ROBotic surgery for Upper tract Urothelial cancer STudy (ROBUUST). Institutional review board approval and data share agreement were obtained at each center. Surgical technique is described in detail in the accompanying video. Descriptive statistics of baseline characteristics and surgical, pathological, and oncological outcomes were analyzed. RESULTSː Overall, 148 patients were included in the analysis; 14% had an ECOG >1 and 68.2% ASA ≥3. Median tumor dimension was 3.0 (IQR:2.0-4.2) cm and 34.5% showed hydronephrosis at diagnosis. Forty-eight% were cT1 tumors. Bladder cuff excision and lymph node dissection were performed in 96% and 38.1% of the procedures, respectively. Median operative time and estimated blood loss were 215.5 (IQR:160.5-290.0) minutes and 100.0 (IQR: 50.0-150.0) mL, respectively. Approximately 56% of patients took opioids during hospital stay for a total morphine equivalent dose of 22.9 (IQR:16.0-60.0) milligrams equivalent. Postoperative complications were 26 (17.7%), with 4 major (15.4%). Seven patients underwent adjuvant chemotherapy, with median number of cycles of 4.0 (IQR:3.0-6.0). Conclusions Single stage Xi® RNU is a reproducible and safe minimally invasive procedure for treatment of UTUC. Additional potential advantages of the robot might be a wider implementation of LND with a minimally invasive approach.

Background Multi-targeted tyrosine kinase inhibitors (TKIs) are the standard of care for patients with advanced clear cell renal cell carcinoma (ccRCC). However, a significant number of ccRCC patients are primarily refractory to targeted therapeutics, showing neither disease stabilisation nor clinical benefits. Methods We used CRISPR/Cas9-based high-throughput loss of function (LOF) screening to identify cellular factors involved in the resistance to sunitinib. Next, we validated druggable molecular factors that are synthetically lethal with sunitinib treatment using cell and animal models of ccRCC. Results Our screening identified farnesyltransferase among the top hits contributing to sunitinib resistance in ccRCC. Combined treatment with farnesyltransferase inhibitor lonafarnib potently augmented the anti-tumour efficacy of sunitinib both in vitro and in vivo. Conclusion CRISPR/Cas9 LOF screening presents a promising approach to identify and target cellular factors involved in the resistance to anti-cancer therapeutics.

Kidney cancer is one of the 10 most common cancers both in the United States and worldwide. Until this year, there had not previously been a conference focused on translational studies in the broad and heterogeneous group of kidney cancers. Therefore, a group of researchers, clinicians, and patient advocates dedicated to renal cell carcinoma launched the Kidney Cancer Research Summit (KCRS) to spur collaboration and further therapeutic advances in these tumors. This commentary aims to summarize the oral presentations and serve as a record for future iterations of this meeting. The KCRS sessions addressed the tumor microenvironment, novel methods of drug delivery, single cell sequencing strategies, novel immune checkpoint blockade and cellular therapies, predictive biomarkers, and rare variants of kidney cancers. In addition, the meeting included 2 sessions to promote scientific mentoring and kidney cancer research collaborations. A subsequent KCRS will be planned for the fall of 2020.

Introduction:Following transurethral resection of bladder tumor, patients can be discharged home, observed for 24 hours or admitted to the hospital. While disposition can impact care delive...

Context: Over the last decade, several nephrometry scores (NSs) have been introduced with the aim of facilitating preoperative decision making, planning, and counseling in the field of nephron-sparing surgery. However, their predictive role remains controversial. Objective: To describe currently available nephrometry scores and to determine their predictive role for different outcomes by performing a systematic review and meta-analysis of the literature. Evidence acquisition: PubMed, Embase®, and Web of Science were screened to identify eligible studies. Identification and selection of the reports were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). A pooled analysis of NS predictive role of intraoperative, postoperative, oncological, and functional outcomes was performed. Odds ratio was considered the effect size. All the analyses were performed using Stata 15.0, and statistical significance was set at p ≤ 0.05. Evidence synthesis: Overall, 51 studies meeting our inclusion criteria were identified and considered for the analysis. Except for one prospective randomized trial, all the studies were retrospective. All the studies were found to be of intermediate quality, except for one of high quality. Most studies assessed the predictive role of the Radius-Exophytic/Endophytic-Nearness-Anterior/Posterior-Location (RENAL) and Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) scores, mostly regarding complications after nephron-sparing surgery. RENAL was an independent predictor of an on-clamp procedure (p < 0.001). Mayo Adhesive Probability score was related to adhesive perinephric fat (p = 0.005). Continuous and high-complexity RENAL scores were predictors of warm ischemia time (WIT; p = 0.006 and p < 0.001, respectively). Continuous (p < 0.001) and high-complexity (p < 0.001) PADUA scores were related to WIT. Continuous and high-complexity RENAL scores were predictors of overall complications (p = 0.002 and p < 0.001, respectively). PADUA score was related to complications both as continuous (p < 0.001) and as a categorical value (p < 0.002). The RENAL scores R = 3 (p = 0.008), E = 2 (p = 0.039), and hilar location (p = 0.006) were predictors of histological malignancy. Continuous and categorical RENAL scores were independent predictors of an estimated glomerular filtration rate (eGFR) increase (p = 0.006 and p < 0.001, respectively). The Diameter-Axial-Polar score (p = 0.018) and Peritumoral Artery Scoring System (PASS; p = 0.02) were also independent predictors. Conclusions: The literature regarding nephrometry scoring systems is sparse, and mostly focused on RENAL and PADUA, which are easy to calculate and have a good correlation with most outcomes. Renal Pelvic Score is the best predictor of pelvicalyceal entry/repair and urine leak, whereas Surgical Approach Renal Ranking and PASS strongly predict surgical approach and renal function variation, respectively. Other nephrometry scores based on mathematical models are limited by their complexity, and they lack evidence supporting their predictive value. Patient summary: We reviewed the medical literature regarding the use and value of so-called “nephrometry scores,” which are scoring systems based on radiological imaging and made to grade the complexity of a renal tumor. We analyzed whether these scoring systems can predict some of the outcomes of patients undergoing surgical removal of renal tumors. The literature on nephrometry scoring systems is sparse, and it is mostly focused on the Radius-Exophytic/Endophytic-Nearness-Anterior/Posterior-Location (RENAL) and Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) scores. The results of this study can aid in further research effort in this field and foster the development of better predictive tools

Item does not contain fulltext INTRODUCTION: We aimed to compare the outcomes of open vs robotic partial nephrectomy (PN), focusing on predictors of Trifecta failure in patients with highly complex renal masses. PATIENTS AND METHODS: We queried the prospectively collected database from the SIB International Consortium, including 507 consecutive patients with cT1-2N0M0 renal masses treated at 16 high-volume referral centres, to select those with highly complex (PADUA score ≥10) tumors undergoing PN. RT was classified as enucleation, enucleoresection or resection according to the SIB score. Trifecta was defined as achievement of negative surgical margins, no acute kidney injury and no Clavien-Dindo grade ≥2 postoperative surgical complications. Multivariable logistic regression analysis was used to assess independent predictors of Trifecta failure. RESULTS: 113 patients were included. Patients undergoing open PN (n = 47, 41.6%) and robotic PN (n = 66, 58.4%) were comparable in baseline characteristics. RT was classified as enucleation, enucleoresection and resection in 46.9%, 34.0% and 19.1% of open PN, and in 50.0%, 40.9% and 9.1% of robotic PN (p = 0.28). Trifecta was achieved in significantly more patients after robotic PN (69.7% vs. 42.6%, p = 0.004). On multivariable analysis, surgical approach (open vs robotic, OR: 2.62; 95%CI: 1.11-6.15, p = 0.027) and tumor complexity (OR for each additional unit of the PADUA score: 2.27; 95%CI: 1.27-4.06, p = 0.006) were significant predictors of Trifecta failure, while RT was not. The study is limited by lack of randomization; as such, selection bias and confounding cannot be entirely ruled out. CONCLUSIONS: Tumor complexity and surgical approach were independent predictors of Trifecta failure after PN for highly complex renal masses.

INTRODUCTION AND OBJECTIVE:Magnetic resonance imaging (MRI) fusion needle biopsy has been shown to outperform systematic biopsy in detecting clinically significant prostate cancer. This study sough...

INTRODUCTION AND OBJECTIVE:Renal mass biopsy (RMB) has the potential to reduce unnecessary treatment by informing care, however, its utilization varies widely amongst providers and institutions. To...

INTRODUCTION AND OBJECTIVE:In efforts to judiciously utilize resources and contain cost, there has been increasing efforts to reduce postoperative length of stay, resulting in several groups promot...

INTRODUCTION AND OBJECTIVE:The management of patients with high risk non-muscle invasive urothelial carcinoma (UC) is complex due to the biological heterogeneity of the disease. The management of m...

INTRODUCTION AND OBJECTIVE:Minority communities disproportionately shouldered poor COVID-19 outcomes, however the impact of the pandemic on prostate cancer (PCa) surgery is unknown. To that end, we...

INTRODUCTION AND OBJECTIVE:Narcotics are prescribed excessively following surgery and may lead to persistent opioid use. As many urologic oncology procedures are performed minimally invasively, an ...

INTRODUCTION AND OBJECTIVE:Utility of lymph node dissection (LND) in localized upper tract urothelial carcinoma (UTUC) is controversial. We evaluated outcomes of LND in patients with UTUC using a m...

INTRODUCTION AND OBJECTIVE:Immune checkpoint inhibitors (ICI) are gaining acceptance in the management of metastatic renal cell carcinoma (mRCC) with four FDA approved regimens to date. However, da...

INTRODUCTION AND OBJECTIVE:The choice between active surveillance (AS) and surgical treatment for patients with newly diagnosed low risk malignancies is complex. To inform this nuanced decision, we...

Introduction:Bacillus Calmette-Guerin production is limited worldwide with stuttering shortages affecting patient access. Our institution received 50 vials of bacillus Calmette-Guerin label...

Importance: Early in the COVID-19 pandemic, racial/ethnic minority communities disproportionately experienced poor outcomes; however, the association of the pandemic with prostate cancer (PCa) care is unknown. Objective: To assess the association between race and PCa care delivery for Black and White patients during the first wave of the COVID-19 pandemic. Design, Setting, and Participants: This multicenter, regional, collaborative, retrospective cohort study compared prostatectomy rates between Black and White patients with untreated nonmetastatic PCa during the COVID-19 pandemic (269 patients from March 16 to May 15, 2020) and prior (378 patients from March 11 to May 10, 2019). Main Outcomes and Measures: Prostatectomy rates. Results: Of the 647 men with nonmetastatic PCa, 172 (26.6%) were non-Hispanic Black men, and 475 (73.4%) were non-Hispanic White men. Black men were significantly less likely to undergo prostatectomy during the pandemic compared with White patients (1 of 76 [1.3%] vs 50 of 193 [25.9%]; P < .001), despite similar COVID-19 risk factors, biopsy Gleason grade groups, and comparable prostatectomy rates prior to the pandemic (17 of 96 [17.7%] vs 54 of 282 [19.1%]; P = .75). Black men had higher median prostate-specific antigen levels prior to biopsy (8.8 ng/mL [interquartile range, 5.3-15.2 ng/mL] vs 7.2 ng/mL [interquartile range, 5.1-11.1 ng/mL]; P = .04). A linear combination of regression coefficients with an interaction term for year demonstrated an odds ratio for likelihood of surgery of 0.06 (95% CI, 0.01-0.35; P = .002) for Black patients and 1.41 (95% CI, 0.81-2.44; P = .23) for White patients during the pandemic compared with prior to the pandemic. Changes in surgical volume varied by site (from a 33% increase to complete shutdown), with sites that experienced the largest reduction in cancer surgery caring for a greater proportion of Black patients. Conclusions and Relevance: In this large multi-institutional regional collaborative cohort study, the odds of PCa surgery were lower among Black patients compared with White patients during the initial wave of the COVID-19 pandemic. Although localized PCa does not require immediate treatment, the lessons from this study suggest systemic inequities within health care and are likely applicable across medical specialties. Public health efforts are needed to fully recognize the unintended consequence of diversion of cancer resources to the COVID-19 pandemic to develop balanced mitigation strategies as viral rates continue to fluctuate.

Purpose: The use of VEGFR TKIs for the adjuvant treatment of renal cell carcinoma (RCC) remains controversial. We investigated the effects of adjuvant VEGFR TKIs on circulating cytokines in the ECOG-ACRIN 2805 (ASSURE) trial. Experimental Design: Patients with resected high-risk RCC were randomized to sunitinib, sorafenib, or placebo. Plasma from 413 patients was analyzed from post-nephrectomy baseline, 4 weeks, and 6 weeks after treatment initiation. Mixed effects and Cox proportional hazards models were used to test for changes in circulating cytokines and associations between disease-free survival (DFS) and cytokine levels. Results: VEGF and PlGF increased after 4 weeks on sunitinib or sorafenib (P < 0.0001 for both) and returned to baseline at 6 weeks on sunitinib (corresponding to the break in the sunitinib schedule) but not sorafenib (which was administered continuously). sFLT-1 decreased after 4 weeks on sunitinib and 6 weeks on sorafenib (P < 0.0001). sVEGFR-2 decreased after both 4 and 6 weeks of treatment on sunitinib or sorafenib (P < 0.0001). Patients receiving placebo had no significant changes in cytokine levels. CXCL10 was elevated at 4 and 6 weeks on sunitinib and sorafenib but not on placebo. Higher baseline CXCL10 was associated with worse DFS (HR 1.41 per log increase in CXCL10, Bonferroni-adjusted P = 0.003). This remained significant after adjustment for T-stage, Fuhrman grade, and ECOG performance status. Conclusions: Among patients treated with adjuvant VEGFR TKIs for RCC, drug–host interactions mediate changes in circulating cytokines. Elevated baseline CXCL10 was associated with worse DFS. Studies to understand functional consequences of these changes are under way.

PURPOSE To validate currently used recurrence prediction models for renal cell carcinoma (RCC) by using prospective data from the ASSURE (ECOG-ACRIN E2805; Adjuvant Sorafenib or Sunitinib for Unfavorable Renal Carcinoma) adjuvant trial. PATIENTS AND METHODS Eight RCC recurrence models (University of California at Los Angeles Integrated Staging System [UISS]; Stage, Size, Grade, and Necrosis [SSIGN]; Leibovich; Kattan; Memorial Sloan Kettering Cancer Center [MSKCC]; Yaycioglu; Karakiewicz; and Cindolo) were selected on the basis of their use in clinical practice and clinical trial designs. These models along with the TNM staging system were validated using 1,647 patients with resected localized high-grade or locally advanced disease (≥ pT1b grade 3 and 4/pTanyN1Mo) from the ASSURE cohort. The predictive performance of the model was quantified by assessing its discriminatory and calibration abilities. RESULTS Prospective validation of predictive and prognostic models for localized RCC showed a substantial decrease in each of the predictive abilities of the model compared with their original and externally validated discriminatory estimates. Among the models, the SSIGN score performed best (0.688; 95% CI, 0.686 to 0.689), and the UISS model performed worst (0.556; 95% CI, 0.555 to 0.557). Compared with the 2002 TNM staging system (C-index, 0.60), most models only marginally outperformed standard staging. Importantly, all models, including TNM, demonstrated statistically significant variability in their predictive ability over time and were most useful within the first 2 years after diagnosis. CONCLUSION In RCC, as in many other solid malignancies, clinicians rely on retrospective prediction tools to guide patient care and clinical trial selection and largely overestimate their predictive abilities. We used prospective collected adjuvant trial data to validate existing RCC prediction models and demonstrate a sharp decrease in the predictive ability of all models compared with their previous retrospective validations. Accordingly, we recommend prospective validation of any predictive model before implementing it into clinical practice and clinical trial design.

Objectives To develop a clinically applicable predictive model to quantitate the risk of estimated glomerular filtration rate (eGFR) decline to ≤45 mL/min/1.73 m2 after radical nephrectomy (RN) to better inform decisions between RN and partial nephrectomy (PN). Patients and methods Our prospectively maintained kidney cancer registry was reviewed for patients with a preoperative eGFR >60 mL/min/1.73 m2 who underwent RN for a localized renal mass. New baseline renal function was indexed. We used multivariable logistic regression to develop a predictive nomogram and evaluated it using receiver-operating characteristic (ROC) analysis. Decision-curve analysis was used to assess the net clinical benefit. Results A total of 668 patients met the inclusion criteria, of whom 183 (27%) experienced a decline in eGFR to ≤45 mL/min/1.73 m2 . On multivariable analysis, increasing age (P = 0.001), female gender (P ~11%. Conclusions The decision to perform RN vs PN is multifaceted. We have provided a simple quantitative tool to help identify patients at risk of a postoperative eGFR of ≤45 mL/min/1.73 m2 , who may be stronger candidates for nephron preservation.

Cytoreductive nephrectomy (CRN) has long been considered a standard of care in the management of mRCC. This is largely based on randomized trials in the era of interferon (IFN) that demonstrate an improvement in overall survival (OS). With the advent of targeted therapies, the role of CRN has been questioned and multiple retrospective analyses have shown a potential benefit, particularly in intermediate-risk disease. Two long-awaited prospective trials have been published in the past year that explore the role of CRN. The CARMENA trial randomly assigned patients to therapy with sunitinib with or without CRN, showing noninferiority of sunitinib alone versus sunitinib plus CRN with a median OS of 18.4 months versus 13.9 months, respectively (hazard ratio [HR] for mortality, 0.89; 95% CI, 0.71–1.1). The SURTIME trial randomly assigned patients to immediate CRN followed by sunitinib versus a deferred CRN after three cycles of sunitinib. Analysis is limited by early termination as a result of low accrual. Although there was no difference in progression-free survival (PFS), median OS was significantly improved among patients in the deferred CRN arm (HR, 0.57; 95% CI, 0.34–0.95; p = .032). Early systemic therapy is paramount, but there are patients who may derive benefit by incorporating the removal of the primary tumor in their multimodal therapy, perhaps in a deferred setting. As systemic treatment paradigms shift and immunotherapy again moves to the frontline setting with the potential for novel therapeutic approaches, the role of CRN will continue to evolve with the potential to offer surgical interventions with minimal, if any, delay in systemic treatment.

Purpose:We describe contemporary active surveillance utilization and variation in a regional prostate cancer collaborative. We identified demographic and disease specific factors associated with ac...

Objective To perform a comprehensive histopathologic review of sporadic resected solitary cT1 renal masses comparing those with and without radiographic involvement of the hilum. Materials and Methods A prospectively maintained database was queried for all cT1 renal masses undergoing resection classified per the R.E.N.A.L. nephrometry score. Hilar masses were defined as tumors that abut the main renal artery or vein on cross-sectional imaging. Demographic, treatment, renal mass, and histopathologic characteristics were compared between hilar and nonhilar renal masses. Multivariate regression model analyses were performed to assess factors associated with renal mass upstaging and disease recurrence. Results A total of 1324 stage 1 renal masses met criteria for analysis of which 226 (17.1%) were defined as hilar. Hilar masses were larger, scored with higher complexity, and more likely to undergo a radical nephrectomy. On histopathologic analysis, we found no difference between hilar and nonhilar masses regarding the incidence of malignancy, presence of high nuclear grade, or risk of upstaging. On multivariate analysis, a tumor's hilar location was not associated with upstaging or disease recurrence. Conclusion We present a comprehensive histopathologic review of a large cohort of cT1 hilar lesions noting no difference in the risk of malignancy, high nuclear grade, upstaging, or recurrence when compared to nonhilar lesions. Together, these data suggest that there is no compelling cancer-specific rationale to perform a radical nephrectomy when managing renal hilar tumors.

Purpose Partial nephrectomy (PN) is standard for small renal masses, improving renal function by preserving renal parenchyma compared with radical nephrectomy. Recent work demonstrated that postoperative surgeon assessment of volume preservation (SAVP) and 3D imaging measurements agree and correlate with postoperative function. We hypothesize preoperative assessment of volume preservation (PAVP) with PN based on preoperative imaging will reliably indicate postoperative renal function. Materials and Methods Data were collected from 336 patients undergoing PN for suspected renal cancer by 40 surgeons at 12 centers in Europe and the United States within the Surface-Intermediate-Base International Consortium. Surgeons recorded PAVP and SAVP for individual patients; pre- and postoperative glomerular filtration rate (GFR) was estimated by Chronic Kidney Disease Epidemiology Collaboration equations. Correlations between PAVP, SAVP, and postoperative GFR were assessed with linear regression models. Bland–Altman analysis was used to assess agreement between PAVP and SAVP with a significant cutoff of 5%. Results Median PAVP was 90% (interquartile range [IQR] 85%–100%) and SAVP was 90% (IQR: 80%–94%). PAVP and SAVP were moderately correlated (R2 = 0.67, P Conclusion Renal function is closely linked to the amount of parenchymal volume preservation, whether estimated prior to surgery (PAVP) or afterward (SAVP). PAVP provides reasonably accurate information for decision-making in patients considering PN.

Recent adjuvant vascular endothelial growth factor tyrosine kinase inhibitor trials in resected high-risk renal cell carcinoma that compared sunitinib, sorafenib, pazopanib, and axitinib with placebo controls have demonstrated mixed impact on disease-free survival, no improvement in overall survival, and, thus, controversy. Here, we discuss the results and conduct of these trials to provide new insight into the goals and strategies of treating resected renal cell cancer that is at high risk for recurrence. The potential for leveraging what we have learned from these trials to conduct successful contemporary adjuvant and perioperative immune checkpoint inhibition trials and future adjuvant trial design is discussed.

Background Major cancer surgery is associated with significant risks of perioperative morbidity and mortality, resulting in delayed adjuvant therapy, higher recurrence rates, and worse overall survival. Previous retrospective studies have used the Surgical Apgar Score (SAS) for perioperative risk assessment. This study prospectively evaluated the predictive value of SAS to predict serious complication (SC) after elective major cancer surgery. Methods Demographic, comorbidity, procedure, and intraoperative data were collected prospectively for 405 patients undergoing elective major cancer surgery between 2014-17. The SAS was calculated immediately postoperative and outcome data were collected prospectively. Rates of SC according to SAS risk category were compared using Cochran-Armitage trend test. Receiver operating characteristic curves and area under the receiver operating characteristic curves were generated and 95% confidence intervals were calculated. Results Eighty percent, 17.3%, and 2.7% of patients were low (SAS 7-10), intermediate (SAS 5-6), and high risk (SAS 0-4), respectively, for SC based on their SAS. Forty-six (11.4%) had an SC within 30 days; 3.7% returned to the operating room, 3.7% experienced a urinary tract infection, 3.2% experienced a respiratory complication, 2.7% experienced a wound complication, and 1.2% experienced a cardiac complication. Overall, 9.3%, 18.6%, and 27.3% of patients with SAS 7-10, 5-6, and 0-4 experienced an SC, respectively (P = 0.005). The overall discriminatory ability of the SAS was modest (area under the receiver operating characteristic curves 0.661; 95% confidence intervals, 0.582-0.740). Conclusions Although there was an overall association between SAS and higher risk of subsequent postoperative SC in our cohort, the ability of the SAS to accurately predict risk of postoperative SC at the patient level was limited.

We evaluated contemporary practice patterns in the management of small renal masses.We identified 52,804 patients in the NCDB (National Cancer Database) who were diagnosed with a small renal mass (4 cm or less) between 2010 and 2014. Utilization trends of active surveillance, ablation and robotic, laparoscopic and open surgical techniques were compared among all comers, elderly patients 75 years old or older and individuals with competing health risks, defined as a Charlson index of 2 or greater. Multivariable logistic regression models were used to assess factors associated with robotic renal surgery and active surveillance.Surgery remained the primary treatment modality across all years studied, performed in 75.0% and 74.2% of cases in 2010 and 2014, respectively. Although increases in active surveillance from 4.8% in 2010 to 6.0% in 2014 (p0.001) and robotic renal surgery (22.1% in 2010 to 39.7% in 2014, p 0.001) were observed, the increase in the proportion of small renal masses treated with robotic partial and radical nephrectomy was greater than that of active surveillance (82.0% and 63.0%, respectively, vs 25.0%). Subgroup analyses in individuals 75 years old or older, or with a Charlson index of 2 or greater likewise revealed preferential increases in robotic surgery vs active surveillance. On multivariable analysis later year of diagnosis was associated with increased performance of robotic renal surgery compared to active surveillance (2014 vs 2010 OR 1.44, 95% CI 1.20-1.72, p0.001) and nonrobotic procedural interventions (2014 vs 2010 OR 2.59, 95% CI 2.30-2.93, p 0.001).Robotic surgical extirpation has outpaced the adoption of active surveillance of small renal masses. This raises concern that the diffusion of robotic technology propagates overtreatment, particularly among elderly and comorbid individuals.

Background Risk stratification for localized renal cell carcinoma (RCC) relies heavily on retrospective models, limiting their generalizability to contemporary cohorts. Objective To introduce a contemporary RCC prognostic model, developed using prospective, highly annotated data from a phase III adjuvant trial. Design, setting, and participants The model utilizes outcome data from the ECOG-ACRIN 2805 (ASSURE) RCC trial. Outcome measurements and statistical analysis The primary outcome for the model is disease-free survival (DFS), with overall survival (OS) and early disease progression (EDP) as secondary outcomes. Model performance was assessed using discrimination and calibration tests. Results and limitations A total of 1735 patients were included in the analysis, with 887 DFS events occurring over a median follow-up of 9.6 yr. Five common tumor variables (histology, size, grade, tumor necrosis, and nodal involvement) were included in each model. Tumor histology was the single most powerful predictor for each model outcome. The C-statistics at 1 yr were 78.4% and 81.9% for DFS and OS, respectively. Degradation of the DFS, DFS validation set, and OS model's discriminatory ability was seen over time, with a global c-index of 68.0% (95% confidence interval or CI [65.5, 70.4]), 68.6% [65.1%, 72.2%], and 69.4% (95% CI [66.9%, 71.9%], respectively. The EDP model had a c-index of 75.1% (95% CI [71.3, 79.0]). Conclusions We introduce a contemporary RCC recurrence model built and internally validated using prospective and highly annotated data from a clinical trial. Performance characteristics of the current model exceed available prognostic models with the added benefit of being histology inclusive and TNM agnostic. Patient summary Important decisions, including treatment protocols, clinical trial eligibility, and life planning, rest on our ability to predict cancer outcomes accurately. Here, we introduce a contemporary renal cell carcinoma prognostic model leveraging high-quality data from a clinical trial. The current model predicts three outcome measures commonly utilized in clinical practice and exceeds the predictive ability of available prognostic models.

Concern for discordance between clinical staging and final pathology drives current management of patients deemed appropriate candidates for radical cystectomy. Therefore, we set out to prospectively investigate reliability and shortcomings of cystoscopic evaluation in radical cystectomy candidates.Patients undergoing radical cystectomy for urothelial carcinoma were enrolled in a prospective single-arm study to evaluate reliability of Systematic Endoscopic Evaluation in predicting pT0 urothelial carcinoma (NCT02968732). Systematic Endoscopic Evaluation consisted of cystoscopy and tissue sampling at the time of radical cystectomy. Systematic Endoscopic Evaluation results were compared to radical cystectomy pathology. The primary end point was the negative predictive value of Systematic Endoscopic Evaluation findings in predicting radical cystectomy pathology.A total of 61 patients underwent Systematic Endoscopic Evaluation and radical cystectomy. Indications included muscle invasive bladder cancer in 42 (68.9%) and high risk nonmuscle invasive bladder cancer in 19 (31.1%). In all, 38 (62.3%, 90.5% of patients with muscle invasive bladder cancer) received neoadjuvant chemotherapy. On Systematic Endoscopic Evaluation, 31 (50.8%) patients demonstrated no visual nor biopsy-based evidence of disease (seeT0), yet 16/31 (51.6%) harbored residual disease (pT0), including 8 (8/31, 25.8%) with residual ≥pT2 disease upon radical cystectomy. The negative predictive value of Systematic Endoscopic Evaluation predicting a pT0 bladder was 48.4% (CI 30.2-66.9), which was below our prespecified hypothesis. Therefore, the trial was stopped for futility.Approximately 1 of 4 patients with seeT0 at the time of radical cystectomy harbored residual muscle invasive bladder cancer. These prospective data definitively confirm major limitations of endoscopic assessment for pT0 bladder cancer. Future work should focus on novel imaging and biomarker strategies to optimize evaluations before radical cystectomy for improved decision making regarding bladder preservation.

Purpose: No circulating biomarkers are currently available to identify patients at highest risk of recurrence after nephrectomy for renal cell carcinoma (RCC). Kidney injury molecule-1 (KIM-1) is overexpressed in RCC and its ectodomain circulates in plasma. We investigated whether plasma KIM-1 is a prognostic biomarker in patients with localized RCC after nephrectomy. Experimental Design: The ECOG-ACRIN E2805 (ASSURE) trial evaluated adjuvant sunitinib, sorafenib, or placebo in resected high-risk RCC. KIM-1 levels were measured from banked plasma at trial enrollment 4–12 weeks after nephrectomy. Lognormal accelerated failure time models were used to test for association between KIM-1 and disease-free survival (DFS) as well as overall survival (OS). Results: Plasma from 418 patients was analyzed. Higher post-nephrectomy KIM-1 was associated with worse DFS across all study arms after adjustment for Fuhrman grade, T stage, N stage, and tumor histology [survival time ratio 0.56 for 75th vs. 25th percentile of KIM-1; 95% confidence interval (CI), 0.42–0.73; P < 0.001]. The association between KIM-1 and DFS was stronger among patients with pathologic nodal involvement (Pinteraction = 0.0086). The addition of post-nephrectomy KIM-1 improved the concordance of clinical prognostic models [Stage, Size, Grade, and Necrosis (SSIGN) concordance 0.57 vs. 0.43, P = 0.05; UCLA International Staging System (UISS) concordance 0.60 vs. 0.40, P = 0.0005]. Higher post-nephrectomy KIM-1 was also associated with worse OS after multivariable adjustment (survival time ratio 0.71 for 75th vs. 25th percentile of KIM-1; 95% CI, 0.56–0.91; P < 0.001). Conclusions: Post-nephrectomy plasma KIM-1 is associated with DFS and OS in RCC, and may be a biomarker for microscopic residual disease.