Chronic Kidney Disease and Kidney Cancer Surgery: New Perspectives.

PURPOSE: We sought to provide a contemporary understanding of chronic kidney disease and its relevance to kidney cancer surgery. Another purpose was to resolve points of discrepancy regarding the survival benefits of partial vs radical nephrectomy by critically evaluating the results of prospective and retrospective studies in the urological literature. MATERIALS AND METHODS: We performed a comprehensive literature search for relevant articles listed in MEDLINE® from 2002 to 2018 using the key words radical nephrectomy, partial nephrectomy, glomerular filtration rate, kidney function and chronic kidney disease. We also assessed select review articles and society guidelines about chronic kidney disease pertinent to urology and nephrology. RESULTS: Complete evaluation of the potential consequences of chronic kidney disease involves assessment of the cause, the glomerular filtration rate level and the degree of albuminuria. Chronic kidney disease is commonly defined in the urological literature solely as a glomerular filtration rate less than 60 ml/minute/1.73 m2. This ignores the significance of the cause of chronic kidney disease, and the presence and degree of albuminuria. Although this glomerular filtration rate is relevant for preoperative assessment of patients who undergo surgery of kidney tumors, recent studies suggest that a glomerular filtration rate less than 45 ml/minute/1.73 m2 represents a more discerning postoperative prognostic threshold. Reported survival benefits of partial over radical nephrectomy in retrospective studies were likely influenced by selection bias. The lack of survival benefit in the partial nephrectomy cohort in the only randomized trial of partial vs radical nephrectomy was consistent with data demonstrating that patients in each study arm were at relatively low risk for mortality due to chronic kidney disease when accounting for the chronic kidney disease etiology and the postoperative glomerular filtration rate. CONCLUSIONS: The prognostic risk of chronic kidney disease in patients with kidney cancer is increased when the preoperative glomerular filtration rate is less than 60 ml/minute/1.73 m2 or the postoperative rate is less than 45 ml/minute/1.73 m2. Additional factors, including nonsurgical causes of chronic kidney disease and the degree of albuminuria, can also dramatically alter the consequences of chronic kidney disease after kidney cancer surgery. Urologists must have a comprehensive knowledge of chronic kidney disease to assess the risks and benefits of partial vs radical nephrectomy when managing tumors with increased complexity and/or oncologic aggressiveness.

Second primary lung cancer in United States Cancer Survivors, 1992-2008.

PURPOSE: Lung cancer is common and lethal, and can occur in survivors of previous cancers. We sought to describe the incidence and mortality attributable to second primary lung cancers (SPLC) among survivors of other cancers, and to identify survivors at highest risk. METHODS: We identified adults diagnosed with a localized malignancy from non-pulmonary cancer sites from surveillance, epidemiology, and end results (SEER) data from 1992 to 2008. We explored factors associated with the incidence and death from SPLC using bivariable and multivariable models. Finally, we compared standardized incidence rates for SPLC in our cohort with the control arm of the National Lung Screening Trial (NLST), a randomized lung cancer screening trial. RESULTS: We identified 1,450,837 survivors of non-pulmonary cancers, of whom 25,472 developed SPLC at a mean (SD) follow-up of 5.7 (3.6) years. Over half (57%) of patients with SPLC died of the disease. Survivors of cancer of the hypopharynx, oropharynx, tonsil, and larynx, experienced SPLC at standardized incidence rates which greatly exceeded that observed in the control arm of the NLST (572/100,000 person-years). Additionally, survivors of bladder and esophageal cancer had rates that approached the NLST control arm rate. Increasing age and being divorced/widowed/separated were independent risk factors for SPLC in most primary cancer types. CONCLUSION: The incidence of SPLC in survivors of certain primary cancers greatly exceeds the rate observed in the control arm of the NLST. Further study could help determine if screening for lung cancer in these cancer survivors could prevent death from lung cancer.

Adjuvant Therapy for High Risk Localized Kidney Cancer: Emerging Evidence and Future Clinical Trials.

PURPOSE: We reviewed the literature on adjuvant therapies for patients with high risk localized kidney cancer following surgical resection. In this analysis we merge 2 recently published prospective trials with conflicting results within the context of their respective designs. In addition, we spotlight upcoming trials that use novel immunotherapy based checkpoint inhibitors and have the potential to establish a new standard of care. MATERIALS AND METHODS: We searched PubMed® for English language articles published through January 2017 using the keywords "renal cell carcinoma," "kidney cancer," "immunotherapy," "targeted therapy" and "adjuvant therapy." ClinicalTrials.gov was queried for ongoing studies. Relevant data recently presented at major urology and medical oncology meetings are also included. RESULTS: Adjuvant therapies for high risk localized kidney cancer can be grouped into the categories of 1) traditional immunotherapy, 2) inhibitors of the vascular endothelial growth factor and mTOR (mammalian target of rapamycin) pathways, 3) vaccines and antibody dependent cytotoxic agents, and 4) immune checkpoint inhibitors. Several trials of traditional immunotherapy, such as interferon-α and high dose interleukin-2, failed to demonstrate benefit as adjuvant treatment and were associated with significant adverse events. Vascular endothelial growth factor and mTOR inhibitors have less severe toxicity in metastatic disease and, therefore, are natural considerations for adjuvant trials. However, current data are conflicting. The ASSURE (Sunitinib Malate or Sorafenib Tosylate in Treating Patients with Kidney Cancer that was Removed by Surgery, NCT00326898) trial found no recurrence-free survival benefit of sorafenib or sunitinib over placebo, while S-TRAC (Clinical Trial Comparing Efficacy and Safety of Sunitinib versus Placebo for the Treatment of Patients at High Risk of Recurrent Renal Cell Cancer, NCT00375674) revealed that 1 year of sunitinib improved recurrence-free survival by 1.2 years. Vaccine based treatments and antibody dependent cytotoxic agents have had mixed results. New trials evaluating immune checkpoint inhibitors are planned, given the impressive efficacy and tolerability as second line agents in metastatic disease. Future adjuvant trials are likely to be guided by molecular signatures to treat patients most likely to benefit. CONCLUSIONS: Based on the available data, there appears to be no role for traditional immunotherapy as adjuvant treatment in patients with high risk localized kidney cancer following surgical resection. S-TRAC provides evidence that 1 year of adjuvant sunitinib in patients with higher risk locoregional disease increases the median time to recurrence. However, the data on overall survival are immature and adverse effects are common. Results from trials investigating immune checkpoint inhibitors are highly anticipated.

Continuous saline bladder irrigation for two hours following transurethral resection of bladder tumors in patients with non-muscle invasive bladder cancer does not prevent recurrence or progression compared with intravesical Mitomycin-C.

BACKGROUND: Intravesical Mitomycin-C (MMC) following transurethral resection of bladder tumor (TURBT), while efficacious, is associated with side effects and poor utilization. Continuous saline bladder irrigation (CSBI) has been examined as an alternative. In this study we sought to compare the rates of recurrence and/or progression in patients with NMIBC who were treated with either MMC or CSBI after TURBT. METHODS: We retrospectively reviewed records of patients with NMIBC at our institution in 2012-2015. Perioperative use of MMC (40 mg in 20 mL), CSBI (two hours), or neither were recorded. Primary outcome was time to recurrence or progression. Descriptive statistics, chi-squared analysis, Kaplan-Meier survival analysis, and Cox multivariable regression analyses were performed. RESULTS: 205 patients met inclusion criteria. Forty-five (22.0%) patients received CSBI, 71 (34.6%) received MMC, and 89 (43.4%) received no perioperative therapy. On survival analysis, MMC was associated with improved DFS compared with CSBI (p = 0.001) and no treatment (p = 0.0009). On multivariable analysis, high risk disease was associated with increased risk of recurrence or progression (HR 2.77, 95% CI: 1.28-6.01), whereas adjuvant therapy (HR 0.35, 95% CI: 0.20-0.59) and MMC (HR 0.43, 95% CI: 0.25-0.75) were associated with decreased risk. CONCLUSIONS: Postoperative MMC was associated with improved DFS compared with CSBI and no treatment. The DFS benefit seen with CSBI in other studies may be limited to patients receiving prolonged irrigation. New intravesical agents being evaluated may consider saline as a control given our data demonstrating that short-term CSBI is not superior to TURBT alone.

Immunotherapy for the Treatment of Urothelial Carcinoma.

PURPOSE: We review the biological mechanisms of action, clinical safety and efficacy of immunotherapies for urothelial carcinoma. We also describe current areas of research in immunotherapy, and highlight ongoing trials and promising and novel investigational agents. MATERIALS AND METHODS: Data were obtained by a search of PubMed®, ClinicalTrials.gov and Cochrane databases for English language articles published through February 2016. Applicable abstracts from recent Society of Urologic Oncology, European Association of Urology, American Urological Association and ASCO® meetings were used. RESULTS: Bacillus Calmette-Guérin is one of the most successful immunotherapies in cancer treatment and remains the gold standard of care for patients with high risk, nonmuscle invasive bladder cancer, with initial response rates of approximately 70%. However, with the exception of valrubicin and standard chemotherapeutics there is a paucity of available treatment options for patients with recurrence or progression to more advanced disease. Recently there has been significant interest in novel immunotherapeutic agents in the management of cases where bacillus Calmette-Guérin fails, as well as cases of more advanced cancer. These investigational therapies can generally be classified into several broad categories, including recombinant bacillus Calmette-Guérin and cell wall derived therapies, cytokines, gene therapy, cancer vaccines, immune checkpoint inhibitors, oncolytic viruses, adoptive immunotherapies and immune agonists, as well as several additional immunomodulatory agents. The majority of these agents are currently under investigation in phase I or II clinical trials. Recently investigators reported evidence that inhibition of the PD-1/PD-L1 pathway has clinical activity in patients with advanced bladder cancer. These findings, along with successful phase III trials and U.S. Food and Drug Administration approvals of other checkpoint inhibitors in melanoma, nonsmall cell lung cancer and renal cell carcinoma, ultimately led to Food and Drug Administration approval of atezolizumab for advanced disease, the first new treatment approved for advanced urothelial carcinoma in 20 years. CONCLUSIONS: While bacillus Calmette-Guérin has demonstrated significant clinical efficacy in the treatment of patients with bladder cancer, additional therapies are needed for those in whom bacillus Calmette-Guérin fails, as well as for those with advanced disease. Immunotherapy for urothelial carcinoma remains a promising and active area of research, and numerous agents, particularly the monoclonal antibodies targeting checkpoint inhibition pathways, are showing encouraging signs of clinical activity.

Epigenetic-mediated dysfunction of the bone morphogenetic protein pathway inhibits differentiation of glioblastoma-initiating cells.

Despite similarities between tumor-initiating cells with stem-like properties (TICs) and normal neural stem cells, we hypothesized that there may be differences in their differentiation potentials. We now demonstrate that both bone morphogenetic protein (BMP)-mediated and ciliary neurotrophic factor (CNTF)-mediated Jak/STAT-dependent astroglial differentiation is impaired due to EZH2-dependent epigenetic silencing of BMP receptor 1B (BMPR1B) in a subset of glioblastoma TICs. Forced expression of BMPR1B either by transgene expression or demethylation of the promoter restores their differentiation capabilities and induces loss of their tumorigenicity. We propose that deregulation of the BMP developmental pathway in a subset of glioblastoma TICs contributes to their tumorigenicity both by desensitizing TICs to normal differentiation cues and by converting otherwise cytostatic signals to proproliferative signals.

MRI features of renal cell carcinoma that predict favorable clinicopathologic outcomes.

OBJECTIVE: The purpose of this article is to determine whether MRI features of renal cell carcinoma (RCC), such as enhancing solid component and T1 signal intensity, are associated with clinicopathologic outcomes. MATERIALS AND METHODS: This retrospective study included 241 RCCs in 230 patients who underwent preoperative MRI, had pathologic analysis results available, and were monitored for at least 3 months. A radiologist assessed tumor features on MRI, including unenhanced T1 signal relative to renal cortex and the percentage of solid enhancing components. The electronic medical record or follow-up images were reviewed to assess for the development of local recurrence or metastases. Statistical analysis was performed to correlate imaging features at MRI with pathologic and clinical outcome. RESULTS: The following tumor features were observed: predominantly cystic morphologic features (defined as solid component≤25%, n=33), solid component greater than 25% (n=208), T1 hypointensity (n=97), and T1 intermediate intensity or hyperintensity (n=144). Local recurrence or metastases were observed in 14 patients. Compared with T1-intermediate or -hyperintense lesions, T1-hypointense RCCs were more likely to be low stage (90.7% vs 74.3%; p=0.001) and low grade (78.9% vs 41.8%; p<0.001) and had a lower rate of recurrence or metastases (3.3% vs 8%; p=0.167). Compared with lesions with greater than 25% solid enhancement, predominantly cystic RCCs were more likely to be lower stage (93.9% vs 78.8%; p=0.053) and lower grade (94.7 vs 56.5%; p<0.001) and to have no incidence of recurrence or metastasis (0% vs 6.9%; p=0.227). RCCs that were both cystic and T1 hypointense (n=14) were lower stage (100% vs 79.6%; p=0.047) and lower grade (92.9% vs 58.1%; p=0.01) and had no recurrence or metastases on follow-up. CONCLUSION: Cystic and T1-hypointense RCC show less-aggressive pathologic features and favorable clinical behavior.

Genetically adjusted prostate-specific antigen values may prevent delayed biopsies in African-American men.

OBJECTIVE: To evaluate whether genetic correction using the genetic variants prostate-specific antigen (PSA)-single nucleotide polymorphisms (SNPs) could reduce potentially unnecessary and/or delayed biopsies in African-American men. SUBJECTS AND METHODS: We compared the genotypes of four PSA-SNPs between 964 Caucasian and 363 African-American men without known prostate cancer (PCa). We adjusted the PSA values based on an individual's PSA-SNP carrier status, and calculated the percentage of men that would meet commonly used PSA thresholds for biopsy (≥ 2.5 or ≥ 4.0 ng/mL) before and after genetic correction. Potentially unnecessary and delayed biopsies were defined as those men who were below and above the biopsy threshold after genetic correction, respectively. RESULTS: Overall, 349 (96.1%) and 354 (97.5%) African-American men had measured PSA levels <2.5 and <4.0 ng/mL. Genetic correction in African-American men did not avoid any potentially unnecessary biopsies, but resulted in a significant (P < 0.001) reduction in potentially delayed biopsies by 2.5% and 3.9%, based on the biopsy threshold level. CONCLUSIONS: There are significant differences in the influence of the PSA-SNPs between African-American and Caucasian men without known PCa, as genetic correction resulted in an increased proportion of African-American men crossing the threshold for biopsy. These results raise the question of whether genetic differences in PSA might contribute to delayed PCa diagnosis in African-American men.

Gleason 6 prostate cancer: serious malignancy or toothless lion?

Autopsy studies of men without known prostate cancer suggest that a substantial reservoir of prostate cancer that does not cause symptoms or death exists within the population. The majority of these cancers are Gleason 6 tumors and are frequently detected by prostate-specific antigen-based prostate cancer screening.There is strong evidence from longitudinal cohort studies of men with both treated and untreated Gleason 6 prostate cancer to suggest that Gleason 6 disease, when not associated with higher-grade cancer, virtually never demonstrates the ability to metastasize and thus represents an indolent entity that does not require treatment. Whether Gleason 6 has a propensity to progress to higher-grade cancer is still under investigation. Because the term "cancer" has historically been used to represent a disease state that leads to progressive illness that is uniformly fatal without treatment, we believe Gleason 6 disease should not be labeled with this term. Our challenge now is to develop the technology to differentiate true Gleason 6 disease from the higher grades of dysplasia with which it can be associated.

Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines.

The concept of tumor stem cells (TSCs) provides a new paradigm for understanding tumor biology, although it remains unclear whether TSCs will prove to be a more robust model than traditional cancer cell lines. We demonstrate marked phenotypic and genotypic differences between primary human tumor-derived TSCs and their matched glioma cell lines. Unlike the matched, traditionally grown tumor cell lines, TSCs derived directly from primary glioblastomas harbor extensive similarities to normal neural stem cells and recapitulate the genotype, gene expression patterns, and in vivo biology of human glioblastomas. These findings suggest that TSCs may be a more reliable model than many commonly utilized cancer cell lines for understanding the biology of primary human tumors.

A middle-aged man with hyperandrogenic state.

Hyperandrogenism secondary to testicular cancer typically arises in patients in whom Leydig cell hyperplasia or neoplasia can be identified. Additionally, benign and malignant adrenocortical tumors can also present with signs and symptoms of hyperandrogenism. We report a case of a 40-year-old gentleman who experienced several months of weight gain, worsening gynecomastia, and mood changes secondary to high testosterone and estradiol levels. Workup initially was negative for testicular malignancy and positive for a benign-appearing lesion in the adrenal gland. Despite adrenalectomy, symptoms continued to persist and ultimately a testicular cancer without Leydig cell involvement was identified.

Should I freeze my sperm?-readability and quality of health resources for sperm banking.

Background: Sperm banking refers to the collection and storage of sperm cells for future use. Despite the recommendations of major medical societies, sperm banking is not discussed sufficiently with patients at risk of future fertility. Majority of Americans utilize the internet regarding health information. The aim of this study is to assess the reading level and the quality of online health information on sperm banking. Methods: The top 50 search results from Google, Bing, and Yahoo were selected after searching for the term "sperm banking". Duplicate pages, advertisements, news and magazines, blog posts, videos, paid subscriptions, articles intended for health professionals, and non-related pages were excluded. Four validated readability and two quality assessment tools were used to score the text. Websites were divided into five categories: academic, hospital-affiliated, commercial, non-profit health advocacy, and non-categorized. Descriptive statistics, one sample t-test, and Pearson's correlation coefficient were used to analyze the data. Results: Forty-one webpages were included. The mean Flesch Reading Ease Score (FRES) for all pages was 46.9/100 and the mean reading level was 11th grade, compared to the recommended 6th grade level, across various assessment tools. Utilizing the DISCERN Instrument, quality of online health information was fair. Seven percent of pages received a "good" quality score and no pages received a score of "excellent". On average, 1.5 out of 4 criteria categorized by the JAMA Benchmark, a validated quality assessment tool, were met. The hospital-affiliated webpages received the best reading scores and commercial pages received the highest quality scores. Conclusions: Online health information on sperm banking available in English is of poor quality based on several quality assessment tools and at a reading level significantly higher than what is recommended. Further efforts are needed by providers and healthcare institutions to improve the quality of information available to patients.

Tumour diameter and decreased preoperative estimated glomerular filtration rate are independently correlated in patients with renal cell carcinoma.

OBJECTIVE: To examine the relationship between tumour diameter and estimated GFR (eGFR) in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: In total, 1009 patients undergoing partial or radical nephrectomy for unilateral RCC were identified in the Columbia Urologic Database. eGFR was calculated using the modification of diet in renal disease equation using demographic data and preoperative serum creatinine values. Data on patient demographics, tumour characteristics, and comorbidities were analyzed using univariate and multivariate regression analysis. RESULTS: Mean (sd, range) tumour diameter was 5.29 (3.8, 0.3-29) cm. Mean (sd, range) eGFR was 75 (23.4, 3-173) mL/min per 1.73 m(2) . In multivariate regression analysis, tumour diameter independently predicted decreased preoperative eGFR (coefficient, -0.513; P= 0.008) when controlling for hypertension and race. Consistent with this, decreased preoperative eGFR independently predicted increased tumour diameter (coefficient, -0.013; P= 0.007) when controlling for race, histology and smoking status. CONCLUSION: Tumour diameter and decreased preoperative eGFR are independently correlated in patients with RCC.

Ureteritis cystica mimicking upper tract urothelial cancer in a patient with bladder cancer.

Ureteritis cystica is a rare condition of the upper urinary tract characterized by the presence of numerous small cystic lesions. Associated urinary tract malignancy is exceedingly rare, and ureteritis cystica is not thought to have malignant potential. We present the case of a 62-year-old male who was found to have both urothelial carcinoma of the bladder and numerous filling defects of the bilateral upper urinary tracts which were subsequently diagnosed as ureteritis cystica. To our knowledge this is the only published case of ureteritis cystica associated with bladder cancer and the clinical challenges it poses.

Why Targeting PSMA Is a Game Changer in the Management of Prostate Cancer.

Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein that is highly expressed on prostate adenocarcinomas, exhibits only limited expression in benign and extraprostatic tissues, and thus represents an ideal target for the diagnosis and management of prostate cancer. Since its discovery over 30 y ago, significant effort has been made to develop clinical technology targeting PSMA. The last 5 y have seen an explosion of development of new agents targeting PSMA for diagnostic and therapeutic use. Imaging agents targeting PSMA have been developed for SPECT and PET platforms. PSMA PET imaging appears to outperform traditional imaging in the high-risk localized-disease state, in patients with biochemical recurrence after treatment, and in advanced disease. To date, most of the reported clinical studies of therapeutic agents have used PSMA-targeted radiometals to deliver ß-radiation to metastatic disease sites, with 177Lu being the most widely investigated therapeutic radioisotope. Studies of both antibodies and small-molecule agents have been published and have demonstrated encouraging results. Safety appears generally limited to mild transient bone marrow toxicity and xerostomia because of uptake of the small-molecule agents in the salivary glands. Radiologic responses can be dramatic, and decreases in pain have been observed. The effect on overall survival, however, has yet to be demonstrated.

Association between Metabolic Syndrome and Recurrence of Nonmuscle Invasive Bladder Cancer following bacillus Calmette-Guérin Treatment.

INTRODUCTION: Intravesical bacillus Calmette-Guérin (BCG) therapy is the gold standard adjuvant treatment for patients with high-grade non-muscle-invasive bladder cancer (NMIBC). Despite the association between metabolic syndrome (MetS) and bladder cancer, the association between MetS and BCG failure is unknown. The objective of this study was to characterize disease recurrence following BCG in patients with and without MetS. METHODS: We retrospectively evaluated the records of patients undergoing TURBT at our institution in 2012-2015 for NMIBC and identified those who received adjuvant BCG therapy. MetS was defined as having three of four components: diabetes mellitus, hyperlipidemia, hypertension, or body mass index (BMI)≥30kg/m2. The primary outcome was recurrence or progression. Descriptive statistics, chi-squared analysis, Kaplan-Meier survival analysis, and Cox multivariable regression analyses were performed. RESULTS: High grade was present in 83/90 (92.2%) patients. MetS was present in 27/90 (30%) patients. Median follow-up was 20 months. On Kaplan-Meier analysis, patients with MetS had worse DFS compared with patient without MetS. On multivariable analysis, BMI≥30 kg/m2 was a significant predictor of recurrence or progression (HR 2.94, 95% CI: 1.43-6.03). Presence of MetS did not significantly affect the type of BCG failure. CONCLUSIONS: The association between MetS and failure to respond to BCG therapy is multifactorial but is in part associated with obesity. Elevated BMI is strongly associated with recurrence or progression. Further studies are warranted to investigate the relationship between increased adiposity and response to BCG, especially as other novel immunotherapeutic agents are likely to enter the NMIBC space.

Effect of Malnutrition on Radical Nephroureterectomy Morbidity and Mortality: Opportunity for Preoperative Optimization.

INTRODUCTION: Nutritional status has been increasingly recognized as an important predictor of prognosis and surgical outcomes for cancer patients. We evaluated the effect of preoperative malnutrition on the development of surgical complications and mortality after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: Using data from the American College of Surgeons National Surgical Quality Improvement Program, we evaluated the association of poor nutritional status with 30-day postoperative complications and overall mortality after RNU from 2005 to 2015. The preoperative variables suggestive of poor nutritional status included hypoalbuminemia (< 3.5 g/dL), weight loss within 6 months before surgery (> 10%), and a low body mass index. RESULTS: A total of 1200 patients were identified who had undergone RNU for UTUC. The overall complication rate was 20.5% (n = 246), and mortality rate was 1.75% (n = 21). On univariate analysis, patients who experienced a postoperative complication were more likely to have hypoalbuminemia (25.0% vs. 11.4%; P < .001) and weight loss (3.7% vs. 1.0%; P = .003). After controlling for baseline characteristics and comorbidities, hypoalbuminemia was found to be a significant independent predictor of postoperative complications (odds ratio, 2.09; 95% confidence interval, 1.29-3.38; P = .003). Hypoalbuminemia was also a significant independent predictor of mortality (odds ratio, 4.31; 95% confidence interval, 1.45-12.79; P = .008) on multivariable regression analysis. CONCLUSION: Our results have shown that hypoalbuminemia is a significant predictor of surgical complications and mortality after RNU for UTUC. This finding supports the importance of patients' preoperative nutritional status in this population and suggests that effective nutritional interventions in the preoperative setting could improve patient outcomes.

Trends in usage of cytoreductive partial nephrectomy and effect on overall survival in patients with metastatic renal cell carcinoma.

PURPOSE: Cytoreductive radical nephrectomy (cRN) improves survival in select patients with metastatic renal cell carcinoma (mRCC). It is unclear, however, whether cytoreductive partial nephrectomy (cPN) compromises oncologic efficacy. We evaluated trends in utilization of cPN and compared overall survival (OS) in patients who underwent cRN or cPN for mRCC. MATERIALS AND METHODS: We queried the National Cancer Database from 2006 to 2013 and identified patients who underwent cPN and cRN for mRCC. We analyzed rates of cPN over time. Logistic regression identified predictors of cPN. We matched patients based on propensity score for treatment. We used matched Kaplan-Meier survival analyses to compare OS, stratified by tumor size. We used multivariable Cox proportional hazards models to determine the effect of cPN and cRN on OS. RESULTS: A total of 10,144 patients met inclusion criteria, with 9,764 (96.2%) undergoing cRN and 381 (3.8%) undergoing cPN. Rates of cPN increased over time from 1.8% to 4.3% over the study period. Treatment at an academic/research facility, papillary and chromophobe histology, and more recent year of treatment were associated with increased odds of cPN. In a matched survival analysis, cPN was associated with improved OS compared with cRN (log rank, P = 0.001). This effect was limited to primary tumors<4cm. In a propensity-score adjusted multivariable Cox model, cPN was associated with improved OS (hazard ratio = 0.81; 95% CI: 0.71-0.93; P = 0.002). CONCLUSIONS: The use of cPN in patients with mRCC is increasing. cPN is associated with improved OS in patients with mRCC, although this effect is limited to patients with primary tumors<4cm.

Role of surgical approach on lymph node dissection yield and survival in patients with upper tract urothelial carcinoma.

OBJECTIVES: With increasing utilization of robot-assisted surgery in urologic oncology, robotic nephroureterectomy (RNU) is becoming the surgical modality of choice for patients with upper tract urothelial carcinoma (UTUC). The role of surgical approach on lymph node dissection (LND) and lymph node (LN) yield is unclear, and potential therapeutic effects are unknown. Here we analyze the effects of surgical approach on LN yield, performance of LND, and overall survival (OS). METHODS AND MATERIALS: Patients with UTUC who underwent nephroureterectomy from 2010 to 2013 were identified in the National Cancer Database. Outcomes of interest included rate of LND, LN yield, and OS. Logistic regression analyses were used to predict performance of LND. Negative binomial regression was used to derive incidence rate ratios for LN yield. Cox proportional hazards models were used to quantify survival outcomes. RESULTS: A total of 3,116 patients met inclusion criteria. LND was performed in 41% (314/762) of RNU, 27% (380/1385) of LNU cases, and 35% (340/969) of ONU (P<0.001). Compared with an ONU, patients who underwent a LNU had significantly lower odds of receiving a LND (OR = 0.70, 95% CI: 0.55-0.87) and had fewer LNs removed (IRR = 0.69, 95% CI: 0.60-0.80), while RNU trended toward increased LN yield (IRR = 1.14, 95% CI: 0.98-1.33). In a Cox proportional hazards model, increasing LN yield was associated with improved OS in patients with pN0 disease (HR = 0.97 per 1 unit increase in LN yield, 95% CI: 0.95-0.99). CONCLUSIONS: Compared with an ONU, RNU does not compromise performance of a LND and may be associated with improved LN yield. LNU is associated with the lowest rates of LND and LN yield. Increasing LN yield is associated with improved OS in patients with pN0 disease. Despite differential rates of LND and LN yield, surgical approach did not independently affect OS.

Overall survival in patients with metastatic renal cell carcinoma and clinical N1 disease undergoing cytoreductive nephrectomy and lymph node dissection.

BACKGROUND: Patients with metastatic renal cell carcinoma (mRCC) have limited treatment options. Cytoreductive nephrectomy (CN) in select patients has been associated with improved survival. We aim to assess the survival in patients with mRCC and cN1 disease who underwent CN with and without lymph node dissection (LND). METHODS: Data were abstracted from the National Cancer Database for patients diagnosed with mRCC and cN1 from 2003 to 2014. Using propensity matching, we compared overall survival (OS) in patients who underwent a LND. Kaplan-Meier survival analysis and multivariable Cox proportional hazards modeling were used. We performed a logistic regression to assess predictors of LND. RESULTS: We identified 1,780 patients in the matched cohort, of which 71% underwent a LND. Patients undergoing LND were younger (P = 0.01) and had similar size tumors (5cm; P = 0.31). Increased LN yield was associated with LND at an academic center (odds ratio = 1.91; 95% CI: 1.51-2.42; P<0.01). LND was associated with worse OS on KM analysis (log rank; P = 0.01). However, on multivariable analysis, we found no significant difference in OS (hazard ratio = 1.10; 95% CI: 0.94-1.29; P = 0.22). However, when adjusting for number of positive LN removed, an increase in LN yield was associated with improved OS (hazard ratio = 0.97; 95% CI: 0.95-0.99; P = 0.01). CONCLUSION: We demonstrate that patients with mRCC and cN1 disease undergoing LND did not have a survival benefit when compared with patients undergoing CN. However, lymph node yield showed an increase in survival when adjusting for the number of positive lymph nodes. Further research and validation of the ideal number of LN removed that may benefit patients is warranted.