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Objectives To assess the utility of genomic testing in risk-stratifying Black patients with low and intermediate risk prostate cancer. Methods We retrospectively identified 63 Black men deemed eligible for active surveillance based on National Comprehensive Cancer Network® (NCCN) guidelines, who underwent OncotypeDx® Genomic Prostate Score™ testing between April 2016 and July 2020. Nonparametric statistical testing was used to compare relevant features between patients reclassified to a higher NCCN risk after genomic testing and those who were not reclassified. Results The median age was 66 years and median pre-biopsy PSA was 7.3. Initial risk classifications were: very low risk: seven(11.1%), low risk: 24(38.1%), favorable intermediate risk: 31(49.2%), and unfavorable intermediate risk: one(1.6%). Overall, NCCN risk classifications after Genomic Prostate Score testing were significantly higher than initial classifications (p=0.003, Wilcoxon signed-rank). Among patients with discordant risk designations, 28(28/40, 70%) were reclassified to a higher NCCN risk after genomic testing. A pre-biopsy prostate specific antigen of greater than 10 did not have significantly higher odds of HBR (OR:2.16 [95% CI: 0.64,7.59, p=0.2). Of favorable intermediate risk patients, 20(64.5%) were reclassified to a higher NCCN risk. Ultimately, 18 patients underwent definitive treatment. Conclusions Incorporation of genomic testing in risk stratifying Black men with low and intermediate-risk prostate cancer resulted in overall higher NCCN risk classifications. Our findings suggest a role for increased utilization of genomic testing in refining risk-stratification within this patient population. These tests may better inform treatment decisions on an individualized basis.

Introduction:We sought to determine the accuracy of self-reported urology applicant match data and determine which factors were most influential on successful application outcomes.Methods:A...

Recent literature has separately identified multiple determinants of the use of neoadjuvant chemotherapy (NAC) and adherence to pelvic lymph node dissection (PLND) guidelines in the management of non-metastatic bladder cancer. However, such NAC/PLND analyses tend not to account for the other modality, despite the fact that NAC may impact the extent of dissectible lymph nodes. We aimed to determine the predictors of adequate PLND in patients with non-metastatic urothelial muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC) following receipt of NAC. We queried the National Cancer Database to identify patients from 2006–2015 with cT2-cT4a/N0M0 urothelial MIBC who underwent RC and were pre-treated with NAC. Multivariate logistic regression analysis was used to identify independent predictors of undergoing an adequate PLND (defined as > 8 nodes). A total of 1518 patients met the criteria for inclusion (74.4% underwent adequate PLND). Adequate PLND was associated with treatment at an academic research facility (OR 2.762 [95% CI 2.119–3.599], p

Background and Objectives: The National Cancer Database (NCDB) captures nearly 70% of all new cancer diagnoses in the United States, but there exists significant variation in this capture rate based on primary tumor location and other patient demographic factors. Prostate cancer has the lowest coverage rate of all major cancers, and other genitourinary malignancies likewise fall below the average NCDB case coverage rate. We aimed to explore NCDB coverage rates for patients with genitourinary cancers as a function of race. Materials and Methods: We compared the incidence of cancer cases in the NCDB with contemporary United States Cancer Statistics data. Results: Across all malignancies, American Indian/Alaskan Natives subjects demonstrated the lowest capture rates, and Asian/Pacific Islander subjects exhibited the second-lowest capture rates. Between White and Black subjects, capture rates were significantly higher for White subjects overall and for prostate cancer and kidney cancer in White males, but significantly higher for bladder cancer in Black versus White females. No significant differences were observed in coverage rates for kidney cancer in females, bladder cancer in males, penile cancer, or testicular cancer in White versus Black patients. Conclusions: Differential access to Commission on Cancer-accredited treatment facilities for racial minorities with genitourinary cancer constitutes a unique avenue for health equity research.

Introduction Bladder cancer care has been increasingly concentrated in high-volume metropolitan medical centers (i.e., "regionalization" of care). We aimed to assess the potential role of geographic factors, including facility region and distance to treatment center, as determinants of neoadjuvant chemotherapy (NAC) delivery in patients with non-metastatic urothelial muscle-invasive bladder cancer (MIBC) using nationally-representative data from the United States. Methods We queried the National Cancer Database to identify patients with cT2-cT4a, N0, M0 urothelial MIBC who underwent radical cystectomy from 2006-2015. Patients who received radiation therapy, single-agent chemotherapy, adjuvant chemotherapy, or systemic therapies other than multiagent chemotherapy were excluded. Multivariate logistic regression analysis was performed to identify independent predictors of receiving NAC. Results A total of 5,986 patients met the criteria for inclusion, of whom 1,788 (29.9%) received NAC and 4,108 received RC alone. Younger age, increased Charlson-Deyo score, increased cT stage, increased annual income, increased distance from cancer treatment center, treatment at an Academic Research Program or Integrated Network Cancer Program, and a later year of diagnosis were independently predictive of NAC receipt. Older age, Medicare insurance, and treatment in the East South Central or West South Central regions were independently associated with decreased odds for NAC receipt. Conclusions Distance to treatment center and United States geographic region were found to affect the likelihood of NAC receipt independently of other established predictors of success in this quality-of-care metric. Access to transportation and related resources merits consideration as additional pertinent social determinants of health in bladder cancer care.

Background: Primary small cell carcinoma of the kidney (PSCCK) is exceedingly rare and data on disease characteristics and outcomes are sparse. This study examines a nationally-representative cancer registry to better characterize PSCCK. Methods: We queried the National Cancer Database to identify patients with histology-confirmed PSCCK from 2004 to 2015. Adjusted Cox proportional hazards regression and Kaplan&ndash, Meier analyses were employed to assess predictors of mortality and estimate median survival time, respectively. Results: A total of 110 patients were included (47:53% female:male, 77% &ge, 60 years of age, 86% Caucasian). Significant predictors of mortality included female sex, age 60&ndash, 69 years, treatment at an Integrated Network Cancer Program, stage cM1, and lack of surgical and chemoradiotherapy treatment. Independent protective factors were high socioeconomic status and treatment at an Academic Research Program. The estimated median overall survival time was 9.31 (95% CI 7.28&ndash, 10.98) months for all patients. No differences in estimated survival time were observed across individual treatment modalities among those patients who underwent treatment (p = 0.214). Conclusions: PSCCK is an aggressive malignancy with a median survival time of less than one year. Future studies that correlate clinical tumor staging with specific treatment modalities are needed to optimize and individualize management.

Penile strangulation is an uncommon urologic emergency that requires prompt evaluation and treatment to avoid disastrous consequences. Strangulation has been reported with objects ranging from hair tourniquets, to plastic rings, to iron rings. Strangulation with these devices can result in vascular congestion of the penis, swelling and eventual gangrene of the penis distal to the constricting device. We present a case report of a 43-year-old male who had a 2-day history of penile pain and swelling secondary to a metal ring constricting the proximal phallus. Ring removal was achieved with an orthopedic bolt cutter to cut the ring in two places, using a malleable retractor to act as a “backboard” to prevent iatrogenic injury to the penis.

Radical cystectomy (RC) is associated with significant morbidity. Neuraxial analgesia is recommended by enhanced recovery after surgery guidelines, but largely supported by evidence extrapolated from colorectal surgery outcomes. We synthesized current evidence regarding short- and long-term outcomes associated with neuraxial analgesia versus patient controlled non-neuraxial analgesia following RC. PubMed, Embase, and Cochrane databases were searched for relevant studies published up to May 2020. Studies reporting complications, length of stay (LOS), pain score, opioid usage within 72 hours, overall survival, cancer-specific survival, and recurrence rate were included. Of 550 identified studies, 9 met criteria for inclusion. Four studies demonstrated a higher percentage of 90-day complications in the neuraxial analgesia cohort. Out of 6 studies reporting information regarding LOS, 4 demonstrated no improvement in LOS in the neuraxial cohort. A reduction in 72 hours post-RC opioid usage was observed in 2 out of 3 studies with available data. Information regarding post-RC pain scores were variable up to 3 days post-RC. One out of 2 studies with available data reported a significant association between neuraxial analgesia and an earlier time to recurrence. No significant associations were seen with respect to overall survival or cancer-specific survival. A majority of low-to-moderate quality evidence demonstrates neuraxial analgesia is associated with a higher rate of complications, variable information regarding pain control, no improvements in LOS, and no significant association with long-term oncological outcomes. Further research regarding the incorporation of nonopiate-based analgesic modalities into RC ERAS protocols is warranted.

Purpose Pathologic upstaging in renal cell carcinoma (RCC) is common and confers a significant risk of poor surgical and survival outcomes. Preoperative predictors of upstaging are of great clinical relevance but empirical evidence specific to racial minorities remains scarce. Methods National Cancer Database (NCDB) analysis of T3a-specific upstaging among White, African-American, Hispanic and Asian Pacific Islander (API) patients with AJCC cT1N0M0 RCC who underwent partial or radical nephrectomy between 2010 and 2015. Independent preoperative predictors of tumour upstaging were identified using multivariate logistic regression analyses. Results A total of 81 002 patients met the criteria for inclusion (5.6% T3a-specific upstaging). Increased age, increased Charlson-Deyo comorbidity index, clinical stages cT1b and unspecified cT1, and increased Fuhrman nuclear grade were identified as independent risk factors for upstaging. Independent protective factors for upstaging were younger age, female sex, African-American race and papillary, chromophobe, and unspecified RCC histologic subtypes. Significant risk factors and protective factors within individual racial subgroups were highly consistent with those observed in the overall study sample. All independent factors identified on race-specific subgroup analyses were significant in the same direction relative to the overall study sample. Variables found to be non-significant in the overall study sample remained non-significant across all racial subgroup analyses. Conclusion The present study of nationally representative data found no clinically significant differences in upstaging risk across individual racial subgroups relative to the overall study sample. Preoperative factors that can be used to predict pT3a-specific tumour upstaging in CT1N0M0 RCC likely persist across different racial groups.

Clear cell papillary renal cell carcinoma (CCPRCC) is a recently described tumor entity. Several questions remain about its epidemiology, molecular features, and clinical behavior.To comprehensively evaluate clinicopathologic and molecular features of CCPRCC, and compare it with more common kidney cancer subtypes.We identified 89 CCPRCC patients and compared their clinicopathologic features with 1120 localized clear cell renal cell carcinoma (ccRCC) and 129 type 1 papillary renal cell carcinoma (pRCC) patients.Nonparametric statistical testing was used to compare relevant features between tumor types. Overall, cancer-specific survival (CSS) and metastasis-free survival estimates were calculated from initial diagnosis using the Kaplan-Meier method. Patients with ipsilateral multifocal disease were explored further. A subset of CCPRCC tumors underwent genomic analysis and were compared with other RCC subtypes.A higher proportion of female (45% vs 32%) and African-American (19% vs 3%) patients were observed in the CCPRCC cohort than in the ccRCC and pRCC cohorts. CCPRCC tumors also had increased odds of presenting with additional ipsilateral masses (odds ratio [OR]: 4.41 [confidence interval {CI}: 2.34, 8.15], p 0.001) and bilateral disease (OR: 4.80 [CI: 2.40, 9.59], p 0.001) compared with ccRCC tumors. On molecular analysis, CCPRCC tumors showed fewer somatic aberrations and a greater degree of mitochondrial DNA depletion. In multifocal CCPRCC tumors, histologic concordance among the different renal cell carcinoma masses was estimated at 44% (7/16), and none of the individuals presenting exclusively with CCPRCC tumors developed metastatic disease after 5 yr. In contrast, multifocal tumors with CCPRCC and other nonconcordant histologies were more likely to experience adverse outcomes (CSS, log rank p = 0.034).CCPRCC is characterized by distinct molecular and epidemiologic features that could be used to refine current diagnostic approaches. Although their clinical course is generally indolent, multifocal CCPRCC tumors represent a unique diagnostic challenge. In this context, single-mass biopsies could miss concomitant aggressive disease, with a potential negative impact on patient outcomes. Furthermore, high discordance rates in multifocal CCPRCC tumors have important clinical implications in management.We explored the molecular and clinical features of clear cell papillary renal cell carcinoma (CCPRCC) relative to other kidney cancer subtypes. While CCPRCC generally conveys a good prognosis, additional caution should be taken when it is diagnosed using biopsy if multiple kidney masses are present.

Introduction and objective The lethal necrotizing fasciitis, Fournier's Gangrene, is initially managed with resuscitation, broad-spectrum antibiotics, and aggressive surgical debridement. While the initial management steps are widely described, the subsequent management of skin loss is sparse. Our objective was to focus on the reconstruction of the penile shaft skin loss after wide surgical debridement. Methods A single case was documented from presentation, to treatment, and to recovery. The primary focus was the reconstruction of the penile shaft skin. The combined planning and efforts of genitourinary and plastic surgery were used to reconstruct the penile shaft skin using a split thickness skin graft. Results The penis was tunneled into a viable skin flap of the suprapubic fat pad in response to the wide surgical debridement from the treatment of Fournier's Gangrene. The penis maintained its anatomic function during the healing process. A 12/1000-in. split thickness skin graft from the lateral thigh was chosen to replace the skin deficient. 13 months later, we were able to excise around the preputial collar, un-tunnel the penis and place the skin graft around the penile shaft. A vacuum dressing and foley catheter remained in place for 7 days during an uneventful post-operative course. Ultimately, we found split thickness skin graft successful in this penile reconstruction after Fournier's Gangrene. Conclusion Complete penile shaft skin loss can be managed acutely with tunneling in the suprapubic fat pad, and can be reconstructed with a split thickness skin graft from the lateral thigh.

PURPOSE: Patients undergoing endoscopic management for upper tract urothelial carcinoma often progress to definitive therapy with radical nephroureterectomy. This study examined the rate of progression as well as risk factors for transitions in treatment over time. METHODS: Retrospective review at 2 institutions identified patients undergoing endoscopic management for upper tract urothelial carcinoma. Patients were assessed for progression to radical nephroureterectomy. Baseline characteristics were compared using Chi-Square analysis. Kaplan Meier method analyzed the probability of patients not progressing to radical nephroureterectomy. Cox proportional hazards identified factors associated with progression to radical nephroureterectomy. RESULTS: Eighty-one patients had endoscopic management alone, and 89 progressed to radical nephroureterectomy. The two groups had similar age, histories of bladder cancer, and Charlson Comorbidity Index. Positive urinary cytology, ureteroscopic visualization, and biopsy grade were higher in those progressing to RNU (p

Background The purpose of the study was to identify patient and disease characteristics that have an adverse effect on renal function after partial nephrectomy. Patients and Methods We conducted a retrospective review of 387 patients who underwent partial nephrectomy for renal tumors between 2006 and 2014. A line plot with a locally weighted scatterplot smoothing was generated to visually assess renal function over time. Univariable and multivariable longitudinal regression analyses incorporated a random intercept and slope to evaluate the association between patient and disease characteristics with renal function after surgery. Results Median age was 60 years and most patients were male (255 patients [65.9%]) and white (343 patients [88.6%]). In univariable analysis, advanced age at surgery, larger tumor size, male sex, longer ischemia time, history of smoking, and hypertension were significantly associated with lower preoperative estimated glomerular filtration rate (eGFR). In multivariable analysis, independent predictors of reduced renal function after surgery included advanced age, lower preoperative eGFR, and longer ischemia time. Length of time from surgery was strongly associated with improvement in renal function among all patients. Conclusion Independent predictors of postoperative decline in renal function include advanced age, lower preoperative eGFR, and longer ischemia time. A substantial number of subjects had recovery in renal function over time after surgery, which continued past the 12-month mark. These findings suggest that patients who undergo partial nephrectomy can experience long-term improvement in renal function. This improvement is most pronounced among younger patients with higher preoperative eGFR.

Introduction: We compared characteristics of patients undergoing prostate biopsy in a high-risk inner city population before and after the 2012 USPSTF recommendation against PSA based prostate cancer screening to determine its effect on prostate biopsy practices. Materials and Methods: This was a retrospective study including patients who received biopsies after an abnormal PSA measurement from October 2008-December 2015. Patients with previously diagnosed prostate cancer were excluded. Chi-square tests of independence, two sample t-tests, Mann-Whitney U tests, and Fisher's exact tests were performed. Results: There were 202 and 208 patients in the pre-USPSTF and post-USPSTF recommendation cohorts, respectively. The post-USPSTF cohort had higher median PSA (7.8 versus 7.1ng/mL, p=0.05), greater proportion of patients who were black (96.6% versus 90.5%, p=0.01), and greater percentage of biopsy cores positive for disease (58% versus 29.5%, p

INTRODUCTION AND OBJECTIVES:Primary small cell carcinoma (PSCC) of the kidney represents a rare disease entity. There is little data about the characteristics, optimal therapies, and survival assoc...

INTRODUCTION AND OBJECTIVES:Recent data suggests clear cell renal cell carcinoma (ccRCC) evolutionary subtypes, defined by specific driver mutations and mutation clonality, correlate with clinical ...

INTRODUCTION AND OBJECTIVES:Neoadjuvant chemotherapy (NAC) combined with radical cystectomy (RC) and urinary diversion is the standard of care in the treatment of urothelial muscle invasive bladder...

Improved understanding of renal carcinoma disease biology has led to the discovery and approval of five novel therapies targeting specific molecules in the vascular endothelial growth factor (VEGF) biochemical pathway. Biomarker studies attempting to predict response to VEGF-targeted therapies have largely focused on circulating proteins, tissue-based molecules, and germline polymorphisms. Thus far studies have yielded conflicting results that require prospective validation; therefore no definitive biomarker has yet been integrated into the clinician's armamentarium. However, early analyses featuring genomic biomarkers have generated promising findings. This article provides an overview of available biomarkers evaluated with respect to VEGF-targeted therapies in patients with advanced renal cell carcinoma.

BACKGROUND The exonic single-nucleotide variant rs11762213 located in the MET oncogene has recently been identified as a prognostic marker in clear cell renal cell carcinoma (ccRCC). This finding was validated with The Cancer Genome Atlas (TCGA) cohort, and the biologic implications were explored. METHODS The genotype status for rs11762213 was available for 272 patients. Paired tumor-normal data, genomic data, and clinical information were acquired from ccRCC TCGA data sets. Cancer-specific survival (CSS) was analyzed with the competing risk method, and Cox proportional hazards regression was used for the analysis of the time to recurrence (TTR). Multivariate competing risk models were fitted to adjust for the validated Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score. RESULTS The variant allele of rs11762213 was detected in 10.3% of the cohort. After adjustments for the SSIGN score, the risk allele remained a significant predictor for adverse CSS (hazard ratio [HR], 3.88; 95% confidence interval [CI], 1.99-7.56; P

Objective To assess the impact on recovery of bowel function using an 80 mm versus 60 mm gastrointestinal anastomosis (GIA) stapler following radical cystectomy and urinary diversion (RC/UD) for bladder cancer. Methods We identified 696 patients using a prospectively maintained RC/UD database from January 2006 to November 2010. Two nonrandomized consecutive cohorts were compared. Patients between January 2006- and December 2007 (n = 180) were treated using a 60 mm GIA stapler, and 331 patients between January 2008 and December 2010 were subject to an 80 mm GIA stapler. All patients were treated on the same standardized postoperative recovery pathway. After accounting for baseline patient and perioperative characteristics, using a multivariable logistic regression model, we directly compared rates of postoperative ileus using a standardized definition. Results Of 511 evaluable patients, ileus was observed in 32% (57/180) for 60 mm GIA versus 33% (110/331) for the 80 mm GIA. Preoperative renal function, age, gender, body mass index, and type of diversion were comparable between cohorts. On multivariate analysis, stapler size was not significantly associated with the development of ileus (GIA-60 vs GIA-80: OR 1.11; 95% CI 0.75, 1.66; P = .6). Positive fluid balance was associated with an increased risk ( P = .019) and female sex a decreased risk ( P = .008) of developing ileus compared to patients with negative fluid balance. Conclusion The size of the intestinal bowel anastomosis (GIA 80 mm vs 60 mm) does not independently impact the time to bowel recovery following RC/UD.

PURPOSE: To evaluate the impact of timing of blood transfusion in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). METHODS: Outcomes of consecutive patients with UTUC treated with RNU were analyzed. Clinicopathologic factors were compared using Fisher’s exact test or the Wilcoxon rank-sum test between patients that received any transfusion and no transfusion, and between patients receiving intraoperative transfusion only and patients receiving no transfusion. Cancer-specific and overall survival were estimated and multivariable analyses were performed to assess the impact of timing of transfusion on clinical outcomes. RESULTS: Among 402 patients included in this study, 71 (17.6%) patients received a transfusion at any point and 27 (6.7%) patients received an intraoperative blood transfusion. Transfusion at any time, patient comorbidity, high grade, advanced stage, positive surgical margins, low preoperative hemoglobin, longer operative duration, and increased blood loss were significantly associated with cancer-specific survival (DSS) on univariable analysis (HR 1.85, 95% CI 1.20–2.85, p

The utility of cancer cell lines is affected by the similarity to endogenous tumour cells. Here we compare genomic data from 65 kidney-derived cell lines from the Cancer Cell Line Encyclopedia and the COSMIC Cell Lines Project to three renal cancer subtypes from The Cancer Genome Atlas: clear cell renal cell carcinoma (ccRCC, also known as kidney renal clear cell carcinoma), papillary (pRCC, also known as kidney papillary) and chromophobe (chRCC, also known as kidney chromophobe) renal cell carcinoma. Clustering copy number alterations shows that most cell lines resemble ccRCC, a few (including some often used as models of ccRCC) resemble pRCC, and none resemble chRCC. Human ccRCC tumours clustering with cell lines display clinical and genomic features of more aggressive disease, suggesting that cell lines best represent aggressive tumours. We stratify mutations and copy number alterations for important kidney cancer genes by the consistency between databases, and classify cell lines into established gene expression-based indolent and aggressive subtypes. Our results could aid investigators in analysing appropriate renal cancer cell lines., Cell lines are central to cancer research, but knowing which cell lines are the best representative of actual tumours is a major challenge. Here the authors provide a resource assessment of 65 renal cell lines to assist researchers in selecting suitable lines for studying specific renal carcinoma subtypes.

Background We evaluated the incidence and effect of thromboembolic events (TEEs) in patients with muscle-invasive bladder cancer treated with preoperative chemotherapy (POC) and radical cystectomy (RC) with pelvic lymph node dissection (PLND). Patients and Methods We performed a retrospective review of all patients who had undergone POC followed by RC plus PLND for muscle-invasive bladder cancer from June 2000 to January 2013 (n = 357). The chemotherapy type (neoadjuvant vs. induction), incidence and timing of TEE diagnosis (preoperatively vs. ≤ 90 days postoperatively), and effect of TEEs on clinical outcomes were recorded. Results Overall, 79 patients (22%; 95% confidence interval [CI], 18%-27%) experienced a TEE: 57 (16%) occurred during POC and 22 (6.2%) were diagnosed postoperatively. Forty patients (11%; 95% CI, 8.1%-15%) required an inferior vena cava filter. We found no significant differences in neoadjuvant versus induction chemotherapy and the risk of TEEs (difference, 3.3%; 95% CI, −5% to 12%; P = .5). No significant difference were found in the rates of POC completion according to the presence of a TEE (difference, 1.0%; 95% CI, −11% to 13%; P = .9). The occurrence of TEE did not significantly affect other perioperative outcomes. The risk of recurrence and overall survival were not associated with TEE on multivariable analysis. Conclusion We found a high incidence of TEEs (22%) in patients undergoing POC before RC plus PLND, with a 16% incidence in the preoperative period. TEEs in the POC setting leads to invasive procedures; however, we did not find a significant effect on POC completion or postoperative complication risk. Further research is required to determine whether preventative TEE measures during POC can improve clinical outcomes.

BACKGROUND Prior studies examining the value of lymph node (LN) dissection (LND) in patients with urothelial carcinoma of the upper urinary tract (UTUC) have produced conflicting results. The objective of the current study was to assess the relationship between LN yield and survival among patients undergoing radical nephroureterectomy (RNU). METHODS The National Cancer Data Base was used to identify patients with non-metastatic UTUC who were treated with RNU between 2004 and 2012. The association between LN yield and overall survival (OS) was assessed using Cox proportional hazards regression, with adjustment for patient, tumor, and facility characteristics. RESULTS Of the 14,472 patients, 2926 (20%) underwent LND. The median yield was 2 LNs (interquartile range 1-6 LNs). Among the entire cohort and the LN-negative (pN0) subgroup, a higher LN yield was associated with lower all-cause mortality (multivariable hazard ratio [HR] 0.94 per 5 LNs removed, 95% confidence interval [95% CI] 0.89-1.00 [P = .034] for the entire cohort and HR 0.86, 95% CI 0.79-0.94 [P = .001] for the pN0 subgroup). Among patients with positive LNs (pN+), there was no association noted between LN yield and OS; however, positive and negative LN counts were found to be independent predictors of OS (HR 1.27 per 5 positive LNs, 95% CI 1.16-1.39 [P

e24151Background: Confirmation of prostate cancer in men with elevated PSA and suspicious digital rectal exams currently requires a core needle biopsy, which is associated with risks such as infect...

12070Background: Bladder cancer patients are routinely monitored after treatment by cystoscopy due to a high rate of recurrence. In the absence of an accurate non-invasive screening test to monitor...

Infiltrating T cells in the tumor microenvironment have crucial roles in the competing processes of pro-tumor and anti-tumor immune response. However, the infiltration level of distinct T cell subsets and the signals that draw them into a tumor, such as the expression of antigen presenting machinery (APM) genes, remain poorly characterized across human cancers. Here, we define a novel mRNA-based T cell infiltration score (TIS) and profile infiltration levels in 19 tumor types. We find that clear cell renal cell carcinoma (ccRCC) is the highest for TIS and among the highest for the correlation between TIS and APM expression, despite a modest mutation burden. This finding is contrary to the expectation that immune infiltration and mutation burden are linked. To further characterize the immune infiltration in ccRCC, we use RNA-seq data to computationally infer the infiltration levels of 24 immune cell types in a discovery cohort of 415 ccRCC patients and validate our findings in an independent cohort of 101 ccRCC patients. We find three clusters of tumors that are primarily separated by levels of T cell infiltration and APM gene expression. In ccRCC, the levels of Th17 cells and the ratio of CD8+ T/Treg levels are associated with improved survival whereas the levels of Th2 cells and Tregs are associated with negative clinical outcome. Our analysis illustrates the utility of computational immune cell decomposition for solid tumors, and the potential of this method to guide clinical decision-making.

INTRODUCTION AND OBJECTIVES: Patients with upper tract urothelial carcinoma (UTUC) may undergo endoscopic procedures for diagnostic and therapeutic intentions prior to definitive surgical management with radical nephrouretectomy (RNU). We assessed for differences in survival based on initial management strategy. METHODS: From 2004 to present, patients undergoing RNU for low grade UTUC from Memorial Sloan-Kettering Cancer Center (MSKCC) had their charts reviewed retrospectively to identify those patients who were initially managed endoscopically with ureteroscopy and tumor ablation. Those less than 66 years of age were excluded to provide an age-matched cohort for combined analysis. Data from Surveillance, Epidemiology and End Results (SEER) from this same time period was obtained and the same selection criteria was used. Survival trends were assessed with Kaplan-Meier analyses. Cox-proportional hazard models were constructed to determine the independent effect of initial management strategy on overall survival (OS) and cancer specific survival (CSS) controlling for age, race, gender, comorbidity, and data source. RESULTS: 838 patients went directly to RNU, and 167 had RNU after initial endoscopic management. We found no difference in OS between the groups (p1⁄40.632) with median follow up of 96 months. The Kaplan-Meier survival analysis for CSS comparing endoscopic management with initial RNU is shown in the figure. Conversely, CSS was significantly worse for those treated with endoscopic management first versus immediate definitive surgery (HR 1.69, 95% CI 1.07-2.69, p1⁄40.025). CONCLUSIONS: In elderly patients with low grade UTUC, there is no difference in overall survival for those that start with endoscopic management of their disease. The observed lower CSS in these patients bears further investigation of the possible contributory selection factors in this patient population.

INTRODUCTION AND OBJECTIVES: Aside from a biopsy, little information exists to guide a clinician when evaluating a patient with a solid renal mass. An elevated neutrophil-lymphocyte ratio (NLR) has been associated with adverse outcomes in clear cell renal cell carcinoma (ccRCC). However, its ability to distinguish aggressive RCC from benign, or indolent, renal tumors remains unknown. Therefore, we evaluate the association of NLR with pathologic outcomes at nephrectomy, including the ability to distinguish benign and malignant renal lesions. METHODS: From 1995-2008, 2402 patients underwent nephrectomy for localized renal masses. Of these, 2039 had an NLR collected 90 days prior to nephrectomy. Comparisons of NLR by tumor size, histologic subtype and nuclear grade were evaluated. RESULTS: Overall, benign renal masses had a significantly lower NLR than malignant renal tumors (median 2.92 vs. 3.12; p 1⁄40.037) with the greatest difference noted among renal lesions > 7 cm (median 2.79 vs 3.87; p 4 but 7 cm 1⁄4 3.09 and > 7 cm 1⁄4 3.95) and nuclear grade (G1 1⁄4 2.68, G2 1⁄4 2.87, G3 1⁄4 3.48 and G4 1⁄4 5.18) was associated with greater NLR (both p < 0.001). Finally, after stratifying ccRCC by tumor size, there was a continual increase in NLR with greater nuclear grade. CONCLUSIONS: An elevated NLR is associated with an increased risk of RCC at the time of nephrectomy as well as higher grade tumors and more aggressive histologic subtypes. Therefore, NLR appears to be a preoperative marker of aggressive RCC and may be useful in predicting malignancy and guiding management among patients with suspicious renal lesions.

Background and Objectives The use of patient-controlled epidural analgesia after various operations has been associated with an early return of bowel function, thus decreasing patients’ length of stay (LOS). The primary aim of this study was to compare LOS after radical cystectomy between patients who received epidural analgesia versus those who received intravenous patient-controlled analgesia. Our secondary analysis included the assessment of other metrics such as total opioid requirements, pain scores, return of bowel function, and complication rates between the 2 groups. Methods We conducted a retrospective review using the electronic medical records of 308 patients who underwent radical cystectomies at Memorial Sloan Kettering between 2006 and 2011. We aimed to understand if epidural analgesia was associated with a reduced LOS compared with patient-controlled intravenous opioid analgesia. We also aimed to identify performance improvements as a function of epidural analgesia status using various metrics such as pain management, bowel function return, and complication rates. We used both univariate and multivariate analyses to identify if epidural analgesia was associated with meaningful differences in the aforementioned metrics. Results Median age at radical cystectomy, body mass index, sex, American Society of Anesthesiologists score, and T stage were similar for both groups. For our primary objective of LOS, we found no significant difference between the 2 cohorts (8 vs 7 days, P = 0.2). Analysis of our secondary outcome measures revealed that epidural analgesia use was associated with less total opioid requirement for the first 3 postoperative days (PODs) (P = 0.0001). In addition, epidural analgesia was found to be associated with improved postoperative pain scores compared with intravenous patient-controlled analgesia on PODs 1 (P = 0.0001) and 2 (P = 0.004), and there was a slight improvement on POD 3, but this was not significant (P = 0.77). In contrast, we found no difference between pain management types with regard to proportion of patients who experienced a delay in gastrointestinal recovery, fluid bolus requirements within the first 3 perioperative days, rates of infection, pulmonary complications, and grade 3 or greater complications. Conclusions We have demonstrated that, despite significant improvements in initial pain control and less opioid requirement with patient-controlled epidural analgesia, there was no association between analgesic approach and LOS, return of bowel function, or complications.

Tumor size and stage are important prognostic parameters in renal cell carcinoma. While pathological stage T1 and T2 are defined by size alone, the presence of certain intrinsic features can up stage a tumor to pathological stage T3a regardless of size. We investigate the effect of pathological tumor stage on the relationship between tumor size and risk of disease recurrence.Data were reviewed on patients who underwent nephrectomy at our institution between 2006 and 2013 to identify all those with pathological stage T1, T2 and T3a tumors. A proportional hazards Cox model was built with time to recurrence as outcome, and pathological stage and tumor size as covariates. An interaction term for stage and tumor size was included.The final cohort included 1,809 patients. On multivariable analysis, when adjusted for tumor size, patients with pT3a tumors had a greater risk of tumor recurrence compared to those with pT1/T2 tumors (HR 3.70; 95% CI 2.31, 5.92; p0.0001). The risk of disease recurrence increased more rapidly as tumor size increased only with the presence of perinephric fat invasion (p=0.006).Using the AJCC 2010 staging criteria we validated pathological stage T3a as a poor prognostic factor in renal cell carcinoma regardless of tumor size. Our results also demonstrated an increased rate of risk of recurrence with perinephric fat invasion. Given this increased risk of recurrence, even in tumors less than 4 cm, closer surveillance is warranted in such cases and the role of perinephric involvement necessitates further investigation.

Objective To evaluate clinicopathologic characteristics and treatment outcomes of patients undergoing partial nephrectomy (PN) or radical nephrectomy (RN) for unilateral synchronous multifocal renal tumors. Methods We retrospectively reviewed medical records for 128 patients with nonmetastatic, unilateral, synchronous, multifocal renal tumors who underwent surgical resection at our institution from 1995 to 2012. Five patients with hereditary renal cell carcinoma were excluded. Differences between patient and tumor characteristics from the 2 nephrectomy groups were evaluated. Outcomes in terms of recurrence-free survival, overall survival, and chronic kidney disease upstaging were estimated using Kaplan-Meier methods. The log-rank test was used for group comparisons. Results The study cohort included 78 PN patients (63%) and 45 RN patients (37%); 17 of 95 planned PN (18%) were converted to RN. Tumor diameter and RENAL nephrometry scores were greater in RN patients ( P P = .0002, respectively). Pathologic stage T3 was seen in 40% of RN patients and 10% of PN patients ( P = .0002). Histologic concordance was apparent in 60 of 123 patients (49%). Median follow-up for patients alive without a recurrence was 4 years. Five-year recurrence-free survival was 98% for PN and 85% for RN. Five-year overall survival was 96% for PN and 86% for RN ( P = .5). Five-year freedom from chronic kidney disease upstaging was 74% for PN and 55% for RN ( P = .11). Conclusion Partial nephrectomy for the treatment of unilateral, synchronous, multifocal, renal tumors with favorable characteristics was associated with a low recurrence rate. These findings suggest PN is an appropriate management strategy for this group of carefully selected patients.

Interleukin (IL)–12 has antitumor effects in murine studies. To evaluate this clinically, we investigated whether high levels of circulating IL-12 in patients after allogeneic hematopoietic stem cell transplantation (HSCT) are associated with improved relapse-free survival. We prospectively studied 134 patients undergoing HSCT. Median follow-up was 1158 days (range, 70-1792 days). Plasma IL-12 levels were measured before transplantation and on days 0, +4, +7, and +14 after transplantation. The highest levels were seen on days +4 and +7 and were categorized by a cluster analysis of the logarithmically transformed IL-12 concentrations, which were then correlated with relapse-free survival. Forty-six patients had low levels of IL-12 (median, 2 pg/mL; range, 0-6.5 pg/mL), 49 patients had medium levels (median, 20.5 pg/mL; range, 7-75.5 pg/mL), and 25 patients had high levels (median, 181 pg/mL; range, 84-623 pg/mL). Patients with high IL-12 levels before transplantation had the highest increase after transplantation. With a multivariate Cox model for relapse onset, with the low IL-12 level as the reference, patients in the high–IL-12 group had an adjusted hazard ratio of 0.27 (95% confidence interval, 0.09-0.79), and medium group patients had a hazard ratio of 0.65 (95% confidence interval, 0.31-1.36). The incidences of relapse at 500 days by Kaplan-Meier analysis by IL-12 group were 23.0% (high group), 40.3% (medium group), and 48.8% (low group). There was no association between IL-12 levels and the risk of acute graft-versus-host disease (GVHD; P = .51) or chronic GVHD (P = .28). In conclusion, high IL-12 levels after HSCT are associated with improved relapse-free survival without increasing the risk for GVHD. Patients with high pretransplantation IL-12 levels have an increased likelihood of higher posttransplantation IL-12 levels, possibly because of a host-graft interaction, and this may predispose to better clinical outcomes.