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Background Personalized genomic classifiers have transformed the management of prostate cancer (PCa) by identifying the most aggressive subsets of PCa. Nevertheless, the performance of genomic classifiers to risk classify African American men is thus far lacking in a prospective setting. Methods This is a prospective study of the Decipher genomic classifier for National Comprehensive Cancer Network low- and intermediate-risk PCa. Study-eligible non–African American men were matched to African American men. Diagnostic biopsy specimens were processed to estimate Decipher scores. Samples accrued in NCT02723734, a prospective study, were interrogated to determine the genomic risk of reclassification (GrR) between conventional clinical risk classifiers and the Decipher score. Results The final analysis included a clinically balanced cohort of 226 patients with complete genomic information (113 African American men and 113 non–African American men). A higher proportion of African American men with National Comprehensive Cancer Network–classified low-risk (18.2%) and favorable intermediate-risk (37.8%) PCa had a higher Decipher score than non–African American men. Self-identified African American men were twice more likely than non–African American men to experience GrR (relative risk [RR] = 2.23, 95% confidence interval [CI] = 1.02 to 4.90; P = .04). In an ancestry-determined race model, we consistently validated a higher risk of reclassification in African American men (RR = 5.26, 95% CI = 1.66 to 16.63; P = .004). Race-stratified analysis of GrR vs non-GrR tumors also revealed molecular differences in these tumor subtypes. Conclusions Integration of genomic classifiers with clinically based risk classification can help identify the subset of African American men with localized PCa who harbor high genomic risk of early metastatic disease. It is vital to identify and appropriately risk stratify the subset of African American men with aggressive disease who may benefit from more targeted interventions.

Purpose To assess the association of patient age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer (MIBC). Materials and methods We analyzed data from 1105 patients with MIBC. Patients age was evaluated as continuous variable and stratified in quartiles. Pathologic objective response (pOR; ypT0-Ta-Tis-T1N0) and pathologic complete response (pCR; ypT0N0), as well survival outcomes were assessed. We used data of 395 patients from The Cancer Genome Atlas (TCGA) to investigate the prevalence of TCGA molecular subtypes and DNA damage repair (DDR) gene alterations according to patient age. Results pOR was achieved in 40% of patients. There was no difference in distribution of pOR or pCR between age quartiles. On univariable logistic regression analysis, patient age was not associated with pOR or pCR when evaluated as continuous variables or stratified in quartiles (all p > 0.3). Median follow-up was 18 months (IQR 6–37). On Cox regression and competing risk regression analyses, age was not associated with survival outcomes (all p > 0.05). In the TCGA cohort, patient with age ≤ 60 years has 7% less DDR gene mutations (p = 0.59). We found higher age distribution in patients with luminal (p p = 0.002) compared to those with luminal papillary subtype. Conclusions While younger patients may have less mutational tumor burden, our analysis failed to show an association of age with response to preoperative chemotherapy or survival outcomes. Therefore, the use of preoperative chemotherapy should be considered regardless of patient age.

Objective To assess the effect of patient's sex on response to neoadjuvant chemotherapy (NAC) in patients with clinically nonmetastatic muscle-invasive bladder cancer (MIBC). Methods Complete pathologic response, defined as ypT0N0 at radical cystectomy, and downstaging were evaluated using sex-adjusted univariable and multivariable logistic regression modeling. We used interaction terms to account for age of menopause and smoking status. The association of sex with overall survival and cancer-specific survival was evaluated using Cox regression analyses. Results A total of 1,031 patients were included in the analysis, 227 (22%) of whom were female. Female patients had a higher rate of extravesical disease extension (P = 0.01). After the administration of NAC, ypT stage was equally distributed between sexes (P = 0.39). On multivariable logistic regression analyses, there was no difference between the sexes or age of menopause with regards to ypT0N0 rates or downstaging (all P > 0.5). On Cox regression analyses, sex was associated with neither overall survival (hazard ratio 1.04, 95% confidence interval 0.75–1.45, P = 0.81) nor cancer-specific survival (hazard ratio 1.06, 95% confidence interval 0.71–1.58, P = 0.77). Conclusion Our study generates the hypothesis that NAC equalizes the preoperative disparity in pathologic stage between males and females suggesting a possible differential response between sexes. This might be the explanation underlying the comparable survival outcomes between sexes despite females presenting with more advanced tumor stage.

Introduction The neutrophil-to-lymphocyte ratio (NLR) is an attractive marker because it is derived from routine bloodwork. NLR has shown promise as a prognostic factor in muscle invasive bladder cancer (MIBC) but its value in patients receiving neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) is not yet established. Since NLR is related to an oncogenic environment and poor antitumor host response, we hypothesized that a high NLR would be associated with a poor response to NAC and would remain a poor prognostic indicator in patients receiving NAC. Methods A retrospective analysis was performed on patients with nonmetastatic MIBC (cT2-4aN0M0) who received NAC prior to RC between 2000 and 2013 at 1 of 19 centers across Europe and North America. The pre-NAC NLR was used to split patients into a low (NLR ≤ 3) and high (NLR > 3) group. Demographic and clinical parameters were compared between the groups using Student's t test, chi-squared, or Fisher's exact test. Putative risk factors for disease-specific and overall survival were analyzed using Cox regression, while predictors of response to NAC (defined as absence of MIBC in RC specimen) were investigated using logistic regression. Results Data were available for 340 patients (199 NLR ≤ 3, 141 NLR > 3). Other than age and rate of lymphovascular invasion, demographic and pretreatment characteristics did not differ significantly. More patients in the NLR > 3 group had residual MIBC after NAC than the NLR ≤ 3 group (70.8% vs. 58.3%, P = 0.049). NLR was the only significant predictor of response (odds ratio: 0.36, P = 0.003) in logistic regression. NLR was a significant risk factor for both disease-specific (hazard ratio (HR): 2.4, P = 0.006) and overall survival (HR:1.8, P = 0.02). Conclusion NLR > 3 was associated with a decreased response to NAC and shorter disease-specific and overall survival. This suggests that NLR is a simple tool that can aid in MIBC risk stratification in clinical practice.

5005 Background: Risk stratification of prostate cancer (PC) using routine clinical variables remains suboptimal as they do not account for underlying tumor biology. The genomic classifier provides information on underlying biology and independently predicts an individual patient’s risk of metastasis. Although the performance of the genomic classifier has been tested across different cohorts primarily comprised of White men, its validation as an optimal genomic risk classifier for African American men (AAM) is thus far lacking in a prospective trial. We report the initial results on the prospective validation of the genomic classifier in a matched cohort of AAM and non-AAM (NAAM). Methods: This was a multisite, prospective validation trial of the genomic classifier i.e. Decipher score in AAM. Participants were recruited on a 1:1 enrollment ratio of AAM to NAAM diagnosed with low-intermediate risk PC. Patient on active surveillance were ineligible. NAAM were matched to AAM on PSA, age, biopsy Gleason score, clinical stage, and percent positive biopsy cores. Diagnostic biopsy specimens were processed at a CLIA certified laboratory and Decipher score was assessed using whole transcriptome profiling platform. Total target accrual was 250 men treated for low-intermediate PC over three years. Statistical analyses include categorical comparison of race dependent risk group migration between NCCN risk group and genomic classifier. Relative risk of metastasis was estimated using negative binomial model. Results: Final analytical cohort included 207 evaluable cases (AAM = 102 and NAAM = 107) with comprehensive genomic information. Risk of metastasis was determined based on pretreatment biopsy Decipher score, and patients were classified as low, favorable-, and unfavorable intermediate risk. Despite achieving a robustly matched clinical cohort, we observed significant genomic heterogeneity between AAM and NAAM across NCCN risk groups. In a comparative analysis, 49% of low-favorable intermediate risk AAM harbored high genomic risk tumors as compared to only 10% NAAM, p = 0.02. Similarly, using the modified clinico-genomic risk classifier (cGC), comprised of both Decipher score and clinical variables, AAM experienced an extreme deviation of risk status (difference [δ] between cGC and NCCN ≥ 2) as compared to NAAM (26.8% vs 8.1%, p = 0.03). In a binomial model, low-favorable NCCN risk AAM were 3.9 times more likely to be reclassified as high genomic risk for distant metastasis compared to NAAM (RR = 3.99, 95% CI, 1.15 – 13.86, p = 0.02). Conclusions: Clinical NCCN risk classification is an inadequate surrogate of tumor biology and offers suboptimal risk stratification for AAM with PC. Integration of patient specific genomic classifier into standard of care will improve accuracy in disease risk classification and treatment recommendations for AAM. Clinical trial information: NCT02723734.

Objective: Sarcopenia, or the age-related loss of skeletal muscle mass and function, has been investigated as a potential marker of adverse outcomes among surgical patients. Our aim was to assess for changes in psoas muscle volume (PMV) following administration of neoadjuvant chemotherapy (NAC) in patients with bladder cancer and to examine whether changes in PMV following NAC are predictive of perioperative complications, pathologic response or survival. Methods: During the period of 2009–2013, patients undergoing NAC and radical cystectomy (RC) at our institution with pre and post NAC cross sectional images available were included. Bilateral total psoas muscle volume (PMV) was obtained from pre- and post- NAC images and the proportion of PMV change was calculated by dividing the change PMV by pre-NAC PMV. Analyses for the assessment of factors predicting PMV loss, partial/complete pathologic response (pPR/pCR), complications, readmission, cancer specific (CSS), recurrence-free (RFS) and overall survival (OS) were performed. Results: Total of 60 patients had complete radiological data available. Post-NAC PMV and BMI declines were statistically significant, 4.9% and 0.05%, respectively. NAC dose reduction/delay was a significant predictor of PMV loss (coefficient B 4.6; 95% CI 0.05–9.2; p = 0.047). The proportion of PMV decline during NAC was not a predictor of pPR, pCR, complications, readmission, CSS, RFS, or OS. Conclusions: We observed an interval decline in PMV during the period of NAC administration and this decline was more than it could be appreciated with changes in BMI during the same period. PMV decline was associated with the need for dose reduction/dose delay during NAC. In our series, PMV changes occurring during NAC administration were not predictive of pathologic response to chemotherapy, postoperative complications or survival.

We assessed survival dependent on pathological response after neoadjuvant chemotherapy in a large multicenter patient cohort, with a particular focus on the difference between the absence of residual cancer (pT0) and the presence of only nonmuscle invasive residual cancer (pTa, pTis, pT1).We retrospectively reviewed records of patients with urothelial cancer who received neoadjuvant chemotherapy and underwent radical cystectomy at 19 contributing institutions from 2000 to 2013. Patients with cT2-4aN0M0 and eventual pN0 disease were selected for this analysis. Estimated overall survival was compared between patients with pT0 and pTa/Tis/T1 disease. A multivariable Cox proportional hazards regression model for overall survival was generated to evaluate hazard ratios for variables of interest.Of 1,543 patients treated with neoadjuvant chemotherapy and radical cystectomy during the study period 257 had pT0N0 and 207 had pTa/Tis/T1N0 disease. The Kaplan-Meier mean estimates of overall survival for pT0 and pTa/Tis/T1 cases were 186.7 months (95% CI 145.9-227.6, median 241.1) and 138 months (95% CI 118.2-157.8, median 187.4), respectively (p=0.58). In the Cox proportional hazards regression model for overall survival pTa/Tis/T1N0 status (HR 0.36, 95% CI 0.23-0.67) and pT0N0 status (HR 0.28, 95% CI 0.17-0.47) compared to pT2N0 pathology, positive surgical margin (HR 1.75, 95% CI 1.07-2.86), and receiving a methotrexate, vinblastine, doxorubicin and cisplatin regimen compared to an "other" regimen (HR 0.45, 95% CI 0.27-0.76) were predictors of overall survival.pTa/Tis/T1N0 and pT0N0 stage on the final cystectomy specimen are strong predictors of survival in patients treated with neoadjuvant chemotherapy and radical cystectomy. We did not discern a statistically significant difference in overall survival when comparing these 2 end points.

Objective To evaluate the impact of extended warm ischemia on incidence of acute kidney injury (AKI) and ultimate functional recovery after partial nephrectomy (PN), incorporating rigorous control for loss of parenchymal mass, and embedded within comparison to cohorts of patients managed with hypothermia or limited warm ischemia. Materials and Methods From 2007 to 2014, 277 patients managed with PN had appropriate studies to evaluate changes in function/mass specifically within the operated kidney. Recovery from ischemia was defined as %function saved/%parenchymal mass saved. AKI was based on global renal function and defined as a ≥1.5-fold increase in serum creatinine above the preoperative level. Results Hypothermia was utilized in 112 patients (median = 27 minutes) and warm ischemia in 165 (median = 21 minutes). AKI strongly correlated with solitary kidney ( P P P = .49) of ischemia. Median recovery from ischemia in the operated kidney was 100% (interquartile range [IQR] = 88%-109%) for cold ischemia, with 6 (5%) noted to have P P 35 minutes (n = 16), median recovery from ischemia was 92% (IQR = 86%-100%), 90% (IQR = 78%-104%), and 91% (IQR = 80%-96%), respectively ( P = .77). Conclusion Our results suggest that AKI after PN correlates with duration but not with type of ischemia. However, subsequent recovery, which ultimately defines the new baseline glomerular filtration rate, is most reliable with hypothermia. However, most patients undergoing PN with warm ischemia still recover relatively strongly from ischemia, even if extended to 35-45 minutes.

Introduction: The treatment of pelvic malignancies with radiotherapy can develop severe sequelae, especially radiation-induced hemorrhagic cystitis. It is a progressive disease that can lead to the need for blood transfusion, hospitalizations, and surgical interventions. This tends to affect the quality of life of these patients, and management can at times be difficult. We have evaluated the GreenLight Xcelerated Performance System (XPS) with TruCoag, although primarily used for management of benign prostatic hypertrophy (BPH), for the treatment of radiation-induced hemorrhagic cystitis. Materials and Methods: After International Review Board (IRB) approval, a retrospective chart review was performed in addition to a literature search. A series of four male patients, mean age of 81 years, with radiation-induced hemorrhagic cystitis secondary to radiotherapy for pelvic malignancies (3 prostate cancer, 1 rectal cancer) were successfully treated with the GreenLight laser after unsuccessful treatment with current therapies described in the literature. Results: All four patients treated with the GreenLight laser had resolution of their hematuria after one treatment and were discharge from the hospital with clear urine. Conclusion: The GreenLight XPS laser shows promising results for the treatment of patients with radiation-induced hemorrhagic cystitis, and deserves further evaluation and validation, especially since there is limited data available in the literature regarding the use of this technology for the treatment of this devastating condition.

Objective Ischemia is a potential contributor to decline of function after partial nephrectomy (PN), although loss of parenchymal mass related to excision and reconstruction appears to be a more significant factor. However, loss of parenchymal mass could also be due to global effects of ischemia leading to parenchymal atrophy. In this study, we evaluated parenchymal volumes in regions away from the operated site to assess for atrophy. Materials and Methods A total of 164 patients undergoing PN for whom detailed analysis of function and parenchymal mass within the operated kidney could be performed were assessed for opposite pole volume (OPV) before and 4-12 months after surgery. Tumor location was required to be ≥2 cm away from the opposite polar line to exclude local effects related to excision or reconstruction. OPV was estimated by software analysis, and the ratio of the estimates (OPV ratio = postoperative OPV to preoperative OPV) was used to assess for atrophy. Results Patient demographics and tumor characteristics were representative of conventional PN populations, and warm ischemia (n = 101; median, 21 minutes) and cold ischemia (n = 63; median, 26 minutes) were applied by surgeon discretion. OPVs before and after PN were 63.2 and 62.5 cm 3 , respectively ( P = .76). The median OPV ratio was 0.99 suggesting that significant atrophy did not occur. OPV ratio was 0.99 for warm ischemia cases and 0.99 for cold ischemia cases ( P = .95). Conclusion Limited warm ischemia or hypothermia was not associated with significant parenchymal atrophy after PN, which suggests that parenchymal volume loss in this setting is primarily due to excision or reconstruction.

Active surveillance (AS) has been widely implemented within Veterans Affairs' medical centers (VAMCs) as a standard of care for low-risk prostate cancer (PCa). Patient characteristics such as age, race, and Agent Orange (AO) exposure may influence advisability of AS in veterans. The 17-gene assay may improve risk stratification and management selection.To compare management strategies for PCa at 6 VAMCs before and after introduction of the Oncotype DX Genomic Prostate Score (GPS) assay.We reviewed records of patients diagnosed with PCa between 2013 and 2014 to identify management patterns in an untested cohort. From 2015 to 2016, these patients received GPS testing in a prospective study. Charts from 6 months post biopsy were reviewed for both cohorts to compare management received in the untested and tested cohorts.Men who just received their diagnosis and have National Comprehensive Cancer Network (NCCN) very low-, low-, and select cases of intermediate-risk PCa.Patient characteristics were generally similar in the untested and tested cohorts. AS utilization was 12% higher in the tested cohort compared with the untested cohort. In men younger than 60 years, utilization of AS in tested men was 33% higher than in untested men. AS in tested men was higher across all NCCN risk groups and races, particular in low-risk men (72% vs 90% for untested vs tested, respectively). Tested veterans exposed to AO received less AS than untested veterans. Tested nonexposed veterans received 19% more AS than untested veterans. Median GPS results did not significantly differ as a factor of race or AO exposure.Men who receive GPS testing are more likely to utilize AS within the year post diagnosis, regardless of age, race, and NCCN risk group. Median GPS was similar across racial groups and AO exposure groups, suggesting similar biology across these groups. The GPS assay may be a useful tool to refine risk assessment of PCa and increase rates of AS among clinically and biologically low-risk patients, which is in line with guideline-based care.

This review highlights the significant advances made in the diagnosis and management of penile cancer. This often-aggressive tumor phenotype has been characterized by its poor prognosis, mostly attributable to its late presentation and heterogeneity of surgical care because of the paucity of cases treated at most centers. Recent advances in understanding of the risk factors predisposing to penile cancer, including its association with the human papilloma virus (HPV), have brought forth the socioepidemiologic concept of HPV vaccination in certain high-risk populations and countries, which remains highly debated. The management of penile cancer has evolved in recent years with the adoption of penile-sparing and minimally invasive surgical approaches to the inguinal lymph nodes, which are a frequent site of regional spread for this malignancy. Lastly, this review highlights the importance of adopting a multimodal approach consisting of neoadjuvant systemic chemotherapy followed by consolidative surgical resection in patients presenting with bulky/locally advanced nodal metastases from penile cancer.

Study Type – Therapy (case series) Level of Evidence 4 OBJECTIVE To report the functional and oncological outcome of nephron-sparing surgery (NSS) for pathological stage pT3bNxMx (2002 Tumour-Node-Metastasis staging) renal cell carcinoma (RCC) with tumour thrombus confined to the renal vein. PATIENTS AND METHODS Of the 305 patients who underwent NSS at our institute from October 2004 to July 2009, seven (2%) were found to have stage T3bNxMx RCC on final pathology. Their charts were reviewed to identify demographic, operative and pathology details of these patients, in addition to obtaining functional and oncological outcome data. RESULTS All seven patients had centrally located endophytic tumours. There were absolute indications for NSS in six patients (solitary kidney in five, renal insufficiency in one). The clinical stage was T1a in five and T3b in two patients; in those with cT1a, thrombus was first identified with intraoperative ultrasonography in two and by palpation of the renal vein or during the NSS in the remaining three. Renal surface hypothermia was applied in four cases (mean 77 min) and warm ischaemia in three (mean 38 min). The mean (range) tumour size was 3.9 (2.5–6) cm and all the tumours were clear cell RCC on histology, and all had negative surgical margins. The mean estimated glomerular filtration rate (eGFR) decreased by 24% after surgery. One patient developed new-onset renal failure (eGFR

Currently, radical prostatectomy is the most commonly used treatment option for clinically localized prostate cancer in the United States. Surgical advances have been made due to better understanding of the prostatic and periprostatic anatomy, and technological developments of robotic instrumentation. In return, there have been improvements in oncological and functional outcomes: continence and potency. In part due to its minimally invasive approach, robotic-assisted laparoscopic radical prostatectomy has increased in popularity over the past decade and has supplanted the open, retropubic approach as the most common surgical intervention. However, case series from centers of excellence for open, laparoscopic, and robotic-assisted laparoscopic radical prostatectomy have comparable outcomes. Determining factors on which procedure is best suited for the patient are based on surgeon experience and comfort with procedure, clinical judgment, and well-defined expectations for the patients. There are advantages and disadvantages with each approach, yet impact on outcomes remains to be better clarified. As the minimally invasive techniques increase in use, learning curves and cost of instruments have to be considered when comparing open and laparoscopic/robotic-assisted series. Ongoing developments in surgical techniques (open or minimally invasive) and increasing understanding of the local anatomy will serve to further improve oncological and functional outcomes.

available at http://www.ncbi.nlm.nih.gov/pubmed/25216271 Editorial Comment: What is the best pharmacological regimen for men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia? The authors perform a systematic network analysis of 66 randomized controlled trials covering 7 different types of therapeutic regimens in 29,384 men. None of the trials analyzed was longer than 24 weeks. Interestingly the best regimen for improving symptoms was the combination of phosphodiesterase type 5 inhibitors and alpha blockers (ABs). The best regimen for improving maximum flow rate was an alpha blocker and 5alpha-reductase inhibitor. It is noteworthy that the second best regimen for LUTS improvement was an AB and an antimuscarinic receptor antagonist. These approaches all outperformed monotherapies. Some caveats include limiting analyzed studies to those 24 weeks or less. This approach tends to preclude landmark longer term studies, such as those using a combination of ABs and 5alphareductase inhibitors, which is generally thought to be the best regimen by the urological community. Moreover, these analyses do not filter out prostate size, concomitant sexual dysfunction and/or predominant symptoms, ie storage vs voiding. Ultimately monotherapies will be the first-line treatment for most men with LUTS secondary to benign prostatic hyperplasia. Prostate size, type of symptom, ie storage vs voiding, as well as the presence of concomitant sexual dysfunction will help drive the second drug used, if needed. Steven A. Kaplan, MD Suggested Reading Dmochowski R, Roehrborn CG, Klise S et al: Urodynamic effects of once daily tadalafil in men with lower urinary tract symptoms secondary to clinical benign prostatic hyperplasia: a randomized, placebo controlled 12-week clinical trial. J Urol 2010; 183: 1092. Re: A Novel Approach for the Treatment of Radiation-Induced Hemorrhagic Cystitis with the GreenLight XPS Laser D. R. Martinez, C. E. Ercole, J. G. Lopez, J. Parker and M. K. Hall Department of Urology, University of South Florida, Tampa, Florida Int Braz J Urol 2015; 41: 584e587. doi: 10.1590/S1677-5538.IBJU.2014.0411 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26200555available at http://www.ncbi.nlm.nih.gov/pubmed/26200555 Editorial Comment: Each of us faces clinical scenarios where virtually everything we try does not work. Refractory hemorrhagic cystitis secondary to radiation is often hard to definitively treat and manage, and may often lead to aggressive therapeutic regimens. Traditional therapies BENIGN PROSTATIC HYPERPLASIA 851 include bladder irrigation with saline/water, electrocauterization (monopolar or bipolar), hyperbaric oxygen and bladder instillation using alum 1% silver nitrate or formalin. The authors report using the GreenLight XPS Xcelerated Performance System in 4 men with refractory hemorrhagic cystitis. In theory the 1,064 nm wavelength may be ideal for lysing red blood cells, and its minimal absorption by surrounding tissue may preclude further damage. Only a coagulation setting of 40 watts was used. This therapy may be a useful adjunct in patients with refractory hemorrhagic cystitis. Steven A. Kaplan, MD Suggested Reading Hoffman RM, MacDonald R, Slaton JW et al: Laser prostatectomy versus transurethral resection for treating benign prostatic obstruction: a systematic review. J Urol 2003; 169: 210.

Several disease characteristics have been identified as potential predictors for pathological node involvement (pN+) following radical cystectomy (RC). However, these have not been assessed in patients treated with neoadjuvant chemotherapy (NAC). We endeavored to assess factors predicting adverse pathology in clinically node-negative patients treated with NAC and RC.Patients from four North American institutions with cT2-4aN0M0 UC who received three or four cycles of NAC followed by RC were selected. Logistic regression was used to predict pN+,pT2 and pT4 disease.One hundred and ninety-six patients were included. The clinical stage was cT2 in 115 (61 %), cT3 in 62 (33 %) and cT4 in 12 (6 %) cases. NAC regiments were gemcitabine-cisplatin (GC)-4 cycles 57 (29 %), GC-3 cycles 77 (39 %), methotrexate, vinblastine, adriamycin, cisplatin (MVAC)-3 cycle 22 (11 %) and MVAC-4 cycles 40 (21 %). pN+ was seen in 35 (18 %) patients. In the logistic regression analysis, cT4 stage (OR 7.50; 95 % CI 1.58-33.3) and three compared to four cycles of GC (OR 3.44; 95 % CI 1.09-10.9) were significant predictors of pN+ status. Additionally, when controlling for clinical stage, three cycles of GC, compared to four, were significantly associated with higher rates of pT4 disease and lower rates of downstaging to non-muscle-invasive disease.The results suggest that four cycles of neoadjuvant GC may be superior to three cycles, and the latter regimen may be associated with adverse pathological findings. Although this would require validation in a prospective trial, it does encourage the completion of the conventional four cycles GC whenever possible.

INTRODUCTION AND OBJECTIVES: Following radical cystectomy (RC) for urothelial carcinoma (UC) of the bladder cancer, a proportion of clinically node negative patients will be diagnosed with metastasis in the regional lymph nodes (pNþ). A number of clinical factors such as local stage and lymphovascular invasion (LVI) have been identified as potential predictors for pNþ status; however, these have not been assessed in patients treated with neoadjuvant chemotherapy (NAC). Our objective is to assess clinical and therapeutic factors predicting pNþ in clinically node negative patients treated with NAC and RC. METHODS: Patients from four North American institutions with cT2-4N0M0 UC who received three or four cycles of NAC followed by RC were included. A logistic regression model was formulated for predicting pNþ status. The variables included were age, gender, clinical T-stage, transurethral resection (TUR) histology (UC or UC variant) and LVI, number of cycles of NAC, the regimen administered and the extent of pelvic node dissection. RESULTS: The analysis was conducted on 238 patients. Median age was 64 years (IQR: 58-71) and 79% of patients were male. The clinical stage was cT2 in 143 (60.1%), cT3 in 76 (39.1%) and cT4 in 19 (8%) cases. MVAC was used in 26.9% and GC in the remainder of the patients. 60.9% of the MVAC group received four cycles of NAC compared to 42.5% of the GC group (p1⁄40.013). Pathological Nþ was seen in 45 (19.5%) patients. In the logistic regression analysis, cT4 stage (OR: 3.32, [95% CI: 1.15-9.56]) and the fewer cycles of NAC (3 vs. 4 cycles OR: 2.10, [95% CI: 1.03-4.29]) were significant predictors of pNþ status. LVI was not significant in this cohort of patients (OR: 1.15, [95%CI 0.50-2.63]). The observed advantage of the additional cycle of NAC was persistent in subanalysis of the GC patients (OR: 2.67, [CI: 1.11-6.41]) but not MVAC patients (OR: 1.11, [CI: 0.25-4.92]). CONCLUSIONS: Patients with locally advanced disease are at higher risk of harboring lymph node metastasis at the time of RC following NAC. LVI in the TUR specimen was not a significant predictor of nodal metastasis in these patients. Potential advantage of an additional cycle of NAC in GC patients requires further confirmation.

Partial nephrectomy is the reference standard for the management of small renal tumors and is commonly used for localized kidney cancer. A primary goal of partial nephrectomy is to preserve as much renal function as possible. New baseline glomerular filtration rate after partial nephrectomy can have prognostic significance with respect to long-term outcomes. Recent studies provide an increased understanding of the factors that determine functional outcomes after partial nephrectomy as well as preventive measures to minimize functional decline. We review these advances, highlight ongoing controversies and stimulate further research.A comprehensive literature review consistent with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria was performed from January 2006 to April 2014 using PubMed®, Cochrane and Ovid Medline. Key words included partial nephrectomy, renal function, warm ischemia, hypothermia, nephron mass, parenchymal volume, surgical approaches to partial nephrectomy, preoperative and intraoperative imaging, enucleation, hemostatic agents and energy based resection. Relevant reviews were also examined as well as their cited references. An additional Google Scholar search was conducted to broaden the scope of the review. Only English language articles were included in the analysis. The primary outcomes of interest were the new baseline level of function after early postoperative recovery, percent decline in function, potential etiologies and preventive measures.Decline in function after partial nephrectomy averages approximately 20% in the operated kidney, and can be due to incomplete recovery from the ischemic insult or loss of nephron mass related to parenchymal excision or collateral damage during reconstruction. Compensatory hypertrophy in the contralateral kidney after partial nephrectomy in adults is marginal and decline in global renal function for patients with 2 kidneys averages about 10%, although there is some variance based on tumor size and location. Irreversible ischemic injury can be minimized by pharmacological intervention or surgical approaches such as hypothermia, limited warm ischemia, or zero or segmental ischemia. Excessive loss of nephron mass can be minimized by improved preoperative or intraoperative imaging, use of a bloodless field, enucleation and vascular microdissection. Hemostatic agents or energy based resection that minimizes the need for parenchymal and capsular suturing can also optimize preservation of the vascularized nephron mass.Our understanding of the decline in renal function after partial nephrectomy has advanced considerably, including better appreciation of its magnitude and impact in various settings, possible etiologies and potential preventive measures. Many controversies persist and this remains an important area of investigation.

Nomograms facilitate the conversation between the physician and the patient when discussing all the potential treatment options for localized prostate cancer. By using continuous, multivariable models—nomograms—the patient has an accurate means to determine estimation of success and make decisions on therapy that are most in line with his beliefs and fit his lifestyle. Currently, there are multiple nomograms that address all the different variables present at each of the clinical states of prostate cancer. As therapies evolve and series mature, these prediction models need to be updated and revalidated to best predict the likelihood of long-term urinary and sexual function, as well as oncological outcomes.

To determine whether presurgical sunitinib reduces primary renal cell carcinoma (RCC) size and facilitates partial nephrectomy (PN).Data from potential candidates for PN treated with sunitinib with primary RCC in situ were reviewed retrospectively. Primary outcome was reduction in tumor bidirectional area.Included were 72 potential candidates for PN who received sunitinib before definitive renal surgery on 78 kidneys. Median primary tumor size was 7.2 cm (interquartile range [IQR]: 5.3-8.7 cm) before and 5.3 cm (IQR: 4.1-7.5 cm) after sunitinib treatment (P0.0001), resulting in 32% reduction in tumor bidirectional area (IQR: 14%-46%). Downsizing occurred in 65 tumors (83%), with 15 partial responses (19%). Tumor complexity per R.E.N.A.L. score was reduced in 59%, with median posttreatment score of 9 (IQR: 8-10). Predictors of lesser tumor downsizing included clinical evidence of lymph node metastases (P0.0001), non-clear cell histology (P = 0.0017), and higher nuclear grade (P = 0.023). Surgery was performed for 68 tumors (87%) and was not delayed in any patient owing to sunitinib toxicity. Grade ≥ 3 surgical complications occurred in 5 patients (7%). PN was performed for 49 kidneys (63%) after sunitinib, including 76% of patients without and 41% with metastatic disease (P = 0.0026). PN was completed in 100%, 86%, 65%, and 60% of localized cT1a, cT1b, cT2, and cT3 tumors, respectively.Presurgical sunitinib leads to modest tumor reduction in most primary RCC, and many patients can be subsequently treated with PN with acceptable morbidity and preserved renal function. A randomized trial is required to definitively determine whether presurgical therapy enhances feasibility of PN.

Many renal tumor complexity scoring systems can be complicated and make it difficult to accurately measure end points. Here we introduce the zonal NePhRO scoring system. This retrospective study demonstrates that the zonal NePhRO scoring system predicts perioperative complication rates more accurately than does the RENAL nephrometry scoring system. Background: Since the advent of the first standardized renal tumor complexity system, many subsequent scoring systems have been introduced, many of which are complicated and can make it difficult to accurately measure data end points. In light of these limitations, we introduce the new zonal NePhRO scoring system. Patients and Methods: The zonal NePhRO score is based on 4 anatomical components that are assigned a score of 1, 2, or 3, and their sum is used to classify renal tumors. The zonal NePhRO scoring system is made up of the (Ne)arness to collecting system, (Ph)ysical location of the tumor in the kidney, (R)adius of the tumor, and (O)rganization of the tumor. In this retrospective study, we evaluated patients exhibiting clinical stage T1a or T1b who underwent open partial nephrectomy performed by 2 genitourinary surgeons. Each renal unit was assigned both a zonal NePhRO score and a RENAL (radius, exophytic/endophytic properties, nearness of tumor to the collecting system or sinus in millimeters, anterior/ posterior, location relative to polar lines) score, and a blinded reviewer used the same preoperative imaging study to obtain both scores. Additional data points gathered included age, clamp time, complication rate, urine leak rate, intraoperative blood loss, and pathologic tumor size. Results: One hundred sixty-six patients underwent open partial nephrectomy. There were 37 perioperative complications quantitated using the validated Clavien-Dindo system; their occurrence was predicted by the NePhRO score on both univariate and multivariate analyses (P ¼ .0008). Clinical stage, intraoperative blood loss, and tumor diameter were all correlated with the zonal NePhRO score on univariate analysis only. Conclusion: The zonal NePhRO scoring system is a simpler tool that accurately predicts the surgical complexity of a renal lesion.

54 Background: Active surveillance (AS) is a recommended management approach for low risk prostate cancer (PCa). Studies have shown high rates of AS in the Veterans Administration (VA), but concerns about missing aggressive disease lead to variation between centers. The 17-gene Genomic Prostate Score (GPS) has been validated to predict likelihood of favorable pathology (LFP) in men with clinically low risk PCa. This study compared treatment patterns before and after introduction of the GPS to determine if the assay influenced treatment patterns. Methods: Men newly diagnosed with PCa who met NCCN criteria for very low (VL), low (L), or intermediate (INT) risk PCa were eligible. Chart review of men across 6 VA medical centers (VAMCs) established treatment in untested patients in 2013-2014. In 2015, Veterans at the same VAMCs were offered the assay in a prospective study measuring treatment recommendations before and after the assay and treatment implemented based on chart review. Results: There were 200 men in the untested cohort. Characteristics: age (median = 66, range:43-83), Gleason Score (GS) (3+3:64%, 3+4:37%), PSA (mean = 6.6, range:0.7-20), NCCN risk (VL:18%, L:37%, INT:46%). There were 190 men in the prospective study with complete data. NCCN risk group: age (median = 66, range:50-85), GS (3+3:74%, 3+4:26%), PSA (mean = 6.4, range:0.4-18.1), VL:22%, L:43%, INT:35%. GPS ranged from 0-61 and LFP ranged from 38%-91%. GPS identified 24 patients who had more favorable pathology and 13 patients who had less favorable pathology than would be expected using NCCN alone. 62% of untested Veterans pursued AS compared to 74% of tested Veterans. AS increases between untested and tested cohorts were 1% in VL, 16% in L, and 3% in INT. Conclusions: Both untested and tested patients had clinical characteristics representative of low risk PCa in the VA. Use of AS increased in tested Veterans compared to untested, with the largest increases observed in NCCN low risk patients. The 17-gene assay used biological information to provide refined risk estimates in tested Veterans, assisting physicians in appropriately identifying candidates for AS or immediate treatment.

The pattern of metastasis for penile cancer occurs in a predictable fashion, first spreading to the inguinal lymph nodes (ILN) and then to the pelvic nodes. Paramount to proper patient management is early identification and treatment of metastases, especially in the patient that presents with palpable disease. A proper metastatic workup will assist in determining the best way to move forward with either an ILN dissection or a multimodality approach to provide the most favorable outcomes. Several advances have been made in the surgical techniques that have helped minimize the morbidity associated with an ILN dissection.

e16611Background: Active surveillance (AS) is a recommended treatment option for low risk prostate cancer (PCa). Studies have shown high rates of AS in the Veterans Administration (VA) yet treatmen...

Objectives Inguinal lymph node dissection (ILND) for the treatment of metastatic penile squamous cell carcinoma (SCC) has historically been associated with significant morbidity. This review addresses the surgical principles and techniques to decrease its perioperative morbidity, while optimizing its oncologic outcomes. Materials and methods A review of the English scientific literature from 1966 to present was conducted using the PubMed search engine as well as of additional cited works not initially noted in the search using as keywords penile cancer, inguinal lymph node dissection, inguinal lymph node metastasis, morbidity, and complications. Results The contemporary outcomes of ILND in the context of penile cancer have built on the significant contributions made by surgeons and scientists worldwide. In this review, we provide a comprehensive overview of the principles of ILND optimizing oncological outcomes, while minimizing its attributable morbidity. It is hoped this review will serve as a benchmark for clinicians to approach this often highly aggressive tumor phenotype. Conclusions ILND remains an important diagnostic and therapeutic procedure for patients with penile SCC, as contemporary ILND series have reported a decrease in its associated morbidity, with the potential for further treatment outcomes in years to come. ILND can in appropriately selected patients render them disease-free, thus justifying its associated morbidity.

e15512 Background: Sarcopenia (loss of skeletal muscle mass) at the time of RC has been associated with lower cancer-specific and overall survival (OS) in bladder cancer patients. Change in muscle ...

Objectifs Le recours a la therapie ciblee pour faciliter l’exerese de tumeurs renales a cellules claires (ccRCC) a deja ete rapporte. L’objectif de cette etude etait d’evaluer l’effet du sunitinib sur la conversion de la nephrectomie radicale (NR) en nephrectomie partielle (NP) chez des patients avec des ccRCC ou la NP n’etait pas envisageable en premiere intention. Methodes Les patients traites par du sunitinib en neoadjuvant dans 4 centres ont ete retrospectivement analyses. Le type histologique « ccRCC » a ete confirme par une biopsie renale. L’effet du sunitinib chez les patients qui avaient une masse renale classee de moyenne a haute complexite selon le score RENAL et qui etaient recuses pour une NP en premiere attention a ete analyse. Les patients avec une atteinte ganglionnaire etaient exclus. Le critere de jugement principal etait la faisabilite de la NP (taux d’evitement de la NR) apres therapie ciblee. Les complications (classification de Clavien) chirurgicales ont egalement ete analysees. Resultats Quarante-trois patients (49 reins) avec une taille et un score RENAL medians (IQR) respectivement de 7,2 cm (5,2–8,2) et 10 (9–11) etaient inclus. Les indications imperatives de NP comprenaient un rein unique ( n = 9), des masses bilaterales ( n = 8) et un DFG n = 27). Au total, 48 (98 %) tumeurs etaient operees. La NP a pu etre realisee dans 36 (75 %) tumeurs a la place de la NR dont 10 (21 %) par voie robot-assistee. Une reduction de la taille tumorale a ete notee dans 94 % des tumeurs (mediane de la baisse : 32,5 %, IQR : 19,5–46,5 %) et une reduction du score RENAL a ete observe dans 74 % (baisse d’un1 point, n = 27 ; baisse de 2 points, n = 10). Le taux de complications majeures (Clavien ≥ 3) etait de 5 %. Conclusion La NP est faisable apres un traitement neoadjuvant par le sunitinib avec un taux de complication acceptable. Une approche neoadjuvante apres biopsie chez des patients avec ccRCC recuses pour NP pour des difficultes techniques est une approche raisonnable notamment dans les indications imperatives.

225 Background: Understanding adrenal androgen metabolism in the prostate provides the opportunity to better define mechanisms of resistance for patients with prostate cancer. This is especially important with men who have a recurrence after their initial treatment (e.g., surgery or radiation) and are subsequently treated with androgen deprivation therapy by chemical or surgical castration. Unfortunately, these patients tend to progress to castrate resistant prostate cancer. With the contribution of adrenal androgens in mind, we sought to determine the feasibility of characterizing the metabolites of dehydroepiandrosterone (DHEA) in the human prostate. Methods: With institutional review board approval, tissue procurement occurred via the Department of Pathology at the Cleveland Clinic. We obtained prostate tissue from patients immediately after radical prostatectomy. The tissue was processed in culture withserum free medium in triplicate and was treated with tritiated-DHEA ([3H]-DHEA; 100 nM, 300,000–600,000cpm; PerkinElmer). Media was collected at specific time intervals (6, 24, 48, and 72 hours). Once all the time points were collected, they were treated with a β-glucuronidase and steroids were extracted. These samples were processed and analyzed with high-performance liquid chromatography (HPLC) and a radioactivity detector for comparison with known standards (DHEA, androstenedione, 5α-androstanedione, testosterone, and dihydrotestosterone). Results: Evaluation of the HPLC tracings showed metabolism of [3H]-DHEA to downstream androgen products and correlated with standard peaks. These tracings were reproducible and consistent with each sample’s triplicate and from specimen to specimen. Conclusions: It is feasible to consistently determine the products of DHEA metabolism in fresh prostate tissues. By obtaining a better understanding of how androgen metabolites are formed we can dissect how response and resistance to hormonal therapy are regulated.

The efficacy of neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (BCa) was established primarily with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), with complete response rates (pT0) as high as 38%. However, because of the comparable efficacy with better tolerability of gemcitabine and cisplatin (GC) in patients with metastatic disease, GC has become the most commonly used regimen in the neoadjuvant setting.We aimed to assess real-world pathologic response rates to NAC with different regimens in a large, multicenter cohort.Data were collected retrospectively at 19 centers on patients with clinical cT2-4aN0M0 urothelial carcinoma of the bladder who received at least three cycles of NAC, followed by radical cystectomy (RC), between 2000 and 2013.NAC and RC.The primary outcome was pathologic stage at cystectomy. Univariable and multivariable analyses were used to determine factors predictive of pT0N0 and ≤pT1N0 stages.Data were collected on 935 patients who met inclusion criteria. GC was used in the majority of the patients (n=602; 64.4%), followed by MVAC (n=183; 19.6%) and other regimens (n=144; 15.4%). The rates of pT0N0 and ≤pT1N0 pathologic response were 22.7% and 40.8%, respectively. The rate of pT0N0 disease for patients receiving GC was 23.9%, compared with 24.5% for MVAC (p=0.2). There was no difference between MVAC and GC in pT0N0 on multivariable analysis (odds ratio: 0.89 [95% confidence interval, 0.61-1.34]; p=0.6).Response rates to NAC were lower than those reported in prospective randomized trials, and we did not discern a difference between MVAC and GC. Without any evidence from randomized prospective trials, the best NAC regimen for invasive BCa remains to be determined.There was no apparent difference in the response rates to the two most common presurgical chemotherapy regimens for patients with bladder cancer.