Search

Treatment paradigms for management of metastatic renal cell carcinoma (mRCC) are evolving. We examined impact of surgical metastasectomy on survival across in mRCC stratified by risk-group.Multicenter retrospective analysis from the Registry of Metastatic RCC database. The cohort was subdivided utilizing Motzer criteria (favorable-, intermediate-, high-risk). Primary outcome was all-cause mortality (ACM)/overall survival (OS); secondary outcome was cancer-specific mortality (CSM)/cancer-specific survival (CSS). Impact of metastasectomy was analyzed via Cox-Regression analysis adjusting for potential prognostic variables and Kaplan-Meier analysis (KMA) within each risk-group.Four hundred thirty-one patients (59 favorable-risk, 274 intermediate-risk, 98 high-risk; median follow-up 27.2 months) were analyzed. Metastasectomy was performed in 22 (37%), 66 (24%), and 32 (16%) of favorable-, intermediate- and high-risk groups (P = .012). Median number of metastases at diagnosis differed significantly (favorable-risk 2, intermediate-risk 3.4, high-risk 5.1, P.001). On Cox-regression, high-risk (HR = 1.72, P = .002) was associated with worsened ACM, while metastasectomy was associated with improved ACM (HR = 0.56, P = .005). On KMA, median OS (months) was longer with metastasectomy in favorable- (92.7 vs. 25.8, P = .003) and intermediate-risk (26.3 vs. 20.1, P = .038), but not high-risk (P = .911) groups. Metastasectomy was associated with longer CSS in favorable- (76.1 vs. 32.8, P = .004) but not intermediate- (P = .06) and high-risk (P = .595) groups.Metastasectomy was independently associated with improved ACM and CSM, as well as improved CSS and OS in favorable- and intermediate-risk mRCC patients. Metastasectomy may be considered as component of multimodal management strategy in favorable and intermediate-risk subgroups. In high-risk patients, metastasectomy should be deferred except in select circumstances.

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

BACKGROUND: Several groups have proposed features to identify low-risk patients who may benefit from endoscopic kidney-sparing surgery in upper tract urothelial carcinoma (UTUC). OBJECTIVE: To evaluate standard risk stratification features, develop an optimal model to identify ≥pT2/N+ stage at radical nephroureterectomy (RNU), and compare it with the existing unvalidated models. DESIGN, SETTING, AND PARTICIPANTS: This was a collaborative retrospective study that included 1214 patients who underwent ureterorenoscopy with biopsy followed by RNU for nonmetastatic UTUC between 2000 and 2017. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We performed multiple imputation of chained equations for missing data and multivariable logistic regression analysis with a stepwise selection algorithm to create the optimal predictive model. The area under the curve and a decision curve analysis were used to compare the models. RESULTS AND LIMITATIONS: Overall, 659 (54.3%) and 555 (45.7%) patients had ≤pT1N0/Nx and ≥pT2/N+ disease, respectively. In the multivariable logistic regression analysis of our model, age (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.0-1.03, p = 0.013), high-grade biopsy (OR 1.81, 95% CI 1.37-2.40, p

BACKGROUND: Selection of patients for upfront cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) has to be improved. OBJECTIVE: To evaluate a new scoring system for the prediction of overall mortality (OM) in mRCC patients undergoing CN. DESIGN, SETTING, AND PARTICIPANTS: We identified a total of 519 patients with synchronous mRCC undergoing CN between 2005 and 2019 from a multi-institutional registry (Registry for Metastatic RCC [REMARCC]). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cox proportional hazard regression was used to test the main predictors of OM. Restricted mean survival time was estimated as a measure of the average overall survival time up to 36 mo of follow-up. The concordance index (C-index) was used to determine the model's discrimination. Decision curve analyses were used to compare the net benefit from the REMARCC model with International mRCC Database Consortium (IMDC) or Memorial Sloan Kettering Cancer Center (MSKCC) risk scores. RESULTS AND LIMITATIONS: The median follow-up period was 18 mo (interquartile range: 5.9-39.7). Our models showed lower mortality rates in obese patients (p = 0.007). Higher OM rates were recorded in those with bone (p = 0.010), liver (p = 0.002), and lung metastases (p < 0.001). Those with poor performance status (

Background Cytoreductive nephrectomy (CN) plays an important role in the treatment of a subgroup of metastatic renal cell carcinoma (mRCC) patients. Objective We aimed to evaluate morbidity associated with this procedure and identify potential predictors thereof to aid patient selection for this procedure and potentially improve patient outcomes. Design, setting, and participants Data from 736 mRCC patients undergoing CN at 14 institutions were retrospectively recorded in the Registry for Metastatic RCC (REMARCC). Outcome measurements and statistical analysis Logistic regression analysis was used to identify predictors for intraoperative, any-grade (AGCs), low-grade, and high-grade (HGCs) postoperative complications (according to the Clavien-Dindo classification) as well as 30-d readmission rates. Results and limitations Intraoperative complications were observed in 69 patients (10.9%). Thrombectomy (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.08–1.75, p = 0.009) and adjacent organ removal (OR 2.7, 95% CI 1.38–5.30) were significant predictors of intraoperative complications at multivariable analysis. Two hundred seventeen patients (29.5%) encountered AGCs, while 45 (6.1%) encountered an HGC, of whom 10 (1.4%) died. Twenty-four (3.3%) patients had multiple postoperative complications. Estimated blood loss (EBL; OR 1.49, 95% CI 1.08–2.05, p = 0.01) was a significant predictor of AGCs at multivariable analysis. CN case load (OR 0.13, 95% CI 0.03–0.59, p = 0.009) and EBL (OR 2.93, 95% CI 1.20–7.15, p = 0.02) were significant predictors solely for HGCs at multivariable analysis. Forty-one patients (11.5%) were readmitted within 30 d of surgery. No significant predictors were identified. Results were confirmed in a subanalysis focusing solely on patients treated in the contemporary targeted therapy era. Conclusions Morbidity associated with CN is not negligible. Predictors of high-grade postoperative morbidity are predominantly indicators of complex surgery. EBL is a strong predictor of postoperative complications. CN case load correlates with lower high-grade morbidity and highlights the benefit of centralization of complex surgery. However, risks and benefits should be balanced when considering CN in mRCC patients. Patient summary We studied patients with metastatic renal cancer to evaluate the outcomes associated with the surgical removal of the primary kidney tumor. We found that this procedure is often complex and adverse events are not uncommon. High intraoperative blood loss and a small number of cases performed at the treating center are associated with a higher rate of postoperative complications.

We developed and tested a method to detect COVID-19 disease, using urine specimens. The technology is based on Raman spectroscopy and computational analysis. It does not detect SARS-CoV-2 virus or viral components, but rather a urine ‘molecular fingerprint’, representing systemic metabolic, inflammatory, and immunologic reactions to infection. We analyzed voided urine specimens from 46 symptomatic COVID-19 patients with positive real time-polymerase chain reaction (RT-PCR) tests for infection or household contact with test-positive patients. We compared their urine Raman spectra with urine Raman spectra from healthy individuals (n = 185), peritoneal dialysis patients (n = 20), and patients with active bladder cancer (n = 17), collected between 2016–2018 (i.e., pre-COVID-19). We also compared all urine Raman spectra with urine specimens collected from healthy, fully vaccinated volunteers (n = 19) from July to September 2021. Disease severity (primarily respiratory) ranged among mild (n = 25), moderate (n = 14), and severe (n = 7). Seventy percent of patients sought evaluation within 14 days of onset. One severely affected patient was hospitalized, the remainder being managed with home/ambulatory care. Twenty patients had clinical pathology profiling. Seven of 20 patients had mildly elevated serum creatinine values (>0.9 mg/dl; range 0.9–1.34 mg/dl) and 6/7 of these patients also had estimated glomerular filtration rates (eGFR) 2 (range 59–84 mL/min/1.73m2). We could not determine if any of these patients had antecedent clinical pathology abnormalities. Our technology (Raman Chemometric Urinalysis—Rametrix®) had an overall prediction accuracy of 97.6% for detecting complex, multimolecular fingerprints in urine associated with COVID-19 disease. The sensitivity of this model for detecting COVID-19 was 90.9%. The specificity was 98.8%, the positive predictive value was 93.0%, and the negative predictive value was 98.4%. In assessing severity, the method showed to be accurate in identifying symptoms as mild, moderate, or severe (random chance = 33%) based on the urine multimolecular fingerprint. Finally, a fingerprint of ‘Long COVID-19’ symptoms (defined as lasting longer than 30 days) was located in urine. Our methods were able to locate the presence of this fingerprint with 70.0% sensitivity and 98.7% specificity in leave-one-out cross-validation analysis. Further validation testing will include sampling more patients, examining correlations of disease severity and/or duration, and employing metabolomic analysis (Gas Chromatography–Mass Spectrometry [GC-MS], High Performance Liquid Chromatography [HPLC]) to identify individual components contributing to COVID-19 molecular fingerprints.

Background: To report a single-center experience with robot-assisted ureteral reimplantation (RAUR) and to compare its outcomes with those of open ureteral reimplantation (OUR). Materials ...

The main objective of this experiment was to determine and study the effects of combining two epigenetic modifiers, 5-azacyticidine (5-AzaC) and SB939, on a RM-1 murine prostate cancer cell model. The effectiveness of this combination on prostate cancer cells has not been previously studied. The study was implemented on ex vivo cell models to gain a better understanding of the true effects of the combination therapy on prostate cancer cells. Two variations of the combination therapy were tested in this study, each with different concentrations of SB939 (100nm and 200nm).To determine the effectivity of the combination therapy on prostate cancer cells, three factors were measured: cell proliferation, cancer testis antigen (CTA) expression, and apoptosis rate. To measure cell proliferation, a cell proliferation assay was conducted, and absorption rate was measured through a 450 nm wavelength. CTA expression was measured through a quantitative polymerase chain reaction (quant-PCR). For this study, the expression rates of five CTAs were measured (TEX15, CEP55, CCNA1, P1A, SPA17). Apoptosis rate was measured through an Annexin-V assay, in which two markers, Annexin-V and 7-AAD, were used.We found that SB939 combined with 5-AzaC show highest efficacy compare to each drug alone in terms of inhibiting tumor cell proliferation, as well as inducing tumor cells apoptosis and enhancing tumor cell immunogenicity by the induction of the expression of CTAs. This combination proved to be effective in combating murine prostate cancer cells, and can potentially be effective within in vivo models due to its high toxicity to these cancer cells, and its ability to render prostate cancer more immunogenic.

INTRODUCTION Radical cystectomy (RC) is the current mainstay for muscle-invasive bladder cancer (MIBC). Concerns regarding morbidity, mortality and quality of life have favored the introduction of bladder sparing strategies. Trimodal therapy, combining transurethral resection, chemotherapy and radiotherapy is the current standard of care for bladder preservation strategies in selected patients with MIBC. EVIDENCE ACQUISITION A comprehensive search of the Medline and Embase databases was performed. A total of 19 studies were included in a systematic review of bladder sparing strategies in MIBC management was carried out following the preferred reporting items for systematic reviews and meta-analysis (PRISMA). EVIDENCE SYNTHESIS The overall median complete response rate after trimodal therapy (TMT) was 77% (55-93). Salvage cystectomy rate with TMT was 17% on average (8-30). For TMT, the 5-year cancer-specific survival and overall survival rates range from 42-82% and 32-74%, respectively. Currently data supporting neoadjuvant or adjuvant chemotherapy in bladder sparing approaches are emerging, but robust definitive conclusions are still lacking. Gastrointestinal toxicity rates are low around 4% (0.5-16), whereas genitourinary toxicity rates reached 8% (1-24). Quality of life outcomes are still underreported. CONCLUSIONS Published data and clinical experience strongly support trimodal therapy as an acceptable bladder sparing strategy in terms of oncological outcomes and quality of life in selected patients with MIBC. A strong need exists for specialized centers, to increase awareness among urologists, to discuss these options with patients and to stress the increased participation of patients and their families in treatment path decision-making.

Background Although breast cancer mortality is a result of distant recurrences associated with the establishment of tumor dormancy, current clinical practice guidelines recommend a wait and watch approach for tumor recurrences. This is because of our limited understanding of tumor dormancy and insufficient evidence in support of immunological control of tumor dormancy. Methods We used FVBN202 transgenic mice expressing rat neu oncogene in the mammary glands, and their parental FVB strain lacking neu expression. These models allowed the detection of tumor dormancy at distant sites using the rat neu protein as a tumor marker. We also used Ki67 for the detection of the indolent and quiescent types of tumor dormancy. Multicolor flow cytometry was used to detect dormant tumor cells and T cell subsets. Co-culture studies were performed to determine the role of T cells in preventing regrowth of dormant cells. Results We demonstrated that dormant tumor cells were present at the site of primary breast cancer and at distant sites in the lungs and in the liver very early in the course of early stage breast cancer when no distant metastasis was evident. Dormant tumor cells were characterized as neu expressing Ki67− and Ki67low fractions associated with the induction of local immune responses predominated by CD4+ and CD8+ T effector cell subsets. The presence of neu-autoreactive T cells from FVBN202 mice only prevented regrowth of dormant cells. On the other hand, presence of neu-alloreactive anti-tumor T cells in FVB mice prior to tumor challenge resulted in the protection of mice from the dissemination of dormant tumor cells to distant organs. Conclusion Our results suggest that immunotherapeutic targeting of semi-allogeneic mutant neoantigens during tumor dormancy might prevent distant recurrence of the disease.

To evaluate the prognostic value of tumor location in patients with upper tract urothelial carcinoma.Within the Surveillance, Epidemiology and End Results Incidence Database, 6619 upper tract urothelial carcinoma cases were identified, including 3719 confined to the renal pelvis and 2971 to the ureter. Predictors of surgical technique (kidney sparing surgery versus radical nephroureterectomy), as well as 2- and 5-year cancer-specific survival and overall survival were evaluated.Median follow-up time was 29 months (interquartile range 0-126 months) for both groups. Multivariate logistic analysis showed tumor dimension as the only factor associated with radical nephroureterectomy (odds ratio 1.02; P 0.001). Ureteral 2- and 5-year overall survival were lower (log-rank P = 0.001) compared with renal pelvis. When stratifying tumor location according to dimensions, a ureteral carcinoma3 cm was associated with the worst 2- and 5-year cancer-specific mortality (Pepe-Mori P 0.001), and overall survival (log-rank P 0.001). The 2- and 5-year cancer-specific mortality (Pepe-Mori P 0.001) and overall survival were the worst for ureteral ≥T3 tumors (log-rank P 0.001). The 2- and 5-year cancer-specific mortality (Pepe-Mori P 0.001) and overall survival (log-rank P 0.001) were the worst for ureteral grade III-IV cancers. Ureteral tumor location (subdistribution hazard ratio 1.18, P 0.001), tumor dimension ≥3 (subdistribution hazard ratio 1.25, P 0.001), T staging (T2-4 all P 0.001), grading (grade III subdistribution hazard ratio 2.20, P = 0.001; grade IV subdistribution hazard ratio 2.39, P 0.001) were found to be associated with higher cancer mortality.Ureteral tumor location in upper tract urothelial carcinoma seems to be associated with worse oncological outcomes, especially in the case of advanced disease. Although the type of surgical treatment does not seem to impact survival, surgeons should use caution in adopting a kidney-sparing surgery for patients with ureteral upper tract urothelial carcinoma.

Background The use of organ sparing strategies to treat penile cancer (PC) is currently supported by evidence that has indicated the safety, efficacy and benefit of this surgery. However, radical penectomy still represents up to 15-20% of primary tumor treatments in PC patients. The aim of the study was to evaluate efficacy in terms of overall survival (OS) and disease-free survival (DFS) of radical penectomy in PC patients. Methods Data from a retrospective multicenter study (PEnile Cancer ADherence study, PECAD Study) on PC patients treated at 13 European and American urological centers (Hospital "Sant'Andrea", Sapienza University, Roma, Italy; "G.D'Annunzio" University, Chieti and ASL 2 Abruzzo, Hospital "S. Pio da Pietrelcina", Vasto, Italy; Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL, USA; Hospital of Budapest, Hungary; Department of Emergency and Organ Transplantation, Urology and Andrology Unit II, University of Bari, Italy; Hospital "Spedali Civili", Brescia, Italy; Istituto Europeo di Oncologia, University of Milan, Milan, Italy; University of Modena & Reggio Emilia, Modena, Italy; Hospital Universitario La Paz, Madrid, Spain; Ceara Cancer Institute, Fortaleza, Brazil; Virginia Commonwealth University, Richmond, VA, USA; Aristotle University of Thessaloniki, Thessaloniki, Greece; Maria Sklodowska-Curie Memorial Cancer Center, Warsaw, Poland) between 2010 and 2016 were used. Medical records of patients who specifically underwent radical penectomy were reviewed to identify main clinical and pathological variables. Kaplan-Meier method was used to estimate 1- and 5-year OS and DFS. Results Of the entire cohort of 425 patients, 72 patients (16.9%) treated with radical penectomy were extracted and were considered for the analysis. The median age was 64.5 (IQR, 57.5-73.2) years. Of all, 41 (56.9%) patients had pT3/pT4 and 31 (43.1%) pT1/pT2. Moreover, 36 (50.0%) were classified as pN1-3 and 5 (6.9%) M1. Furthermore, 61 (84.7%) had a high grade (G2-G3) with 6 (8.3%) positive surgical margins. The 1- and 5-year OS rates were respectively 73.3% and 59.9%, while the 1- and 5-year DFS rates were respectively 67.3% and 35.1%. Conclusions PC is an aggressive cancer particularly in more advanced stage. Overall, more than a third of patients do not survive at 5 years and more than 60% report a disease recurrence, despite the use of a radical treatment.

To perform a systematic review and meta-analysis of the literature inherent robotic nephroureterectomy (RNU) and to compare its outcomes with those of other nephroureterectomy (NU) techniques. A systematic literature search was performed up to April 2019 using PubMed, Embase®, and Web of Science. The Preferred Reporting Items for Systematic Review and Meta-analysis Statement was followed for study selection. The following data were extracted for each study: baseline features, surgical outcomes, oncological outcomes, and survival outcomes. Stata® 15.0 was used for statistical analysis. Literature search identified 80 studies eligible for the meta-analysis and overall 87,291 patients were included in the analysis: open NU (ONU; n = 45,601), hand-assisted laparoscopic NU (HALNU; n = 442), laparoscopic NU (LNU n = 31,093), and RNU (n = 10,155). RNU was more likely to be performed in those patients with multifocal tumor location (proportion: 0.19; 95% CI 0.14, 0.24) and high-grade disease (proportion: 0.70; 95% CI 0.53, 0.68). The lowest EBL was recorded in the RNU group (weighted mean (WM) 163.31 mL; 95% CI 88.94, 237.68), whereas the highest was in the ONU group (414.99 mL; 95% CI 378.52, 451.46). Operative time was shorter for ONU (224.98 mL; 95% CI 212.26, 237.69). RNU had lower rate of intraoperative complications (0.02; 95% CI 0.01, 0.05). ONU showed higher odds of transfusions (0.20; 95% CI 0.15, 0.25). LOS was statistically significantly shorter for the RNU group (5.35 days; 95% CI 4.97, 5.82). HALNU seemed to present lower risk of PSM (0.02; 95% CI − 0.01, 0.05), and lower risk of recurrence (0.22; 95% CI 0.15, 0.30), metastasis (0.07; 95% CI 0.05, 0.10), and cancer-related death (0.03; 95% CI 0.01, 0.06). ONU showed the lowest 5 years cancer specific survival (proportion: 0.77; 95% CI 0.74, 0.80). No correlation was found between the surgical technique and recurrence-free and cancer-specific survival. Evidence regarding RNU for the treatment of UTUC is increasing but it remains quite sparse and of low quality. Despite this, RNU seems to be safe, and to offer the advantages of a minimally invasive approach without impairing the oncological outcomes. Nevertheless, ONU, HALNU, and LNU still represent a valid, and commonly used surgical treatment option. As RNU becomes more popular, and concerns related to its use remain, the best surgical technique for NU remains to be determined.

Radical nephroureterectomy (RNU) represents the standard of care for high-risk upper tract urothelial carcinoma (UTUC). In selected patients with ureteral UTUC, a conservative approach such as segmental ureterectomy (SU) can be considered. However, this therapeutic option remains controversial. The aim of this study was to perform a systematic review and meta-analysis of studies assessing the outcomes of SU versus RNU in patients with UTUC. Three search engines (Scopus, Embase, and Web of Science) were queried up to May 2019. The Preferred Reporting Items for Systematic Review and Meta-analysis Statement (PRISMA Statement) was used as a guideline for study selection. The clinical question was established as stated in the PICO (Population, Intervention, Comparator, Outcome) process. Patients in the SU group were more likely to have history of bladder cancer (odds ratio [OR], 1.99; 95% confidence interval [CI], 1.12-3.51; P = .02), but less likely to present with preoperative hydronephrosis (OR, 0.52; 95% CI: 0.31-0.88; P = .02). A higher rate of ureteral tumor location was found in the SU group (OR, 7.54; 95% CI, 4.15-13.68; P < .00001). The SU group presented with a lower rate of higher (pT ≥ 2) stage (OR, 0.66; 95% CI, 0.53-0.82; P = .0002), and high-grade tumors (OR, 0.62; 95% CI, 0.50-0.78; P < .0001). The SU group was found to have shorter 5-year relapse-free survival (OR, 0.64; 95% CI, 0.43-0.95; P = .03), but higher postoperative estimated glomular filtration rate (weighted mean difference, 10.97 mL/min; 95% CI, 2.97-18.98; P = .007). Selected patients might benefit from SU as a therapeutic option for UTUC. In advanced high-risk disease, RNU still remains the standard of care.

NTRODUCTION AND OBJECTIVE: In metastatic renal cell carcinoma (mRCC), the use of upfront cytoreductive nephrectomy (CN) has become controversial due to the outcomes of two randomized controlled trials (CARMENA/SURTIME). The objective of the current study was to examine overall survival (OS) and identify risk factors associated with patients not benefiting from CN in the targeted therapy era. METHODS: A purpose built multi-institutional international database (REgistry of MetAstatic RCC- REMARCC project) was used for this retrospective analysis. Patients with diagnosis of mRCC undergoing CN between 2004 and 2019 at participating centers were included. The Kaplan Meier method and Cox proportional hazards regression analyses were used to assess overall survival (OS). Covariates statistically significant at univariable analyses were included after stepwise selection in multivariable Cox regression model. The obtained coefficients from the multivariable model were used to compute a risk score. The latter was used to predict overall mortality (OM) at 1 year. Concordance index (c-index) and decision curve analyses (DCA) were fitted to test the score as continuous variable and after stratification according to the first and second tertiles, and for comparison with standard Heng criteria. RESULTS: A total of 484 patients were included with a median follow-up of 48 mo (IQR:22.7-90.2). On multivariable analysis, clinical risk factors associated with decreased OS included in the final model were: presence of sarcomatoid features (HR: 1.38, 95%CI:1.03-1.84, p[0.029), pN1 stage vs. pN0 (HR: 1.58, 95%CI:1.17-2.13, p[0.003), LDH >210 U/l (HR:1.32, 95%CI:1.04-1.68, p[0.020), calcium level >10.2 mg/dl (HR:1.98, 95%CI: 1.12-3.48, p[0.018) and bone metastases (HR:1.51, 95%CI: 1.13-2.02, p[0.005). Cox regression model showed a statistically significant correlation of the score with OM (HR:2.08, 95%CI:1.67-2.58, p

Introduction & Objectives: As treatment paradigms for management of metastatic renal cell carcinoma (mRCC) have shifted, the role of surgical metastasectomy in management of mRCC has been in similar flux. We examined impact on survival of surgical metastatectomy stratified in the setting of different mRCC risk groups. Materials & Methods: Multicenter retrospective analysis of patients from the REMARCC (REgistry of MetAstatic RCC) database. The cohort was subdivided utilizing Motzer RCC criteria (low, intermediate, and high risk), and impact of metastasectomy was analyzed via multivariable analysis (MVA) and Kaplan Meier analysis within each Motzer subgroup (KMA). Primary outcome was overall survival (OS) and secondary outcome was cancer specific mortality (CSM). Results: 431 patients (59 low risk, 274 intermediate risk, 98 high risk) with median follow-up of 19.2 months were analyzed. Metastasectomy was performed in 22 (37%), 66 (24%), and 32 (16%) of low, intermediate and high risk groups (p=0.012). Risk groups differed significantly with respect to ECOG performance status (p

INTRODUCTION AND OBJECTIVES: The role of cytoreductive nephrectomy (CN) in the setting of metastatic renal cell carcinoma (mRCC) is still object of great debate within the Urology community. In this regard, assessing the harms of CN is key to select patients most likely to benefit from this procedure. The aim of the study was to evaluate potential predictors of major complications (MC) after CN in a multicentre international cohort of patients with mRCC. METHODS: Data from patients with mRCC undergoing CN at 11 centers included in the REgistry of MetAstatic RCC (REMARCC) from January 2014 to December 2017 were retrospectively collected and analyzed. Patients with complete data on comorbidity profiles, intraoperative outcomes and perioperative complications formed the analytic cohort. Postoperative complications were assessed and graded using the modified Clavien-Dindo scale. MCs were defined as Clavien-Dindo grade 3 or more. Multivariable logistic regression analysiswas used to assess potential clinical predictors of 30-day readmission. RESULTS: Overall, 374 patients were included in the study. Twenty-three patients (6.1%) experienced MCs. Patient age, sex, BMI, Charlson comorbidity index, ECOG performance status, baseline Hb levels, estimated glomerular filtration rate, cT and cN status, as well as location of metastatic lesions, were comparable among patients who did and did not experience MCs. Conversely, median tumor size was significantly higher in patients experiencing MCs (11.0 vs 8.5 cm, p=0.002). Surgical approach was significantly different in the two study groups (87.0% of patients who experienced MCs were treated with open CN as compared to 65.4% of patients who did not; p=0.034). Performance of LDN was comparable among the study groups; on the contrary, removal of adjacent organs (43.5 % vs 23.4%, p=0.03), renal vein/vena cava thrombectomy (43.5% vs 17.4%, p=0.002) and metastasectomy at the time of CN (21.7% vs 7.1%, p=0.012) were significantly higher in patients who experienced MCs. Rate of hospital readmission within 30 days after surgery was significantly higher in patients who experienced MCs (11.1% vs 6.7%, p

Introduction: We aimed to evaluate adherence to the EAU guidelines (GL) on penile cancer (PC) with regard to primary surgical treatment and management of lymph nodes and to estimate the influence of adherence to GL on clinical outcome. Materials and methods: This is a retrospective multicenter study (PEnile Cancer ADherence study, PECAD Study) on PC patients treated at 12 European and American centers between 2010 and 2016. Adherence to the EAU GL on the surgical management of the primary penile tumor and lymphadenectomy was evaluated. Descriptive analyses were performed, and survival curves were estimated. Results: Data on 425 patients were considered for the analysis. The EAU GL on surgical treatment of the primary tumor and lymphadenectomy were respected in 74.8% and 73.7% of cases, respectively. Survival analysis showed that adherence to the GL on primary penile surgery was significantly associated with a good overall survival [adjusted HR 0.40 (95% CI 0.20-0.83, p value = 0.014)]. Also, the adherence to the GL on lymphadenectomy was statistically significantly associated with overall survival [adjusted HR 0.48 (95% CI 0.24-0.96, p value = 0.038)]. Limited follow-up and retrospective design represent limitations of this study. Conclusions: Our findings suggest that there is a good adherence to the EAU GL on PC. However, this should be further reinforced, endorsed and encouraged as it might translate into better clinical outcomes for PC patients.

Aim of the study: Recent evidence outlined that not all patients with mRCC might benefit from CN. However, there is lack of data on perioperative morbidity after this procedure. We aimed to investigate the impact of surgical approach on perioperative outcomes and surgical complications relying on a multicenter international registry. Materials and methods: Clinical data of 681 patients with mRCC undergoing CN at 11 centers included in the REgistry of MetAstatic RCC (REMARCC) from January 2014 to December 2017 were retrospectively collected. Patients with complete data on demographics and comorbidity profiles were included in final analysis. Study endpoints were: a) postoperative complications, assessed and graded using the modified Clavien-Dindo scale, and b) 30th day readmission rate. Results: Overall, 369 (54.2%) patients (247 open CN [OCN] and 122 minimally-invasive CN [MICN]) were considered. Patients treated with OCN had a significantly higher cT stage (p = 0.01), tumor size (p < 0.0001) and cN stage (p = 0.04). Conversely, there was no difference in terms of gender, age, Charlson comorbidity index, body mass index, site of metastasic lesions and baseline hemoglobin level, LDH level, glomerular filtration rate and calcemia. Lymph node dissection (LND) rate and renal vein/vena cava thrombectomy were significantly higher in the OCN compared to the MICN (p < 0.0001 and p = 0.001, respectively). Median estimated blood loss was significantly lower in the MICN compared to the OCN group (100 vs 450 cc, p < 0.0001). The rate of removal of adjacent organs beyond the tumorbearing kidney was not significantly different among the two groups. Patients with MICN compared to OCN had a significantly lower intraoperative (10% vs 22.6%, p = 0.004), overall postoperative (18% vs 38.6%, p < 0.0001) and major postoperative (2.5 vs 8.2%, p = 0.03) complications and lower median length of stay (5 vs 8 days, p < 0.0001). Perioperative mortality was reported in 3 patients in the OCN group. Readmission rate was 7.1% in both groups. Discussion: MICN was feasible and achieved acceptable perioperative morbidity in selected patients with mRCC. The main study limitation is the retrospective design with risk of selection and attrition bias.

INTRODUCTION Decreased expression of highly immunogenic cancer-testis antigens (CTA) might help tumor to achieve low immunogenicity, escape immune surveillance and grow unimpeded. Our aim was to evaluate CTA expression in tumor and normal tissues and to investigate possible means of improving the immune response in a murine prostate cancer (CaP) model by using the combination of epigenetic modifier 5-azacitidine (5-AzaC) and immunomodulator lenalidomide. No study to date has examined the effect of this combination on the prostate cancer or its impact on antigen-presenting cells (APC). MATERIALS AND METHODS Gene microarrays were performed to compare expression of several CTA in murine prostate cancer (RM-1 cells) and normal prostate. RM-1 cells were treated with 5-AzaC and real-time PCR was performed to investigate the expression of several CTA. Western blotting was used to determine whether expression of CTA-specific mRNA induced by 5-AzaC resulted in increase in the corresponding protein. Effect of the epigenetic agents and immunomodulators was assessed on dendritic cells (DC) using flow cytometry, ELISA and T-cell proliferation assay. RESULTS Gene arrays demonstrated decreased expression of 35 CTA in CaP tissue compared to normal prostate. 5-AzaC treatment of RM-1 prostate cancer cells upregulated the expression of all 13 CTA tested in a dose-dependent fashion. DC were treated with 5-AzaC and lenalidomide and the expression of surface markers MHC Class I, MHC Class II, CD80, CD86, CD 205, and CD40 was increased. Combination of 5-AzaC and lenalidomide enhances the ability of DC to stimulate T-cell proliferation in mixed leukocyte reaction. Secretion of IL-12 and IL-15 by DC increased significantly with addition of 5-AzaC or 5-AzaC and lenalidomide. CONCLUSIONS Decreased expression of CTA by prostate cancer may be a means of escaping immune monitoring. Combination of epigenetic modifications and immunomodulation by 5-AzaC and lenalidomide increased tumor immunogenicity and enhanced DC function and may be used in the treatment of advanced prostate cancer. Prostate 77: 361-373, 2017. © 2016 Wiley Periodicals, Inc.

Urinary diversion is a surgical technique to redirect the stream of urine, most often after cystectomy. Cystectomy may be performed both for benign and for malignant conditions. Bladder cancer is the most common indication for cystectomy, and most patients who undergo radical cystectomy and urinary diversion have muscle-invasive or high-risk non-muscle-invasive bladder cancer. There are two major surgical approaches for urinary diversions performed after radical cystectomy: continent and incontinent diversions. For incontinent urinary diversions, a cutaneous ostomy is used for continuous urine drainage (eg, ileal conduit). With a continent diversion procedure, the patient may void through the native urethra or self-catheterize through a surgically created stoma. The goals of imaging after urinary diversion are to assess postoperative anatomy, detect postoperative complications, evaluate for residual or recurrent tumor and metastatic disease, and monitor for upper tract distention and/or deterioration. Multiple imaging modalities and techniques may be used to evaluate urinary diversions, including computed tomographic and magnetic resonance urography, intravenous pyelography, ultrasonography, pouchography, loopography, and nephrostomy studies. Knowledge of the expected postoperative appearance after urinary diversions and potential postoperative complications is crucial because many complications may be clinically silent. Radiologists must be able to recognize the expected postoperative appearance as well as complications to facilitate appropriate diagnosis and treatment of patients after cystectomy and urinary diversion. (©)RSNA, 2016.

Bladder cancer (BCA) is relatively common and potentially recurrent/progressive disease. It is also costly to detect, treat, and control. Definitive diagnosis is made by examination of urine sediment, imaging, direct visualization (cystoscopy), and invasive biopsy of suspect bladder lesions. There are currently no widely-used BCA-specific biomarker urine screening tests for early BCA or for following patients during/after therapy. Urine metabolomic screening for biomarkers is costly and generally unavailable for clinical use. In response, we developed Raman spectroscopy-based chemometric urinalysis (Rametrix (TM)) as a direct liquid urine screening method for detecting complex molecular signatures in urine associated with BCA and other genitourinary tract pathologies. In particular, the Rametrix(TM)screen used principal components (PCs) of urine Raman spectra to build discriminant analysis models that indicate the presence/absence of disease. The number of PCs included was varied, and all models were cross-validated by leave-one-out analysis. In Study 1 reported here, we tested the Rametrix (TM) screen using urine specimens from 56 consented patients from a urology clinic. This proof-of-concept study contained 17 urine specimens with active BCA (BCA-positive), 32 urine specimens from patients with other genitourinary tract pathologies, seven specimens from healthy patients, and the urinalysis control Surine(TM). Using a model built with 22 PCs, BCA was detected with 80.4% accuracy, 82.4% sensitivity, 79.5% specificity, 63.6% positive predictive value (PPV), and 91.2% negative predictive value (NPV). Based on the number of PCs included, we found the Rametrix(TM)screen could be fine-tuned for either high sensitivity or specificity. In other studies reported here, Rametrix(TM)was also able to differentiate between urine specimens from patients with BCA and other genitourinary pathologies and those obtained from patients with end-stage kidney disease (ESKD). While larger studies are needed to improve Rametrix(TM)models and demonstrate clinical relevance, this study demonstrates the ability of the Rametrix(TM)screen to differentiate urine of BCA-positive patients. Molecular signature variances in the urine metabolome of BCA patients included changes in: phosphatidylinositol, nucleic acids, protein (particularly collagen), aromatic amino acids, and carotenoids. Center for Innovative Technology [CP15015-LS]; Virginia Tech Foundation; HATCHUnited States Department of Agriculture (USDA) [VA-160057] This research was funded in part the Center for Innovative Technology (award CP15015-LS), the Virginia Tech Foundation, and HATCH (project VA-160057). These funders provided support in salaries for authors (RSS) and materials. They had no role in study design, data collection and analysis, the decision to publish, and preparation of the manuscript. RSS and JLR are unsalaried co-founders of DialySensors, Inc., which was involved with study design, data collection and analysis, the decision to publish, and preparation of the manuscript.

753 Background: The role of metastasectomy has been in flux as treatment paradigms for management of metastatic renal cell carcinoma (mRCC) have shifted. We examined outcomes of surgical metastasectomy stratified in the setting of different mRCC risk groups. Methods: Multicenter retrospective analysis of patients from the REMARCC (REgistry of MetAstatic RCC) database. The cohort was subdivided by Motzer RCC criteria (low, intermediate, and high risk), and impact of metastasectomy was analyzed via multivariable analysis (MVA) and Kaplan Meier analyses (KMA). Primary outcome was progression free survival (PFS) and secondary outcome was overall survival (OS). Results: 438 patients (46 low risk, 262 intermediate risk, 140 high risk) with median follow-up 16 months were analyzed. Metastasectomy was performed in 18 (39%), 63 (24%), and 32 (23%) of low, intermediate and high risk groups (p=0.04). Risk groups differed significantly with respect to ECOG performance status (p

BACKGROUND Originally implemented for colorectal surgery, enhanced perioperative protocols have been incorporated into many surgical fields in an effort to improve outcomes. The cornerstone of many strategies includes patient education, liberalized oral intake on the day of surgery, no routine bowel prep, targeted multimodal analgesia, cautious use of IV hydration, early extubation, avoidance of NG tubes and/or surgical drains, and encouraging early postoperative ambulation. CASE REPORT We report on the successful outcome of a single patient with a rare autosomal dominant disorder (hereditary hemorrhagic telangiectasia) with multisystem involvement including pulmonary, cardiac, hematologic, gastrointestinal, renal, oncologic, and hepatic comorbidities, scheduled for open nephrectomy. CONCLUSIONS Prospective and retrospective studies are needed to specifically elucidate the role of similar management in higher-risk surgical candidates.

Aims The biomechanical properties of length adaptation and adjustable preload have been previously identified in detrusor smooth muscle in animal models. This in vitro study aims to show that human detrusor smooth muscle exhibits length adaptation and adjustable preload tension which could play an important role in both overactive bladder and detrusor underactivity. Methods In order to demonstrate length adaptation, human detrusor smooth muscle strips are stretched and contracted beyond an optimum length and then contracted three times at the previous optimum length to determine if maximum active tension could be re-established. To demonstrate adjustable preload (Tap), human detrusor smooth muscle strips are subjected to a pre-defined loading–unloading (strain softening) sequence to reduce preload. Then, tissues are contracted and the sequence is repeated to determine if this active process restored preload. Results Nine patients (average age, 62) provide tissue: 89% are men with urothelial carcinoma and a minority (22%) also have neurogenic bladder dysfunction. In the length adaptation protocol, contractions show progressive increases in active tension (P

Prostate cancer is one of the leading causes of cancer deaths, with no curative treatments once it spreads. Alternative therapies, including immunotherapy, have shown limited efficacy. Dendritic cells (DC) have been widely used in the treatment of various malignancies. DC capture antigens and move to the lymphoid organs where they prime naive T cells. Interaction between DC and T cells are most active in lymph nodes and suppression of DC trafficking to lymph nodes impairs the immune response. In this work, we aimed to study trafficking of DC in vivo via various routes of delivery, to optimize the effectiveness of DC-based therapy. A DC labeling system was developed using 1,1'-dioctadecyltetramethyl indotricarbocyanine Iodine for in vivo fluorescent imaging. DC harvested from C57B/6 mice were matured, labeled, and injected intravenously, subcutaneously, or intratumorally, with or without antigen loading with whole tumor lysate, into C57B/6 mice inoculated with RM-1 murine prostate tumor cells. Signal intensity was measured in vivo and ex vivo. Signal intensity at the tumor site increased over time, suggesting trafficking of DC to the tumor with all modes of injection. Subcutaneous injection showed preferential trafficking to lymph nodes and tumor. Intravenous injection showed trafficking to lungs, intestines, and spleen. Subcutaneous injection of DC pulsed with whole tumor lysate resulted in the highest increase in signal intensity at the tumor site and lymph nodes, suggesting subcutaneous injection of primed DC leads to highest preferential trafficking of DC to the immunocompetent organs.

Immunotherapeutic targeting of advanced stage cancers has prolonged the survival of cancer patients, yet its curative efficacy is limited due to tumor immunoediting and escape. On the other hand, human vaccines have been able to eradicate smallpox and control several other infectious diseases. The success has resulted from the administration of vaccines in prophylactic settings, or during latency periods in order to protect an individual during future exposure to the disease rather than curing an established disease. Therefore, administration of immunotherapy at the right time is the key to success. However, instead of focusing on the prevention of cancer, current cancer immunotherapies are often being used in a therapeutic setting with the goal of eliminating tumor cells. The present review of evidence related to cancer immunotherapeutics suggests that immunotherapeutic targeting of tumor dormancy could be more promising than targeting of advanced stage disease to achieve a cure for cancer.

Recent advances in the treatment of melanoma and non-small cell lung cancer (NSCLC) by combining conventional therapies with anti-PD1/PD-L1 immunotherapies, have renewed interests in immunotherapy of cancer. The emerging concept of conventional cancer therapies combined with immunotherapy differs from the classical concept in that it is not simply taking advantage of their additive anti-tumor effects, but it is to use certain therapeutic regimens to condition the tumor microenvironment for optimal response to immunotherapy. To this end, low dose immunogenic chemotherapies, epigenetic modulators and inhibitors of cell cycle progression are potential candidates for rendering tumors highly responsive to immunotherapy. Next generation immunotherapeutics are therefore predicted to be highly effective against cancer, when they are used following appropriate immune modulatory compounds or targeted delivery of tumor cell cycle inhibitors using nanotechnology.

Prostate cancer is the most common non-cutaneous cancer among men; yet, current diagnostic methods are insufficient, and more reliable diagnostic markers need to be developed. One answer that can bridge this gap may lie in microRNAs. These small RNA molecules impact protein expression at the translational level, regulating important cellular pathways, the dysregulation of which can exert tumorigenic effects contributing to cancer. In this study, high throughput sequencing of small RNAs extracted from blood from 28 prostate cancer patients at initial stages of diagnosis and prior to treatment was used to identify microRNAs that could be utilized as diagnostic biomarkers for prostate cancer compared to 12 healthy controls. In addition, a group of four microRNAs (miR-1468-3p, miR-146a-5p, miR-1538 and miR-197-3p) was identified as normalization standards for subsequent qRT-PCR confirmation. qRT-PCR analysis corroborated microRNA sequencing results for the seven top dysregulated microRNAs. The abundance of four microRNAs (miR-127-3p, miR-204-5p, miR-329-3p and miR-487b-3p) was upregulated in blood, whereas the levels of three microRNAs (miR-32-5p, miR-20a-5p and miR-454-3p) were downregulated. Data analysis of the receiver operating curves for these selected microRNAs exhibited a better correlation with prostate cancer than PSA (prostate-specific antigen), the current gold standard for prostate cancer detection. In summary, a panel of seven microRNAs is proposed, many of which have prostate-specific targets, which may represent a significant improvement over current testing methods.

Purpose To analyze the association between the use of diagnostic ureteroscopy (URS) and development of intra-vesical recurrence (IVR) in patients undergoing radical nephroureterectomy (RNU) for high risk upper tract urothelial cancer. Methods A systematic review of the published data was performed up to December 2016 using multiple search engines to identify eligible studies. A formal meta-analysis was conducted for studies comparing patients who underwent URS before RNU to those with did not. HRs with their 95% CIs from each study were used to calculate pooled HRs. Pooled estimates were calculated using a fixed-effects or random-effects model according to heterogeneity. Statistical analyses were performed using RevMan, version 5. Results Seven studies were included in the systematic review, but only six of were deemed fully eligible for meta-analysis. Among the 2,382 patients included in the meta-analysis, 765 underwent diagnostic URS prior to RNU. All examined studies were retrospective, and the majority examined Asian populations. The IVR rate ranged from 39.2% to 60.7% and from 16.7% to 46% in patients with and without prior URS, respectively. At pooled analysis, a statistically significant association was found between occurrence of URS prior to RNU and IVR (HR=1.56; 95% CI 1.33 to 1.88; p < 0.001). There was not heterogeneity in the observed outcomes according to the I2 statistic of 2% (p = 0.40). Conclusions Within the intrinsic limitations of this type of analysis, these findings suggest a significant association between the use of diagnostic URS and higher risk of developing IVR after RNU. Further research is this area should be encouraged to further investigate the possible causality behind this association and it potential clinical implications. This article is protected by copyright. All rights reserved.

Low amplitude rhythmic contractions (LARC) occur in detrusor smooth muscle and may play a role in storage disorders such as overactive bladder and detrusor overactivity. The purpose of this study was to determine whether LARC frequencies identified in vitro from strips of human urinary bladder tissue correlate with in vivo LARC frequencies, visualized as phasic intravesical pressure (p ves) waves during urodynamics (UD). After IRB approval, fresh strips of human urinary bladder were obtained from patients. LARC was recorded with tissue strips at low tension (

Decreased expression of highly immunogenic cancer-testis antigens (CTA) might help tumor to achieve low immunogenicity, escape immune surveillance and grow unimpeded. Our aim was to evaluate CTA expression in tumor and normal tissues and to investigate possible means of improving the immune response in a murine prostate cancer (CaP) model by using the combination of epigenetic modifier 5-azacitidine (5-AzaC) and immunomodulator lenalidomide. No study to date has examined the effect of this combination on the prostate cancer or its impact on antigen-presenting cells (APC).Gene microarrays were performed to compare expression of several CTA in murine prostate cancer (RM-1 cells) and normal prostate. RM-1 cells were treated with 5-AzaC and real-time PCR was performed to investigate the expression of several CTA. Western blotting was used to determine whether expression of CTA-specific mRNA induced by 5-AzaC resulted in increase in the corresponding protein. Effect of the epigenetic agents and immunomodulators was assessed on dendritic cells (DC) using flow cytometry, ELISA and T-cell proliferation assay.Gene arrays demonstrated decreased expression of 35 CTA in CaP tissue compared to normal prostate. 5-AzaC treatment of RM-1 prostate cancer cells upregulated the expression of all 13 CTA tested in a dose-dependent fashion. DC were treated with 5-AzaC and lenalidomide and the expression of surface markers MHC Class I, MHC Class II, CD80, CD86, CD 205, and CD40 was increased. Combination of 5-AzaC and lenalidomide enhances the ability of DC to stimulate T-cell proliferation in mixed leukocyte reaction. Secretion of IL-12 and IL-15 by DC increased significantly with addition of 5-AzaC or 5-AzaC and lenalidomide.Decreased expression of CTA by prostate cancer may be a means of escaping immune monitoring. Combination of epigenetic modifications and immunomodulation by 5-AzaC and lenalidomide increased tumor immunogenicity and enhanced DC function and may be used in the treatment of advanced prostate cancer. Prostate 77: 361-373, 2017. © 2016 Wiley Periodicals, Inc.

common precursor of testosterone (T) and dihydrotestosterone (DHT). We reported 5a-androstane-3b,17b-diol (3b-diol), which is inactive androgen metabolized from DHT, can be converted back to DHEA and finally to DHT. In this pathway, 3b-hydroxysteroid dehydrogenase (3bHSD) is the key enzyme for the conversion from DHEA and epiandrosterone (epiAND) to DHT, and Rui et al. reported abiraterone inhibited 3b-HSD in CRPC. We examined the effect of CYP17 inhibitors on the intracrine back-conversion pathway induced by 3b-diol in prostate cancer cells. METHODS: LNCaP cells were incubated in the presence of 3bdiol or DHEA 10nmol/L with or without CYP17 inhibitors (abiraterone, ketoconazole, or orteronel) 10nmol/L. In all experiments, LNCaP cells were incubated without any androgens and CYP17 inhibitors as a control (CTRL). After incubation, PSA levels in the media were determined by enzyme immunoassay, and androgen levels in media were measured by LC-MS/MS. RESULTS: By adding DHEA or 3b-diol in media, PSA levels were increased (p 1⁄4 0.013 and p < 0.001, respectively). 3b-diol highly activated AR about five-times compared to DHEA. Inhibition of PSA secretion by abiraterone, ketoconazole and orteronel was found in the presence of DHEA (p < 0.001, p 1⁄4 0.002, and p 1⁄4 0.017, respectively). 3b-diol-induced PSA accumulation in media was inhibited by abiraterone, not ketoconazole or orteronel. By adding 3b-diol in medium, DHEA, androstenediol (A-diol), androstendione (A-dione), T, and DHT levels were increased compared to CTRL. In the media with 3b-diol and abiraterone, A-dione, T, DHT, and 5a-androstanedione (5a-A-dione) levels were decreased, DHEA, 5-diol, and epiAND levels increased compared to 3b-diol only. CONCLUSIONS: AR was highly activated by 3b-diol compared to DHEA through the conversion of 3b-diol to DHT by way of epiAND and 5a-A-dione, which abiraterone blocked by inhibiting 3b-HSD. Abiraterone has a potential to inhibit the intracrine back-conversion pathway.