Robot-assisted laparoscopic nephrectomy: early outcome measures with the implementation of multimodal analgesia and intrathecal morphine via the acute pain service.

PURPOSE: The objective of this study was to perform a retrospective cohort analysis, in which we measured the association of an acute pain service (APS)-driven multimodal analgesia protocol that included preoperative intrathecal morphine (ITM) compared to historic controls (i.e., surgeon-driven analgesia protocol without ITM) with postoperative opioid use. METHODS: This was a retrospective cohort study in which the primary objective was to determine whether there was a decrease in median 24-h opioid consumption (intravenous morphine equivalents [MEQ]) among robotic nephrectomy patients whose pain was managed by the surgical team prior to the APS, versus pain managed by APS. Secondary outcomes included opioid consumption during the 24-48 h and 48-72 h period and hospital length of stay. To create matched cohorts, we performed 1:1 (APS:non-APS) propensity score matching. Due to the cohorts occurring at the different time periods, we performed a segmented regression analysis of an interrupted time series. RESULTS: There were 76 patients in the propensity-matched cohorts, in which 38 (50.0%) were in the APS cohort. The median difference in 24-h opioid consumption in the pre-APS versus APS cohort was 23.0 mg [95% CI 15.0, 31.0] (p < 0.0001), in favor of APS. There were no differences in the secondary outcomes. On segmented regression, there was a statistically significant drop in 24-h opioid consumption in the APS cohort versus pre-APS cohort (p = 0.005). CONCLUSIONS: The implementation of an APS-driven multimodal analgesia protocol with ITM demonstrated a beneficial association with postoperative 24-h opioid consumption following robot-assisted nephrectomy.

PI-RADS Version 2 Category on 3 Tesla Multiparametric Prostate Magnetic Resonance Imaging Predicts Oncologic Outcomes in Gleason 3 + 4 Prostate Cancer on Biopsy.

PURPOSE: Three Tesla multiparametric magnetic resonance imaging with PI-RADS™ (Prostate Imaging Reporting and Data System) version 2 scoring is a common tool in prostate cancer diagnosis which informs the likelihood of a cancerous lesion. We investigated whether PI-RADS version 2 also predicts adverse pathology features mainly in patients with biopsy Gleason score 3 + 4 disease. MATERIALS AND METHODS: We reviewed the records of 326 consecutive men with a preoperative template and/or magnetic resonance imaging-ultrasound fusion biopsy Gleason score of 6-7 from a prospectively maintained database of men who underwent robotic radical prostatectomy. The primary analysis was done in patients with biopsy Gleason score 3 + 4 to assess the primary outcome of adverse pathology features on univariate and multivariate logistic regression. The secondary outcome was biochemical recurrence-free survival using the Kaplan-Meier method. Similar analysis was done in patients with a biopsy Gleason score of 6-7. RESULTS: Of men with Gleason score 3 + 4 findings 27%, 15%, 36% and 23% showed a PI-RADS version 2 score of 0-2, 3, 4 and 5, respectively. On univariate analysis PI-RADS version 2 category 5 predicted adverse pathology features vs categories 0-2 (OR 10.7, 95% CI 3.7-31, p ≤0.001). On multivariate analysis the PI-RADS version 2 category 5 was associated with adverse pathology when adjusting for preoperative magnetic resonance imaging targeted biopsy (OR 11.4, 95% CI 3.7-35, p ≤0.0001). In men with a targeted biopsy Gleason score of 3 + 4 prostate cancer PI-RADS version 2 category 5 was associated with adverse pathology (OR 14.7, 95% CI 1.5-146.9, p = 0.02). Of men with biopsy Gleason score 3 + 4 disease 92% and 58% with a PI-RADS version 2 score of 4 and 5, respectively, had 2-year biochemical recurrence-free survival. CONCLUSIONS: A PI-RADS version 2 category 5 lesion in patients with a biopsy Gleason score 3 + 4 lesion predicted adverse pathology features and biochemical recurrence-free survival. These findings suggest that preoperative 3 Tesla multiparametric magnetic resonance imaging may serve as a prognostic marker of treatment outcomes independently of biopsy Gleason score or biopsy type.

PI-RADS Version 2 Category on 3 Tesla Multiparametric Prostate Magnetic Resonance Imaging Predicts Oncologic Outcomes in Gleason 3 + 4 Prostate Cancer on Biopsy.

PURPOSE: Three Tesla multiparametric magnetic resonance imaging with PI-RADS™ (Prostate Imaging Reporting and Data System) version 2 scoring is a common tool in prostate cancer diagnosis which informs the likelihood of a cancerous lesion. We investigated whether PI-RADS version 2 also predicts adverse pathology features mainly in patients with biopsy Gleason score 3 + 4 disease. MATERIALS AND METHODS: We reviewed the records of 326 consecutive men with a preoperative template and/or magnetic resonance imaging-ultrasound fusion biopsy Gleason score of 6-7 from a prospectively maintained database of men who underwent robotic radical prostatectomy. The primary analysis was done in patients with biopsy Gleason score 3 + 4 to assess the primary outcome of adverse pathology features on univariate and multivariate logistic regression. The secondary outcome was biochemical recurrence-free survival using the Kaplan-Meier method. Similar analysis was done in patients with a biopsy Gleason score of 6-7. RESULTS: Of men with Gleason score 3 + 4 findings 27%, 15%, 36% and 23% showed a PI-RADS version 2 score of 0-2, 3, 4 and 5, respectively. On univariate analysis PI-RADS version 2 category 5 predicted adverse pathology features vs categories 0-2 (OR 10.7, 95% CI 3.7-31, p ≤0.001). On multivariate analysis the PI-RADS version 2 category 5 was associated with adverse pathology when adjusting for preoperative magnetic resonance imaging targeted biopsy (OR 11.4, 95% CI 3.7-35, p ≤0.0001). In men with a targeted biopsy Gleason score of 3 + 4 prostate cancer PI-RADS version 2 category 5 was associated with adverse pathology (OR 14.7, 95% CI 1.5-146.9, p = 0.02). Of men with biopsy Gleason score 3 + 4 disease 92% and 58% with a PI-RADS version 2 score of 4 and 5, respectively, had 2-year biochemical recurrence-free survival. CONCLUSIONS: A PI-RADS version 2 category 5 lesion in patients with a biopsy Gleason score 3 + 4 lesion predicted adverse pathology features and biochemical recurrence-free survival. These findings suggest that preoperative 3 Tesla multiparametric magnetic resonance imaging may serve as a prognostic marker of treatment outcomes independently of biopsy Gleason score or biopsy type.

Treatment utilization and overall survival in patients receiving radical nephroureterectomy versus endoscopic management for upper tract urothelial carcinoma: evaluation of updated treatment guidelines.

PURPOSE: While radical nephroureterectomy (RNU) is the gold standard treatment for upper tract urothelial carcinoma (UTUC), select patients may benefit from endoscopic treatment (ET). European Association of Urology guidelines recommend ET for patients with low-risk (LR) disease: unifocal, < 2 cm, low-grade lesions without local invasion. To inform the utility of ET, we compare the overall survival (OS) of patients receiving ET and RNU using current and previous guidelines of LR disease. MATERIALS AND METHODS: Patients with non-metastatic, cT1 or less UTUC diagnosed in 2004-2012 were collected from the National Cancer Database. OS was analyzed with inverse probability of treatment weighted Cox proportional hazard regression. Analyses were conducted for LR disease under updated (size < 2 cm) and previous guidelines (size < 1 cm). RESULTS: Patients who were older, healthier, and treated at an academic facility had higher odds of receiving ET. In 851 identified patients with LR disease, RNU was associated with increased OS compared with ET (p = 0.006); however, there was no difference between ET and RNU (p = 0.79, n = 202) under the previous guidelines (size < 1 cm). In, otherwise, LR patients, the largest tumor size with no difference between ET and RNU was ≤ 1.5 cm (p = 0.07). CONCLUSIONS: RNU is associated with improved survival when compared with ET in the management of LR UTUC using current guidelines with a size threshold of < 2 cm. In appropriately selected LR patients, we find no difference between RNU and ET up to a tumor size of ≤ 1.5 cm. However, in the absence of prospective studies, the usage of ET is best left up to clinician discretion.

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

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

A 17-Gene Genomic Prostate Score Assay Provides Independent Information on Adverse Pathology in the Setting of Combined Multiparametric Magnetic Resonance Imaging Fusion Targeted and Systematic Prostate Biopsy.

PURPOSE: Multiparametric magnetic resonance imaging and biopsy based molecular tests such as the 17-gene Oncotype DX® Genomic Prostate Score™ assay are increasingly performed to improve risk stratification in men with clinically localized prostate cancer. The prostate score assay was previously shown to be a significant independent predictor of adverse pathology findings at radical prostatectomy in men diagnosed by systematic biopsies only. Therefore, we investigated the ability of the prostate score assay to predict adverse pathology findings in the setting of magnetic resonance imaging guided prostate biopsy. MATERIALS AND METHODS: We identified men diagnosed with NCCN® (National Comprehensive Cancer Network®) very low, low or intermediate risk prostate cancer who underwent simultaneous multiparametric magnetic resonance imaging fusion targeted and systematic prostate biopsy with subsequent radical prostatectomy within 6 months. Prostate score assay testing was performed on biopsy tissue with the highest Gleason score. The primary outcome of the study was adverse pathology findings, defined as Gleason score 4 + 3 or greater disease and/or pT3+ at radical prostatectomy. Independent predictors of adverse pathology findings were determined in a multivariable model to adjust for clinical parameters. RESULTS: A total of 134 men were eligible for primary analysis. On univariable analysis the UCLA score, magnetic resonance imaging, prostate score assay results and biopsy Gleason score were significant predictors of adverse pathology findings. After multivariable adjustment prostate score assay values remained a significant predictor of adverse pathology results (prostate score assay per 20 U OR 3.28, 95% CI 1.74-6.62, p <0.001). A wide and overlapping distribution of prostate score assay results was seen across PI-RADS® (Prostate Imaging Reporting and Data System) version 2 scores. CONCLUSIONS: The prostate score assay result is an independent predictor of adverse pathology findings in patients who were diagnosed with very low, low or intermediate risk prostate cancer in the setting of multiparametric magnetic resonance imaging fusion prostate biopsy. This assay can be useful as an independent technology or an adjunct technology to multiparametric magnetic resonance imaging to individualize risk stratification of low and intermediate risk prostate cancer.

Trends in urinary diversion after radical cystectomy for urothelial carcinoma.

PURPOSE: To assess how trends in urinary diversion (UD) type following radical cystectomy (RC) have changed in recent years and investigate pre-operative predictors of UD type. METHODS: Data were abstracted from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) from 2011 to 2015. We quantified the percentages of continent diversions (CD) versus incontinent diversions (ID) completed over this time frame. Using univariate and multivariable logistic regression analyses, we compared UD type across year of operation as well as predictors of type of diversion. RESULTS: We identified 4790 patients in the cohort, of which 81% underwent an incontinent diversion. Patients undergoing incontinent diversions were older (p < 0.001), more likely to be female (p < 0.001), had higher American Society of Anesthesiologists (ASA) classification (p < 0.001) and had more comorbidities with worse preoperative lab values. On multivariable analysis, the odds of incontinent diversion increased per year (OR 1.16, 95% CI 1.06-1.26; p = 0.001). Neoadjuvant chemotherapy (NAC) was associated with lower odds of receiving an ID (OR 0.33, 95% CI 0.17-0.64; p = 0.001). Being male, healthy and young were associated with higher odds of CD. CONCLUSION: We demonstrate that there has been a decrease in continent diversion use in recent years. Neoadjuvant chemotherapy, proxies of life expectancy and gender are significant predictors of continent diversion. Further investigation to determine the underlying cause of decreased utilization of CD is warranted.

Overall survival in patients with residual disease after radical cystectomy and neoadjuvant chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy (NAC) has been shown to improve survival in patients with urothelial carcinoma (UC). However, there are a subset of patients who do not respond or progress despite systemic treatment. METHODS: Data from the National Cancer Database on patients who underwent a radical cystectomy (RC) with or without NAC from 2006 to 2013 were abstracted. Covariates were balanced using inverse probability weighting methods. The primary outcome of overall survival in patients with residual disease by stage was evaluated using 90-day conditional landmark analysis and Cox proportional hazards modeling. Secondary outcome of predictors of residual disease was evaluated using multivariable logistic regression analysis. RESULTS: A total of 20,128 patients met our inclusion criteria; 16,058 patients underwent RC only (80%) and 4070 underwent RC with NAC (20%). Patients who received NAC were younger and healthier, treated at an academic center, and presented with higher stage. NAC was associated with improved overall survival amongst patients with cT3-4aN0 (HR 0.84 95% CI 0.73-0.97; p = 0.02) and cN+ (HR 0.70, 95% CI 0.58-0.86; p = 0.001). Predictors of no residual disease were NAC (OR 0.17, 95% CI 0.14-0.21; p < 0.001) and treatment at an academic facility (OR 0.47, 95% CI 0.37-0.60; p < 0.001). Patients with cT3-4a or cN+ had increased odds of having residual UC (OR 2.01, 95% CI 1.53-2.64; p < 0.001, and OR 2.14, 95% CI 1.43-3.21; p < 0.001, respectively) compared with cT2. CONCLUSION: In patients with residual UC, NAC is associated with a significant survival benefit in higher stage disease only. Furthermore, those treated with NAC or at an academic center were less likely to have residual disease. Given the toxicity of NAC, more prudent patient selection for NAC is warranted and requires further study.

Adrenalectomy for benign and malignant disease: utilization and outcomes by surgeon specialty and surgical approach from 2003-2013.

INTRODUCTION: Data on the utilization of open, laparoscopic and robotic adrenalectomy on a national level is limited. MATERIALS AND METHODS: Data on patients who underwent open, laparoscopic, or robotic adrenalectomy for benign or malignant disease in the US from 2003-2013 were extracted using ICD-9 codes from the Premier Hospital Database. Surgeon specialty, patient demographics, hospital characteristics, and complications were compared. Data were analyzed using univariate and multivariable logistic regression analyses. RESULTS: A total of 8,831 adrenalectomies were performed for benign and malignant tumors. There was no significant difference in rate of adrenalectomy with regards to comorbidities, insurance status, or hospital characteristics. Non-urologists performed adrenalectomy more often for both benign (57% versus 43%; p = 0.011) and malignant disease (66% versus 34%; p = 0.011). Across all indications, non-urologists performed open surgery most often followed by laparoscopic and robotic approaches (56.3% versus 37.4% versus 6.4%, respectively), compared to urologists (48.8% versus 38.4% versus 12.9%, respectively). Overall, urologists were more likely to use laparoscopic or robotic approaches (p = 0.001). There was no difference in complication rates or operative times between surgical specialties or by surgeon/hospital case volume. On multivariable regression analysis, the best predictor of major complication was a Charlson Comorbidity Index (CCI) ≥ 2 (OR 3.9, 95%CI 2.1-7.1; p = < 0.001). Compared to open surgery, laparoscopy had significantly reduced odds of major complication (OR 0.6, 95%CI 0.3-0.9; p = 0.03). Patients undergoing robotic procedures had the shortest length of stay. CONCLUSION: In this retrospective study, adrenalectomy was more commonly performed by non-urologists via an open approach. Patients with CCI ≥ 2 were more likely to have postoperative complications while surgeon volume, hospital volume, and surgical approach did not influence complication rates.

Off-Target Effect of Sildenafil on Postsurgical Erectile Dysfunction: Alternate Pathways and Localized Delivery System.

INTRODUCTION: There is no consensus on the best oral phosphodiesterase type 5 inhibitor (PDE5I) for patients undergoing penile rehabilitation after surgical nerve injury. AIM: To determine the mechanism of PDE5I on cultured neuronal cells and the effectiveness of local drug delivery using nanospheres (NSPs) to sites of nerve injury in a rat model of bilateral cavernous nerve injury (BCNI). METHODS: The effects of sildenafil, tadalafil, and vardenafil on cyclic adenosine monophosphate, cyclic guanosine monophosphate, and cell survival after exposure to hypoxia and H2O2 were measured in PC12, SH-SY5Y, and NTERA-2 (NT2) cell cultures. The effects of phosphodiesterase type 4 inhibitor (PDE4I) and PDE5I on neuronal cell survival were evaluated. Male rats underwent BCNI and were untreated (BCNI), immediately treated with application of empty NSPs (BCNI + NSP), NSPs containing sildenafil (Sild + NSP), or NSPs containing rolipram (Rol + NSP). MAIN OUTCOME MEASURES: Viability of neuronal cells was measured. Intracavernous pressure changes after cavernous nerve electrostimulation and expression of neurofilament, nitric oxide synthase, and actin in mid-shaft of penis were analyzed 14 days after injury. RESULTS: Sildenafil and rolipram significantly decreased cell death after exposure to H2O2 and hypoxia in PC12, SH-SY5Y, and NT2 cells. PC12 cells did not express PDE5 and knockdown of PDE4 significantly increased cell viability in PC12, SH-SY5Y, and NT2 cells exposed to hypoxia. The ratio of intracavernous pressure to mean arterial pressure and expression of penile neurofilament, nitric oxide synthase, and actin were significantly higher in the Sild + NSP and Rol + NSP groups than in the BCNI and BCNI + NSP groups. Limitations included analysis in only two PDE families using only a single dose. CONCLUSION: Sildenafil showed the most profound neuroprotective effect compared with tadalafil and vardenafil. Sildenafil- or rolipram-loaded NSP delivery to the site of nerve injury prevented erectile dysfunction and led to increased neurofilament, nitric oxide synthase, smooth muscle content in rat penile tissue after BCNI.

Oncologic outcomes in men with metastasis to the prostatic anterior fat pad lymph nodes: a multi-institution international study.

BACKGROUND: The presence of lymph nodes (LN) within the prostatic anterior fat pad (PAFP) has been reported in several recent reports. These PAFP LNs rarely harbor metastatic disease, and the characteristics of patients with PAFP LN metastasis are not well-described in the literature. Our previous study suggested that metastatic disease to the PAFP LN was associated with less severe oncologic outcomes than those that involve the pelvic lymph node (PLN). Therefore, the objective of this study is to assess the oncologic outcome of prostate cancer (PCa) patients with PAFP LN metastasis in a larger patient population. METHODS: Data were analyzed on 8800 patients from eleven international centers in three countries. Eighty-eight patients were found to have metastatic disease to the PAFP LNs (PAFP+) and 206 men had isolated metastasis to the pelvic LNs (PLN+). Clinicopathologic features were compared using ANOVA and Chi square tests. The Kaplan-Meier method was used to calculate the time to biochemical recurrence (BCR). RESULTS: Of the eighty-eight patients with PAFP LN metastasis, sixty-three (71.6%) were up-staged based on the pathologic analysis of PAFP and eight (9.1%) had a low-risk disease. Patients with LNs present in the PAFP had a higher incidence of biopsy Gleason score (GS) 8-10, pathologic N1 disease, and positive surgical margin in prostatectomy specimens than those with no LNs detected in the PAFP. Men who were PAFP+ with or without PLN involvement had more aggressive pathologic features than those with PLN disease only. However, there was no significant difference in BCR-free survival regardless of adjuvant therapy. In 300 patients who underwent PAFP LN mapping, 65 LNs were detected. It was also found that 44 out of 65 (67.7%) nodes were located in the middle portion of the PAFP. CONCLUSIONS: There was no significant difference in the rate of BCR between the PAFP LN+ and PLN+ groups. The PAFP likely represents a landing zone that is different from the PLNs for PCa metastasis. Therefore, the removal and pathologic analysis of PAFP should be adopted as a standard procedure in all patients undergoing radical prostatectomy.

Concern for overtreatment using the AUA/ASTRO guideline on adjuvant radiotherapy after radical prostatectomy.

BACKGROUND: Recently, three prospective randomized trials have shown that adjuvant radiotherapy (ART) after radical prostatectomy for the patients with pT3 and/or positive margins improves biochemical progression-free survival and local recurrence free survival. But, the optimal management of these patients after radical prostatectomy is an issue which has been debated continuously. The object of this study was to determine the necessity of adjuvant radiotherapy (ART) by reviewing the outcomes of observation without ART after radical prostatectomy (RP) in patients with pathologic indications for ART according to the American Urological Association (AUA)/American Society for Radiation Oncology (ASTRO) guideline. METHODS: From a prospectively maintained database, 163 patients were eligible for inclusion in this study. These men had a pathological stage pT2-3 N0 with undetectable PSA level after RP and met one or more of the three following risk factors: capsular perforation, positive surgical margins, or seminal vesicle invasion. We excluded the patients who had received neoadjuvant hormonal therapy or adjuvant treatment, or had less than 24 months of follow-up. To determine the factors that influenced biochemical recurrence-free (BCR), univariate and multivariate Cox proportional hazards analyses were performed. RESULTS: Among the 163 patients, median follow-up was 50.5 months (24.0-88.2 months). Of those men under observation, 27 patients had BCR and received salvage radiotherapy (SRT). The multivariate Cox analysis showed that BCR was marginally associated with pre-operative serum PSA (P = 0.082), and the pathologic GS (HR, 4.063; P = 0.001) was an independent predictor of BCR. More importantly, in 87 patients with pre-operative PSA < 6.35 ng/ml and GS ≤ 7, only 3 developed BCR. CONCLUSIONS: Of the 163 patients who qualified for ART based on the current AUA/ASTRO guideline, only 27 (16.6%) developed BCR and received SRT. Therefore, using ART following RP using the current recommendation may be an overtreatment in an overwhelming majority of the patients.

Inadvertent foley catheterization of the ureter.

We present a case of an 83-year-old woman with multiple sclerosis and chronic indwelling urethral catheter who was found to have a ureteral injury after inadvertent placement of a foley catheter into the proximal right ureter. Cystoscopy and retrograde ureteral stenting was attempted, but unsuccessful. The patient ultimately underwent successful antegrade ureteral stenting and nephrostomy placement. We review the limited literature on the topic of aberrant foley catheter placement into the ureter.

Favorable risk factors in patients with positive surgical margin after robot-assisted radical prostatectomy.

INTRODUCTION: Positive surgical margin (PSM) has classically been associated with biochemical recurrence (BCR) following radical prostatectomy (RP) and immediate adjuvant radiotherapy has been advocated based on two large randomized prospective clinical studies. However, a significant percentage of patients with PSM never experience BCR. This study evaluated factors potentially affecting risk of BCR among the patients with PSM after robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: From a prospectively maintained database, 699 patients with localized prostate cancer who underwent a RARP without any adjuvant therapy were identified. Median follow up was 46.0 months. To determine the pathologic and clinical factors that influenced BCR, univariate and multivariate analyses using the Cox proportional hazards model were performed. BCR-free survival curves were estimated with Kaplan-Meier method. RESULTS: Surgical margins were positive in 115 patients (16.5%), of whom 23 (20%) had BCR. In the univariate analyses, serum PSA level, surgical Gleason score (GS), and non-organ confined disease were significantly associated with BCR in men with PSM. Multivariate Cox analysis showed that BCR was significantly associated with PSA (p = 0.011), and the surgical GS (p = 0.008). In patients with lower PSA cutoff (5.3 ng/mL), GS ≤ 7, and organ-confined disease, there were no BCR. CONCLUSIONS: In this study, we identified favorable risk factors in patients with PSM following RARP. The results suggest that immediate adjuvant therapy for PSM may not be necessary in men with Gleason score 7 or less, organ-confined disease, and low preoperative PSA.

The Role of Radical Cystectomy in Clinically Node Positive Bladder Cancer: A US Veterans Health Administration Study.

INTRODUCTION: The role of local definitive therapy in addition to systemic treatment in clinically positive regional lymph node (cN+) bladder cancer is yet to be determined. Herein, we sought to investigate the role of radical cystectomy (RC) in management of patients with cN+ bladder cancer at US Veterans Health Administration Facilities. METHODS: We identified patients diagnosed with cN+ bladder cancer between 2000-2017 using the Department of Veterans Affairs (VA) Informatics and Computing Infrastructure (VINCI). We employed a combination of database/registry coded values and chart review for data collection. To minimize mortality bias, we excluded patients who died within 90 days of diagnosis. We divided the patients into cystectomy (C) versus "no cystectomy" (NOC) cohorts. Propensity score matching was performed based on predictors of undergoing RC. Multivariable Cox models and Kaplan-Meier survival curves were used to estimate overall survival (OS) and cancer specific survival (CCS). RESULT: After matching, 158 patients were included in the C and NOC groups. In the C-group, 85(54%) patients received pre-cystectomy chemotherapy, and 73(46%) patients underwent post-cystectomy chemotherapy. In the C-group, 65(41%) patients and in the NOC-group, 66(42%) patients had clinical N1 disease (P = .77). In multivariable Cox model, undergoing RC was associated with improved OS (HR0.62; 95%CI 0.47-0.81), P < .001) and CSS (HR0.58; 95%CI 0.42-0.80; P < .001). CONCLUSION: As part of multimodal treatment, undergoing RC was associated with improved OS and CSS in subset of patients with cN+ bladder cancer. Prospective randomized trials are warranted to further investigate the role of local definitive therapy in this specific patient population.

Characterization and impact of non-canonical WNT signaling on outcomes of urothelial carcinoma.

BACKGROUND: Non-canonical WNT family (WNT5A pathway) signaling via WNT5A through ROR1 and its partner, ROR2, or Frizzled2 (FZD2) is linked to processes driving tumorigenesis and therapy resistance. We utilized a large dataset of urothelial carcinoma (UC) tumors to characterize non-canonical WNT signaling through WNT5A, ROR1, ROR2, or FZD2 expression. METHODS: NextGen Sequencing of DNA (592 genes or WES)/RNA (WTS) was performed for 4125 UC tumors submitted to Caris Life Sciences. High and low expression of WNT5A, ROR1, ROR2, and FZD2 was defined as ≥ top and

Treatment Landscape for Metastatic Castrate-Sensitive Prostate Cancer: A Review.

With the advent of new therapeutic modalities, management of metastatic castrate-sensitive prostate cancer (mCSPC) has been in flux. From androgen-deprivation therapy to docetaxel to androgen receptor-signaling inhibitors, each agent has heralded a new treatment paradigm. As such, the optimal first-line therapy for mCSPC remains incompletely defined. This review provides a narrative of recent advances to systemic therapy within the mCSPC treatment space, particularly with regard to expansion to triplet therapy.

Absence of prostatic growth in large cohort of adult female patients with congenital adrenal hyperplasia.

PURPOSE: In girls with congenital adrenal hyperplasia the degree to which excess androgen exposure leads to the development of prostatic tissue is largely uncharacterized, except in rare case reports of prostatic growth and adenocarcinoma. Such growth yields concern for future malignant degeneration. MATERIALS AND METHODS: Chart review identified 43 adult women with congenital adrenal hyperplasia who had been longitudinally followed from birth, of whom 11 were available for history and physical examination, laboratory testing for androgen metabolites, and pelvic magnetic resonance imaging. RESULTS: Periurethral thickening was noted on digital rectal examination in 1 patient with increased 17-hydroxyprogesterone and tissue analogous to prostatic tissue was impalpable in the remaining 10. Prostate specific antigen was 0.2 ng/ml in another patient with notably increased testosterone, androstenedione, dihydrotestosterone and 17-hydroxyprogesterone, and was less than 0.1 ng/ml in the remaining patients. Magnetic resonance imaging revealed an absence of definitive prostatic tissue in all 11 patients despite evidence of genitourinary masculinization in all. Of the 11 women 7 had marked androgen excess. CONCLUSIONS: Despite androgen excess and genitourinary masculinization in patients with congenital adrenal hyperplasia, as well as case reports citing evidence of prostatic tissue and adenocarcinoma in these women, our study successfully documents the absence of notable prostatic growth in these patients. A better understanding of the timing and factors involved in prostatic growth would aid in identifying the degree to which adult women with congenital adrenal hyperplasia are at risk for adverse sequelae of Skene gland growth.

The Current and Future Promises of Combination Radiation and Immunotherapy for Genitourinary Cancers.

As the indications for the use of immunotherapy in genitourinary malignancies expand, its role in combination with standard or conventional therapies has become the subject of contemporary studies. Radiotherapy has multiple immunomodulating effects on anti-tumor immune response, which highlights potential synergistic role with immunotherapy agents. We sought to review the body of published data studying the combination of immunotherapy and radiotherapy as well as the rationale for combination therapy. Trial information and primary articles were obtained using the following terms "immunotherapy", "radiotherapy", "prostate cancer", and "bladder cancer." All articles and trials were screened to ensure they included combination radiotherapy and immunotherapy. The effects of radiation on the immune system, including both immunogenic and immunosuppressive effects, have been reported. There is a potential for combinatorial or synergistic effects between radiation therapy and immunotherapy in treating bladder and prostate cancers. However, results from ongoing and future clinical trials are needed to best integrate immunotherapy into current standard of care treatments for GU cancers.

Prostate cancer multiparametric magnetic resonance imaging visibility is a tumor-intrinsic phenomena.

Multiparametric magnetic resonance imaging (mpMRI) is an emerging standard for diagnosing and prognosing prostate cancer, but ~ 20% of clinically significant tumors are invisible to mpMRI, as defined by the Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) score of one or two. To understand the biological underpinnings of tumor visibility on mpMRI, we examined the proteomes of forty clinically significant tumors (i.e., International Society of Urological Pathology (ISUP) Grade Group 2)-twenty mpMRI-visible and twenty mpMRI-invisible, with matched histologically normal prostate. Normal prostate tissue was indistinguishable between patients with visible and invisible tumors, and invisible tumors closely resembled the normal prostate. These data indicate that mpMRI-visibility arises when tumor evolution leads to large-magnitude proteomic divergences from histologically normal prostate.