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Background: Several studies have demonstrated that abnormal levels of nuclear matrix protein 22 (NMP22) are associated with bladder cancer and have led to the approval of NMP22 as a urinary biomarker by the US Food and Drug Administration. Nonetheless, the clinical significance of NMP22 remains unclear. The objective of this study was to use decision analysis to determine whether NMP22 improves medical decision-making.Methods: The current study included 2222 patients who had a history of nonmuscle-invasive bladder cancer and current negative cytology. The authors developed models to predict cancer recurrence or progression to muscle-invasive disease using voided NMP22 levels, cystoscopy, age, and sex. Clinical net benefit was calculated by summing the benefits (true-positives), subtracting the harms (false-positives), and weighting these values by the threshold probability at which a patient or clinician would opt for cytoscopy.Results: After cystoscopy, 581 patients (26%) had cancer identified. The NMP22 level was associated significantly with bladder cancer recurrence and progression (P < .001 for both). The use of NMP22 in a model with age and sex was associated with better patient outcomes than performing cystoscopy on everyone and produced threshold probabilities > 8% for recurrence and > 3% for progression. Only offering cystoscopy to those who had a risk > 15% reduced the number of cystoscopies by 229 while missing only 25 cancer recurrences per 1000 men with negative cytology. The current study was limited by its multicenter design.Conclusions: For clinicians who would perform a cystoscopy at a threshold of 5% for recurrence or 1% for progression, NMP22 did not aid clinical decision-making. For less risk-averse clinicians who would only perform a cystoscopy at a threshold probability >thinsp;8% for recurrence or > 3% for progression, NMP22 helped to indicate which patients required cystoscopy and which could be spared this procedure. [ABSTRACT FROM AUTHOR]

Prostate cancer is the second most common cancer in men and affects 1 in 9 men in the United States. Early screening for prostate cancer often involves monitoring levels of prostate-specific antigen (PSA) and performing digital rectal exams. However, a prostate biopsy is always required for definitive cancer diagnosis. The Early Detection Research Network (EDRN) is a consortium within the National Cancer Institute aimed at improving screening approaches and early detection of cancers. As part of this effort, the Weill Cornell EDRN Prostate Cancer has collected and biobanked specimens from men undergoing a prostate biopsy between 2008 and 2017. In this report, we describe blood metabolomics measurements for a subset of this population. The dataset includes detailed clinical and prospective records for 580 patients who underwent prostate biopsy, 287 of which were subsequentially diagnosed with prostate cancer, combined with profiling of 1,482 metabolites from plasma samples collected at the time of biopsy. We expect this dataset to provide a valuable resource for scientists investigating prostate cancer metabolism., (© 2023. The Author(s).)

Background: Ultra-hypofractionated image-guided stereotactic body radiotherapy (SBRT) is increasingly used for definitive treatment of localized prostate cancer. Magnetic resonance imaging-guided radiotherapy (MRgRT) facilitates improved visualization, real-time tracking of targets and/or organs-at-risk (OAR), and capacity for adaptive planning which may translate to improved targeting and reduced toxicity to surrounding tissues. Given promising results from NRG-GU003 comparing conventional and moderate hypofractionation in the post-operative setting, there is growing interest in exploring ultra-hypofractionated post-operative regimens. It remains unclear whether this can be done safely and whether MRgRT may help mitigate potential toxicity. SHORTER (NCT04422132) is a phase II randomized trial prospectively evaluating whether salvage MRgRT delivered in 5 fractions versus 20 fractions is non-inferior with respect to gastrointestinal (GI) and genitourinary (GU) toxicities at 2-years post-treatment., Methods: A total of 136 patients will be randomized in a 1:1 ratio to salvage MRgRT in 5 fractions or 20 fractions using permuted block randomization. Patients will be stratified according to baseline Expanded Prostate Cancer Index Composite (EPIC) bowel and urinary domain scores as well as nodal treatment and androgen deprivation therapy (ADT). Patients undergoing 5 fractions will receive a total of 32.5 Gy over 2 weeks and patients undergoing 20 fractions will receive a total of 55 Gy over 4 weeks, with or without nodal coverage (25.5 Gy over 2 weeks and 42 Gy over 4 weeks) and ADT as per the investigator's discretion. The co-primary endpoints are change scores in the bowel and the urinary domains of the EPIC. The change scores will reflect the 2-year score minus the pre-treatment (baseline) score. The secondary endpoints include safety endpoints, including change in GI and GU symptoms at 3, 6, 12 and 60 months from completion of treatment, and efficacy endpoints, including time to progression, prostate cancer specific survival and overall survival., Discussion: The SHORTER trial is the first randomized phase II trial comparing toxicity of ultra-hypofractionated and hypofractionated MRgRT in the salvage setting. The primary hypothesis is that salvage MRgRT delivered in 5 fractions will not significantly increase GI and GU toxicities when compared to salvage MRgRT delivered in 20 fractions., Trial Registration: ClinicalTrials.gov Identifier: NCT04422132. Date of registration: June 9, 2020., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose: Biobanking tissue of high quality and fidelity is imperative for cancer genomics research. Since it is a challenging process, we sought to develop a protocol that improves the fidelity and quantity of biobanked primary prostate cancer (CaP) tissue., Materials and Methods: We conducted a pilot study evaluating pathologic concordance of biobanked tissue and the radical prostatectomy specimen using either standard protocol (SP) vs. next-generation protocol (NGP)., Results: There were no significant differences in clinical and pathologic characteristics (age, BMI, preoperative PSA, prostate weight, race, final prostatectomy Gleason score, or pathologic tumor and nodal stages) between the two protocol arms. Utilization of the NGP compared to the standard protocol resulted in a significantly higher rate of pathologic concordance between the biobanked and RP specimens (61.8% vs. 37.9%, P = 0.0231) as well as a nearly two-fold increase in the amount of biobanked tumor tissue (330 mm 3 vs. 174 mm 3 , P < 0.001). When looking at relevant clinical and pathologic characteristics, NGP was associated with pathologic concordance on both univariate [OR 2.65 (95% CI 1.13-6.21), P = 0.025] and multivariate analysis [OR 3.11 (95% CI 1.09-8.88), P = 0.034]., Conclusions: Our study validates the NGP as a multidisciplinary approach for improving the fidelity and amount of biobanked primary CaP tissue for future studies. Given the challenges to banking tissue from primary CaP as tumors are often difficult to visualize grossly and are frequently multifocal, optimizing the fidelity and volume of biobanked tissue is an important step forward to improve the generalizability of genomic data as we move towards precision medicine., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: We sought to evaluate sociodemographic disparities in access to neoadjuvant (NAC) and adjuvant (AC) chemotherapy in the United States and their effect on survival., Methods: The National Cancer Database was used to identify all patients from 2004 to 2016 eligible for NAC and AC. Univariate and multivariate logistic regression was performed to identify sociodemographic predictors associated with receipt of NAC and AC. Kaplan-Meier and Cox proportional hazard models were used for survival analysis., Results: A total of 17,121 patients were eligible for NAC, and 18,962 for AC. Older (OR 0.94, P < .001), Medicare (OR 0.88, P = .047), Medicaid (OR 0.66, P = .001), uninsured (OR 0.47, P < .001), rural (OR 0.70, P = .042), and community hospital patients (OR 0.72, P < .001) were less likely to receive NAC. Older, (OR 0.95, P < .001), female (OR 0.79, P < .001), Medicaid (OR 0.71, P = .003), uninsured (OR 0.60, P = .001), and lower income patients (OR 0.86, P = .017) were less likely to receive AC. In NAC-eligible patients, older (HR 1.02, P < .001), Medicare (HR 1.11, P = .024), Medicaid (HR 1.25, P = .012), and community hospital patients (HR 1.09, P = .021) were at an increased risk of death. In AC-eligible patients, older (HR 1.01, P < .001), Black (HR 1.15, P = .011), Medicaid (HR 1.14, P = .042), lower income (HR 1.07, P = .038) and community hospital patients (HR 1.07, P = .021) were at an increased risk of death., Conclusions: Significant sociodemographic disparities currently exist in the United States in access to neoadjuvant and adjuvant chemotherapy for bladder cancer. Uninsured and Medicaid insurance status are the strongest predictors of not receiving chemotherapy. Efforts must be made to deliver this critical standard-of-care treatment to these patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Sex-specific survival disparities for bladder cancer outcomes after radical cystectomy (RC) have been demonstrated in several studies. However, these studies predate the widespread adoption of neoadjuvant chemotherapy (NAC). We evaluated the differences in sex-specific survival between patients who received NAC with those who did not, using a contemporary national outcomes database., Methods: The National Cancer Data Base was queried from 2004 to 2015 to identify subjects who underwent RC. Kaplan-Meier method with log-rank test was performed to compare all-cause mortality between men and women at each pathologic (p) TNM stage group: T1-4N0, N+ and M+ disease. Associations for all-cause mortality were identified using an adjusted Cox regression analysis, and our findings were confirmed with a subgroup analysis., Results: A total of 9,835 subjects (7,483 men and 2,532 women) were included in the analysis. Kaplan-Meier survival curves and Cox regression analysis demonstrated female sex was not associated with worse overall survival compared to males (HR 0.947, 95%CI 0.852-1.053, P = 0.947) in the overall cohort. Stratified by pT stage and node positivity, worse overall survival was seen in women with pT4 disease who did not receive NAC compared to men (5-year OS 9.6% women vs. 15.2% men, P < 0.001), but no sex-specific difference was seen across all groups in patients who received NAC. Subgroup multivariable analysis showed that female sex conferred a survival disadvantage for pT4 (HR 1.369, P = 0.026) disease only in patients who did not receive NAC., Conclusions: In a contemporary cohort of subjects who underwent RC, administration of NAC narrows the sex survival-gap in advanced stage bladder cancer. Strategies to improve NAC usage in women should be adopted to overcome potential sex-specific differences such as delayed diagnosis, anatomic differences in higher stage disease, or altered tumor biology which may contribute to differences in oncologic outcomes., Competing Interests: Declaration of Competing Interest None, (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To develop accurate preoperative nomograms for prediction of muscle-invasive disease and lymph node metastasis in upper tract urothelial carcinoma (UTUC), to assist surgeons in risk stratifying patients and help guide treatment decisions., Materials/methods: The National Cancer Database was used to identify all patients from 2004 to 2016 with UTUC who underwent extirpative surgery and lymphadenectomy. Univariate and multivariate logistic regression was performed to identify variables predicting muscle-invasive and node-positive disease. The data set was split 80:20 into a derivation and validation cohort and used to generate and test two nomograms. Nomograms were assessed using area under the curve (AUC) and calibration plots., Results: A total of 6,143 patients met inclusion criteria. Predictors of muscle-invasive disease were age, grade, lymphovascular invasion (LVI), tumor size, and positive clinical lymph node status. Predictors of node-positive disease were grade, LVI, tumor size, and positive clinical lymph node status. The accuracy of the final nomogram predicting muscle-invasive disease was 80.0% (AUC 0.800, corrected C-index 0.813), and the accuracy of the nomogram predicting node-positive disease was 87.8% (AUC 0.878, corrected C-index 0.887)., Conclusions: With data readily available after imaging and biopsy (age, tumor grade, LVI status, tumor size, and clinical lymph node status), we developed the first preoperative nomograms to quantitatively predict muscle-invasive disease and lymph node metastasis in UTUC, with an accuracy of 80.0% and 87.8% respectively. This information could be helpful to assist surgeons with pre-operative risk stratification., Competing Interests: Conflict of interest Authors have no conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Accurate diagnosis of localized prostate cancer (PCa) is limited by inadequacy of multiparametric (mp) MRI to fully identify and differentiate localized malignant tissue from benign pathologies. Prostate-specific membrane antigen (PSMA) represents an excellent target for molecular imaging. IAB2M, an 85-kD minibody derived from a de-immunized monoclonal antibody directed at the extracellular domain of human PSMA (huJ591), and PSMA-11, a small molecule ligand have been previously tested as probes for visualization of recurrent/metastatic PCa with PET/CT. This pilot, non-randomized trial studied their diagnostic utility in patients (pts) with localized PCa., Methods: Pts planned for radical prostatectomy (RP) were enrolled and underwent mpMRI and PET/CT imaging with 89 Zr-df-IAB2M and/or 68 Ga-PSMA-PET/CT. Image results were read by a radiologist blinded to clinical information and pathology results, mapped and compared to corresponding histopathology findings from all lesions, both clinically significant and nonsignificant. The detection rates of all three imaging modalities were measured and correlated., Results: 20 pts with median age of 64.5 (46-79) years and PSA level of 7.5 (1.6-36.56) ng/ml were enrolled. 19 pts underwent RP and were imaged pre-operatively with 89 Zr-Df-IAB2M PET/CT and mpMRI. Nine of those were imaged using 68 Ga-PSMA-11 as well. Out of 48 intraprostatic lesions verified on surgical pathology, IAB2M PET/CT was able to detect 36 (75%). A similar proportion of pathologically confirmed, clinically significant lesions (22/29, 76%) was detected. IAB2M PET/CT was also able to identify 14/19 (74%) extraprostatic lesions. The performance of mpMRI was inferior, with 24/48 detectable lesions (50%) and 18/29 clinically significant intraprostatic lesions (62%). Compared to the current standard (mpMRI), IAB2M PET/CT had a sensitivity of 88%, specificity 38%, positive predictive value 58%, and accuracy 63%. In 9 pts who underwent Ga-PSMA-11 as well, the latter yielded a detection rate of 70% (14/20), which was also seen in clinically significant lesions (10/14, 71%). Ga-PSMA-11 PET/CT also detected 4/6 (67%) extraprostatic lesions., Conclusions: In this pilot study, the performance of 89 Zr-df-IAB2M was superior to mpMRI and similar to 68 Ga-PSMA-11 PET/CT. The higher detection rate of PSMA-PET supports its use as a diagnostic tool with consequent management change implications in men with localized PCa., (© 2022 Wiley Periodicals LLC.)

BACKGROUNDProstate cancer is multifocal with distinct molecular subtypes. The utility of genomic subtyping has been challenged due to inter- and intrafocal heterogeneity. We sought to characterize the subtype-defining molecular alterations of primary prostate cancer across all tumor foci within radical prostatectomy (RP) specimens and determine the prevalence of collision tumors.METHODSFrom the Early Detection Research Network cohort, we identified 333 prospectively collected RPs from 2010 to 2014 and assessed ETS-related gene (ERG), serine peptidase inhibitor Kazal type 1 (SPINK1), phosphatase and tensin homolog (PTEN), and speckle type BTB/POZ protein (SPOP) molecular status. We utilized dual ERG/SPINK1 immunohistochemistry and fluorescence in situ hybridization to confirm ERG rearrangements and characterize PTEN deletion, as well as high-resolution melting curve analysis and Sanger sequencing to determine SPOP mutation status.RESULTSBased on index focus alone, ERG, SPINK1, PTEN, and SPOP alterations were identified in 47.5%, 10.8%, 14.3%, and 5.1% of RP specimens, respectively. In 233 multifocal RPs with ERG/SPINK1 status in all foci, 139 (59.7%) had discordant molecular alterations between foci. Collision tumors, as defined by discrepant ERG/SPINK1 status within a single focus, were identified in 29 (9.4%) RP specimens.CONCLUSIONInterfocal molecular heterogeneity was identified in about 60% of multifocal RP specimens, and collision tumors were present in about 10%. We present this phenomenon as a model for the intrafocal heterogeneity observed in previous studies and propose that future genomic studies screen for collision tumors to better characterize molecular heterogeneity.FUNDINGEarly Detection Research Network US National Cancer Institute (NCI) 5U01 CA111275-09, Center for Translational Pathology at Weill Cornell Medicine (WCM) Department of Pathology and Laboratory Medicine, US NCI (WCM SPORE in Prostate Cancer, P50CA211024-01), R37CA215040, Damon Runyon Cancer Research Foundation, US MetLife Foundation Family Clinical Investigator Award, Norwegian Cancer Society (grant 208197), and South-Eastern Norway Regional Health Authority (grant 2019016 and 2020063).

Men diagnosed with low-risk prostate cancer (PC) are increasingly electing active surveillance (AS) as their initial management strategy. While this may reduce the side effects of treatment for prostate cancer, many men on AS eventually convert to active treatment. PC is one of the most heritable cancers, and genetic factors that predispose to aggressive tumors may help distinguish men who are more likely to discontinue AS. To investigate this, we undertook a multi-institutional genome-wide association study (GWAS) of 5,222 PC patients and 1,139 other patients from replication cohorts, all of whom initially elected AS and were followed over time for the potential outcome of conversion from AS to active treatment. In the GWAS we detected 18 variants associated with conversion, 15 of which were not previously associated with PC risk. With a transcriptome-wide association study (TWAS), we found two genes associated with conversion ( MAST3 , p = 6.9×10 -7 and GAB2 , p = 2.0×10 -6 ). Moreover, increasing values of a previously validated 269-variant genetic risk score (GRS) for PC was positively associated with conversion (e.g., comparing the highest to the two middle deciles gave a hazard ratio [HR] = 1.13; 95% Confidence Interval [CI]= 0.94-1.36); whereas, decreasing values of a 36-variant GRS for prostate-specific antigen (PSA) levels were positively associated with conversion (e.g., comparing the lowest to the two middle deciles gave a HR = 1.25; 95% CI, 1.04-1.50). These results suggest that germline genetics may help inform and individualize the decision of AS-or the intensity of monitoring on AS- versus treatment for the initial management of patients with low-risk PC., Competing Interests: Declaration of Interests The authors declare no competing interests.

Background and Objectives: We examined pathologic complete response (pCR) and pathologic downstaging (pDS) rates after neoadjuvant chemotherapy (NAC) in high-risk upper tract urothelial carcinoma, as well as their predictors. We further sought to determine their effects on overall survival and examine prognosticators of survival after NAC., Methods: The National Cancer Database was used to identify all patients from 2004 to 2016 with nonmetastatic high grade upper tract urothelial carcinoma who received NAC followed by nephroureterectomy. pCR and pDS rates were examined, and univariate and multivariate logistic regression was performed to identify clinical predictors. Kaplan-Meier and Cox proportional hazard methods were used to estimate overall survival., Results: 309 patients met inclusion criteria. 27 patients (8.74%) had pCR, and 92 (29.77%) had pDS. pCR and pDS rates for N+ subgroup were 6.82% and 47.73% respectively, and for N0 subgroup, 9.50% and 22.62%. Female sex (OR 2.94, p  = 0.010) was the only predictor of pCR. Node-positive disease (cN1 vs. cN0: OR 6.40, p  < 0.001; cN2 vs. cN0: OR 7.46, p  < 0.001) was a positive predictor of pDS, and the presence of lymphovascular invasion (LVI) (OR 0.14, p  < 0.001) was a negative predictor of pDS. The median OS for all patients was 45.5 months. pCR and pDS were both associated with improved OS, ( p  < 0.001 for both); median was 99.1 months for both. LVI was the strongest negative prognostic factor for OS (HR 2.85, p  < 0.001)., Conclusions: Overall pathological complete response and downstaging rates were 8.74% and 29.77% respectively after multi-agent neoadjuvant chemotherapy. Node-negative and node-positive disease had equivalent rates of complete response, but node-positive disease had a significantly higher rate of downstaging. The presence of LVI was associated with worse overall survival., Competing Interests: S Venkat: No conflicts of interest. P Lewicki: No conflicts of interest. S Basourakos: No conflicts of interest. D Scherr: No conflicts of interest., (© 2021 – The authors. Published by IOS Press.)

Background: Optical coherence tomography (OCT) is a novel imaging modality that provides microstructural information of different tissue layers using near-infrared light. This prospective, multicenter phase II trial aimed to assess the accuracy of OCT-assisted cystoscopy for bladder tumor staging., Methods: Patients with primary or recurrent bladder tumors (Ta,T1) identified by outpatient cystoscopy were included. The primary objective was to assess the accuracy and positive predictive value of for determining tumor stage ≥T1 correlated by histopathology. 72 suspicious lesions from 63 patients were eligible to analyze in the study. All suspected lesions were evaluated with conventional cystoscopy, interpreted in real-time using OCT, and then resected. All results were compared to pathology. A total of 363 OCT images of tumor and normal mucosa in 25 patients were obtained to evaluate diagnostic efficacy of the computer-aided texture analysis algorithm., Results: Sensitivity and specificity for predicting invasive tumors (≥ T1, n = 17) were 58.8% and 92.7% for cystoscopy, 64.7% and 100% for OCT-assisted cystoscopy, respectively. Accuracy of cystoscopy and OCT-assisted cystoscopy for predicting invasive tumor was 84.7% and 91.7% (P = 0.063), respectively. Cystoscopy and OCT-assisted cystoscopy correctly predicted T stage in 52/72 and 59/72 cases, respectively (P = 0.016). Cystoscopy missed 2 more invasive tumors than OCT-assisted cystoscopy. Cystoscopy (14.3%, 1/7) and OCT-assisted cystoscopy (28.6%, 2/7) showed relatively low sensitivity in detecting muscle invasion. Computer aided texture analysis demonstrated 75.1% sensitivity, 64.0% specificity, and 74.4% accuracy for differentiating tumor and normal urothelium., Conclusion: OCT-assisted cystoscopy is a real time noninvasive and simple procedure that enhanced the accuracy of staging bladder tumors and prediction of any tumor invasion. Though the study did not meet the prespecified primary endpoint, OCT imaging is a promising adjunct to cystoscopy that may supplement intraoperative decision-making during transurethral resection of bladder tumors and additional prospective studies are warranted., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To analyze population-level changes in operative practice since the onset of the COVID-19 pandemic to contextualize observations made by individual practices and optimize future responses., Materials and Methods: This US retrospective analysis used the Premier Perspectives Database. We investigated changes in operative volume through March 2020. Baseline operative volume for urologic surgery was calculated using data from the preceding 12 months and compared on a total and by procedure basis. Multivariable linear regression was used to identify hospital-level predictors of change in response to the pandemic., Results: At baseline, we captured 23,788 urologic procedural encounters per month as compared with 19,071 during March 2020- a 19.9% decrease. Urologic oncology-related cases were relatively preserved as compared to others (average change in March 2020: +1.1% versus -32.2%). Northeastern (β = -5.66, 95% confidence interval [CI]: -10.2 to -1.18, p = 0.013) and Midwestern hospitals (β = -4.17, 95% CI: -7.89 to -0.45, p = 0.027; both with South as reference region), and those with an increasing percentage of patients insured by Medicaid (β= -0.17 per percentage point, 95% CI: -0.33 to -0.01, p = 0.04) experienced a significantly larger decrease in volume., Conclusions: There was a 20% decline in urologic operative volume in March 2020, compared with baseline, that preferentially affected hospitals serving Medicaid patients, and those in Northeast and Midwest. In the face of varying mandates on elective surgery, widespread declines in operative volume may also represent hesitancy on behalf of patients to interface with healthcare during the pandemic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lewicki, Arenas-Gallo, Basourakos, Punjani, Venkat, Scherr, Hu and Shoag.)

"The robotic approach for radical cystectomy has become increasingly adopted by the urologic oncology community, as it has been shown to have equivalent oncologic outcomes with shorter hospital stay and fewer perioperative transfusions. Consensus guidelines from expert surgeons have been published to provide guidance on all aspects of how to implement the robotic approach in the urologic oncology clinic.", Competing Interests: Disclosure Supported by The Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust (JES)., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Robot-assisted radical cystectomy (RARC) remains one of the most complex urological procedures. Due to regionalization of bladder cancer care, there is likely an imbalance in experience among urologists performing RARC. We sought to describe changes in patient selection, surgical quality surrogates and rates of complications in relation to surgical experience., Methods: We retrospectively reviewed 409 consecutive patients with bladder cancer who underwent RARC between 2006 and 2017 by a single surgeon. The cohort was divided into 4 quartiles (Q1-Q4) according to surgical experience, based on the chronologic order at which RARC was performed. Baseline, perioperative and pathologic characteristics of patients were compared among the 4 groups. 30-day and 90-day complications were assessed using the Clavien-Dindo system. The association between surgical experience (quartile) and complications was assessed using multivariable logistic regression analyses., Results: Median age (interquartile range [IQR] from 70-73 years), body mass index (IQR from 25 to 27 kg/m 2 ) and preoperative glomerular filtration rate (IQR from 59 to 65 ml/min) were similar among all quartiles (all P > 0.05). Patients in Q4 had higher rates of previous abdominopelvic surgery (46.1% vs. 30.4%, P = 0.031) and American Society of Anesthesiologists score of 3 to 4 (72.3% vs. 47.1%, P = 0.003) compared to patients in Q1. Patients who underwent RARC in Q4 compared to Q1, had less estimated blood loss (250 ml vs. 350 ml, P < 0.001), shorter operative time (346 vs. 360 minutes, P < 0.001), and higher lymph node yield (22 vs. 17 nodes, P < 0.001). The 30-day and 90-day complication rates were 53% and 62%, respectively. Thirty-day complication rates were similar among all 4 quartiles (P > 0.05), but higher among patients in Q4 compared to Q1 within 90 days (74% vs. 54%, P = 0.01). On multivariable analysis, patients in Q4 were more likely to experience any 90-day complication (OR 2.03, 95%Cl 1.11-3.70) compared to Q1., Conclusion: Our results show that with surgical experience, more complex cases can be performed while continuing to improve surgical quality. Nonetheless, there appears to be a trade-off between the increase in complexity of cases performed with experience and accepting higher rates of complications., (Copyright © 2020. Published by Elsevier Inc.)

Objective: To assess the impact of neoadjuvant chemotherapy (NAC) on survival outcomes in a contemporary cohort of patients with in upper tract urothelial carcinoma (UTUC)., Methods: The National Cancer Database was queried from 2004 to 2015 to identify subjects who underwent nephroureterectomy for UTUC. Kaplan-Meier method with log-rank test was performed to compare all-cause mortality between patients who received preoperative chemotherapy to those who did not at each pathologic (p) TNM stage group: T1-4N0, N+, and M+ disease. Associations for all-cause mortality were identified using an adjusted Cox regression analysis., Results: A total of 10,315 chemoeligible subjects were included in the analysis. A total of 296 (2.9%) of patients received NAC prior to NU. Kaplan-Meier survival curves of the entire cohort demonstrated an overall survival advantage associated with administration of NAC (P = .017). Stratified by clinical staging, subjects with nonorgan-confined tumors had improved overall survival outcomes with NAC administration (P = .012). On multivariate analysis there was a statistically significant improvement in overall survival between in patients who received NAC. Of patients in the preoperative chemotherapy group who had clinically nonorgan-confined disease, 27.1% had organ-confined disease at time of surgery compared to 1.4% of those who underwent surgery as initial therapy., Conclusion: In a contemporary cohort of subjects who underwent nephroureterectomy for UTUC, administration of NAC in patients with high-grade nonorgan-confined disease led to higher rates of pathologic downstaging and was associated with improved overall survival., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Adoption of prostate magnetic resonance imaging (MRI) before biopsy is based on evidence demonstrating superior detection of clinically significant prostate cancer on biopsy. Whether this is due to the detection of otherwise occult higher grade cancers or preferential sampling of higher grade areas within an otherwise low-grade cancer is unknown., Methods: To distinguish these two possibilities, this study examined the effect of prebiopsy MRI on the rate of pathologic upgrading and downgrading at prostatectomy in Surveillance, Epidemiology, and End Results-Medicare linked data from 2010 to 2015. Logistic regression was performed to assess the effect of MRI use on the Gleason grade change between biopsy and prostatectomy., Results: Among biopsy-naive men, those who underwent prebiopsy MRI had higher odds of downgrading at prostatectomy (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.05-1.66). In contrast, the odds of upgrading were significantly lower for men who underwent prebiopsy MRI (OR, 0.78; 95% CI, 0.61-0.99). Limitations included a low overall rate of MRI-utilization prior to biopsy and an inability to distinguish between template, software-assisted and cognitive fusion biopsy., Conclusions: Prebiopsy MRI is associated with both oversampling of higher grade areas, which results in downgrading at prostatectomy, and the detection of otherwise occult higher grade lesions, which results in less upgrading at prostatectomy., (© 2020 American Cancer Society.)

Purpose: Clinical guidelines have recently included renal mass biopsy (RMB) in management algorithms, especially in the setting of small renal masses ≤ 4 cm (SRM) and ablative therapy. We sought to evaluate the diagnostic rates of RMB, factors associated with a non-diagnostic biopsy, its clinical utility, and its safety profile in the setting of ablative therapy., Materials and Methods: A total of 174 RMB from 167 patients, performed in a tertiary academic center from 01/2015 to 01/2019, were included. Patient demographics, radiographic mass size, RMB diagnoses, subsequent clinical management, and complications were retrospectively reviewed. RMBs were classified as diagnostic or non-diagnostic based on set criteria., Results: The mean mass size was 3.0 cm (range: 0.5-15.3 cm) and 140 biopsies (80%) were SRM. Among all RMB, 159 (91%) were diagnostic and 15 (9%) were non-diagnostic. Non-diagnostic biopsies were associated with small mass size, the presence of a cystic component (p < 0.00001) and fewer number of cores submitted (p = 0.0046). All non-diagnostic biopsies occurred in SRMs, where the mean mass size was significantly smaller than diagnostic biopsies (1.3 versus 3.2 cm, p = 0.001). RMB with concurrent ablation yielded non-diagnostic results more frequently than isolated RMBs (15% vs 2%, respectively)., Conclusions: RMB is useful for definitive diagnosis and clinical management in the setting of ablative therapy. Small mass size, cystic lesions, and fewer number of passes obtained are associated with non-diagnostic biopsies. When a renal mass diagnosis is particularly critical, a separate biopsy procedure prior to ablative therapy is recommended., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: To validate prognostic factors and determine the impact of obesity, hypertension, smoking and diabetes mellitus (DM) on risk of recurrence after surgery in patients with localized renal cell carcinoma (RCC)., Materials and Methods: We performed a retrospective cohort study among patients that underwent partial or radical nephrectomy at Weill Cornell Medicine for RCC and collected preoperative information on RCC risk factors, as well as pathological data. Cases were reviewed for radiographic evidence of RCC recurrence. A Cox proportional-hazards model was developed to determine the contribution of RCC risk factors to recurrence risk. Disease-free survival and overall survival were analyzed using the Kaplan-Meier method and log-rank test., Results: We identified 873 patients who underwent surgery for RCC between the years 2000-2015. In total 115 patients (13.2%) experienced a disease recurrence after a median follow up of 4.9 years. In multivariate analysis, increasing pathological T-stage (HR 1.429, 95% CI 1.265-1.614) and Nuclear grade (HR 2.376, 95% CI 1.734-3.255) were independently associated with RCC recurrence. In patients with T1-2 tumors, DM was identified as an additional independent risk factor for RCC recurrence (HR 2.744, 95% CI 1.343-5.605). Patients with DM had a significantly shorter median disease-free survival (1.5 years versus 2.6 years, p = 0.004), as well as median overall survival (4.1 years, versus 5.8 years, p<0.001)., Conclusions: We validated high pathological T-stage and nuclear grade as independent risk factors for RCC recurrence following nephrectomy. DM is associated with an increased risk of recurrence among patients with early stage disease., Competing Interests: The authors have declared that no competing interests exist.

Purpose: We explored the association between tobacco use and genitourinary cancer specific survival in a contemporary, nationally representative sample of the United States civilian population., Materials and Methods: A total of 493,282 participants in the National Longitudinal Mortality Study who provided detailed tobacco information from 1993 to 2005 were included in study. Our primary outcome was death from bladder, kidney or prostate cancer. Cause of death was determined from death certificates. Analyzed smoking parameters included smoking status at the time of the survey, age at the start of smoking and home smoking rules. Multivariable Cox regression models were used to assess associations of different smoking parameters with bladder, kidney and prostate cancer specific mortality., Results: During a 5-year followup 5.6% of participants who had ever smoked died compared to 3.1% of those who had never smoked (p <0.0001). Of those who died of bladder, kidney and prostate cancer 62%, 58% and 62%, respectively, were ever smokers. On multivariable analysis ever smoking was associated with bladder and kidney cancer mortality (HR 1.92, 95% CI 1.25-2.97, and HR 1.54, 95% CI 1.01-2.34, respectively). Additionally, starting to smoke during teenage years and smoking at home were associated with bladder cancer specific mortality (HR 2.14, 95% CI 1.28-3.56 and HR 2.99, 95% CI 1.34-6.65) and kidney cancer specific mortality (HR 1.65, 95% CI 1.03-2.66 and HR 2.84, 95% CI 1.54-5.23, respectively). However, only everyday smoking was associated with an increased risk of prostate cancer mortality (HR 1.81, 95% CI 1.30-2.53)., Conclusions: In a nationally representative study we confirmed the association between smoking intensity and mortality from genitourinary malignancies. Starting to smoke at a younger age and smoking at home conferred a significantly higher risk of death from bladder and kidney cancers.

Objectives: Our aim was to determine whether using an organ transplant-based(TB) approach reduces postoperative complications(PCs) following radical nephrectomy(RN) and tumor thrombectomy(TT) in renal cell carcinoma(RCC) patients with level II-IV thrombi., Methods: A total of 390(292 non-TB/98 TB) IRCC-VT Consortium patients who received no preoperative embolization/IVC filter were included. Stepwise linear/logistic regression analyses were performed to determine significant multivariable predictors of intraoperative estimated blood loss(IEBL), number blood transfusions received, and overall/major PC development within 30days following surgery. Propensity to receive the TB approach was controlled., Results: The TB approach was clearly superior in limiting IEBL, blood transfusions, and PC development, even after controlling for other significant prognosticators/propensity score(P < .000001 in each case). Median IEBL for non-TB/TB approaches was 1000 cc/300 cc and 1500 cc/500 cc for tumor thrombus Level II-III patients, respectively, with no notable differences for Level IV patients(2000 cc each). In comparing PC outcomes between non-TB/TB patients with a non-Right-Atrium Cranial Limit, the observed percentage developing a: i) PC was 65.8%(133/202) vs. 4.3%(3/69) for ECOG Performance Status(ECOG-PS) 0-1, and 84.8%(28/33) vs. 25.0%(4/16) for ECOG-PS 2-4, and ii) major PC was 16.8%(34/202) vs. 1.4%(1/69) for ECOG-PS 0-1, and 27.3%(9/33) vs. 12.5%(2/16) for ECOG-PS 2-4. Major study limitation was the fact that all TB patients were treated by a single, experienced, high volume surgeon from one center (non-TB patients were treated by various surgeons at 13 other centers)., Conclusions: Despite this major study limitation, the observed dramatic differences in PC outcomes suggest that the TB approach offers a major breakthrough in limiting operative morbidity in RCC patients receiving RN and TT., (Copyright © 2019. Published by Elsevier Ltd.)

Objectives: To compare trends in the use of robot-assisted radical cystectomy (RARC) and changes over time in peri-operative outcomes in selected North American and European centres., Materials and Methods: We conducted a retrospective evaluation of 2401 patients treated with open radical cystectomy (ORC) or RARC for bladder cancer at 12 centres in North America and Europe between 2006 and 2018. We used the Kruskal-Wallis and chi-squared test to evaluate differences between continuous and categorical variables., Results: Overall, 49.5% of patients underwent RARC and 51.5% ORC. RARC became the most commonly performed procedure in contemporary patients, with an increase from 29% in 2006-2008 to 54% in 2015-2018 (P < 0.001). In the North American centres the use of RARC was higher than that of ORC from 2006, and remained stable over time, whereas in the European centres its use increased exponentially from 2% to 50%. In both groups patients who underwent RARC had less advanced T stages (P < 0.001), lower American Society of Anesthesiologists scores (P < 0.05), lower blood loss (P = 0.001) and shorter length of hospital stay (P < 0.05). No differences were found in early complications. Early readmission and re-operation rates were worse for patients treated with RARC in the European centres; however, when contemporary patients only were considered, the statistical significance was lost., Conclusion: The present study shows that the use of RARC has constantly increased since its introduction, overtaking ORC in the most contemporary series. While RARC was more frequently performed than ORC since its introduction in the North American centres and its use remained substantially stable over time, its use increased exponentially in the European centres. The different trends in use of RARC/ORC and changes over time in peri-operative outcomes between the North American and European centres can be attributed to the earlier introduction and spread of RARC in the former compared with the latter., (© 2019 The Authors BJU International © 2019 BJU International Published by John Wiley & Sons Ltd.)

Objective: To evaluate programmed death ligand 1 (PD-L1) staining fidelity between the primary tumor and associated lymph node metastases in bladder cancer. To secondarily evaluate whether neoadjuvant chemotherapy (NAC) affects this relationship., Methods: Sixty-seven subjects with residual bladder cancer on cystectomy and associated positive lymph nodes were identified between 2008 and 2015. PD-L1 staining of tumor cells was evaluated using H score and 49 specimens were also evaluated using combined positive score (CPS). Univariable and multivariable logistic regression analysis were used to assess how various clinical variables affected odds of PD-L1 fidelity between primary and metastatic tumors., Results: Tumor PD-L1 staining was concordant in 79.1% of cases and CPS was concordant in 79.6% of cases. NAC did not significantly impact odds of PD-L1 or CPS fidelity (OR 1.974, 95% CI 0.673-5.784, OR 0.500, 95% CI 0.093-2.700). Among clinical variables analyzed on univariable analysis of tumor PD-L1 fidelity, H-score, and PD-L1 staining intensity were associated with significantly increased odds of PD-L1 fidelity and the association with staining intensity was confirmed on multivariable analysis., Conclusion: PD-L1 fidelity between primary bladder tumors and nodal metastases was observed in >75% of cases in this study. Additionally, NAC was not shown to diminish this propensity to maintain PD-L1 staining status. Further standardization of immunohistochemistry of tumor and infiltrating imsmune cells in metastatic bladder cancer is needed to improve application of therapeutics., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: To assess the differential effect of robotic assisted radical cystectomy (RARC) versus open radical cystectomy (ORC) on survival outcomes in matched analyses performed on a large multicentric cohort., Methods: The study included 9757 patients with urothelial bladder cancer (BCa) treated in a consecutive manner at each of 25 institutions. All patients underwent radical cystectomy with bilateral pelvic lymphadenectomy. To adjust for potential selection bias, propensity score matching 2:1 was performed with two ORC patients matched to one RARC patient. The propensity-matched cohort included 1374 patients. Multivariable competing risk analyses accounting for death of other causes, tested association of surgical technique with recurrence and cancer specific mortality (CSM), before and after propensity score matching., Results: Overall, 767 (7.8%) patients underwent RARC and 8990 (92.2%) ORC. The median follow-up before and after propensity matching was 81 and 102 months, respectively. In the overall population, the 3-year recurrence rates and CSM were 37% vs. 26% and 34% vs. 24% for ORC vs. RARC (all p values > 0.1), respectively. On multivariable Cox regression analyses, RARC and ORC had similar recurrence and CSM rates before and after matching (all p values > 0.1)., Conclusions: Patients treated with RARC and ORC have similar survival outcomes. This data is helpful in consulting patients until long term survival outcomes of level one evidence is available.

Obesity is associated with an increased incidence of high-grade prostate cancer (PC) and worse prognosis for PC patients. Recently, we showed in men that obesity-related periprostatic white adipose tissue (WAT) inflammation, characterized by macrophages surrounding dead or dying adipocytes forming crown-like structures, was associated with high-grade PC. Possibly, interventions that suppress periprostatic WAT inflammation will improve outcomes for men with PC. Here, we tested the hypothesis that supplemental 17β-estradiol (E2) could decrease periprostatic WAT inflammation in obese male mice. Mice were fed a high-fat diet to induce periprostatic WAT inflammation before being treated with supplemental E2. E2 supplementation suppressed caloric intake, induced weight loss, decreased periprostatic WAT inflammation and downregulated the expression of genes linked to inflammation including Cd68, Mcp1 and Tnf. Similar to the effects of E2 supplementation, treatment with diethylstilbestrol, a synthetic estrogen, also suppressed caloric intake and reduced periprostatic WAT inflammation. To determine whether the observed effects of supplemental estrogen could be reproduced by caloric restriction (CR) alone, obese mice were put on a 30% CR diet. Like estrogen treatment, CR was effective in reducing body weight, periprostatic WAT inflammation and the expression of pro-inflammatory genes. Transcriptomic analyses of periprostatic fat showed that obesity was associated with enrichment in inflammatory response pathways, which were normalized by both supplemental E2 and CR. Taken together, these findings strengthen the rationale for future efforts to determine whether either CR or supplemental estrogen will decrease periprostatic WAT inflammation and thereby improve outcomes for men with PC., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Upper tract urothelial carcinoma (UTUC) is characterized by a distinctly aggressive clinical phenotype. To define the biological features driving this phenotype, we performed an integrated analysis of whole-exome and RNA sequencing of UTUC. Here we report several key insights from our molecular dissection of this disease: 1) Most UTUCs are luminal-papillary; 2) UTUC has a T-cell depleted immune contexture; 3) High FGFR3 expression is enriched in UTUC and correlates with its T-cell depleted immune microenvironment; 4) Sporadic UTUC is characterized by a lower total mutational burden than urothelial carcinoma of the bladder. Our findings lay the foundation for a deeper understanding of UTUC biology and provide a rationale for the development of UTUC-specific treatment strategies.

Introduction: Contemporary data on bladder cancer care in the United States are lacking. We used nationally representative data to characterize outpatient bladder cancer care in the U.S. and identify potential areas for quality improvement., Methods: The NAMCS (National Ambulatory Medical Care Survey), conducted annually by the Centers for Disease Control and Prevention, is designed to generate weighted estimates of national ambulatory care practice patterns. We evaluated NAMCS data from 2001 to 2014 to characterize patient, physician and visit characteristics associated with a diagnosis of bladder cancer., Results: During the 14-year study period there were 7,410,240 weighted visits to a urologist for a diagnosis of bladder cancer. The total number of urology visits for bladder cancer significantly increased during the study period (p=0.03). Overall 35% of patients with bladder cancer saw their urologist 6 or more times annually. Mean visit duration was 21.8 minutes. Mean age of patients with a bladder cancer diagnosis was 71.3 years. Men and women accounted for 8,106,756 and 3,052,690 visits, respectively (p <0.01). Medicare coverage represented the largest payer system (60.7%). Urologists provided smoking cessation counseling to only 21.2% of current smokers and nutrition counseling was provided for just 14.7% of all obese patients with bladder cancer., Conclusions: Bladder cancer visits account for more than half a million ambulatory urology visits annually. Routine lifestyle interventions such as smoking cessation and nutrition counseling should be implemented during urology visits to further improve the care of patients with bladder cancer.

Introduction: The use of robotic-assisted radical cystectomy (RARC) is becoming more widespread. While its safety is accepted, its oncological efficacy as compared to the current standard, open radical cystectomy (ORC), remains debatable., Materials and Methods: The aim of this study is to compare the rates of positive soft tissue surgical margins (STSM), between patients treated with RARC or ORC, using a large contemporaneous collaborative database. We included 2,536 patients with urothelial carcinoma of the bladder treated at 26 institutions. A propensity-score matching 1:1 was performed with 3 ORC patients matched to 1 RARC patient. The final cohort included 1,614 patients. Uni- and multivariable logistic regression analyses tested the impact of surgical technique on STSM status, before and after propensity-score matching., Results: Overall, 870 (34%) patients underwent RARC and 1,666 (66%) ORC. The overall STSM rate was 11%; 10% in the ORC group and 13% in the RARC group. Within the propensity-score-matched cohort, the positive STSM rate were 14% and 13% in the ORC and RARC group, respectively (P = 0.1). In multivariable analysis, after propensity match RARC approach was not associated with the risk of a positive STSM (P = 0.1). These results were confirmed in the subgroup of patients with pathologic non-organ-confined or organ-confined diseases., Conclusions: While treatment with RARC is associated with a higher absolute rate of STSM, the difference did not remain after adjustment for the effects of other established prognostic factors. Results from ongoing trials are awaited to assess the validity of these findings., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Urothelial carcinoma (UC) is a common and frequently lethal cancer. Despite the presence of genomic alterations creating dependency on particular signaling pathways, the use of targeted therapies in advanced and metastatic UC has been limited. We performed an integrated analysis of whole-exome and RNA sequencing of primary and metastatic tumors in a patient with platinum-resistant UC. We found a strikingly high ERBB2 mRNA expression and enrichment of downstream oncogenic ERBB2 signaling in this patient's tumors compared with tumors from an unselected group of patients with UC (N=17). This patient had an exceptional sustained response to trastuzumab. Our findings show that oncogenic addiction to ERBB2 signaling potentially predicts response to ERBB2-directed therapy of UC.

Background: In the setting of value-based care, it is critical to improve our understanding of surgical risk and greater health care resource utilization (HRU) as it relates to frailty., Objective: To evaluate the impact of frailty on HRU and surgical morbidity in urologic oncology surgery using the five-item frailty index., Design, Setting, and Participants: A retrospective cohort study was conducted using subjects from the 2012-2016 American College of Surgeons National Surgical Quality Improvement Program who underwent radical cystectomy or minimally invasive or open radical prostatectomy, radical nephrectomy, or partial nephrectomy., Outcome Measurements and Statistical Analysis: Multivariable logistic regression was performed to determine the association between frailty index and any increase in HRU, which was defined as prolonged length of stay greater than the 75th percentile, discharge to continued care, or unplanned readmission within 30 d., Results and Limitations: In the overall cohort of 92 999 subjects and within each surgery type, increasing frailty score was associated with significant stepwise increases in HRU. Logistic regression adjusting for patient demographics revealed statistically significant odds ratios of 1.2 (95% confidence interval [CI] 1.2-1.3; p<0.001), 1.5 (95% CI 1.4-1.6; p<0.001), and 2.0 (95% CI 1.8-2.1; p<0.001) at frailty indices of 1, 2, and ≥3, respectively, for increased HRU relative to no frailty. In subanalyses, each categorical increase in frailty index was independently associated with prolonged length of stay, more discharges to continued care, and unplanned readmission. Increasing frailty score was associated with increasing rates of any complication and serious complications within each surgery type. The analysis is limited by the retrospective design and available data within a large hospital-based database., Conclusions: Frailty in major urologic oncology surgery is associated with greater HRU and surgical morbidity., Patient Summary: We assessed the impact of frailty on greater health care resource utilization and complications after major urologic cancer surgery in a large US population. With each increase in a frailty score, there was an increase in the likelihood of having complications, prolonged hospital stay, more discharges to continued care, and unplanned readmissions within 30 d., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: To determine a subset of women who could undergo ovary-sparing radical cystectomy (OSRC) for bladder cancer without compromising oncologic safety., Patients and Methods: A retrospective review was performed of 164 consecutive women who underwent cystectomy at a single tertiary-care center from 1997 to 2018. Clinicopathologic and preoperative radiographic data were reviewed. Univariable and multivariable logistic regression models adjusting for pathologic stage, lymphovascular invasion (LVI), and carcinomain-situ were performed to evaluate the risk of ovarian and reproductive organ (RO) involvement., Results: A total of 123 women with a median age of 71 years underwent radical cystectomy (RC) with removal of ROs for primary bladder cancer. Nineteen women (15%) had RO involvement by bladder cancer, and 5 of them (4%) were specifically found to have ovarian involvement. Patients with ovarian involvement of bladder cancer had more locally advanced disease (P = .01), LVI (P = .003) and positive margins (P = .003). On multivariable logistic regression, ≥ pT3 (odds ratio = 10.2; 95% confidence interval, 2.0-51.6; P = .005) and LVI (odds ratio = 3.9; 95% confidence interval, 1.1-14.2; P = .037) were associated with increased risk of RO involvement. Among 15 patients excluded for having a nonbladder primary malignancy, a third had RO involvement, and 2 (13%) had ovarian metastases. No women in our cohort had a primary ovarian malignancy detected at the time of RC., Conclusion: Women with ovarian involvement by malignancy at the time of RC either had locally advanced disease with LVI or a non-bladder primary malignancy. The risk of incompletely resecting the primary malignancy would be rare if OSRC was performed on women with organ-confined (≤T2) urothelial carcinoma., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: While surgical approach has recently been associated with positive surgical margin (PSM) after partial nephrectomy (PN) for small (<4 cm) renal masses, its impact on margin status for large (>4 cm) masses is unclear. We sought to evaluate the relationship between margin and surgical approach in patients undergoing PN for large renal masses., Materials and Methods: Using the National Cancer Database (NCDB), we identified patients undergoing PN for pathological T 1b and T 2a renal-cell carcinoma diagnosed from 2010 to 2013. Conversions to open surgery were also included in our analysis. The primary outcome was surgical margin status. Multivariable regression modeling was performed to identify factors associated with PSM. A propensity score matching analysis was then performed to evaluate the impact of margin status on overall survival (OS)., Results: Of the 7495 patients undergoing PN for pT 1b and pT 2a renal masses over the study period, 504 (6.7%) had PSM. On multivariable analysis, surgical approach (laparoscopic or robot assisted vs open) was not significantly associated with surgical margin (p = 0.12 and p = 0.44, respectively). Tumor stage (T 2a vs T 1b ) also showed no significant association (p = 0.18). A subsequent multivariable analysis using clinical staging showed that surgical approach (p = 0.28 and p = 0.54, respectively), tumor stage (p = 0.78), and conversion-to-open surgery (p = 0.98) had no significant association with PSM. Propensity score matched analysis showed that PSM was not significantly associated with OS (hazard ratio 0.95 [95% confidence interval 0.47-1.92] p = 0.88)., Conclusion: In a contemporary nation-wide cohort, surgical approach was not associated with an increased risk of PSM for large, noninvasive renal masses. Furthermore, increased size from T 1b to T 2a was not associated with an increased risk of PSM. These data suggest that surgical approach should be selected by surgeon comfort level with an individual tumor, rather than the size of the tumor itself.

Purpose: We developed a precision medicine program for patients with advanced cancer using integrative whole-exome sequencing and transcriptome analysis., Patients and Methods: Five hundred fifteen patients with locally advanced/metastatic solid tumors were prospectively enrolled, and paired tumor/normal sequencing was performed. Seven hundred fifty-nine tumors from 515 patients were evaluated., Results: Most frequent tumor types were prostate (19.4%), brain (16.5%), bladder (15.4%), and kidney cancer (9.2%). Most frequently altered genes were TP53 (33%), CDKN2A (11%), APC (10%), KTM2D (8%), PTEN (8%), and BRCA2 (8%). Pathogenic germline alterations were present in 10.7% of patients, most frequently CHEK2 (1.9%), BRCA1 (1.5%), BRCA2 (1.5%), and MSH6 (1.4%). Novel gene fusions were identified, including a RBM47-CDK12 fusion in a metastatic prostate cancer sample. The rate of clinically relevant alterations was 39% by whole-exome sequencing, which was improved by 16% by adding RNA sequencing. In patients with more than one sequenced tumor sample (n = 146), 84.62% of actionable mutations were concordant., Conclusion: Integrative analysis may uncover informative alterations for an advanced pan-cancer patient population. These alterations are consistent in spatially and temporally heterogeneous samples., Competing Interests: AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center. Alexandros Sigaras Employment: Weill Cornell Medical College Loredana Puca Employment: Petra Pharma Corporation Bishoy M. Faltas Honoraria: Digital Science Press publications Research Funding: Eli Lilly David Rickman Research Funding: Janssen Oncology Eleni Andreopoulou Honoraria: AstraZeneca, Sirtex, SVB Leerink, AbbVie, Eisai, NanoString Technologies Consulting or Advisory Role: AstraZeneca, Sirtex, SVB Leerink, AbbVie, Eisai, NanoString Technologies Speakers’ Bureau: R-Pharm US Travel, Accommodations, Expenses: AstraZeneca, Sirtex, SVB Leerink, AbbVie, Eisai, NanoString Technologies Kevin Holcomb Research Funding: Fujirebio Diagnostics Expert Testimony: Johnson & Johnson Linda T. Vahdat Honoraria: Polyphor, R-Pharm, Athenex, Seattle Genetics, Osmol Therapeutics Consulting or Advisory Role: Berg Pharma Speakers’ Bureau: Eisai Research Funding: Polyphor (Inst), Immunomedics (Inst), Seattle Genetics (Inst) Patents, Royalties, Other Intellectual Property: Patent pending on the application for BMD progenitor cells (Inst) Douglas S. Scherr Research Funding: Urogen Pharma (Inst), Cepheid (Inst), Anchiano (Inst), CryoLife (Inst) Koen van Besien Stock and Other Ownership Interests: Hemogenyx Consulting or Advisory Role: Hemogenyx, Actinium Pharmaceuticals, Cellectis, Tessa Therapeutics Research Funding: Miltenyi Biotec, Actinium Pharmaceuticals, Juno Therapeutics, Fate Therapeutics Christopher E. Barbieri Patents, Royalties, Other Intellectual Property: Coinventor on a patent application filed regarding SPOP mutations in prostate cancer by Weill Cornell Medicine Brian D. Robinson Consulting or Advisory Role: Bristol-Myers Squibb Patents, Royalties, Other Intellectual Property: Methods for diagnosing and treating prostate cancer Allyson J. Ocean Consulting or Advisory Role: Celgene, Tyme Speakers’ Bureau: Daiichi Sankyo Travel, Accommodations, Expenses: Daiichi Sankyo Ana Molina Honoraria: American Society of Clinical Oncology Consulting or Advisory Role: Eisai, Exelixis, Novartis, Janssen Oncology Manish A. Shah Consulting or Advisory Role: Astellas Pharma, Eli Lilly Research Funding: Gilead Sciences (Inst), Merck (Inst), Boston Biomedical (Inst), Oncolys BioPharma (Inst), Bristol-Myers Squibb (Inst) David M. Nanus Consulting or Advisory Role: Genentech Research Funding: Novartis (Inst), Boehringer Ingelheim (Inst), Zenith Epigenetics (Inst) Qiulu Pan Employment: Caris Life Sciences Stock and Other Ownership Interests: Caris Life Sciences Francesca Demichelis Patents, Royalties, Other Intellectual Property: Co-inventor on a patent filed by the University of Michigan and Brigham and Women’s Hospital covering the diagnostic and therapeutic fields for ETS fusions in prostate cancer, diagnostic field licensed to Gen-Probe Scott T. Tagawa Consulting or Advisory Role: Medivation, Astellas Pharma, Dendreon, Janssen Oncology, Bayer, Genentech, Endocyte, Immunomedics, Karyopharm Therapeutics, AbbVie, Tolmar, QED, Amgen, Sanofi, Pfizer Research Funding: Eli Lilly (Inst), Sanofi (Inst), Janssen Oncology (Inst), Astellas Pharma (Inst), Progenics (Inst), Millennium Pharmaceuticals (Inst), Amgen (Inst), Bristol-Myers Squibb (Inst), Dendreon (Inst), Rexahn Pharmaceuticals (Inst), Bayer (Inst), Genentech (Inst), Newlink Genetics (Inst), Inovio Pharmaceuticals (Inst), AstraZeneca (Inst), Immunomedics (Inst), Novartis (Inst), AVEO (Inst), Boehringer Ingelheim (Inst), Merck (Inst), Stem CentRx (Inst), Karyopharm Therapeutics (Inst), AbbVie (Inst), Medivation (Inst), Endocyte (Inst), Exelixis (Inst), Clovis Oncology (Inst) Travel, Accommodations, Expenses: Sanofi, Immunomedics, Amgen Wei Song Employment: Genentech (I), Cytokinetics (I) Honoraria: Foundation Medicine, Loxo Consulting or Advisory Role: Foundation Medicine, Loxo Juan Miguel Mosquera Research Funding: Personal Genome Diagnostics Travel, Accommodations, Expenses: Personal Genome Diagnostics Mark A. Rubin Honoraria: F Hoffmann-La Roche, Novartis, Astellas Pharma Research Funding: Eli Lilly, Janssen Oncology, Millennium Pharmaceuticals, Sanofi Patents, Royalties, Other Intellectual Property: US Patent (7,767,393 and 7,229,774), Expression Profile of Prostate Cancer, 2007; US Patent (7,332,290), Detection of AMACR Cancer Markers in Urine, 2008; US Patent (7,718,369), Recurrent Gene Fusions in Prostate Cancer, 2010; US Patent (7,803,552 and 7,666,595), Biomarkers for Predicting Prostate Cancer Progression, 2010; US Patent (7,981,609 B2), Methods for Identifying and Using SNP Panels, 2011; US Patent (8,106,037 B2), Identification and Treatment of Estrogen Responsive PCa, 2012; US Patent (9,090,899 B2), Methods of Diagnosing and Treating Prostate Cancer Characterized by NDRG1-ERG Fusion, 2015; US Patent (9,458,213 B2), Compositions and Methods for Diagnosing Prostate Cancer Based on Detection of SLC45A3-ELK4 Fusion Transcript, 2016; US Patent (9,568,483 B2), Molecular Subtyping, Prognosis and Treatment of Prostate Cancer, 2017; US Patent (9,678,077 B2), ERG/TFF3/HMWCK Triple Immunostain for Detection of Prostate Cancer, 2017; US Patent (61,408,341), Exploration of Novel Gene Fusion in Prostate Cancer by RNA-Seq Travel, Accommodations, Expenses: F Hoffmann-La Roche, Novartis, Astellas Pharma Olivier Elemento Stock and Other Ownership Interests: Volastra, Owkin, One Three Biotech Himisha Beltran Consulting or Advisory Role: Janssen Oncology, Genzyme, GlaxoSmithKline, AbbVie, Astellas Pharma, AstraZeneca Research Funding: Janssen Oncology (Inst), AbbVie (Inst), Stemcentrx (Inst), Eli Lilly (Inst) Travel, Accommodations, Expenses: Janssen Oncology No other potential conflicts of interest were reported.

Introduction: To evaluate the effect of urine pH on tumor recurrence rates in patients undergoing surveillance after initial diagnosis of non-muscle invasive bladder cancer (NMIBC)., Materials and Methods: All patients diagnosed with NMIBC at a tertiary referral center from January 2004 to March 2015 were reviewed. Our primary outcome was time to first recurrence after transurethral resection of bladder tumor (TURBT). Patients were analyzed according to the average urine pH of all urinalysis data over the surveillance period from TURBT to first recurrence. Kaplan-Meier survival analysis was used to determine differences in median time to recurrence. Cox proportional hazards regression was used to assess independent predictors of cancer recurrence., Results: A total of 252 patients were included, of which 155 patients had average pH ≤ 6 (median pH 5.5) and 97 patients had average pH > 6 (median pH 6.8), p < 0.001. There was no significant difference in median time to recurrence between low/acidic pH (≤ 6) and high/basic pH (> 6) groups (28 months versus 17 months, respectively, p = 0.3444). Similarly, urine pH did not affect the risk of recurrence in a subgroup analysis stratified by smoking status. On multivariable Cox regression analysis, there was no association between average pH and recurrence among high grade tumors (HR = 1.33, 95% CI = 0.76 to 2.34, p = 0.3186), or low grade tumors (HR = 1.013, 95% CI = 1.01 to 1.58, p = 0.96)., Conclusions: There was no association between urine pH and risk of tumor recurrence, regardless of smoking status. These findings suggest that modification of urine pH is unlikely to decrease the frequency of tumor recurrence in patients with NMIBC.

Objective: To compare perioperative 30-day outcomes between minimally invasive radical prostatectomy (MIRP) with and without concurrent inguinal hernia repair (IHR) using a national database., Methods: The National Surgical Quality Improvement Program database was queried for MIRP from 2012 to 2015. Concurrent IHR was identified using relevant Current Procedural Terminology codes. Primary outcomes were overall complications, reoperations, unplanned readmissions, and mortality within 30 days of MIRP. Secondary outcomes included operative time (OT), length of stay (LOS), prolonged length of stay (PLOS, >2 days), and discharged to continued care (DCC). Multivariable logistic regression was performed to identify the association between concurrent IHR and outcomes., Results: A total of 18,065 patients were included; 375 (2.1%) had concurrent IHR. The unadjusted comparison showed no significant difference in overall complication, reoperation, unplanned readmission, or mortality rates between MIRP+IHR and MIRP only groups. OT was longer in the MIRP+IHR group (229 vs 195 minutes, p < 0.001) but no differences were found in LOS, PLOS, or DCC rates. Multivariable logistic regression showed concurrent IHR was not associated with increased odds of overall complication (odds ratio [OR] = 0.83, 95% confidence interval [CI] = 0.49-1.40, p = 0.479), reoperation (OR = 0.57, 95% CI = 0.14-2.30, p = 0.426), unplanned readmission (OR = 0.92, 95% CI = 0.51-1.64, p = 0.771), PLOS (OR = 1.19, 95% CI = 0.86-1.63, p = 0.297), or DCC (OR = 1.94, 95% CI = 0.70-5.34, p = 0.202)., Conclusions: Concurrent IHR with MIRP was associated with longer OT, but there were no increased 30-day adverse outcomes within the National Surgical Quality Improvement Program (NSQIP) database. These data support the safety of performing concurrent IHR at the time of MIRP and it should be considered to spare men an additional procedure.