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To evaluate whether racial disparities in MRI-Bx usage persisted after correction for socioeconomic, demographic, and clinical factors.This is a retrospective cohort study of patients who received either MRI-Bx or systematic biopsy (SB) within a single academic medical center between January 2018 - June 2020. For each patient, socioeconomic variables including household income, education, percent below poverty, and unemployment were estimated using 2015 American Community Survey census-tract level data. Chi-square analysis was used to examine differences in clinical and demographic characteristics between the two groups. The Benjamini-Hochberg procedure was used to control false discovery rate (FDR) for multiple testing.Eighteen percent of Black men (53/295) received MRI-Bx while 41% (228/561) of white men received MRI-Bx. Patients coming from highly impoverished areas were less likely to receive MRI-Bx, 25% vs 75%, respectively. In multivariate analysis, race remained significantly different across MRI-Bx and SB groups. Clinical factors including family history, DRE, BMI, and prostate volume were not significantly different between patients receiving MRI-Bx and SB.Black men are less likely to receive MRI-Bx than white men, even after adjusting for clinical and socioeconomic characteristics. Further work is necessary to identify and study methods to increase equity in PCa diagnostic testing.

Objective To examine the performance of Leibovich score versus GRade, Age, Nodes, and Tumor score in predicting disease recurrence in renal cell carcinoma. Methods In total, 7653 patients diagnosed with renal cell carcinoma from 2010 to 2018 were captured in the nationwide DaRenCa database; 2652 underwent radical or partial nephrectomy and had full datasets regarding the GRade, Age, Nodes, and Tumor score and Leibovich score. Discrimination was assessed with a Cox regression model. The results were evaluated with concordance index analysis. Results Median follow-up was 40 months (interquartile range 24-56). Recurrence occurred in 17%, and 15% died. A significant proportion of patients (36%) had missing data for the calculation of the Leibovich score. Among 1957 clear cell renal cell carcinoma patients the distribution of GRade, Age, Nodes, and Tumor score of 0, 1, 2, or 3/4 was 21%, 56%, 21% and 1.4%, respectively, and for Leibovich score of low/intermediate/high this was 47%, 36% and 18%, respectively. A similar distribution was seen in 655 non-clear cell patients. Both Leibovich and GRade, Age, Nodes, and Tumor scores performed well in predicting outcomes for the favorable patient risk groups. The Leibovich score was better at predicting recurrence-free survival (concordance index 0.736 versus 0.643), but not overall survival (concordance index 0.657 versus 0.648). Similar results were obtained in non-clear cell renal cell carcinoma. Conclusion GRade, Age, Nodes, and Tumor and Leibovich scores were validated in clear cell and non-clear cell renal cell carcinoma. Leibovich score outperformed the GRade, Age, Nodes, and Tumor score in predicting recurrence-free survival and should remain the standard approach to risk stratify patients during follow-up when all data are available.

To study the effect of surgeon-administered Transversus Abdominis Plane block (sTAP) on opioid usage and length of stay (LOS).Starting in April 2018, two surgeons at our institution gradually introduced sTAP for radical cystectomy (RC) patients. We performed a retrospective observational cohort analysis of RC patients catalogued in a prospectively maintained database using the Enhanced Recovery After Surgery Interactive Auditing System. Two surgeons adopted the sTAP block technique in April 2018. We included patients undergoing RC for bladder malignancy under Enhanced Recovery After Surgery protocol between January 2017 and August 2020. Primary outcomes included LOS, and postoperative day (POD) 0-3 total opioids consumption measured by morphine milligram equivalents (MME). Multivariable linear or logistic models evaluated the association of TAP with outcomes while controlling for potential confounders.Among 178 patients included in analysis, 84 patients underwent sTAP block and 94 did not. Multivariable analysis demonstrated significantly lower POD 0-3 total opioid usage (106.4 vs 192.2 MME, P = .004), and mean LOS (5.6 vs 7.7 days, P.001) among the sTAP group.sTAP appears to be an effective adjunct to RC care associated with improved LOS, and POD 0-3 opioid consumption. Further studies are needed to optimize TAP block technique and anesthetic composition.

Supplemental Figures 1-5 with figure legends embedded.

Castration-resistant prostate cancer can be treated with the antiandrogen enzalutamide, but responses and duration of response are variable. To identify genes that support enzalutamide resistance, we performed a short hairpin RNA (shRNA) screen in the bone-homing, castration-resistant prostate cancer cell line, C4-2B. We identified 11 genes (TFAP2C, CAD, SPDEF, EIF6, GABRG2, CDC37, PSMD12, COL5A2, AR, MAP3K11, and ACAT1) whose loss resulted in decreased cell survival in response to enzalutamide. To validate our screen, we performed transient knockdowns in C4-2B and 22Rv1 cells and evaluated cell survival in response to enzalutamide. Through these studies, we validated three genes (ACAT1, MAP3K11, and PSMD12) as supporters of enzalutamide resistance in vitro. Although ACAT1 expression is lower in metastatic castration-resistant prostate cancer samples versus primary prostate cancer samples, knockdown of ACAT1 was sufficient to reduce cell survival in C4-2B and 22Rv1 cells. MAP3K11 expression increases with Gleason grade, and the highest expression is observed in metastatic castration-resistant disease. Knockdown of MAP3K11 reduced cell survival, and pharmacologic inhibition of MAP3K11 with CEP-1347 in combination with enzalutamide resulted in a dramatic increase in cell death. This was associated with decreased phosphorylation of AR-Serine650, which is required for maximal AR activation. Finally, although PSMD12 expression did not change during disease progression, knockdown of PSMD12 resulted in decreased AR and AR splice variant expression, likely contributing to the C4-2B and 22Rv1 decrease in cell survival. Our study has therefore identified at least three new supporters of enzalutamide resistance in castration-resistant prostate cancer cells in vitro.

In many patients with prostate cancer, the cancer will be recurrent and eventually progress to lethal metastatic disease after primary treatment, such as surgery or radiation therapy. Therefore, it would be beneficial to better predict which patients with early-stage prostate cancer would progress or recur after primary definitive treatment. In addition, many studies indicate that activation of NF-κB signaling correlates with prostate cancer progression; however, the precise underlying mechanism is not fully understood. Our studies show that activation of NF-κB signaling via deletion of one allele of its inhibitor, IκBα, did not induce prostatic tumorigenesis in our mouse model. However, activation of NF-κB signaling did increase the rate of tumor progression in the Hi-Myc mouse prostate cancer model when compared with Hi-Myc alone. Using the nonmalignant NF-κB–activated androgen-depleted mouse prostate, a NF-κB–activated recurrence predictor 21 (NARP21) gene signature was generated. The NARP21 signature successfully predicted disease-specific survival and distant metastases-free survival in patients with prostate cancer. This transgenic mouse model–derived gene signature provides a useful and unique molecular profile for human prostate cancer prognosis, which could be used on a prostatic biopsy to predict indolent versus aggressive behavior of the cancer after surgery. Cancer Res; 74(10); 2763–72. ©2014 AACR.

PDF file - 453KB, Supplementary Figure 1. NF-kappaB signaling is continuously activated in the prostate of IkappaBalpha+/- mouse. Supplementary Figure 2. NF-kappaB signaling activated in the prostate of Myc/IkappaBalpha bigenic mouse. Supplementary Figure 3. Continuous activation of NF-kappaB signaling promotes PCa progression in the Hi-Myc transgenic mouse. Supplementary Figure 4. The NF24 gene signature predicts significant differences in the overall cancer-specific survival of the PCa patients. Supplemental Figure 5. Molecular network analysis using Ingenuity Pathway Analysis (IPA). Supplemental Figure 6. NF-kappaB signaling is activated/inactivated in PCa cells by infecting with IKK2-EE or IKK2-KD retroviral vectors. Supplemental Figure 7. Activation of NF-kappaB signaling increases JNK phosphorylation in PCa cells. Supplemental Figure 8. Blocking JNK signaling inhibits NF-kappaB induced invasive ability efficiently in PCa cells. Tables 1 and 2. Matched human homolog genes. Supplementary Table 3. Stratification of 77 PCa patients.

Background: Genetic factors play an important role in prostate cancer (PCa) susceptibility.Objective: To discover common genetic variants contributing to the risk of PCa in men of African ancestry.Design, setting, and participants: We conducted a meta-analysis of ten genome-wide association studies consisting of 19378 cases and 61620 controls of African ancestry.Outcome measurements and statistical analysis: Common genotyped and imputed variants were tested for their association with PCa risk. Novel susceptibility loci were identified and incorporated into a multiancestry polygenic risk score (PRS). The PRS was evaluated for associations with PCa risk and disease aggressiveness.Results and limitations: Nine novel susceptibility loci for PCa were identified, of which seven were only found or substantially more common in men of African ancestry, including an African-specific stop-gain variant in the prostate-specific gene anoctamin 7 (ANO7). A multiancestry PRS of 278 risk variants conferred strong associations with PCa risk in African ancestry studies (odds ratios [ORs] >3 and >5 for men in the top PRS decile and percentile, respectively). More importantly, compared with men in the 40-60% PRS category, men in the top PRS decile had a significantly higher risk of aggressive PCa (OR = 1.23, 95% confidence interval = 1.10-1.38, p = 4.4 × 10-4).Conclusions: This study demonstrates the importance of large-scale genetic studies in men of African ancestry for a better understanding of PCa susceptibility in this high-risk population and suggests a potential clinical utility of PRS in differentiating between the risks of developing aggressive and nonaggressive disease in men of African ancestry.Patient summary: In this large genetic study in men of African ancestry, we discovered nine novel prostate cancer (PCa) risk variants. We also showed that a multiancestry polygenic risk score was effective in stratifying PCa risk, and was able to differentiate risk of aggressive and nonaggressive disease.

Introduction:5-Alpha reductase inhibitor (5-ARI) use leads to a 50% decline in serum prostate specific antigen (PSA) without a concomitant decrease in prostate cancer (PCa) risk. We hypothe...

This AUA Guideline focuses on evaluation/counseling/management of adult patients with clinically-localized renal masses suspicious for cancer, including solid-enhancing tumors and Bosniak 3/4 complex-cystic lesions.The Renal Mass and Localized Renal Cancer guideline underwent an update literature review which resulted in the 2021 amendment. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text]).Great progress has been made regarding the evaluation/management of clinically-localized renal masses. These guidelines provide updated, evidence-based recommendations regarding evaluation/counseling including the evolving role of renal-mass-biopsy (RMB). Given great variability of clinical/oncologic/functional characteristics, index patients are not utilized and the panel advocates individualized counseling/management. Options for intervention (partial-nephrectomy (PN), radical-nephrectomy (RN), and thermal-ablation (TA)) are reviewed including recent data about comparative-effectiveness/potential morbidities. Oncologic issues are prioritized while recognizing the importance of functional-outcomes for survivorship. Granular criteria for RN are provided to help reduce overutilization of RN while also avoiding imprudent PN. Priority for PN is recommended for clinical T1a lesions, along with selective utilization of TA, which has good efficacy for tumors≤3.0 cm. Recommendations for genetic-counseling have been revised and considerations for adjuvant-therapies are addressed. Active-surveillance and follow-up after intervention are discussed in an adjunctive article.Several factors require consideration during counseling/management of patients with clinically-localized renal masses including general health/comorbidities, oncologic-considerations, functional-consequences, and relative efficacy/potential morbidities of various management-strategies.

Background Intravesical bacillus Calmette-Guerin (BCG) therapy is standard treatment for high-risk non-muscle invasive bladder cancer (NMIBC) but overall efficacy is low, and no reliable predictive biomarkers currently exist to refine patient selection. We performed genomic analysis on high-grade (HG) T1 NMIBCs to determine if response to therapy is predicted by certain mutational and/or expressional changes. Methods Patients with HG T1 NMIBC treated with induction BCG were stratified by response into durable and non-durable responders. Baseline tumor samples were subjected to targeted DNA sequencing and whole-exome RNAseq. Genomic variants differing significantly between response groups were analyzed using Ingenuity Pathway Analysis (IPA) software. Variant selection was refined to target potential biomarker candidates for responsiveness to BCG. Results Among 42 patients, the median follow-up was 51.7 months and 40.5% (n=17) were durable BCG responders. Deleterious mutations in the RNA sequence of JCHAIN, S100A7, CLEC2B, and ANXA10 were more common in non-durable responders. Mutations in MCL1 and MSH6 detected on targeted sequencing were more commonly found in durable responders. Of all deleterious DNA and RNA mutations identified, only MCL1 was significantly associated with longer recurrence free survival (RFS) (P=0.031). Conclusions Differences in the genomic profiles of HG T1 NMIBC tumors exist between those who show durable response to BCG and those who do not. Using pathway analysis, those differences imply upregulation of several interconnected inflammatory pathways among responders. Specific variants identified here, namely MCL1, are candidates for further study and, if clinically validated, may serve as useful biomarkers in the future.

To determine the influence of socioeconomic parameters on urinary stone surgeries.A retrospective cohort study analyzed patients undergoing urolithiasis surgery in our community network hospital in North Carolina from 2005-2018.Of 7731 patients, 2160 (28%), 5,174 (67%), and 397 (5%) underwent SWL, URS, and PCNL, respectively. A higher proportion of Whites underwent URS (67%) and SWL (74%) than PCNL (56%); whereas a larger percentage of Blacks underwent PCNL (24%) than URS (20%) and SWL (15%) groups (P.001). Private insurance payers were greater in the SWL (95%) group than URS (80%) and PCNL (81%) (P.001). The distribution of median income was significantly different amongst the 3 surgeries with higher income classes overutilizing SWL and underutilizing PCNL compared to lower income classes (P.001). In linear regression modeling, the proportion of SWL in a postal code was positively associated with median income (ROur study suggests that socioeconomic status impacts urolithiasis surgical management, underscoring disparity recognition importance in endourologic care and ensuring appropriate surgical care regardless of socioeconomic status.

Castration-resistant prostate cancer can be treated with the anti-androgen enzalutamide, but responses and duration of response are variable. To identify genes that support enzalutamide resistance, we performed a short hairpin RNA (shRNA) screen in the bone-homing, castration-resistant prostate cancer cell line, C4-2B. We identified eleven genes (TFAP2C, CAD, SPDEF, EIF6, GABRG2, CDC37, PSMD12, COL5A2, AR, MAP3K11, andACAT1), whose loss resulted in decreased cell survival in response to enzalutamide. To validate our screen, we performed transient knockdowns in C4-2B and 22Rv1 cells and evaluated cell survival in response to enzalutamide. Through these studies, we validated three genes (ACAT1, MAP3K11, andPSMD12) as supporters of enzalutamide resistancein vitro. AlthoughACAT1expression is lower in metastatic castration-resistant prostate cancer samples versus primary prostate cancer samples, knockdown ofACAT1was sufficient to reduce cell survival in C4-2B and 22Rv1 cells.MAP3K11expression increases with Gleason grade, and the highest expression is observed in metastatic castration-resistant disease. Knockdown ofMAP3K11reduced cell survival and pharmacologic inhibition of MAP3K11 with CEP-1347 in combination with enzalutamide resulted in a dramatic increase in cell death. This was associated with decreased phosphorylation of AR-Serine650, which is required for maximal AR activation. Finally, whilePSMD12expression did not change during disease progression, knockdown ofPSMD12resulted in decreased AR and AR splice variant expression, likely contributing to the C4-2B and 22Rv1 decrease in cell survival. Our study has therefore identified at least three new supporters of enzalutamide resistance in castration-resistant prostate cancer cellsin vitro.Financial supportThe authors would like to acknowledge funding from the Joe C. Davis Foundation (to RJM), the Vanderbilt Institute for Clinical and Translational Research (VICTR, to YY, PEC, and RJM). The Vanderbilt Institute for Clinical and Translational Research (VICTR) is funded by the National Center for Advancing Translational Sciences (NCATS) Clinical Translational Science Award (CTSA) Program, Award Number 5UL1TR002243. The content of this manuscript solely the responsibility of the authors and does not necessarily represent the official views of the NIH. We would also like to acknowledge the Case Research Institute, a joint venture between University Hospitals and Case Western Reserve University, start-up funds (to MMG), and the Cell and Molecular Biology Training Program (T32 GM 008056 to SEK).

Summary Human epidermal growth factor receptor 2 (HER2) overexpression occurs in 5–10% of primary urothelial carcinomas (UCs) but has not reliably predicted benefit from HER2-targeted agents in the metastatic setting. HER2 testing of primary tumors may not reflect the HER2 status of distant metastases. We assessed the concordance of HER2 expression in paired primary and distant metastatic UC lesions. Specimens from 149 patients with metastatic UC underwent immunohistochemical staining for HER2, including 79 paired primary and distant metastatic tumors. HER2 status was defined using 2018 ASCO/CAP guidelines. HER2 intratumoral heterogeneity (ITH) was defined as HER2 3+ expression in 5–50% of tumor cells. The HER2-positive, -equivocal, and -negative rates observed were 10.6%, 24.7%, and 64.7% for primary tumors and 9.8%, 12.6%, and 77.6% for metastatic tumors, respectively. HER2 ITH occurred in 44% of HER2-positive primary tumors. Low agreement of HER2-positive status between primary and metastatic tumors was observed (к = 0.193, P = 0.079). Loss of HER2 overexpression in the metastatic lesion was observed in 55% (5 of 9 cases) of HER2-positive primary cases and was associated with the presence of HER2 ITH in the primary tumor (Fisher's exact P = 0.048). Change from negative primary to positive metastasis was seen in 2% (1 of 50) of cases. No differences in metastasis-free survival or overall survival were observed in accordance with HER2 status defined by either the primary or metastatic lesion. These findings are likely to impact patient selection for HER2 targeted therapies in UC. Confirmation and evaluation of the clinical significance of HER2 discordance is warranted, preferably in the context of a clinical trial.

Introduction:For muscle invasive bladder cancer, computerized tomography scans are often used before cystectomy to optimize surgical decision planning. The aim of this study is to evaluate ...

Substantial management changes in endocrine-related malignancies have been required as a response to the COVID-19 pandemic, including a draconian reduction in the screening of asymptomatic subjects, delay in planned surgery and radiotherapy for primary tumors deemed to be indolent, and dose reductions and/or delays in initiation of some systemic therapies. An added key factor has been a patient-initiated delay in the presentation because of the fear of viral infection. Patterns of clinical consultation have changed, including a greater level of virtual visits, physical spacing, masking, staffing changes to ensure a COVID-free population and significant changes in patterns of family involvement. While this has occurred to improve safety from COVID-19 infection, the implications for cancer outcomes have not yet been defined. Based on prior epidemics and financial recessions, it is likely that delayed presentation and treatment of high-grade malignancy will be associated with worse cancer outcomes. Cancer patients are also at increased risk from COVID-19 infection compared to the general population. Pandemic management strategies for patients with tumors of breast, prostate, thyroid, parathyroid and adrenal gland are reviewed.

International audience; Although men of African ancestry have a high risk of prostate cancer (PCa), no genes or mutations have been identified that contribute to familial clustering of PCa in this population. We investigated whether the African ancestry-specific PCa risk variant at 8q24, rs72725854, is enriched in men with a PCa family history in 9052 cases, 143 cases from high-risk families, and 8595 controls of African ancestry. We found the risk allele to be significantly associated with earlier age at diagnosis, more aggressive disease, and enriched in men with a PCa family history (32% of high-risk familial cases carried the variant vs 23% of cases without a family history and 12% of controls). For cases with two or more first-degree relatives with PCa who had at least one family member diagnosed at age

We aim to assess the safety of decreasing ureteral stenting duration following Radical Cystectomy with Urinary Diversion (RCUD). We analyzed a prospectively and retrospectively collected dataset for cystectomy patients at our tertiary center. Adult patient who underwent RCUD for malignancy from January 2013 to February 2018 were included. Patients with a history of abdominal/pelvic radiation and continent diversions were excluded. The patient population was divided to late stent removal group (LSR-POD 14) and early stent removal group (ESR-POD5). Our endpoints were total stent duration, 90-day readmission, 90-day total-UTI, 90-day urinary-readmissions, complications and Ureteroenteric Stricture (UES) rates. Statistical methods included t test, Chi-squared test and multivariate logistic regression. One hundred and seventy-eight patients were included in the final analysis after inclusion/exclusion criteria were applied. The LSR (n = 74) and ESR (n = 104) groups were similar in preoperative characteristics except higher intracorporeal ileal conduit formation in ESR. The duration of stenting decreased significantly from approximately 15.5–5 days (P

BACKGROUND: Limited stage small cell bladder cancer is curable with multi-modality therapy using external beam radiotherapy or radical cystectomy. The optimal management strategy for this rare disease is still debated, yet few case series have described patients treated after 2010. OBJECTIVE: To analyze outcomes from a contemporary cohort of patients undergoing definitive treatment. METHODS: Patients diagnosed with small cell bladder cancer after January 1, 2010 were identified from an institutional database. Clinical histories were collected by chart review. Survival outcomes were analyzed in patients who received curative-intent therapy consisting of bladder radiotherapy or cystectomy. RESULTS: Thirty patients with limited stage disease that received definitive therapy were identified. Seventeen patients received primary radiotherapy, and thirteen underwent cystectomy. Median age was 70 years. Median follow up was 39.6 months (range 7.2–95.8). The median overall survival of patients undergoing radiotherapy or cystectomy were 36.8 and 30.6 months, respectively (hazard ratio 0.99, 95% confidence interval 0.35–2.85). The median metastasis free survival for patients receiving radiotherapy was not reached, and 18.9 months in the cystectomy group (hazard ratio 0.94, 95% confidence interval 0.34–2.61). The most common sites of relapse were lymph node (n = 6) and bone (n = 5). Brain metastases were less common (n = 3). CONCLUSIONS: Patients receiving cystectomy or radiotherapy had similar outcomes in this contemporary series, but definitive comparisons are limited by the cohort size and high censoring rate (53%). Survival in our cohort is improved compared with older reports, though outcomes remain poor, reiterating the need for better therapeutic options.

Objective To investigate complications and treatment failure rates of percutaneous renal cryoablation (PRC) for small renal masses under local anaesthesia and conscious sedation (LACS), to assess the safety and effectiveness of this approach, as PRC is typically performed under general anaesthesia (GA). Patients and methods We retrospectively reviewed PRC under LACS from 2003 to 2017. We analysed perioperative parameters between patients who successfully underwent PRC under LACS and patients with post-procedural complications or treatment failure (renal mass enhancement after successful intraoperative tumour ablation). Two-sided non-parametric and Fisher’s exact tests were performed to compare uncomplicated or disease-free PRC with the complication or treatment failure group, respectively. Results A total of 100 PRCs under LACS were performed during the study period. Of these patients, six patients had at least one postoperative complication (6%), and treatment failure was diagnosed in nine patients (9%) after PRC [mean (SD) follow-up of 42.7 (26.6) months]. The procedural failure rate was 1%. No ablations were converted to GA. The mean tumour size was smaller in patients who had no complications during PRC compared to those who did, at a mean (SD) of 2.2 (0.6) cm vs 3.0 (1.0) cm (P = 0.039). The use of more intraoperative probes during the PRC was also associated with complications, at a mean (SD) 3.0 (1.4) vs 1.8 (0.8) (P = 0.021). Conclusions PRC under LACS is an effective and safe procedural approach for managing small renal masses with low complication, treatment failure, and procedural failure rates. Larger renal masses and intraoperative use of multiple probes is associated with an increased risk of PRC complications. Abbreviations BMI: body mass index; CCI: Charlson Comorbidity Index; GA: general anaesthesia; LACS: local anaesthesia and conscious sedation; PRC: percutaneous renal cryoablation; R.E.N.A.L.: Radius, Exophytic/Endophytic, Nearness, Anterior/Posterior, Location

To elucidate regional trends of infectious complications following transrectal ultrasound prostate biopsy (TRUS-PB) from a national, privately-insured database.Using Market Scan, we identified all men who underwent TRUS-PB from 2010 to 2015. Infectious complications (UTI, prostatitis, sepsis) occurring 30 days after the prostate biopsy from emergency room (ER) visits or hospital admissions constituted the primary outcomes. We analyzed unadjusted and adjusted rates of infectious complications from ER visits and hospital admissions per 100 prostate biopsies by state. Multivariable logistic regression analyses were used to identify patient covariates associated with infectious complications.During the study interval, we identified 193,490 patients who underwent TRUS-PB. The mean age was 57.6 years (SD: 5.0). Over time the unadjusted national rates of infectious complications remained similar from 0.4 ER visits per 100 prostate biopsies in 2010 -0.2 in 2015 (P = 0.83), and 1.2 hospital admissions per 100 prostate biopsies in 2010 to 1.1 in 2015 (P= 0.58). Connecticut had the lowest unadjusted infectious complication rate per 100 biopsies at 0.64, whereas West Virginia had the highest at 2.34. Multivariable analysis revealed higher Elixhauser status and patient age were associated with higher odds of infectious complications (P0.05).While rates of infectious complications attributable to prostate biopsies remain relatively stable, significant variation exists at the state level regarding this adverse outcome.

533 Background: Activation of HER2 and cMET signaling has been implicated in the pathogenesis of urothelial carcinoma subsets, and the use of anti-PD-(L)1 agents is well established in this disease. Novel therapeutic combinations targeting both immune checkpoints and the cMET or HER2 pathways are currently under investigation in metastatic urothelial carcinoma (mUC). Co-expression of these molecular targets has not been characterized in mUC. We hypothesized that the rate of PD-L1 co-expression with cMET and HER2 may be low. Therefore, we sought to define tumor protein co-expression of PD-L1, HER2 and cMET in a cohort of mUC patients. Methods: Patients with mUC were identified from an institutional database. FFPE tumor specimens from metastatic sites and available paired primary tumors underwent immunohistochemical staining for PD-L1 (SP-142), cMET, and HER2 expression. High expression was defined using the following thresholds: PD-L1: >=5% of infiltrated immune cells; cMET: >=50% of tumor cells; HER2: score=3+ (complete membrane staining that is intense and >10% of tumor cells). Simple and Weighted Cohen’s kappa Statistics (κ) were utilized to assess the agreement in expression and co-expression between paired primary and metastatic samples. Cohen’s interpretation of the κ results is provided. Results: Specimens from 143 mUC patients were analyzed, including 79 with available paired primary tumors. In primary tumors (N=79), high expression of PD-L1, cMET, and HER2 was observed in 15.2%, 34.2%, and 12.7%, respectively. In metastatic samples (N=143), high expression of PD-L1, cMET and HER2 was detected in 9.8%, 41.3%, and 9.8%, respectively. Expression agreement rates between primary and metastatic specimens (n=79) were PD-L1: 79.7% (κ=0.09, slight agreement), cMET: 69.6% (κ=0.35, fair agreement), HER2: 84.8% (κ=0.17, slight agreement) and were driven by high prevalence of low expression. High PD-L1/cMET co-expression was observed in only 5.1% (n = 4) of primary and 4.9% (n =7) of metastatic specimens. High co-expression of PD-L1/HER2 occurred in only 3.8% (n=3) of primary samples and in no metastatic samples. The overall co-expression agreement rate between paired primary and metastatic samples was 55.7% (κ = 0.22, fair agreement) for PD-L1/cMET and 67.1% (κ = 0.06, slight agreement) for PD-L1/HER2. Importantly, however, agreements rates for high co-expression between primary and metastatic samples were very low (2.5% for PD-L1/cMET and 0% for PD-L1/HER2). Conclusions: Tumor co-expression of high cMET or HER2 and PD-L1 is low in this cohort of metastatic urothelial carcinoma patients. Furthermore, agreement of high co-expression between primary and metastatic sites is rare. These results suggest that investigational strategies combining immune checkpoint inhibition with either cMET or HER2 targeted agents in mUC may have limited synergistic activity.

Small cell bladder carcinoma (SCBC) represents a rare histologic variant with a poor prognosis and for which no routine biomarkers exist. Limited reports of genomic sequencing in SCBC have demonstrated a high prevalence of TP53 and RB1 gene mutations, though the prognostic value of these and other gene variants in SCBC remains undefined. In this study, we performed targeted genomic sequencing on a cohort of SCBC patients and correlated genomic findings with clinical outcomes to identify potential novel biomarkers.Thirty-one patients with SCBC and available treatment-naïve tumor specimens were identified from an institutional database (23 limited stage [LS], 8 extensive stage [ES]). Small cell carcinoma specimens were microdissected and subjected to tumor next-generation whole-exon sequencing with a 592 gene panel. Kaplan-Meier techniques and Cox proportional hazards models were used to evaluate genomic aberration association with relapse-free survival (RFS) and overall survival (OS) in the limited stage cohort.The most common pathogenic gene variants included ARID1A (48%), TP53 (48%) and RB1 (48%). Mutations in genes with potential therapeutic targets not routinely evaluated in SCBC included BRCA1/2 (16%), POLE (13%), JAK2 (13%), PDGFB (13%) and FGFR3 (3%). Multiple novel biomarker candidates showed trends for improvements in OS in the LS subset including ERCC2 (HR 0.322, P = 0.122) and RB1 (HR 0.481, P = 0.182), while LS patients with TP53 mutations (HR 2.730, P = 0.056), and MCL1 gene amplification (HR 4.183, P = 0.018) suggested inferior OS. Additionally, gene or copy number variants with potential prognostic benefit included UBR5 and DAXX (P = 0.02, [hazard ratios nonestimable due to zero events in biomarker positive groups]).These results support the role for tumor genomic profiling in SCBC and identify multiple potential novel biomarkers and therapeutic targets in this rare disease. Efforts to validate these findings should lead to improved decision-making and treatment outcomes in SCBC.

INTRODUCTION AND OBJECTIVE:Prostate cancer (PCa) risk is often modeled at referral based on Prostate Cancer Prevention Trial (PCPT) and Prostate Biopsy Collaborative Group (PBCG) risk calculators, ...