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Background: Bladder cancer and therapy responses hinge on immune profiles in the tumor microenvironment (TME) and blood, yet studies linking tumor-infiltrating immune cells to peripheral immune profiles are limited. Methods: DNA methylation cytometry quantified TME and matched peripheral blood immune cell proportions. With tumor immune profile data as the input, subjects were grouped by immune infiltration status and consensus clustering. Results: Immune hot and cold groups had different immune compositions in the TME but not in circulating blood. Two clusters of patients identified with consensus clustering had different immune compositions not only in the TME but also in blood. Conclusion: Detailed immune profiling via methylation cytometry reveals the significance of understanding tumor and systemic immune relationships in cancer patients.

Background: Immune profiles have been associated with bladder cancer outcomes and may have clinical applications for prognosis. However, associations of detailed immune cell subtypes with patient outcomes remain underexplored and may contribute crucial prognostic information for better managing bladder cancer recurrence and survival., Methods: Bladder cancer case peripheral blood DNA methylation was measured using the Illumina HumanMethylationEPIC array. Extended cell-type deconvolution quantified 12 immune cell-type proportions, including memory, naïve T and B cells, and granulocyte subtypes. DNA methylation clocks determined biological age. Cox proportional hazards models tested associations of immune cell profiles and age acceleration with bladder cancer outcomes. The partDSA algorithm discriminated 10-year overall survival groups from clinical variables and immune cell profiles, and a semi-supervised recursively partitioned mixture model (SS-RPMM) with DNA methylation data was applied to identify a classifier for 10-year overall survival., Results: Higher CD8T memory cell proportions were associated with better overall survival [HR = 0.95, 95% confidence interval (CI) = 0.93-0.98], while higher neutrophil-to-lymphocyte ratio (HR = 1.36, 95% CI = 1.23-1.50), CD8T naïve (HR = 1.21, 95% CI = 1.04-1.41), neutrophil (HR = 1.04, 95% CI = 1.03-1.06) proportions, and age acceleration (HR = 1.06, 95% CI = 1.03-1.08) were associated with worse overall survival in patient with bladder cancer. partDSA and SS-RPMM classified five groups of subjects with significant differences in overall survival., Conclusions: We identified associations between immune cell subtypes and age acceleration with bladder cancer outcomes., Impact: The findings of this study suggest that bladder cancer outcomes are associated with specific methylation-derived immune cell-type proportions and age acceleration, and these factors could be potential prognostic biomarkers., (©2023 The Authors; Published by the American Association for Cancer Research.)

Objectives: The aim of this study was to determine the frequency and reasons for long-term opioid prescriptions (rxs) after surgery in the setting of guideline-directed prescribing and a high rate of excess opioid disposal., Background: Although previous studies have demonstrated that 5% to 10% of opioid-naïve patients prescribed opioids after surgery will receive long-term (3-12 months after surgery) opioid rxs, little is known about the reasons why long-term opioids are prescribed., Methods: We studied 221 opioid-naïve surgical patients enrolled in a previously reported prospective clinical trial which used a patient-centric guideline for discharge opioid prescribing and achieved a high rate of excess opioid disposal. Patients were treated on a wide variety of services; 88% of individuals underwent cancer-related surgery. Long-term opioid rxs were identified using a Prescription Drug Monitoring Program search and reasons for rxs and opioid adverse events were ascertained by medical record review. We used a consensus definition for persistent opioid use: opioid rx 3 to 12 months after surgery and >60day supply., Results: 15.3% (34/221) filled an opioid rx 3 to 12 months after surgery, with 5.4% and 12.2% filling an rx 3 to 6 and 6 to 12 months after surgery, respectively. The median opioid rx days supply per patient was 7, interquartile range 5 to 27, range 1 to 447 days. The reasons for long-term opioid rxs were: 51% new painful medical condition, 40% new surgery, 6% related to the index operation; only 1 patient on 1 occasion was given an opioid rx for a nonspecific reason. Five patients (2.3%) developed persistent opioid use, 2 due to pain from recurrent cancer, 2 for new medical conditions, and 1 for a chronic abscess., Conclusions: In a group of prospectively studied opioid-naïve surgical patients discharged with guideline-directed opioid rxs and who achieved high rates of excess opioid disposal, no patients became persistent opioid users solely as a result of the opioid rx given after their index surgery. Long-term opioid use did occur for other, well-defined, medical or surgical reasons., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To quantify the short-term burden associated with continent diversion relative to ileal conduit creation., Methods: Bladder cancer patients who underwent radical cystectomy in 2019 and 2020 were identified in the American College of Surgeons National Surgical Improvement Program database using current procedural terminology codes and pathology reports. Patients were grouped by urinary diversion performed: ileal conduit versus continent diversion (neobladder or cutaneous reservoir). Multiple logistic regression was used to examine the association between type of urinary diversion and 30-day outcomes, including postoperative complications, all-cause readmissions, and mortality, adjusting for baseline differences., Results: Of 4,755 patients who underwent radical cystectomy, 677 underwent continent diversion (14.2%). These patients were significantly younger (median 62 vs 71 years, P <.01) and less likely to have diabetes (13.6% vs 20.1%, P <.01), COPD (3.7% vs 7.1%, P<0.01), and prior pelvic radiation (5.5% vs 13.1%, P <.01). A greater proportion of continent diversion patients experienced a postoperative complication (56.0% vs 48.9%, P <.01) and all-cause readmission (30.3% vs 20.4%, P <.0). After adjustment, continent diversion patients had 1.4 (95% CI: 1.1-1.7) and 1.7 (95% CI: 1.4-2.1) times the odds of experiencing a postoperative complication or all-cause readmission, respectively. There was no statistically significant difference in mortality (OR 1.2, 95% CI: 0.5-2.9)., Conclusion: Compared to ileal conduit creation, continent urinary diversion is associated with increased odds of postoperative complications and readmission to the hospital within 30 days of surgery. Bladder cancer patients undergoing cystectomy and seeking continent diversion should be counseled on the increased short-term morbidity associated with this specific type of diversion., (Copyright © 2022. Published by Elsevier Inc.)

Objective: To demonstrate the surgical technique for prophylactic mesh placement in the sublay position during ileal conduit creation because literature suggests that prophylactic mesh placement at the time of cystectomy may reduce the risk of parastomal hernias with low risk of mesh-related complications. Parastomal hernias are one of the most common complications following ileal conduit construction and occur in 17-65% of patients undergoing cystectomy with urinary diversion. Review of our institutions data demonstrated a high incidence of hernias associated with ileal conduits, which have substantial burden to patients, surgeons, and the healthcare system., Methods: This is a retrospective chart review of data from a single surgeon who performed cystectomy with ileal conduit for 12 patients with bladder cancer between January, 2021-March, 2022 at our institution. These dates were chosen based on the timing of availability of literature suggesting a benefit from prophylactic mesh placement. Preliminary data was analyzed determine the incidence of parastomal hernia and mesh-related complications., Results: A total of 12 patients underwent cystectomy with ileal conduit between January, 2021-March, 2022 at our institution. Eleven patients (92%) had prophylactic mesh placed during their procedure. Median follow up was 5.4 months (0.8-8 months). Two patients (17%) developed a parastomal hernia which was detected clinically and/or radiographically. The hernias occurred in patients with mesh and within 6 months of cystectomy. One patient had stomal stenosis eventually requiring surgical revision. There were no mesh infections or mesh removals., Conclusion: Parastomal hernias are a common and morbid complication of ileal conduit urinary diversion. Our early experience demonstrates that the procedure is straightforward, adds little time to the surgical procedure, and is associated with a low complication rate. Our experience is too small and follow up too short to confirm that the results of the randomized trial can be matched at our center., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Traditional soft tissue registration methods require direct intraoperative visualization of a significant portion of the target anatomy in order to produce acceptable surface alignment. Image guidance is therefore generally not available during the robotic exposure of structures like the kidneys which are not immediately visualized upon entry into the abdomen. This paper proposes guiding surgical exposure with an iterative state estimator that assimilates small visual cues into an a priori anatomical model as exposure progresses, thereby evolving pose estimates for the occluded structures of interest., Methods: Intraoperative surface observations of a right kidney are simulated using endoscope tracking and preoperative tomography from a representative robotic partial nephrectomy case. Clinically relevant random perturbations of the true kidney pose are corrected using this sequence of observations in a particle filter framework to estimate an optimal similarity transform for fitting a patient-specific kidney model at each step. The temporal response of registration error is compared against that of serial rigid coherent point drift (CPD) in both static and simulated dynamic surgical fields, and for varying levels of observation persistence., Results: In the static case, both particle filtering and persistent CPD achieved sub-5 mm accuracy, with CPD processing observations 75% faster. Particle filtering outperformed CPD in the dynamic case under equivalent computation times due to the former requiring only minimal persistence., Conclusion: This proof-of-concept simulation study suggests that Bayesian state estimation may provide a viable pathway to image guidance for surgical exposure in the abdomen, especially in the presence of dynamic intraoperative tissue displacement and deformation., (© 2022. CARS.)

Aims: To determine whether phosphodiesterase inhibitors (PDEi) or α-antagonists (AA) were associated with differences in region of interest (ROI) characteristics or prostate cancer detection on fusion biopsy (FB)., Materials and Methods: Records from 847 consecutive patients undergoing FB at three separate institutions over a period of 2 years were retrospectively reviewed. Associations between medication use, Prostate Imaging Reporting & Data System (PIRADS) scores, and ROI locations were assessed with ordinal logistic regression. Associations with lesion size and International Society of Urologic Pathology (ISUP) grade group (GG) on biopsy were tested using multivariate regression., Results: Medication use included PDEi in 14.2% and AA in 23.0%. PDEi use was associated with 19.3% smaller lesion diameter (-2.8 mm; CI from -4.8 to -0.7; p < 0.01) and lower PIRADS scores on MRI (OR 0.60; CI 0.40 - 1.00; p = 0.05). AA use was associated with higher PIRADS scores (OR 1.43; CI 0.97 - 2.11; p = 0.06), fewer positive fusion-directed biopsy cores (-28.6%, CI from -57.9 to 0.01%, p = 0.05), and downgrading on final pathology (-19%; CI from -40 to 2%; p = 0.06)., Conclusion: For PIRADS scores ≥ 3, PDEi use is associated with smaller ROI and lower PIRADS scores, while AA use is associated with higher PIRADS scores. Neither medication was associated with differences in biopsy GG. Prospective studies are needed to investigate the discordance between multi-parametric magnetic resonance imaging (mpMRI) results and oncologic outcomes associated with PDEi and AA use.

Background: Non-muscle-invasive bladder cancer (NMIBC) patients receive frequent monitoring because ≥ 70% will have recurrent disease. However, screening is invasive, expensive, and associated with significant morbidity making bladder cancer the most expensive cancer to treat per capita. There is an urgent need to expand the understanding of markers related to recurrence and survival outcomes of NMIBC., Methods and Results: We used the Illumina HumanMethylationEPIC array to measure peripheral blood DNA methylation profiles of NMIBC patients (N = 603) enrolled in a population-based cohort study in New Hampshire and applied cell type deconvolution to estimate immune cell-type proportions. Using Cox proportional hazard models, we identified that increasing CD4T and CD8T cell proportions were associated with a statistically significant decreased hazard of tumor recurrence or death (CD4T: HR = 0.98, 95% CI = 0.97-1.00; CD8T: HR = 0.97, 95% CI = 0.95-1.00), whereas increasing monocyte proportion and methylation-derived neutrophil-to-lymphocyte ratio (mdNLR) were associated with the increased hazard of tumor recurrence or death (monocyte: HR = 1.04, 95% CI = 1.00-1.07; mdNLR: HR = 1.12, 95% CI = 1.04-1.20). Then, using an epigenome-wide association study (EWAS) approach adjusting for age, sex, smoking status, BCG treatment status, and immune cell profiles, we identified 2528 CpGs associated with the hazard of tumor recurrence or death (P < 0.005). Among these CpGs, the 1572 were associated with an increased hazard and were significantly enriched in open sea regions; the 956 remaining CpGs were associated with a decreased hazard and were significantly enriched in enhancer regions and DNase hypersensitive sites., Conclusions: Our results expand on the knowledge of immune profiles and methylation alteration associated with NMIBC outcomes and represent a first step toward the development of DNA methylation-based biomarkers of tumor recurrence., (© 2022. The Author(s).)

Nutrition may impact bladder cancer survival. We examined the association between diet quality and overall and bladder cancer-specific survival. Bladder cancer cases from a population-based study reported pre-diagnosis diet. Diet quality was assessed using the 2010 Alternate Healthy Eating Index (AHEI-2010). Vital status was ascertained from the National Death Index. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated using proportional hazards and competing risks regression models. Overall AHEI-2010 adherence was not associated with overall or bladder cancer-specific survival among non-muscle invasive bladder cancer (NMIBC) cases (HR, 1.00; 95% CI, 0.98-1.01; HR, 1.00; 95% CI, 0.97-1.02) or muscle invasive bladder cancer (MIBC) cases (HR, 0.99; 95% CI, 0.96-1.03; HR, 1.01, 95% CI 0.97-1.06). AHEI-2010 sugar-sweetened beverages adherence was associated with poorer overall survival (HR, 1.04; 95% CI, 1.01-1.08) and AHEI-2010 sodium adherence was associated with better overall and bladder cancer-specific survival after NMIBC diagnosis (HR, 0.92, 95% CI, 0.85-1.00; HR, 0.82; 95% CI, 0.68-0.98). AHEI-2010 fruit adherence was associated with poorer overall and bladder cancer-specific survival after MIBC diagnosis (HR, 1.17; 95% CI, 1.02-1.33; HR, 1.26; 95% CI, 1.03-1.55). Consumption of sugar-sweetened beverages, sodium, and fruit, not overall AHEI-2010 adherence, may be associated with bladder cancer survival.

Background: Sipuleucel-T (sip-T) is a Food and Drug Administration (FDA)-approved autologous cellular immunotherapy for metastatic castration-resistant prostate cancer (mCRPC). We hypothesized that combining sip-T with interleukin (IL)-7, a homeostatic cytokine that enhances both B and T cell development and proliferation, would augment and prolong antigen-specific immune responses against both PA2024 (the immunogen for sip-T) and prostatic acid phosphatase (PAP)., Methods: Fifty-four patients with mCRPC treated with sip-T were subsequently enrolled and randomized 1:1 into observation (n=26) or IL-7 (n=28) arms of a phase II clinical trial (NCT01881867). Recombinant human (rh) IL-7 (CYT107) was given weekly×4. Immune responses were evaluated using flow cytometry, mass cytometry (CyTOF), interferon (IFN)-γ ELISpot, 3 H-thymidine incorporation, and ELISA., Results: Treatment with rhIL-7 was well tolerated. For the rhIL-7-treated, but not observation group, statistically significant lymphocyte subset expansion was found, with 2.3-2.6-fold increases in CD4+T, CD8+T, and CD56 bright NK cells at week 6 compared with baseline. No significant differences in PA2024 or PAP-specific T cell responses measured by IFN-γ ELISpot assay were found between rhIL-7 and observation groups. However, antigen-specific T cell proliferative responses and humoral IgG and IgG/IgM responses significantly increased over time in the rhIL-7-treated group only. CyTOF analyses revealed pleiotropic effects of rhIL-7 on lymphocyte subsets, including increases in CD137 and intracellular IL-2 and IFN-γ expression. While not powered to detect clinical outcomes, we found that 31% of patients in the rhIL-7 group had prostate specific antigen (PSA) doubling times of >6 months, compared with 14% in the observation group., Conclusions: Treatment with rhIL-7 led to a significant expansion of CD4+ and CD8+ T cells, and CD56 bright natural killer (NK) cells compared with observation after treatment with sip-T. The rhIL-7 treatment also led to improved antigen-specific humoral and T cell proliferative responses over time as well as to increased expression of activation markers and beneficial cytokines. This is the first study to evaluate the use of rhIL-7 after sip-T in patients with mCRPC and demonstrates encouraging results for combination approaches to augment beneficial immune responses., Competing Interests: Competing interests: MM and AG are employees of RevImmune who provided CYT107 for this trial. LF, RKP and PM served in advisory/consulting roles for Dendreon. EYY has received grant funding from Dendreon., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: It is important to understand the implications of reduced bacillus Calmette-Guérin (BCG) treatment intensity, given global shortages and early termination of the NIMBUS trial., Objective: To assess the association of partial versus complete BCG induction with outcomes., Design Setting and Participants: This is a retrospective cohort study of veterans diagnosed with high-risk non-muscle-invasive bladder cancer (NMIBC; high grade [HG] Ta, T1, or carcinoma in situ) between 2005 and 2011 with follow-up through 2014., Intervention: Patients were categorized into partial versus complete BCG induction (one to five vs five or more instillations). Partial BCG induction subgroups were defined for comparison with the NIMBUS trial., Outcome Measurements and Statistical Analysis: Propensity score-adjusted regression models were used to assess the association of partial BCG induction with risk of recurrence and bladder cancer death., Results and Limitations: Among 540 patients, 114 (21.1%) underwent partial BCG induction. Partial versus complete BCG induction was not significantly associated with the risk of recurrence in HG Ta (cumulative incidence [CIn] 46.6% vs 53.9% at 5 yr, p  =  0.38) or T1 (CIn 47.1% vs 56.7 at 5 yr, p  = 0.19) disease. Similarly, we found no increased risk of bladder cancer death (HG Ta: CIn 4.7%7vs 5.4% at 5 yr, p  = 0.87; T1: CIn 10.0% vs 11.4% at 5 yr, p  =  0.77). NIMBUS-like induction was associated with an increased risk of recurrence in patients with HG Ta disease, although not statistically significant. Unmeasured confounding is a limitation., Conclusions: Cancer outcomes were similar among high-risk NMIBC patients who underwent partial versus complete BCG induction, suggesting that future research is needed to determine how to optimize BCG delivery for the greatest number of patients, especially during global shortages., Patient Summary: Outcomes were similar between patients receiving partial and complete courses of bacillus Calmette-Guérin (BCG) therapy. Future research is needed to determine how to best deliver BCG to the greatest number of patients, particularly during medication shortages.

Adrenal masses are commonly found on radiographic studies performed for unrelated reasons. We report on a case of a non-functioning adrenal mass from which a needle biopsy showed a nonspecific infiltrate of polyclonal plasma cells and small lymphocytes. A definitive diagnosis of the plasma cell variant of Castleman lymphadenopathy was made only after surgical excision. While the hyaline vascular variant of Castleman lymphadenopathy has been identified in adrenal glands, this is the first report of the plasma cell variant in an adrenal mass. This case particularly underscores the importance of an excisional biopsy for proper diagnosis., Competing Interests: No author has any conflict of interest or competing interest with respect to this work., (Published by Elsevier Inc.)

Introduction: Magnetic resonance imaging fusion biopsy is diagnostically superior to transrectal ultrasound guided biopsy for detecting clinically significant prostate cancer. Fusion biopsy has an expanding role at major academic centers. However, the reproducibility of outcomes in the community setting is unknown. Our goal was to determine if there are significant differences in the yield of clinically significant prostate cancer upon implementation of fusion biopsy in the community setting., Methods: We compared biopsy results from the first consecutive 175 patients undergoing fusion biopsy at an academic setting to the first 175 patients undergoing fusion biopsy at a community practice. Patients treated at an academic setting were matched to nonacademic setting treated patients using Mahalonobis distance matching. A treatment effects model was used to evaluate the effect of practice setting on the rate of clinically significant prostate cancer detection., Results: The matching model resulted in 160 community based patients matched to 150 academic based patients. Balance was verified by reduction in standardized differences and variances ratios between samples. Standard errors and the 95% CI were calculated from 3,000 bootstrap samples. Practice setting had no significant effect on clinically significant prostate cancer detection, clinically significant prostate cancer detection by fusion biopsy, upgrading by fusion cores, upgrading by template cores, clinically significant prostate cancer missed by template cores or clinically significant prostate cancer missed by fusion cores., Conclusions: A sample-matched analysis of the first consecutive patients enrolled in fusion biopsy at an academic versus a community setting indicates that practice setting did not have a significant effect on the overall detection of clinically significant prostate cancer. This lends support to the use of fusion biopsy outside of academic centers.

INTRODUCTION Limited information exists regarding parastomal hernia development in bladder cancer patients. The purpose of this investigation was to describe the natural history of parastomal hernias and identify risk factors for hernia development in patients who undergo cystectomy with ileal conduit urinary diversion., Materials and Methods: A retrospective cohort study was performed of bladder cancer patients who underwent cystectomy with ileal conduit urinary diversion between January 1st 2009 and July 31st 2018 at Dartmouth-Hitchcock Medical Center. The primary outcome of interest was the presence of a parastomal hernia as evident on postoperative cross-sectional imaging obtained for disease surveillance., Results: A total of 107 patients were included with a mean age of 70.9 years and 29.9% being female. Parastomal hernias were identified in 68.2% of bladder cancer patients who underwent cystectomy with ileal conduit urinary diversion. Forty percent of patients with a parastomal hernia reported symptoms related to their hernia, while 12.5% underwent operative repair. After multivariate adjustment, patients with a postop body mass index (BMI) > 30 kg/m² (odds ratio [OR]: 21.8, 95% CI: 1.6-305.2) or stage III or IV bladder cancer (OR: 18, 95% CI: 2.1-157.5), had significantly greater odds of parastomal hernia development. Fifty percent of parastomal hernias were identified 1.3 years from surgery, while 75% were identified by 2 years after cystectomy., Conclusion: Parastomal hernias developed in over two-thirds of bladder cancer patients and occurred rapidly following cystectomy and ileal conduit urinary diversion. Greater postoperative BMI and bladder cancer stage were identified as significant risk factors for parastomal hernia development. Significant opportunity exists to reduce morbidity associated with parastomal hernias in this population.

Improving the consistency and reproducibility of bladder cancer prognoses necessitates the development of accurate, predictive prognostic models. Current methods of determining the prognosis of bladder cancer patients rely on manual decision-making, including factors with high intra- and inter-observer variability, such as tumor grade. To advance the long-term prediction of bladder cancer prognoses, we developed and tested a computational model to predict the 10-year overall survival outcome using population-based bladder cancer data, without considering tumor grade classification. The resulted predictive model demonstrated promising performance using a combination of clinical and molecular features, and was also strongly related to patient overall survival in Cox models. Our study suggests that machine learning methods can provide reliable long-term prognoses for bladder cancer patients, without relying on the less consistent tumor grade. If validated in clinical trials, this automated approach could guide and improve personalized management and treatment for bladder cancer patients., (©2020 AMIA - All rights reserved.)

Interpretation of multiparametric magnetic resonance imaging (mpMRI) for prostate cancer diagnosis and staging can be challenging and, in some cases, benign prostate disease can mimic locally advanced malignancy. We present the case of a 57 year-old male with biopsy-proven Gleason 3 + 4 prostate cancer and a preoperative mpMRI showing extraprostatic extension who was later found to have infiltrating malakoplakia on final surgical pathology. This case highlights the importance of recognizing that malakoplakia of the prostate can present as a PI-RADS 5 lesion with extracapsular extension on mpMRI. Such cases can result in wide-excision, non-nerve sparing radical prostatectomies that may be unwarranted., Competing Interests: The author(s) declare(s) that there is no conflict of interest regarding the publication of this article., (© 2020 Published by Elsevier Inc.)

Purpose: To assess the association of low- vs. guideline-recommended high-intensity cystoscopic surveillance with outcomes among patients with high-risk non-muscle invasive bladder cancer (NMIBC)., Materials & Methods: A retrospective cohort study of Veterans Affairs patients diagnosed with high-risk NMIBC between 2005 and 2011 with follow-up through 2014. Patients were categorized by number of surveillance cystoscopies over two years following diagnosis: low- (1-5) vs. high-intensity (6 or more) surveillance. Propensity score adjusted regression models were used to assess the association of low-intensity cystoscopic surveillance with frequency of transurethral resections, and risk of progression to invasive disease and bladder cancer death., Results: Among 1,542 patients, 520 (33.7%) underwent low-intensity cystoscopic surveillance. Patients undergoing low-intensity surveillance had fewer transurethral resections (37 vs. 99 per 100 person-years; p<0.001). Risk of death from bladder cancer did not differ significantly by low (cumulative incidence [CIn] 8.4% [95% CI 6.5-10.9) at 5 years) vs. high-intensity surveillance (CIn 9.1% [95% CI 7.4-11.2) at 5 years, p = 0.61). Low vs. high-intensity surveillance was not associated with increased risk of bladder cancer death among patients with Ta (CIn 5.7% vs. 8.2% at 5 years p = 0.24) or T1 disease at diagnosis (CIn 10.2% vs. 9.1% at 5 years, p = 0.58). Among patients with Ta disease, low-intensity surveillance was associated with decreased risk of progression to invasive disease (T1 or T2) or bladder cancer death (CIn 19.3% vs. 31.3% at 5 years, p = 0.002)., Conclusions: Patients with high-risk NMIBC undergoing low- vs. high-intensity cystoscopic surveillance underwent fewer transurethral resections, but did not experience an increased risk of progression or bladder cancer death. These findings provide a strong rationale for a clinical trial to determine whether low-intensity surveillance is comparable to high-intensity surveillance for cancer control in high-risk NMIBC., Competing Interests: The authors have declared that no competing interests exist.

Background: Among patients diagnosed with non-muscle invasive bladder cancer (NMIBC), 30% to 70% experience recurrences within 6 to 12 years of diagnosis. The need to screen for these events every 3 to 6 months and ultimately annually by cystoscopy makes bladder cancer one of the most expensive malignancies to manage., Objective: The purpose of this study was to identify reproducible prognostic microRNAs in resected non-muscle invasive bladder tumor tissue that are predictive of the recurrent tumor phenotype as potential biomarkers and molecular therapeutic targets., Methods: Two independent cohorts of NMIBC patients were analyzed using a biomarker discovery and validation approach, respectively., Results: miRNA Let-7f-5p showed the strongest association with recurrence across both cohorts. Let-7f-5p levels in urine and plasma were both found to be significantly correlated with levels in tumor tissue. We assessed the therapeutic potential of targeting Lin28, a negative regulator of Let-7f-5p, with small-molecule inhibitor C1632. Lin28 inhibition significantly increased levels of Let-7f-5p expression and led to significant inhibition of viability and migration of HTB-2 cells., Conclusions: We have identified Let-7f-5p as a miRNA biomarker of recurrence in NMIBC tumors. We further demonstrate that targeting Lin28, a negative regulator of Let-7f-5p, represents a novel potential therapeutic opportunity in NMIBC.

Objectives: To examine trends in online search behaviours related to prostate cancer on a national and regional scale using a dominant major search engine., Materials and Methods: Google Trends was queried using the terms 'prostate cancer', 'prostate-specific antigen' (PSA), and 'prostate biopsy' between January 2004 and January 2019. Search volume index (SVI), a measure of relative search volume on Google, was obtained for all terms and examined by region and time period: pre-US Preventive Services Task Force (USPSTF) Grade D draft recommendation on PSA screening; during the active Grade D recommendation; and after publication of the recent Grade C draft recommendation., Results: Online interest in PSA screening differed by time period (P < 0.01). The SVI for PSA screening was greater pre-Grade D draft recommendation (82.7) compared to during the recommendation (74.5), while the SVI for PSA screening was higher post-Grade C draft recommendation (90.4) compared to both prior time periods. Similar results were observed for prostate biopsy and prostate cancer searches. At the US state level, online interest in prostate cancer was highest in South Carolina (SVI 100) and lowest in Hawaii (SVI 64). For prostate cancer treatment options, online interest in cryotherapy, prostatectomy and prostate cancer surgery overall increased, while searches for active surveillance, external beam radiation, brachytherapy and high-intensity focused ultrasonography remained stable., Conclusion: Online interest in prostate cancer has changed over time, particularly in accordance with USPSTF screening guidelines. Google Trends may be a useful tool in tracking public interest in prostate cancer screening, diagnosis, and treatment, especially as it relates to major shifts in practice guidelines., (© 2019 The Authors BJU International © 2019 BJU International Published by John Wiley & Sons Ltd.)

Background: Surveillance recommendations for patients with low-risk, non-muscle-invasive bladder cancer (NMIBC) are based on limited evidence. The objective of this study was to add to the evidence by assessing outcomes after frequent versus recommended cystoscopic surveillance., Methods: This was a retrospective cohort study of patients diagnosed with low-risk (low-grade Ta (AJCC)) NMIBC from 2005 to 2011 with follow-up through 2014 from the Department of Veterans Affairs. Patients were classified as having undergone frequent versus recommended cystoscopic surveillance (>3 vs 1-3 cystoscopies in the first 2 years after diagnosis). By using propensity score-adjusted models, the authors estimated the impact of frequent cystoscopy on the number of transurethral resections, the number of resections without cancer in the specimen, and the risk of progression to muscle-invasive cancer or bladder cancer death., Results: Among 1042 patients, 798 (77%) had more frequent cystoscopy than recommended. In adjusted analyses, the frequent cystoscopy group had twice as many transurethral resections (55 vs 26 per 100 person-years; P < .001) and more than 3 times as many resections without cancer in the specimen (5.7 vs 1.6 per 100 person-years; P < .001). Frequent cystoscopy was not associated with time to progression or bladder cancer death (3% at 5 years in both groups; P = .990)., Conclusions: Frequent cystoscopy among patients with low-risk NMIBC was associated with twice as many transurethral resections and did not decrease the risk for bladder cancer progression or death, supporting current guidelines., (© 2019 American Cancer Society.)

Metastatic embyronal carcinoma to the subcutaneous tissues is rare. Prior cases have occurred in the setting of undiagnosed widely metastatic disease. Here we present the first case of metastatic embyronal cancer to the contralateral subcutaneous inguinal region in the absence of any other sites of metastatic disease., (© 2019 The Authors.)

Objective: To understand cystoscopic surveillance practices among patients with low-risk non-muscle-invasive bladder cancer (NMIBC) within the Department of Veterans Affairs (VA)., Methods: Using a validated natural language processing algorithm, we included patients newly diagnosed with low-risk (ie low-grade Ta) NMIBC from 2005 to 2011 in the VA. Patients were followed until cancer recurrence, death, last contact, or 2 years after diagnosis. Based on guidelines, surveillance overuse was defined as >1 cystoscopy if followed <1 year, >2 cystoscopies if followed 1 to <2 years, or >3 cystoscopies if followed for 2 years. We identified patient, provider, and facility factors associated with overuse using multilevel logistic regression., Results: Overuse occurred in 75% of patients (852/1135) - with an excess of 1846 more cystoscopies performed than recommended. Adjusting for 14 factors, overuse was associated with patient race (odds ratio [OR] 0.49, 95% confidence interval [CI]: 0.28, 0.85 unlisted race vs White), having 2 comorbidities (OR 1.60, 95% CI: 1.00, 2.55 vs no comorbidities), and earlier year of diagnosis (OR 2.50, 95% CI: 1.29, 4.83 for 2005 vs 2011, and OR 2.03, 95% CI: 1.11, 3.69 for 2006 vs 2011). On sensitivity analyses assuming all patients were diagnosed with multifocal or large low-grade tumors (ie, intermediate-risk), overuse would have still occurred in 45% of patients., Conclusion: Overuse of cystoscopy among patients with low-risk NMIBC was common, raising concerns about bladder cancer surveillance cost and quality. However, few factors were associated with overuse. Further qualitative research is needed to identify other determinants of overuse not readily captured in administrative data., (Published by Elsevier Inc.)

Background: The high rate of non-muscle-invasive bladder cancer recurrence is a major challenge in patient management. miRNAs functionally regulate tumor cell proliferation and invasion, and have strong potential as biomarkers because they are robust to degradation. The objective of this project was to identify reproducible prognostic miRNAs in resected non-muscle-invasive bladder tumor tissue that are predictive of the recurrent tumor phenotype., Methods: We utilized patients diagnosed with primary non-muscle-invasive bladder cancer in three independent cohorts for a biomarker discovery/validation approach. Baseline tumor tissue from patients with the clinically challenging, non-muscle-invasive primary low stage (Ta), high grade, and T1 tumors (tumors extending into the lamina propria) comprised the discovery cohort ( n = 38). We isolated the tumor tissue RNA and assessed a panel of approximately 800 miRNAs., Results: miR-26b-5p was the top-ranking prognostic tumor tissue miRNA, with a time-to-recurrence HR 0.043 for levels above versus below median, ( P adj = 0.0003). miR-26b-5p was related to a dose-response reduction in tumor recurrence, and levels above the median were also associated with reduced time-to-progression ( P adj = 0.02). We used two independent longitudinal cohorts that included both low-grade and high-grade Ta and T1 tumors for validation and found a consistent relationship between miR-26b-5p and recurrence and progression., Conclusions: Our results suggest that miR-26b-5p levels may be prognostic for non-muscle-invasive bladder cancer recurrence, and can feasibly be assessed in baseline tumor tissue from a wide variety of clinical settings., Impact: Early identification of those non-muscle-invasive bladder tumor patients with refractory phenotypes would enable individualized treatment and surveillance., (©2019 American Association for Cancer Research.)

We report an approach in diagnostic imaging based on nanoscale-resolution scanning of surfaces of cells collected from body fluids using a recent modality of atomic force microscopy (AFM), subresonance tapping, and machine-leaning analysis. The surface parameters, which are typically used in engineering to describe surfaces, are used to classify cells. The method is applied to the detection of bladder cancer, which is one of the most common human malignancies and the most expensive cancer to treat. The frequent visual examinations of bladder (cytoscopy) required for follow-up are not only uncomfortable for the patient but a serious cost for the health care system. Our method addresses an unmet need in noninvasive and accurate detection of bladder cancer, which may eliminate unnecessary and expensive cystoscopies. The method, which evaluates cells collected from urine, shows 94% diagnostic accuracy when examining five cells per patient's urine sample. It is a statistically significant improvement ( P < 0.05) in diagnostic accuracy compared with the currently used clinical standard, cystoscopy, as verified on 43 control and 25 bladder cancer patients., Competing Interests: Conflict of interest statement: After acceptance of the manuscript in its current form, Tufts University has applied for a patent protection for the AFM machine-learning method described in this paper (invented by I. Sokolov and M. Miljkovic). Other authors declare no conflict of interest.

Objective: To assess geographic variation in cystoscopy rates among women vs men with suspected bladder cancer, lending insight into gender-specific differences in cystoscopic evaluation., Methods: We conducted a cross-sectional study of all fee-for-service Medicare beneficiaries within 306 Hospital Referral Regions (HRRs) who received care in 2014. For each HRR, we calculated the age- and race-adjusted cystoscopy rate for women and men as our primary outcome. The rate was the number of beneficiaries who underwent cystoscopy for bladder cancer symptoms (using procedure and ICD-9 diagnosis codes) divided by all beneficiaries in the HRR. We used the coefficient of variation to compare relative variability of cystoscopy rates., Results: Overall, 173,551 women (n = 14.8 million) and 286,090 men (n = 11.5 million) underwent cystoscopy in 2014. While women received less cystoscopies compared to men (mean 11.0 vs 23.5 per 1000, P < .001), there was greater variation in cystoscopy rates among women (coefficient of variation 27.5 vs 23.5, P = .010). When restricting to ICD-9 codes for hematuria only, women continued to demonstrate greater variation in cystoscopy rates (coefficient of variation 27.8 vs 24.2, P = .022). Findings were robust across larger HRR sizes-thereby removing some random variation seen in smaller HRRs-as well as across years 2010, 2011, 2012, and 2013., Conclusion: Cystoscopy rates are lower in women than men, likely due to their lower bladder cancer incidence. However, there is greater variation in cystoscopy rates among women with symptoms of bladder cancer. This may reflect increased provider uncertainty whether to refer and work-up women with suspected bladder cancer., (Copyright © 2018. Published by Elsevier Inc.)

Importance: Cancer care guidelines recommend aligning surveillance frequency with underlying cancer risk, ie, more frequent surveillance for patients at high vs low risk of cancer recurrence., Objective: To assess the extent to which such risk-aligned surveillance is practiced within US Department of Veterans Affairs facilities by classifying surveillance patterns for low- vs high-risk patients with early-stage bladder cancer., Design Setting and Participants: US national retrospective cohort study of a population-based sample of patients diagnosed with low-risk or high-risk early-stage bladder between January 1, 2005, and December 31, 2011, with follow-up through December 31, 2014. Analyses were performed March 2017 to April 2018. The study included all Veterans Affairs facilities (n = 85) where both low-and high-risk patients were treated., Exposures: Low-risk vs high-risk cancer status, based on definitions from the European Association of Urology risk stratification guidelines and on data extracted from diagnostic pathology reports via validated natural language processing algorithms., Main Outcomes and Measures: Adjusted cystoscopy frequency for low-risk and high-risk patients for each facility, estimated using multilevel modeling., Results: The study included 1278 low-risk and 2115 high-risk patients (median [interquartile range] age, 77 [71-82] years; 99% [3368 of 3393] male). Across facilities, the adjusted frequency of surveillance cystoscopy ranged from 3.7 to 6.2 (mean, 4.8) procedures over 2 years per patient for low-risk patients and from 4.6 to 6.0 (mean, 5.4) procedures over 2 years per patient for high-risk patients. In 70 of 85 facilities, surveillance was performed at a comparable frequency for low- and high-risk patients, differing by less than 1 cystoscopy over 2 years. Surveillance frequency among high-risk patients statistically significantly exceeded surveillance among low-risk patients at only 4 facilities. Across all facilities, surveillance frequencies for low- vs high-risk patients were moderately strongly correlated ( r = 0.52; P < .001)., Conclusions and Relevance: Patients with early-stage bladder cancer undergo cystoscopic surveillance at comparable frequencies regardless of risk. This finding highlights the need to understand barriers to risk-aligned surveillance with the goal of making it easier for clinicians to deliver it in routine practice., Competing Interests: Conflict of Interest Disclosures: Dr Schroeck is site primary investigator (without compensation) for a clinical trial of Vicinium, sponsored by Eleven Biotherapeutics. Mr Seigne owns 100 common stock of Johnson & Johnson. No other disclosures were reported.

A rare condition in itself, acquired hemophilia A, seldom presents as isolated gross hematuria. It is a serious condition with a high mortality rate and thus clinical suspicion followed by prompt diagnosis is imperative (1). In fact, only 8 cases of such presentation of this condition have been reported thus far in the literature. Of these, none describe the initial presentation of hematuria with the inciting event of a kidney stone. We present a case of a 67-year-old man with signs and symptoms of nephrolithiasis accompanied by profuse hematuria, who was subsequently found to have developed expression of factor VIII inhibitor leading to acquired hemophilia A., Competing Interests: Conflict of interest: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Objective: To take the first step toward assembling population-based cohorts of patients with bladder cancer with longitudinal pathology data, we developed and validated a natural language processing (NLP) engine that abstracts pathology data from full-text pathology reports., Methods: Using 600 bladder pathology reports randomly selected from the Department of Veterans Affairs, we developed and validated an NLP engine to abstract data on histology, invasion (presence vs absence and depth), grade, the presence of muscularis propria, and the presence of carcinoma in situ. Our gold standard was based on an independent review of reports by 2 urologists, followed by adjudication. We assessed the NLP performance by calculating the accuracy, the positive predictive value, and the sensitivity. We subsequently applied the NLP engine to pathology reports from 10,725 patients with bladder cancer., Results: When comparing the NLP output to the gold standard, NLP achieved the highest accuracy (0.98) for the presence vs the absence of carcinoma in situ. Accuracy for histology, invasion (presence vs absence), grade, and the presence of muscularis propria ranged from 0.83 to 0.96. The most challenging variable was depth of invasion (accuracy 0.68), with an acceptable positive predictive value for lamina propria (0.82) and for muscularis propria (0.87) invasion. The validated engine was capable of abstracting pathologic characteristics for 99% of the patients with bladder cancer., Conclusion: NLP had high accuracy for 5 of 6 variables and abstracted data for the vast majority of the patients. This now allows for the assembly of population-based cohorts with longitudinal pathology data., (Published by Elsevier Inc.)

Objective: To examine discomfort, anxiety, and preferences for decision making in patients undergoing surveillance cystoscopy for non-muscle-invasive bladder cancer (NMIBC)., Methods: Veterans with a prior diagnosis of NMIBC completed validated survey instruments assessing procedural discomfort, worry, and satisfaction, and were invited to participate in semistructured focus groups about their experience and desire to be involved in surveillance decision making. Focus group transcripts were analyzed qualitatively, using (1) systematic iterative coding, (2) triangulation involving multiple perspectives from urologists and an implementation scientist, and (3) searching and accounting for disconfirming evidence., Results: Twelve patients participated in 3 focus groups. Median number of lifetime cystoscopy procedures was 6.5 (interquartile range 4-10). Based on survey responses, two-thirds of participants (64%) experienced some degree of procedural discomfort or worry, and all participants reported improvement in at least 2 dimensions of overall well-being following cystoscopy. Qualitative analysis of the focus groups indicated that participants experience preprocedural anxiety and worry about their disease. Although many participants did not perceive themselves as having a defined role in decision making surrounding their surveillance care, their preferences to be involved in decision making varied widely, ranging from acceptance of the physician's recommendation, to uncertainty, to dissatisfaction with not being involved more in determining the intensity of surveillance care., Conclusion: Many patients with NMIBC experience discomfort, anxiety, and worry related to disease progression and not only cystoscopy. Although some patients are content to defer surveillance decisions to their physicians, others prefer to be more involved. Future work should focus on defining patient-centered approaches to surveillance decision making., (Published by Elsevier Inc.)

Background: Despite the high prevalence of bladder cancer, research on optimal bladder cancer care is limited. One way to advance observational research on care is to use linked data from multiple sources. Such big data research can provide real-world details of care and outcomes across a large number of patients. We assembled and validated such data including (1) administrative data from the Department of Veterans Affairs (VA), (2) Medicare claims, (3) data abstracted by tumor registrars, (4) data abstracted via chart review from the national electronic health record, and (5) full text pathology reports., Methods: Based on these combined data, we used administrative data to identify patients with newly diagnosed bladder cancer who received care in the VA. To validate these data, we first compared the diagnosis date from the administrative data to that from the tumor registry. Second, we measured accuracy of identifying bladder cancer care in VA administrative data, using a random chart review (n = 100) as gold standard. Lastly, we compared the proportion of patients who received bladder cancer care among those who did versus did not have full text bladder pathology reports available, expecting that those with reports are significantly more likely to receive care in VA., Results: Out of 26,675 patients, 11,323 (42%) had tumor registry data available. 90% of these patients had a difference of 90 days or less between the diagnosis dates from administrative and registry data. Among 100 patients selected for chart review, 59 received bladder cancer care in VA, 58 of which were correctly identified using administrative data (sensitivity 98%, specificity 90%). Receipt of bladder cancer care was substantially more common among those who did versus did not have bladder pathology available (96% vs. 43%, p < 0.001)., Conclusion: Merging administrative with electronic health record and pathology data offers new possibilities to validate the use of administrative data in bladder cancer research.

Objective: To evaluate trends in prostate biopsy and cancer diagnosis at a center with conservative screening practices in the pre- and post-2012 era. More restrictive prostate-specific antigen (PSA) screening guidelines have led to lower rates of screening, biopsy, and diagnosis of prostate cancer. It is not clear, however, how regions with low baseline screening rates (the Lebanon, New Hampshire hospital referral region centered on Dartmouth-Hitchcock Medical Center had the lowest rate of screening among Medicare patients in 2012) have responded to these guidelines., Methods: We retrospectively analyzed patients who underwent prostate biopsy from January 2011 to March 2016. Demographic and clinical characteristics were analyzed by time. Multivariable analysis assessed for factors associated with higher grade cancer., Results: There were 614 prostate biopsies were performed. PSA at biopsy increased with time (7.2 in 2011 vs 10.1 in 2015, P = .0085); age did not. There was a stable proportion of benign findings; proportions of low-grade disease decreased, whereas intermediate- and high-grade disease increased (2011 vs 2015: 21.1% vs 10.8% Gleason 3 + 3, 32.9% vs 43.3% ≥ Gleason 3 + 4, P = .0454). Factors predictive of higher grade disease included abnormal digital examination (odds ratio [OR] 2.19, P = .0076), higher PSA (OR 1.09, P = .0040), and later biopsy date (OR 1.01, P = .0469)., Conclusion: In an environment of conservative baseline screening practices, there has been a shift in prostate biopsy criteria and outcomes, namely a rising PSA threshold for biopsy and a 50% decrease in the diagnosis of low-grade disease. Additional study is needed to ensure these trends are favorably impacting the quality of care., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Active surveillance is a management strategy for men diagnosed with early-stage, low-risk prostate cancer in which their cancer is monitored and treatment is delayed. This study investigated the primary coping mechanisms for men following the active surveillance treatment plan, with a specific focus on how these men interact with their social network as they negotiate the stress and uncertainty of their diagnosis and treatment approach., Methods: Thematic analysis of semi-structured interviews at two academic institutions located in the northeastern US. Participants include 15 men diagnosed with low-risk prostate cancer following active surveillance., Results: The decision to follow active surveillance reflects the desire to avoid potentially life-altering side effects associated with active treatment options. Men on active surveillance cope with their prostate cancer diagnosis by both maintaining a sense of control over their daily lives, as well as relying on the support provided them by their social networks and the medical community. Social networks support men on active surveillance by encouraging lifestyle changes and serving as a resource to discuss and ease cancer-related stress., Conclusions: Support systems for men with low-risk prostate cancer do not always interface directly with the medical community. Spousal and social support play important roles in helping men understand and accept their prostate cancer diagnosis and chosen care plan. It may be beneficial to highlight the role of social support in interventions targeting the psychosocial health of men on active surveillance.

Objective: To compare newly diagnosed localized prostate cancer patients who did and did not view a decision aid (DA) on their knowledge of the rationale for active surveillance (AS)., Methods: A cross-sectional study was conducted among 452 newly diagnosed low-risk localized prostate cancer patients. Patients were mailed the video/DVD DA and completed a web-based questionnaire that contained two multiple choice questions assessing knowledge of the rationale for AS. Multivariable logistic regression was used to estimate the effect of the DA on knowledge of the rationale for AS., Results: Patients who watched the DA were more likely to correctly respond to each rationale for AS question; both comparisons were statistically significant. After adjustment, men who viewed the DA were 2.9 times as likely to correctly respond to both rationale for AS questions than men who did not view the DA (95% CI: 1.9-4.5)., Conclusion: Patients who viewed a DA better understand the reasons why AS is a viable treatment option for localized prostate cancer than patients who did not view a DA., Practice Implications: Urology clinics and practices should implement the utilization of a treatment DA for newly diagnosed, localized prostate cancer prior to the patients' first cancer consultation., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Benefits of early diagnosis and treatment remain debatable for men with low-risk prostate cancer. Active surveillance (AS) is an alternative to treatment. The goal of AS is to identify patients whose cancer is progressing rapidly while avoiding treatment in the majority of patients. The purpose of this study was to explore cognitive and affective representations of AS within a clinical environment that promotes AS a viable option for men with low-risk prostate cancer. Participants included patients for whom AS and active treatment were equally viable options, as well as practitioners who were involved in consultations for prostate cancer. Data were generated from semistructured interviews and audits of consultation notes and were analyzed using thematic analysis. Nineteen patients and 16 practitioners completed a semistructured interview. Patients generally viewed AS as a temporary strategy that was largely equated with inaction. There was variation in the degree to which inaction was viewed as warranted or favorable. Patient perceptions of AS were generally malleable and able to be influenced by information from trusted sources. Encouraging slow deliberation and multiple consultations may facilitate greater understanding and acceptance of AS as a viable treatment option for low-risk prostate cancer.

Objective: To assess a large national sample of bladder cancer pathology reports to determine if they contained the components necessary for clinical decision-making., Methods: We examined a random sample of 507 bladder cancer pathology reports from the national Department of Veterans Affairs Corporate Data Warehouse to assess whether each included information on the 4 report components explicitly recommended by the College of American Pathologists' protocol for the examination of such specimens: histology, grade, presence vs absence of muscularis propria in the specimen, and microscopic extent. We then assessed variation in the proportion of reports lacking at least 1 component across Department of Veterans Affairs facilities., Results: One hundred eight of 507 reports (21%) lacked at least 1 of the 4 components, with microscopic extent and presence vs absence of muscularis propria in the specimen most commonly missing (each in 11% of reports). There was wide variation across facilities in the proportion of reports lacking at least 1 component, ranging from 0% to 80%., Conclusion: One-fifth of bladder cancer pathology reports lack information needed for clinical decision-making. The wide variation in incomplete report rates across facilities implies that some facilities already have implemented best practices assuring complete reporting whereas others have room for improvement. Future work to better understand barriers and facilitators of complete reporting may lead to interventions that improve bladder cancer care., (Published by Elsevier Inc.)

Purpose: Although associated with an overall favorable survival rate, the heterogeneity of non-muscle invasive bladder cancer (NMIBC) affects patients' rates of recurrence and progression. Risk stratification should influence evaluation, treatment and surveillance. This guideline attempts to provide a clinical framework for the management of NMIBC., Materials and Methods: A systematic review utilized research from the Agency for Healthcare Research and Quality (AHRQ) and additional supplementation by the authors and consultant methodologists. Evidence-based statements were based on body of evidence strength Grade A, B, or C and were designated as Strong, Moderate, and Conditional Recommendations with additional statements presented in the form of Clinical Principles or Expert Opinions.(1) RESULTS: A risk-stratified approach categorizes patients into broad groups of low-, intermediate-, and high-risk. Importantly, the evaluation and treatment algorithm takes into account tumor characteristics and uniquely considers a patient's response to therapy. The 38 statements vary in level of evidence, but none include Grade A evidence, and many were Grade C., Conclusion: The intensity and scope of care for NMIBC should focus on patient, disease, and treatment response characteristics. This guideline attempts to improve a clinician's ability to evaluate and treat each patient, but higher quality evidence in future trials will be essential to improve level of care for these patients., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: MicroRNAs have been identified as potential cancer biomarkers due to their presence and stability in many body fluids including urine and plasma, but the relationship of the pattern of expression of these messengers across various biological media has not been addressed and could provide important information in order to translate these biomarkers for epidemiologic or clinical use., Methods: We analyzed microRNA of matched FFPE-tumor tissue, plasma, urine exosomes (n = 16) and WBCs (n = 11) from patients with bladder cancer, using Nanostring miRNA assays and droplet digital PCR for validation. Pearson correlations were used to compare expression between media., Results: Numerous microRNAs were detected and overlapping from specific bio-specimen sources. MiR-4454 and miR-21 overexpression was found in three sources: tumor, WBCs and urine. Additionally, miR-15b-5p, miR-126-3p, miR-93-5p, and miR-150-5p were common to tumor/WBCs, while miR-720/3007a, miR-205, miR-200c-3p and miR-29b-3p common to tumor/urine. Significant associations were noted between the log-adjusted average miRNA counts in tumor vs. WBCs (r = 0.418 p < 0.001), and tumor vs. urine (r = 0.38 p < 0.001). No association was seen tumor vs. plasma exosome miRs (r = 0.07 p = 0.06)., Conclusions: MicroRNA profiling from matched samples in patients shows a significant number of microRNAs up regulated in bladder tumors are identifiable in urine exosomes and WBCs of the same patient, but not in blood plasma. This study demonstrated varying relationships between miRNA detected in biological media from the same patient, and serves to inform the potential of urine-based microRNAs as biomarkers for bladder cancer and potentially other malignancies.

Background: Intraoperative ultrasonography has proven to be a useful tool for tumor identification during robot-assisted laparoscopic partial nephrectomy (RALPN). However, its utility is limited in renal tumors that are completely endophytic and isoechoic in nature. We present a novel approach to intraoperative tumor identification using preoperative percutaneous intratumoral embolization coil placement that may be utilized in the management of such cases., Case Presentation: A 42-year-old Caucasian male was referred with an incidentally discovered right renal mass that was posterior and completely endophytic. He desired a RALPN; however, preoperative renal ultrasound demonstrated an isoechoic lesion. Thus, the patient underwent preoperative image-guided placement of an embolization coil within the tumor. This facilitated identification of the tumor intraoperatively using intracorporeal ultrasound centered on the coil and enabled resection with negative margins., Conclusion: Utilizing a novel approach analogous to preoperative localization of other solid malignancies, such as breast cancer, we were able to effectively identify and resect an isoechoic renal mass during RALPN.

With the rise in detection of incidental renal masses on imaging, there has been a commensurate rise in the use of percutaneous biopsies for evaluation of these tumours. Tumour tract seeding had previously been one of the most feared complications of percutaneous biopsy of renal cell carcinoma (RCC). Recently, less emphasis has been placed on this complication, with the assertion that it has only been reported eight times in literature, and thus must be exceedingly rare. However, we report two cases of tumour tract seeding associated with percutaneous biopsy and treatment of RCC over a short time period at a single institution. This report challenges the current extremely low estimates of the frequency of this complication and calls for a more realistic assessment.

Bladder cancer is the fourth most common cancer among men in the United States and more than half of patients experience recurrences within 5 years after initial diagnosis. Additional clinically informative and actionable biomarkers of the recurrent bladder cancer phenotypes are needed to improve screening and molecular therapeutic approaches for recurrence prevention. MicroRNA-34a (miR-34a) is a short noncoding regulatory RNA with tumor suppressive attributes. We leveraged our unique, large, population-based prognostic study of bladder cancer in New Hampshire, United States to evaluate miR-34a expression levels in individual tumor cells to assess prognostic value. We collected detailed exposure and medical history data, as well as tumor tissue specimens from bladder patients and followed them long-term for recurrence, progression and survival. Fluorescence-based in situ hybridization assays were performed on urothelial carcinoma tissue specimens (n = 229). A larger proportion of the nonmuscle invasive tumors had high levels of miR-34a within the carcinoma cells compared to those tumors that were muscle invasive. Patients with high miR-34a levels in their baseline nonmuscle invasive tumors experienced lower risks of recurrence (adjusted hazard ratio 0.57, 95% confidence interval 0.34-0.93). Consistent with these observations, we demonstrated a functional tumor suppressive role for miR-34a in cultured urothelial cells, including reduced matrigel invasion and growth in soft agar. Our results highlight the need for further clinical studies of miR-34a as a guide for recurrence screening and as a possible candidate therapeutic target in the bladder., (© 2014 UICC.)

Immunoglobulin G4-related disease is a fibroinflammatory condition of unclear etiology that can present with inflammatory changes and enlargement of a wide variety of organs, most commonly in the gastrointestinal tract. A diagnosis requires an elevated serum immunoglobulin G4 concentration and a tissue biopsy showing a dense plasma cell infiltrate with an increased percentage of immunoglobulin G4+ plasma cells. This disease infrequently presents in the genitourinary tract, and as such might be unfamiliar to and potentially overlooked by urologists. Here we present the third reported case of immunoglobulin G4-related disease manifesting as a mass in the urinary bladder., (© 2015 The Japanese Urological Association.)

Objectives: There are numerous reports describing the use of radiofrequency ablation (RFA) to treat renal cell carcinoma. Many series, however, describe heterogeneous populations, lack histologic descriptions, use various RFA systems, and indicate tumor destruction by different ablation end points. This study examined the outcomes of computed tomography-guided, impedance-based RFA of biopsy-proven renal cell carcinoma clinically staged as T1a with a minimum of 1 year of postablation follow-up., Methods and Materials: This retrospective study identified all consecutive patients who had undergone renal RFA since May 2005 at our institution. Patients without biopsy-proven renal cell carcinoma (RCCa) were excluded. Of the patients who met these criteria, evaluation was limited to patients with a minimum of 12 months of follow-up. Data collected from the patients' electronic medical and radiologic records included demographic data, tumor-related data, procedural details, and clinical follow-up visits., Results: A total of 39 patients (46 lesions) met the inclusion criteria. The mean tumor diameter was 2.6 cm (range: 1.2-4.0 cm). The most common histologies were clear cell (n = 27) and papillary (n = 16) renal cancer. The lesion location was equally divided between upper pole (n = 16), middle pole (n = 16), and lower pole (n = 14). Overall, 83% of the tumors were exophytic. No residual or recurrent enhancing mass was identified in the ablation bed on post-RFA imaging during the mean follow-up period of 35.3 months (range: 12-83). All patients were treated in a single encounter and no lesion required a second ablation; technical success (absence of residual tumor) on the initial post-RFA imaging study was 46 of 46 (100%). Clinical success was achieved in 45 of 46 lesions (98%); residual, viable tumor was found in a pretransplant nephrectomy specimen on postprocedure day 127. The mean cancer-free survival was 36.2 months. Comparison of preablation and postablation renal function found no statistically significant change., Conclusions: The consistent outcomes in our post-RFA imaging and clinical surveillance allow us to offer image-guided ablation to patients with T1a RCCa as a valid treatment option offering long-term cancer-free survival. Impedance-based RFA in a carefully selected patient population with T1a RCCa is a reliable treatment option, with disease-free survival rates that are comparable to partial nephrectomy., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: Dysregulation of the hedgehog signaling pathway has been linked to the development and progression of a variety of different human tumors including cancers of the skin, brain, colon, prostate, blood, and pancreas. We assessed the clinicopathological factors that are potentially related to expression of Gli1, the transcription factor that is thought to be the most reliable marker of hedgehog pathway activation in bladder cancer., Methods: Bladder cancer cases were identified from the New Hampshire State Cancer Registry as histologically confirmed primary bladder cancer diagnosed between January 1, 2002, and July 31, 2004. Immunohistochemical analysis was performed on a tissue microarray to detect Gli1 and p53 expression in these bladder tumors. We computed odds ratios (ORs) and their 95% CIs for Gli1 positivity for pathological category using T category (from TNM), invasiveness, and grade with both the World Health Organization 1973 and World Health Organization International Society of Urological Pathology criteria. We calculated hazard ratios and their 95% CI for Gli1 positivity and recurrence for both Ta-category and invasive bladder tumors (T1+)., Results: A total of 194 men and 67 women, whose tumors were assessable for Gli1 staining, were included in the study. No appreciable differences in Gli1 staining were noted by sex, age, smoking status, or high-risk occupation. Ta-category tumors were more likely to stain for Gli1 as compared with T1-category tumors (adjusted OR = 0.38, CI: 0.17-0.87). Similarly, low-grade (grades 1-2) tumors were more likely to stain for Gli1 as compared with high-grade tumors (grade 3) (adjusted OR = 0.44, CI: 0.21-0.93). In a Cox proportional hazards regression analysis, non-muscle-invasive bladder tumors expressing Gli1 were less likely to recur (adjusted hazard ratio = 0.48; CI: 0.28-0.82; P<0.05) than those in which Gli1 was absent., Conclusion: Our findings indicate that Gli1 expression may be a marker of low-stage, low-grade bladder tumors and an indicator of a reduced risk of recurrence in this group., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The presence and depth of urothelial cancer involvement in the prostatic urethra can significantly affect the management of a patient with non-muscle invasive bladder cancer. This article presents an overview of the incidence, diagnosis, management, and follow-up of urothelial cancer., (Copyright © 2013 Elsevier Inc. All rights reserved.)