Matched analysis of detailed peripheral blood and tumor immune microenvironment profiles in bladder cancer.

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.

Bladder cancer and treatment outcomes depend on the immune profiles in the tumor and blood. Our study, using DNA methylation cytometry, measured immune cell proportions in both areas. Patients were grouped based on immune status and consensus clustering. Results showed distinct immune compositions in the tumor, but not in blood, for hot and cold groups. Consensus clustering revealed two patient clusters with differing immune compositions in both tumor and blood. This detailed immune profiling highlights the importance of understanding the complex interplay between tumor and systemic immunity in bladder cancer patients.

Genome-Scale Methylation Analysis Identifies Immune Profiles and Age Acceleration Associations with Bladder Cancer Outcomes.

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.

Reasons for Long-term Opioid Prescriptions After Guideline-directed Opioid Prescribing and Excess Opioid Pill Disposal.

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.

Ileal Conduit Versus Continent Urinary Diversion in Radical Cystectomy: A Retrospective Cohort Study of 30-day Complications, Readmissions, and Mortality.

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.

Prophylactic Parastomal Mesh Sublay at the Time of Ileal Conduit: Surgical Technique.

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.

A particle filter approach to dynamic kidney pose estimation in robotic surgical exposure.

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.

Immune profiles and DNA methylation alterations related with non-muscle-invasive bladder cancer outcomes.

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.

Diet Quality and Survival in a Population-Based Bladder Cancer Study.

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.

Do commonly used prostate medications alter prostate MRI and fusion biopsy performance?

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.

Partial Versus Complete Bacillus Calmette-Guérin Intravesical Therapy and Bladder Cancer Outcomes in High-risk Non-muscle-invasive Bladder Cancer: Is NIMBUS the Full Story?

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.

IL-7 expands lymphocyte populations and enhances immune responses to sipuleucel-T in patients with metastatic castration-resistant prostate cancer (mCRPC).

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, 3H-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 CD56bright 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 CD56bright 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.

Plasma cell variant of Castleman lymphadenopathy presenting as an adrenal mass.

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.

Initial Experience of Magnetic Resonance Imaging Fusion Biopsy in the Community Setting.

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.

Parastomal hernia development after cystectomy and ileal conduit for bladder cancer: results from the Dartmouth ileal conduit enhancement (DICE) project.

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.

Identification of Let-7f-5p as a novel biomarker of recurrence in non-muscle invasive bladder cancer.

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.

A Machine Learning Approach for Long-Term Prognosis of Bladder Cancer based on Clinical and Molecular Features.

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.

Mischievous malakoplakia: A potential pitfall of mpMRI of the prostate?

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.

The impact of low- versus high-intensity surveillance cystoscopy on surgical care and cancer outcomes in patients with high-risk non-muscle-invasive bladder cancer (NMIBC).

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.