Perioperative Immune Checkpoint Blockade for Muscle-Invasive and Metastatic Bladder Cancer.

Checkpoint inhibitors offer promise in treating muscle-invasive and metastatic bladder cancer, but the optimal timing of their administration-neoadjuvant or adjuvant-remains unclear. To determine the efficacy of combining checkpoint inhibition with standard cisplatin-based chemotherapy, we conducted a phase II trial of neoadjuvant anti-PD-1 (αPD-1) and anti-CTLA-4 (αCTLA-4), in combination with cisplatin-gemcitabine, for patients with muscle-invasive bladder cancer prior to radical cystectomy. In addition, a novel murine model of spontaneous metastatic bladder cancer was used to compare the efficacy of neoadjuvant versus adjuvant anti-PD-L1 (αPD-L1) treatment. The clinical trial was closed prematurely due to the industry's withdrawal of drug provision. Adverse events were observed in all patients; however, serious adverse events were not observed in any patient. A complete pathologic response was observed in 50% of the 4 patients enrolled. Response to treatment was significantly associated with elevated urinary T cells including CD8+ and IFNγ+ CD4+ T cells, suggesting potential reinforcement of immune responses by neoadjuvant αPD-1 and αCTLA-4 against bladder tumor cells. These findings suggest that combining chemotherapy and immunotherapy in the neoadjuvant setting could be safe. However, the complete response rate of this four-drug regimen was modest and emphasizes the need for randomized controlled trials to properly assess immunotherapy efficacy in the neoadjuvant setting. In corresponding murine studies, the MB49-met model consistently displayed widespread metastasis, including tumor growth in the lungs, liver, and bowel mesentery, within 20 days of subcutaneous transplantation. Mice receiving surgery plus neoadjuvant αPD-L1 or adjuvant αPD-L1 exhibited improved survival compared to those receiving only αPD-L1. However, no significant difference in survival was observed between the neoadjuvant and adjuvant αPD-L1 cohorts. Furthermore, the timing of neoadjuvant therapy administration (early vs. late) did not significantly impact survival. This study highlights the potential of perioperative immunotherapy in the treatment of locally advanced and metastatic bladder cancer.

Open versus minimally invasive nephroureterectomy in octogenarians: An analysis of surgical approach trends, outcomes, and survival analysis with propensity matching.

INTRODUCTION: Upper tract urothelial carcinoma (UTUC) is a rare disease accounting only for 5%-10% of urothelial carcinoma (UC). For localized high-risk disease, radical nephroureterectomy (RNU) is the standard of care. While minimally invasive (MIS) RNU has not been shown to decisively improve overall survival (OS) compared to open surgery, MIS RNU has been associated with reduced hospital length of stay (LOS), blood transfusion requirements and improved recovery, which are important considerations when treating older patients. The purpose of this study is to examine trends in surgical approach selection and outcomes of open vs. MIS RNU in patients aged ≥80 years. METHODS: Using the National Cancer Database (NCDB), patients aged ≥80 years who underwent open or MIS (either robotic or laparoscopic) RNU were identified from 2010 to 2019. Demographic, patient-related, and disease-specific factors associated with either open or MIS RNU were assessed using multivariate logistic regression models. Survival analysis was conducted using Kaplan-Meier plots and Cox-proportional hazard regression. Inverse probability of treatment weighting (IPTW) was utilized to adjust for confounding variables. Survival analysis was also conducted on the IPTW adjusted cohort using Kaplan-Meier plots and Cox-proportional hazard regression. RESULTS: 5,687 patients were identified, with 1,431 (25.2%) and 4,256 (74.8%) patients undergoing open and MIS RNU respectively. The proportion of RNU performed robotically has increased from 12.5% in 2010 to 50.4% in 2019. MIS was associated with a shorter hospital LOS (4.7 days versus 5.9 days, SMD 23.7%). Multivariate analysis revealed that MIS was associated with a significant reduction in 90-day mortality (OR: 0.571; 95%CI: 0.34-0.96, P = 0.033) and improved median OS (53.8 months [95%CI: 50.9-56.9] vs 42.35 months [95%CI: 38.6-46.8], P < 0.001) compared to open surgery. IPTW-adjusted survival analysis revealed improved median OS with MIS when compared to open surgery, with a survival benefit of 46.1 months (95%CI: 40.2-52.4 months) versus 37.7 months (95%CI: 32.6-46.5 months, P = 0.0034) respectively. IPTW-adjusted cox proportional hazard analysis demonstrated that MIS was significantly associated with reduced mortality (HR 0.76, 95%CI: 0.66-0.87, P < 0.001). CONCLUSION: In octogenarians undergoing RNU, MIS is associated with improved median OS and 90-day mortality.

Current Trends and Challenges of Microbiome Research in Prostate Cancer.

PURPOSE OF REVIEW: The role of the gut microbiome in prostate cancer is an emerging area of research interest. However, no single causative organism has yet been identified. The goal of this paper is to examine the role of the microbiome in prostate cancer and summarize the challenges relating to methodology in specimen collection, sequencing technology, and interpretation of results. RECENT FINDINGS: Significant heterogeneity still exists in methodology for stool sampling/storage, preservative options, DNA extraction, and sequencing database selection/in silico processing. Debate persists over primer choice in amplicon sequencing as well as optimal methods for data normalization. Statistical methods for longitudinal microbiome analysis continue to undergo refinement. While standardization of methodology may help yield more consistent results for organism identification in prostate cancer, this is a difficult task due to considerable procedural variation at each step in the process. Further reproducibility and methodology research is required.

Contemporary Trends of Holmium Laser Enucleation of the Prostate Utilization in the United States: A Comprehensive Analysis Using the National Surgical Quality Improvement Program Database (2011-2020).

Introduction: The most recent American Urological Association (AUA) Guidelines advocated laser enucleation of the prostate (LEP) as a size-independent surgical option for benign prostatic hyperplasia (BPH). Despite its endorsement by AUA and the growing body of evidence supporting its safety and efficacy, the utilization of LEP remains limited in the United States. This study aimed to evaluate the utilization trends and perioperative outcomes of LEP compared with other surgical procedures used for BPH management. Methods: A retrospective cohort analysis was performed using American College of Surgeons National Surgical Quality Improvement Program data from 2011 to 2020. Patients undergoing prostatectomy for BPH were identified using specific current procedural terminology (CPT) codes. Baseline demographic data, preoperative risk factors, and postoperative outcomes were collected. Multivariable logistic regression was employed to assess predictors of holmium laser enucleation of the prostate (HoLEP) utilization and postoperative complications. Results: Out of 8,415,549 patients, 95,144 underwent prostatectomy for BPH. Procedures included HoLEP 5305 cases, transurethral resection of the prostate (TURP) 57,803 cases, repeated TURP (re-TURP) 5549 cases, photoselective vaporization of the prostate (PVP) 23,739 cases, and simple prostatectomy 2748 cases. HoLEP utilization showed a gradual increase, from 4.8% in 2015 to 7.6% in 2020. Multivariable regression revealed that HoLEP selection significantly increased from 2016 to 2020 (odds ratio [OR]: 1.251, p < 0.001), and there was less likelihood of HoLEP selection for African American patients (OR: 0.752, p < 0.001). HoLEP had significantly lower complication rates, including urinary tract infections, blood transfusions, 30-day readmission, and reoperation. Conclusion: Despite underutilization, the adoption of HoLEP has slightly increased since 2015, rising from 4.8% in 2015 to 7.6% in 2020. The underutilization could be attributed to a lack of availability and the steep learning curve.

Isolated Red Patches Seen During Endoscopic Surveillance of Bladder Cancer: Incidence of Malignancy and When Should We Biopsy?

OBJECTIVE: To establish whether the regular biopsy of red patches (RPs) seen during endoscopic surveillance for bladder cancer is worthwhile and determine a suitable time frame for repeat biopsy of prior histologically benign persistent RPs in patients on endoscopic surveillance for bladder cancer. PATIENTS AND METHODS: Four thousand eight hundred five flexible cystoscopy (FC) reports over a 12-month period were retrospectively reviewed at a United Kingdom tertiary teaching hospital and those undergoing cystoscopic surveillance for bladder cancer and found to have solitary RPs at FC were included in the study. A proportion of these cases had biopsies taken for histopathologic analysis. RESULTS: Two hundred forty-one FC performed on 183 patients on endoscopic surveillance for bladder cancer had RPs and 120 (49.8%) of them had previous intravesical Bacillus Calmette-Guerin therapy. Eighty-five patients (35.3%) underwent biopsy of the RP. Malignancy was found in 20 biopsies (23.5%), of which, 11 out of 20 (55%) were carcinoma in-situ. Sixteen of these recurrences were biopsied previously, of which 11 (68.8%) were benign at last biopsy, 6 of which were in the last 12 months. The remaining four recurrences had no previous biopsy. No cases of malignancy were identified in patients with low-risk bladder cancer. CONCLUSION: We recommend the biopsy of all RPs found during endoscopic surveillance of patients with intermediate-/high-risk bladder cancer due to the significant incidence of malignant recurrence identified, particularly if no biopsy has been performed within the previous 12 months. This is independent of previous biopsy histology.