Phase 1 clinical trial evaluating safety, bioavailability, and gut microbiome with a combination of curcumin and ursolic acid in lipid enhanced capsules.

As screening strategies employ better biomarkers and genetics to identify individuals at an increased risk of prostate cancer, there are currently no chemotherapeutic prevention strategies. With any chemoprevention strategy, the population will be younger and healthier; therefore, they will be less tolerant of side effects. This study translated findings from screening a natural product library and pre-clinical evaluation of curcumin (CURC) in combination with ursolic acid (UA) in prostate cancer models. After manufacturing capsules for each compound, 18 subjects were enrolled. The study used a 3 × 3 phase 1 clinical trial to evaluate CURC (1200 mg/day) and UA (300 mg/day) alone and in combination over a 2-week period with endpoints of safety, bioavailability, and microbiome alterations. After enrolling six subjects in each arm, we found no grade 3 or 4 events and only minor changes in the safety laboratory values. In the pooled analysis of groups, we noted a statistically significant difference between median serum levels of UA when administered alone vs administered in the combination (2.7 ng/mL vs 43.8 ng/mL, p = 0.03). Individuals receiving the combination also had a favorable impact on gut microbiome status and a reduction in "microbiome score" predictive of prostate cancer risk.

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.

Impact of rural residence on the presentation, management and survival of patients with non-metastatic muscle-invasive bladder carcinoma.

PURPOSE: To assess the impact of rural and remote residence on the receipt of guidelines-recommended treatment, quality of treatment and overall survival (OS) in patients with non-metastatic muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: Patients with MIBC were identified using National Cancer Database. Patients were classified into three residential areas. Logistic regression models were used to assess associations between geographic residence and receipt of radical cystectomy (RC) or chemoradiation therapy (CRT). Models were fitted to assess quality benchmarks of RC and CRT. RESULTS: We identified 71,395 patients. Of those 58,874 (82.5%) were living in Metro areas, 8,534 (11.9%) in urban-rural adjacent (URA), and 3,987 (5.6%) in urban-rural remote to metro area (URR). URR residence was significantly associated with poor OS compared to URA and Metro residence (HR 0.87, 95% CI 0.81-0.94 and HR 0.90, 95% CI 0.87-0.93, p<0.001). There was no difference in the likelihood of receiving RC and CRT among different residential areas. Among patients who underwent RC; individuals living in URR were less likely to receive neoadjuvant chemotherapy and adequate lymph node dissection, and had a higher probability of positive surgical margin than those living in metro areas. For those who received CRT; individuals living in Metro areas were more likely to receive concomitant systemic therapy compared to URR. CONCLUSIONS: Rural residence is associated with lower OS for MIBC patients and less likelihood of meeting quality benchmarks for RC and CRT. This data should be used to guide further health policy and allocation of resources for rural population.

Robot-assisted retroperitoneal lymph node dissection: a systematic review of perioperative outcomes.

OBJECTIVE: To assess the safety and feasibility of robot-assisted retroperitoneal lymph node dissection (R-RPLND) and to compare the perioperative outcomes of R-RPLND with open RPLND (O-RPLND), as RPLND forms an integral part of the management of testis cancer and R-RPLND is a minimally invasive treatment option for this disease. MATERIALS AND METHODS: The PubMed® , Scopus® , Cochrane Central Register of Controlled Trials, and Web of Science™ databases were searched for studies reporting perioperative outcomes of primary and post-chemotherapy R-RPLND and studies comparing R-RPLND with O-RPLND. RESULTS: The search yielded 42 articles describing R-RPLND, including five comparative studies. The systematic review included 4222 patients (single-arm studies, n = 459; comparative studies, n = 3763). Of 459 patients in the single-arm studies, 271 underwent primary R-RPLND and 188 underwent post-chemotherapy R-RPLND. For primary R-RPLND, the operative time ranged from 175 to 540 min and the major complication rate was 4.1%. For post-chemotherapy R-RPLND, the operative time ranged from 134 to 550 min and the major complication rate was 8.5%. The conversion rate to open surgery was 2.2% in primary R-RPLND and 9.0% in post-chemotherapy R-RPLND. In comparison with O-RPLND, R-RPLND was associated with a lower transfusion rate (14.5% vs 0.9%, P < 0.001) and a lower complication rate (18.5% vs 7.8%, P = 0.002). CONCLUSION: Robot-assisted RPLND has acceptable perioperative outcomes in both the primary and post-chemotherapy settings but a notable rate of conversion to open surgery in the post-chemotherapy setting. Compared with O-RPLND, R-RPLND is associated with a lower transfusion rate and fewer overall complications. Given the potential impact of selection bias, the optimal patient selection criteria for R-RPLND remain to be elucidated.

Patency outcomes of primary inferior vena cava repair in radical nephrectomy and tumor thrombectomy.

OBJECTIVE: The reconstruction of inferior vena cava (IVC) during radical nephrectomy and venous tumor thrombectomy (RN-VTT) is mostly performed with primary repair or with a patch/graft. We sought to systematically evaluate the outcomes of IVC patency over short- to intermediate-term follow-up for patients undergoing primary repair of IVC and to assess the association with survival. METHODS: A retrospective review of patients undergoing RN-VTT between January 2013 and August 2018 was conducted. Patients were followed until death, last available follow-up, or March 2022. The patency outcomes and IVC diameters were studied using follow-up cross-sectional imaging. The χ2 test, Student t test, and Kaplan-Meier survival analysis were used. RESULTS: Seventy-seven patients were included. The mean age was 59.2 ± 12.2 years and 45.4% had Mayo classification level III thrombus or higher. At a median follow-up of 36.5 months (13.3-60.7 months), the 3-year overall survival (OS) was 64%. Sixty patients underwent primary repair of the IVC and 48 of these patients were assessed for IVC patency. Ten patients (20.8%) developed caval occlusion, either from recurrent tumor (8.3%), new-onset bland thrombus (8.3%), or stenosis (4.2). The IVC patency seemed to be a significant predictor of OS (hazard ratio, 2.85; P = .021). Although the IVC diameters decreased significantly at the 3-month postoperative scan at the infrarenal (P = .019), renal (P < .001), and suprarenal (P < .001) levels, they did not decrease further on long-term follow-up imaging. CONCLUSIONS: IVC reconstruction with primary repair results in an overall patency rate of 80.2% with only a 4.0% rate of stenosis. Recurrence of tumor thrombus (8.3%) or bland thrombus (8.3%) are the predominant reasons for IVC occlusion after RN-VTT, and this outcome is associated with poor OS.

Revisiting current National Comprehensive Cancer Network (NCCN) high-risk prostate cancer stratification: a National Cancer Database analysis.

BACKGROUND: High-risk prostate cancer includes heterogenous populations with variable outcomes. This study aimed to compare the prognostic ability of individual high-risk factors, as defined by National Comprehensive Cancer Network (NCCN) risk stratification, in prostate cancer patients undergoing radical prostatectomy. METHODS: We queried the National Cancer Database from 2004 to 2018 for patients with non-metastatic high-risk prostate cancer who underwent radical prostatectomy and stratified them as Group H1: Prostate specific antigen (PSA) > 20 ng/ml alone, Group H2: cT3a stage alone and Group H3: Gleason Grade (GG) group 4/5 as per NCCN guidelines. The histopathological characteristics and rate of adjuvant therapy were compared between different groups. Inverse probability weighting (IPW)-adjusted Kaplan-Meier curves were utilized to compare overall survival (OS) in group H1 and H2 with H3. RESULTS: Overall, 61,491 high-risk prostate cancer patients were identified, and they were classified into Group H1 (n = 14,139), Group H2 (n = 2855) and Group H3 (n = 44,497). Compared to group H1 or H2, pathological GG group > 3 (p < 0.001), pathological stage pT3b or higher (p < 0.001), lymph nodal positive disease (pN1) (p < 0.001) and rate of adjuvant therapy (p < 0.001) were significantly in Group H3. IPW-adjusted Kaplan-Meier curves showed significantly better 5-year OS in group H1 compared to group H3 [95.1% vs 93.3%, p < 0.001] and group H2 compared to group H3 [94.4% vs 92.9%, p < 0.001]. CONCLUSION: PSA > 20 ng/ml or cT3a stage in isolation have better oncologic and survival outcomes compared to GG > 3 disease and sub-stratification of 'High-risk' category might lead to better patient prognostication.

Open vs. robot-assisted radical cystectomy with extracorporeal or intracorporeal urinary diversion for bladder cancer A pairwise meta-analysis of outcomes and a network meta-analysis of complications.

INTRODUCTION: There are no meta-analyses of randomized controlled trials (RCTs) comparing open radical cystectomy (OR C) with robot-assisted radical cystectomy (RARC), inclusive of both intracorporeal (iRARC) and extracorporeal (hybrid RARC, hRARC) urinary reconstruction. METHODS: MEDL INE, Embase, Scopus, the International Clinical Trials Registry Platform and ClinicalTrials.gov registries were searched in May 2022. Outcomes of interest included recurrence- or progression-free survival (RFS/PFS), margin status and lymph node yield, mean estimated blood loss (EBL) and operating room time (ORT ), hospital length of stay (LOS ), 90-day complications and readmissions, and quality of life (QoL). Pairwise meta-analyses and network meta-analyses were performed using random-effects models and Bayesian hierarchical random-effects models, respectively. RESULTS: We found no significant differences between RARC and OR C for oncological and most perioperative outcomes: RFS/PFS (hazard ratio [HR ] 0.91, 95% confidence interval [CI] 0.67-1.23); positive surgical margins (odds ratio [OR ] 1.05, 95% CI 0.60-1.85); lymph node yield (mean difference [MD ] -0.63, 95% CI -2.63-1.37); LOS (MD -0.22, 95% CI -1.10-0.65); overall complications (OR 0.81, 95% CI 0.61-1.07); major complications (OR 0.94, 95% CI 0.69-1.30); readmissions (OR 0.90, 95% CI 0.60-1.35); and QoL (standardized MD -0.02, 95% CI -0.17-0.14). We found significantly lower EBL for RARC compared to OR C (MD -312.61, 95% CI -447 to -178.22) at the expense of significantly prolonged ORT (MD 82.34 minutes, 95% CI 44.82-119.86). Network meta-analysis did not find significant differences in complications between hRARC and iRARC. CONCLUSIONS: This meta-analysis confirms the equivalence of RARC and OR C with respect to oncological outcomes.

Impact of Finasteride on Survival in Bladder Cancer: A Retrospective Multi-institutional Database Analysis.

INTRODUCTION: Androgen suppression therapy has been associated with a lower incidence of bladder cancer (BCa) or improved overall/cancer-specific survival. Results are ofent conflicting; therefore, we aim to assess the impact of use of finasteride on overall survival (OS) for BCa using multi-institutional database. METHODS: The South Texas Veterans Healthcare System from 5 medical centers was queried for patients with BCa with or without use of finasteride after diagnosis of BCa. The primary outcome was the impact of finasteride use after diagnosis on the OS in BCa and in the high-risk Non-muscle invasive BCa (NMIBC) cohort. RESULTS: A total of 1890 patients were included, amongst which 619 (32.8%) men were classified as finasteride users and 1271 (67.2%) men as controls. At a median (IQR) follow up of 53.8 (27.4, 90.9) months, death due to any cause was noted in 272 (43.9%) finasteride-treated, and 672 (49.3%) control groups (P = .028). The patients in the finasteride group had significantly better OS in overall cohort (112.1 months vs. 84.8 months, P < .001) as well as in the NMIBC cohort (129.3months vs. 103.2 months, P = .0046). The use of finasteride was independently associated with improved OS in both, overall cohort (HR 0.74, 95% CI 0.63-0.86; P < .001) and in the NMIBC cohort (HR = 0.71, 95% CI 0.55-0.93; P = .011). CONCLUSION: Finasteride use is associated with the improved overall survival in patients with BCa, specifically in patients with NMIBC. We, further, propose a randomized clinical trial to investigate the use of finasteride in BCa patients.

A comparative analysis of radical cystectomy with perioperative chemotherapy, chemoradiation therapy, or systemic therapy in patients with clinically advanced node-positive bladder cancer (cN2/N3).

Introduction: The management of non-metastatic clinically advanced lymph nodal (cN2/N3) bladder cancer (Stage IIIB) could involve radical cystectomy, chemoradiation, or systemic therapy alone. However, a definitive comparison between these approaches is lacking. This study aims to compare the outcomes of patients undergoing radical cystectomy with pelvic lymph node dissection (RC-PLND), chemoradiation therapy (CRT) or systemic therapy (including immunotherapy) (ST) only in patients with stage IIIB bladder cancer. Materials and methods: A retrospective analysis of the National Cancer Database for patients with stage IIIB urothelial bladder cancer was done from 2004-2019. Patients were classified as Group A: Those who received RC-PLND with perioperative chemotherapy, Group B: Those who received CRT, and Group C: Those who received only ST alone. The primary outcome was overall survival (OS). Inverse probability weighting (IPW)-adjusted Kaplan Meier curves were utilized to compare overall survival (OS) and cox multivariate regression analysis was used to identify predictors for OS. Results: Overall, 2,575 patients were identified. They were classified into Group A (n=1,278), Group B (n=317) and Group C (n=980). Compared to Group B, patients in Group A were younger (SMD=19.6%), had lower comorbidities (SMD=18.2%), had higher income (SMD=31.5%), had private insurance (SMD= 26.7%), were treated at academic centres (SMD=29.3%) and had higher percentage of N2 disease (SMD=31.1%). Using IPW-adjusted survival analysis, compared to Group C, the median OS was significantly higher in Group A (20.7 vs 14.2 months, p<0.001) and Group B (19.7 vs 14.2 months, p<0.001) but similar between Group A and Group B (20.9 vs 19.7 months, p=0.74). Both surgery (HR=0.72 (0.65-0.80), p<0.001) and CRT (0.70 (0.59-0.82), p<0.001) appeared to be independent predictors for OS on cox-regression analysis. The major limitations include bias due to retrospective analysis and non-assessment of cancer-specific survival. Conclusion: In stage IIIB bladder cancer with advanced lymph nodal disease, both RC and CRT offer equivalent survival benefits and are superior to systemic therapy alone.

Diffusion of robot-assisted radical cystectomy: Nationwide trends, predictors, and association with continent urinary diversion.

Objectives: To assess the utilisation trends of robot-assisted radical cystectomy (RARC), rates of performing continent urinary diversions (CUDs), and impact of diffusion of RARC on CUD rates. Methods: We investigated the National Cancer Database for patients with muscle-invasive bladder cancer (MIBC) who underwent RC between 2004 and 2015. Patients were stratified by surgical technique into open (ORC) and RARC groups, and by type of urinary diversion into continent (CUD) and ileal conduit (ICUD) groups. Linear regression models were fitted to evaluate time trends for surgery and conversion techniques. Multivariate logistic regression models were utilised to identify independent predictors of RARC and CUD. Results: A total of 14466 patients underwent RC for MIBC, of which 4914 (34%) underwent RARC. There was a significant increase in adoption of RARC from 22% in 2010 to 40% in 2015 (R2 = 0.96, P < 0.001), this was not associated with a change in the rates of CUD over the same period (P = 0.22). Across all years, ICUD was the primary type of urinary diversion, CUD was only offered in 12% in 2010 compared to 9.9% in 2015 (R2 = 0.33, P = 0.22). Multivariate analysis identified male gender (odds ratio [OR] 1.18, P = 0.03), academic centres (OR 1.74, P = 0.001), and lower T stage (T4 vs T2; OR 0.78, P = 0.03) as independent predictors of CUD, while surgical technique was not associated with odds of receiving CUD (P = 0.8). Conclusions: There is significant nationwide increasing trend of adoption of RARC. This diffusion was not associated with a decline in CUD, which remains significantly underutilised in both ORC and RARC groups. Abbreviations CUD: continent urinary diversion; ICD-O: International Classification of Diseases for Oncology; ICUD: ileal conduit urinary diversion; (N)MIBC: (non-)muscle-invasive bladder cancer; NAC, neoadjuvant chemotherapy; NCDB: National Cancer Database; OR: odds ratio;(O)(RA)RC: (open) (robot-assisted) radical cystectomy.

The Latinx Disparity in Surgery for Kidney Cancer: Data from The South Texas Region.

The South Texas region, with a predominantly Latinx population, has a very high incidence of renal cell carcinoma (RCC), including those with tumor extending into the major blood vessels called venous tumor thrombus (VTT). There is currently no data on outcomes of Latinx patients with VTT as most published studies are from predominantly Caucasian population. Therefore, we performed this study to fill an urgent, unmet need. We reviewed patients who underwent radical nephrectomy with removal of VTT (called tumor thrombectomy) between 2015 and 2020. We collected data on demographics, clinical, pathological characteristics and outcomes of patients. Univariate and multivariate Cox regression analyses were used to evaluate the associations between ethnicity and disease progression or survival. We identified 112 patients, of which 67 (62%) were Latinx, and 41 (38%) were non-Latinx. Approximately 60% of patients had Level II-IV VTT; Latinx presented with a higher level of tumor thrombus (p=0.046). Latinx patients had a higher rate of no insurance (11% vs. 27%, p=0.04) and were more likely to lost to follow-up after surgery (22.4% vs. 13.3%, p=0.23) compared to non-Latinx. Fewer Latinx received systemic therapy (28% vs. 42%; p=0.13). Ninety-day mortality for the entire cohort was 3.8%. The Latinx population in the South Texas region present late, with advanced thrombus level, and do not have access to systemic therapy. Given symptomatic disease, surgical treatment, if feasible, is their only option. Our results highlight disparate treatment patterns which require further investigation and health-care policy changes.

Clinical outcomes and patterns of population-based management of urachal carcinoma of the bladder: An analysis of the National Cancer Database.

BACKGROUND: Given the low incidence of urachal carcinoma of the bladder (UCB), there is limited published data from contemporary population-based cohorts. This study aimed to describe demographic, clinicopathological features, and survival outcomes of patients diagnosed with UCB. METHODS: The National Cancer Database (2004-2016) was queried for UCB patients. Descriptive analyses characterized demographics and clinicopathologic features. We assessed 5-year overall survival (OS) rates of the entire cohort and subgroups of localized/locally advanced and metastatic disease. We utilized Cox proportional hazards models to assess the association between covariates of interest and all-cause mortality and to examine the impact of surgical technique and chemotherapy. RESULTS: We identified 841 patients with UCB. The most common histologic subtype was non-mucinous adenocarcinoma (39.6%). Approximately 50% had ≥cT2 disease, and 14.3% were metastatic at diagnosis. Altogether, partial cystectomy (60%) was most performed, and lymph node dissection was performed in 377 patients (44.8%), with specific temporal increase in utilization over the study period (p < 0.001). Overall, median OS was 59 months, and 5-year OS was 49%. In patients with localized/locally advanced disease, we found no association between partial and radical cystectomy (Hazards ratio [HR] 1.75; 95% CI 0.72-4.3) as well as receipt of perioperative chemotherapy (HR 1.97, 95% CI 0.79-4.90) and outcomes. Lastly, receipt of systemic therapy was not associated with survival benefit (HR 0.785, 95% CI 0.37-1.65) in metastatic disease cohort. CONCLUSION: This large population-based cohort provides insight into the surgical management and systemic therapy, without clear evidence on the association of chemotherapy and survival in the perioperative and metastatic setting.

Absolute Prostate Specific Antigen after 6 Months of Androgen Deprivation Therapy Is a Predictor of Overall and Cancer-Specific Mortality in Men with Hormone-Sensitive Prostate Cancer.

PURPOSE: We sought to determine if absolute prostate specific antigen (PSA) value after 6 months of androgen deprivation therapy (ADT) is predictive of subsequent survival in patients with prostate adenocarcinoma. MATERIALS AND METHODS: We performed a retrospective review of men receiving care within the Veterans Health Administration who initiated ADT for prostate adenocarcinoma. We used low- (≤0.2 ng/ml), intermediate- (>0.2 to 4 ng/ml) and high-risk (>4 ng/ml) absolute PSA values after 6-9 months of ADT, previously described in Southwest Oncology Group trial 9346. The primary endpoints were all-cause mortality and prostate cancer-specific mortality (PCSM). Kaplan-Meier survival curves for each PSA category were estimated and log-rank test was conducted. We employed Cox regression analysis adjusted for covariates and inverse propensity score weights associated with PSA categories to estimate the PSA category association with PCSM and all-cause mortality. RESULTS: We identified 9,170 patients in our cohort. Following ADT induction, 3,508 patients had low, 3,419 had intermediate and 2,243 had high PSA values. Two- and 5-year survival rates for low, intermediate and high PSA groups were 93.9% and 85.2% vs 88.6% and 71.2% vs 63.6% and 38.6%, respectively (p <0.0001). Patients in the high and intermediate PSA categories had a 15-fold and 3-fold higher risk of PCSM compared to those with PSA <0.2 ng/ml (p <0.0001). CONCLUSIONS: Absolute PSA in hormone-sensitive prostate cancer after 6-9 months of ADT is a predictor of overall mortality and PCSM. This measure can rapidly assess the efficacy of new interventions in phase 2 clinical trials.

Survival after minimally invasive vs. open radical nephrectomy for stage I and II renal cell carcinoma.

BACKGROUND: A recently reported phase III randomized trial comparing open and minimally invasive hysterectomy showed significantly higher rates of local recurrence after minimally invasive surgery (MIS) for cervical cancer. This raised concerns regarding patterns of recurrences and survival after MIS in general. This study aims to determine the effect of MIS on all-cause mortality among patients undergoing radical nephrectomy for Stage I and II renal cell carcinoma (RCC). METHODS: We utilized the National Cancer Database to identify patients diagnosed with clinical stage I-II RCCs between 2010 and 2013. Patients for whom a laparoscopic or robotic radical nephrectomy was attempted were compared to patients who underwent open radical nephrectomy (ORN). Adjusted regression models with inverse probability propensity score weighting (IPW) were utilized to identify independent predictors of receiving MIS. All-cause mortality rates were compared using IPW survival functions and log-rank tests. Adjusted Cox proportional hazard models were fitted to determine independent predictors of OS. RESULTS: 27,642 patients were identified; 11,524 (41.7%) had MIS, while 16,118 (58.3%) had ORN. Kaplan-Meier survival curves in the IPW cohort showed significant OS advantage for patients who underwent MIS (p < 0.001). Furthermore, length of hospital stays (3 vs. 4 days), 30 day readmission rates (2.4 vs. 2.87%), 30 day (0.53 vs. 0.96%) and 90 day mortality rates (1.04 vs. 1.77%) were significantly higher in the ORN group (p < 0.001). CONCLUSIONS: MIS was associated with better OS outcomes compared to ORN for stage I and II RCC. In addition, MIS had lower post-operative readmission, 30- and 90 day mortality rates.

Histological variants of non-muscle invasive bladder cancer: Survival outcomes of radical cystectomy vs. bladder preservation therapy.

BACKGROUND: To compare the overall survival (OS) outcomes of non-muscle invasive bladder cancer (NMIBC) patients with variant histology who underwent radical cystectomy (RC) vs. bladder preservation therapy (BPT). METHODS: We investigated the National Cancer Database for NMIBC patients with variant histological features. Patients diagnosed with micropapillary, sarcomatoid, neuroendocrine, squamous, and glandular variants were identified. Inverse probability weighting (IPW)-adjusted Kaplan Meier survival curves and Cox proportional hazard models were utilized to compare OS in the setting of RC versus BPT. RESULTS: A total of 8,920 (2.7%) NMIBC patients presented with variant histology, of whom 2,450 (27.5%) underwent RC, while 6,470 (72.5%) had BPT. When compared with BPT, patients who underwent RC had significantly higher 5-year OS rates for sarcomatoid (31.9% vs. 23.3%, P < 0.001) neuroendocrine (31% vs. 21.7%, P < 0.001), glandular (44% vs. 41%, P = 0.04) and squamous variants (39.7% vs 19.9%, P < 0.001). This OS benefit was not observed with micropapillary variant (43.9% vs. 53.2% P = 0.14). IPW-adjusted log-rank analysis identified RC as an independent predictor of OS for patients with sarcomatoid (hazards ratio [HR] 0.78, confidence interval [CI] 0.71-0.85, P < 0.001), squamous (HR 0.56, CI 0.53-0.59, P < 0.001), and neuroendocrine variants (HR 0.83, CI 0.76-0.91, P < 0.001), but not for micropapillary variant (HR 1.45, CI 1.24-1.7, P < 0.001). CONCLUSIONS: Among NMIBC patients presenting with variant histologies, RC was associated with better OS for sarcomatoid, squamous, glandular, and neuroendocrine variants when compared to BPT. This OS survival benefit was not observed in patients with micropapillary variant suggesting a potential role for bladder preservation in such population.

Association Between Perioperative Chemotherapy and Survival in Men Undergoing Radical Resection for Primary Urethral Urothelial Carcinoma: An Analysis of the National Cancer Database.

INTRODUCTION: The treatment landscape in invasive primary carcinoma of the urethra of urothelial histology closely aligns that of locally advanced urothelial carcinoma of the bladder. The survival benefit of perioperative chemotherapy for men undergoing radical surgery for primary urethral urothelial carcinoma (UUC) has not yet been well-elucidated. PATIENTS AND METHODS: Using the National Cancer Database (NCDB), we identified men diagnosed with non-metastatic invasive UUC (T2-4 N0-2 M0) from 2004 to 2016 treated with radical extirpative surgery. We compared OS between patients who had received peri-operative neoadjuvant (NAC) or adjuvant (AC) chemotherapy and those who had not using Kaplan-Meier curves and multivariable Cox proportional hazards regression model. RESULTS: A total of 191 patients met inclusion criteria. 113 patients (59.2%) did not receive chemotherapy, while 39 (20.4%) and 39 (20.4%) received NAC and AC, respectively. Median follow-up was 28.0 months. Upon multivariable analysis, receipt of NAC (HR 0.50, 95% CI 0.28-0.91, P = .02) decreased the risk of all-cause mortality, while receipt of AC (HR 0.76, 95% CI 0.41-1.41) was not significantly associated with an OS benefit, as compared to no chemotherapy. CONCLUSION: Our study is the first to evaluate treatment specific outcomes in male patients with primary carcinoma of the urethra. We observed that neoadjuvant chemotherapy in men with UUC was associated with OS benefit. The utilization of NAC may improve survival, consistent with urothelial carcinoma of the bladder.

Effects of yoga in men with prostate cancer on quality of life and immune response: a pilot randomized controlled trial.

BACKGROUND: Diagnosis and treatment of prostate cancer is associated with anxiety, fear, and depression in up to one-third of men. Yoga improves health-related quality of life (QoL) in patients with several types of cancer, but evidence of its efficacy in enhancing QoL is lacking in prostate cancer. METHODS: In this randomized controlled study, 29 men newly diagnosed with localized prostate cancer were randomized to yoga for 6 weeks (n = 14) or standard-of-care (n = 15) before radical prostatectomy. The primary outcome was self-reported QoL, assessed by the Expanded Prostate Index Composite (EPIC), Functional Assessment of Cancer Therapy-Prostate (FACT-P), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Functional Assessment of Cancer Therapy-General (FACT-G) at baseline, preoperatively, and 6 weeks postoperatively. Secondary outcomes were changes in immune cell status and cytokine levels with yoga. RESULTS: The greatest benefit of yoga on QoL was seen in EPIC-sexual (mean difference, 8.5 points), FACIT-F (6.3 points), FACT-Functional wellbeing (8.6 points), FACT-physical wellbeing (5.5 points), and FACT-Social wellbeing (14.6 points). The yoga group showed increased numbers of circulating CD4+ and CD8+ T-cells, more production of interferon-gamma by natural killer cells, and increased Fc receptor III expression in natural killer cells. The yoga group also showed decreased numbers of regulatory T-cells, myeloid-derived suppressor cells, indicating antitumor activity, and reduction in inflammatory cytokine levels (granulocyte colony-stimulating factor [0.55 (0.05-1.05), p = 0.03], monocyte chemoattractant protein [0.22 (0.01-0.43), p = 0.04], and FMS-like tyrosine kinase-3 ligand [0.91 (-0.01, 1.82), p = 0.053]. CONCLUSIONS: Perioperative yoga exercise improved QoL, promoted an immune response, and attenuated inflammation in men with prostate cancer. Yoga is feasible in this setting and has benefits that require further investigation. TRIAL REGISTRATION: clinicaltrials.org (NCT02620033).

Utilization and outcomes of metastasectomy for patients with metastatic urothelial cancer: An analysis of the national cancer database.

BACKGROUND: Surgical resection of oligometastatic disease has been shown to be associated with an improved survival in other malignancies, though its role is not established in metastatic urothelial carcinoma (mUC). We sought to examine utilization trends of metastasectomy in mUC and associated outcomes using the NCDB database. METHODS: We queried the NCDB from 2004 to 2016 for patients with metastatic urothelial carcinoma who had undergone metastasectomy. The annual utilization trend of metastasectomy was evaluated by linear regression. We compared overall survival (OS) between propensity score matched patients who had undergone metastasectomy and those who had not using two-sided log-rank and Cox regression models. We also performed sensitivity analyses on subcohorts of mUC. RESULTS: The utilization rate of metastasectomy in mUC was 7% and did not change significantly over time. Patients who received metastasectomy on average were younger, had >cT3 disease, had radical surgery to the primary tumor, and received systemic therapy. After propensity score matching, metastasectomy was not associated with an OS benefit for mUC patients (HR, 0.94; 95% CI, 0.83 to 1.07; P=0.38). Stratified subgroup analysis based on systemic therapy, radical surgery to primary tumor, clinical N stage, and primary location of disease did not show an OS benefit of metastasectomy. CONCLUSION: Metastasectomy is uncommonly used, though utilization has persisted over more than a decade. Despite selection biases and residual confounding favoring patients undergoing metastasectomy, we found similar OS among these individuals and those who did not undergo metastasectomy.

Impact of facility type and volume on survival in patients with metastatic renal cell carcinoma.

INTRODUCTION: To investigate the impact of facility type and volume on survival in patients with metastatic renal cell carcinoma (mRCC). MATERIALS AND METHODS: We investigated the National Cancer Database for patients with mRCC. Patients were stratified according to treatment facility type (academic vs. non-academic) and facility volume (high, intermediate, and low). Kaplan-Meier survival estimates and Cox proportional hazard models were fitted to evaluate overall survival (OS) as a function of facility type, volume, and different treatment modalities. RESULTS: A total of 27,598 patients were identified, of which 10,938 (40%) were treated at academic centers (AC) and 16,131 (60%) at non-academic centers (non-AC). Overall, 19,904 patients (72%) were treated in high-volume hospitals (HVH). Among patients treated at AC, 94% were treated at HVHs. Patients treated at AC were more likely to receive immunotherapy, undergo cytoreductive nephrectomy (CN) and metastasectomy. The 2 and 5 year OS rates for patients treated in AC were 29.7% (CI 28.8%-30.6%) and 13% (CI 12%-14%) vs. 21.7% (CI 21%-22.4%) and 8.4% (CI %7.91-%8.99) in the Non-AC, respectively (p < 0.001). Multivariate Cox regression analysis identified treatment at AC as an independent predictor of survival (HR 0.85, 95% CI 0.81-0.91, p < 0.001). Undergoing CN and receipt of immunotherapy was also associated with a survival benefit (HR 0.41, CI 0.40-0.43 and HR 0.63, CI 0.59-0.68 respectively, p < 0.001). CONCLUSIONS: Treatment at ACs and HVHs was associated with a survival benefit in patients with mRCC. Patients treated at AC were more likely to receive immunotherapy, undergo CN and metastasectomy.