Exposures and Bladder Cancer Risk Among Military Veterans: A Systematic Review and Meta-analysis.

OBJECTIVE: To investigate potential carcinogenic exposures in military personnel that are implicated in the development of bladder cancer. METHODS: This systematic review aimed to evaluate the association between specific military exposures and bladder cancer risk among veterans. PubMed, Scopus, and Ovid MEDLINE databases were searched in December 2023 for relevant articles. Inclusion criteria comprised retrospective cohort studies, reviews, and observational studies documenting bladder cancer incidence among military populations exposed to specific agents. A total of 25 studies, involving 4,320,262 patients, met the inclusion criteria. Data extraction followed PRISMA guidelines, and a random-effects model was used for data synthesis. RESULTS: The meta-analysis revealed significant associations between exposure to Agent Orange (HR 1.17 [95% CI: 1.01-1.36], P < .00001) and depleted uranium (HR 2.13 [95% CI: 1.31-3.48], P = .002) with increased bladder cancer risk among veterans. Contaminated drinking water showed a trend towards increased risk (HR 1.25 [95% CI: 0.97-1.61], P = .08). CONCLUSION: The findings suggest a possible association between specific military exposures and heightened bladder cancer risk among veterans, emphasizing the necessity for targeted screening protocols and preventive measures. Further research is essential to identify specific carcinogenic agents and prevalence of exposures among veterans, enabling more effective prevention and management strategies.

Prostate Specific Antigen Screening on a Nationwide Level: Featuring the Contribution of Race and Life Expectancy in Decision Making.

BACKGROUND: Estimation of life expectancy (LE) is important for the relative benefit of prostate specific antigen (PSA) screening. Limited data exists regarding screening for Black men with extended LE. The aim of the current study was to assess temporal trends in screening in United States (US) Black men with limited vs. extended LE, using a nationally representative dataset. MATERIALS AND METHODS: Using the National Health Institution Survey (NHIS) 2000 to 2018, men aged ≥40 without prior history of prostate cancer (PCa) who underwent PSA screening in the last 12 months were stratified into limited LE (ie, LE <15 years) and extended LE (ie, LE≥15 years) using the validated Schonberg index. LE-stratified temporal trends in PSA screening were analyzed for all men, and then in Black men. Weighted multivariable analyses and dominance analyses identified the predictors of PSA screening. RESULTS: PSA screening declined over the study period both for all eligible men with limited and extended LE, particularly between NHIS 2008 and 2013 (27.9%-20.7% in the extended). Screening increased significantly in Black men with extended LE (17.6% in 2010-25.7% in 2018). However, LE was not an independent predictor of screening in the Black cohort. Prior recipient of colonoscopy (55%-57%) and visit to health care provider (24%-32%) were the most important determinants for screening. CONCLUSION: For US men with extended LE, only 1 in 4 receive PSA screening, with a decline over the study-period. Screening rates increased for Black men. However, these changes were not driven by LE consideration itself, but participation in other screenings and access to a provider.

Assessing the impact of lymphovascular invasion on overall survival in surgically treated renal cell carcinoma patients: A nationwide cohort analysis.

INTRODUCTION: Lymph-vascular invasion (LVI) is recognized as an adverse pathological feature in patients with renal cell carcinoma (RCC). However, its impact on overall survival (OS) is not clear and scarcely addressed in the literature. We aimed to assess the prognostic ability of LVI as a predictor of OS in RCC patients using a large, North American cohort. METHODS: We included 95,783 cM0 RCC patients, diagnosed between 2010 and 2015, who underwent partial or radical nephrectomy within the National Cancer Database. Kaplan-Meier curves and log-rank tests were used to depict and compare survival curves. Cox regression analysis tested the impact of LVI on OS, after adjusting for all available confounders. RESULTS: Mean age (SD) was 59 (12), and most patients had pT1 stage (72.2%). Nodal status was pN0, pN1, and pNx, in 14.5%, 2.3%, and 83.3%, respectively. Overall, 9.0% of patients had LVI. The mean (SD) follow-up of the cohort was 39 months (24). At 5 years, OS was 65% in patients with LVI vs. 86% in patients without LVI (p<.0001). When patients were stratified based on nodal stage, these rates were 64% vs. 78% in pN0 patients, 31% vs. 41% in pN1 patients, and 69% vs. 87% in pNx patients (all P < 0.001). On multivariable analysis, and in comparison to patients without LVI, those with LVI had 1.37- (P < 0.001), 1.18- (P = 0.068), and 1.53-fold (P < 0.001) greater risk of death, when also harboring pN0, pN1, and pNx disease, respectively. CONCLUSIONS: Our findings are the first, to our best knowledge, to illustrate the clear detrimental impact of LVI on OS in surgically treated RCC patients. These findings might be useful in postoperative patient counseling and need to be accounted for when designing future clinical trials.

Characteristics of Biogas Production and Synergistic Effect of Primary Sludge and Food Waste Co-Digestion.

Co-digestion implementation in wastewater treatment plants enhances biogas yield, so this research investigated the optimal ratio of biodegradable waste and sewage sludge. The increase in biogas production was investigated through batch tests using basic BMP equipment, while synergistic effects were evaluated by chemical oxygen demand (COD) balance. Analyses were performed in four volume basis ratios (3/1, 1/1, 1/3, 1/0) of primary sludge and food waste with added low food waste: 3.375%, 4.675%, and 5.35%, respectively. The best proportion was found to be 1/3 with the maximum biogas production (618.7 mL/g VS added) and the organic removal of 52.8% COD elimination. The highest enhancement rate was observed among co-digs 3/1 and 1/1 (105.72 mL/g VS). A positive correlation between biogas yield and COD removal is noticed while microbial flux required an optimal pH, value of 8 significantly decreased daily production rate. COD reductions further supported the synergistic impact; specifically, an additional 7.1%, 12.8%, and 17% of COD were converted into biogas during the co-digestions 1, 2, and 3, respectively. Three mathematical models were applied to estimate the kinetic parameters and check the accuracy of the experiment. The first-order model with a hydrolysis rate of 0.23-0.27 indicated rapidly biodegradable co-/substrates, modified Gompertz confirmed immediate commencement of co-digs through zero lag phase, while the Cone model had the best fit of over 99% for all trials. Finally, the study points out that the COD method based on linear dependence can be used for developing relatively accurate model for biogas potential estimation in anaerobic digestors. Supplementary Information: The online version contains supplementary material available at 10.1007/s12155-023-10620-8.

Risk-Based Assessment Of the Impact Of Intravesical Therapy on Recurrence-Free Survival Rate Following Resection of Suspected Low-grade, Non-muscle-invasive Bladder Cancer (NMIBC): A Southwest Oncology Groups (SWOG) S0337 Posthoc Analysis.

BACKGROUND: Nonmuscle invasive bladder cancer (NMIBC) has an elevated risk of recurrence, and immediate postresection intravesical instillation of chemotherapy (IVC) significantly reduces the risk of recurrence. Questions remain about which subpopulation may maximally benefit from IVC. Our aim was to develop risk groups based on recurrence risk in NMIBC, and then evaluate the impact of a single, postoperative instillation of IVC on the subsequent risk of recurrence for each risk group. MATERIAL AND METHODS: Using the SWOG S0337 trial cohort, we performed a posthoc analysis of 345 patients who were diagnosed with suspected low-grade NMIBC, underwent transurethral resection of the bladder tumor (TURBT), and received post-operative IVC (gemcitabine vs. saline). Using regression tree analysis, the regression tree stratified patients based on their risk of recurrence into low-risk - single tumor and aged < 57 years, intermediate-risk - single tumor and aged ≥ 57 years, and high-risk - multiple tumors. We used Cox proportional hazard models to test the impact of recurrence-free rate, and after adjustment to available covariates. RESULTS: Median age of the cohort was 66.5 (IQR: 59.7-75.8 years) with 85% of patients being males. Median overall follow-up time was 3.07 years (IQR: 0.75-4.01 years). When testing the impact of treatment in each risk group separately, we found that patients in the intermediate-risk treated with gemcitabine had a 24-month recurrence free rate of 77% (95% CI: 68%-86%) vs. 59% (95% CI: 49%-70%) in the saline group. This survival difference was confirmed on multivariable analysis (hazard ratio: 0.39, 95% CI: 23%-66%, P < 0.001). This group represented 53% of our cohort. Conversely, we did not observe a significant difference in recurrence-free survival among patients in the low- (P = 0.7) and high-risk (P = 0.4) groups. CONCLUSION: Our findings indicate that older patients with a single tumor of suspected low-grade NMIBC at TURBT maximally benefit from immediate postresection IVC (gemcitabine).

Impact of Lymphovascular Invasion on Overall Survival in Patients With Prostate Cancer Following Radical Prostatectomy: Stage-per-Stage Analysis.

BACKGROUND: The detrimental impact of lymphovascular invasion (LVI) in prostate cancer (PCa) on biochemical recurrence has been described; the impact of LVI on overall survival (OS) remains unclear. This investigation sought to evaluate the impact of LVI on OS in patients with PCa. METHODS: We examined men with nonmetastatic PCa treated with radical prostatectomy between 2010 and 2015. Only men with documented LVI status were included (n = 232,704). Patients were stratified according to final pathologic T stage (pT2, pT3a, and pT3b). RESULTS: Of the 232,704 patients who met inclusion criteria, 17,758 (8%) were found to have LVI on final pathology. Overall, 174,838 (75%), 40,281 (17%), and 17,585 (8%) patients had pT2, pT3a, and pT3b disease, respectively. Median follow-up was 42.7 months (27.1-58.7). At 5 years, the OS in LVI versus non-LVI patients was 94% versus 95% in pT2 (P = .0004), 92% versus 95% in pT3a (P < .0001), and 86% versus 92% in pT3b (P < .0001). On multivariable analysis, LVI status was not an independent predictor of OS in pT2 disease (hazard ratio, 1.12; 95% confidence interval [CI], 0.93-1.36; P = .2). In pT3a and pT3b disease, presence of LVI had 1.2-fold (95% CI, 1.03-1.44; P = .02) and 1.4-fold (95% CI, 1.20-1.59; P < .001) higher overall mortality than their counterparts without LVI. CONCLUSIONS: Our report demonstrates the detrimental impact of LVI on OS in locally advanced PCa (pT3a and higher). This information may prove valuable when risk stratifying based on final pathology.

Evaluation of lymphovascular invasion as a prognostic predictor of overall survival after radical prostatectomy.

OBJECTIVE: To assess the prognostic ability of lymphovascular invasion (LVI) as a predictor of overall survival (OS). MATERIALS AND METHODS: We included 126,682 prostate cancer (CaP) cM0 patients who underwent radical prostatectomy with lymph node dissection between 2010 and 2015, within the National Cancer Database. Patients who received androgen deprivation therapy were included. Patients were divided into four sub-cohorts based on LVI and lymph node invasion (LNI) status: pL0N0, pL1N0, pL0N1, and pL1N1. Kaplan-Meier curves estimated OS and Cox-regression analysis tested the relationship between LVI and OS. RESULTS: Median (IQR) age and PSA at diagnosis were 62 (57-66) years and 5.7 (4.5-8.9) ng/ml, respectively. Most patients had pT2 stage (68.5%), and pathological Gleason 3+4 (46.7%). 10.0% and 4.0% patients had LVI and LNI, respectively. Median follow-up was 42 months (27-58). At 5-years, OS was 96.5% in pL0N0 patients vs 93.1% pL1N0 patients vs 93.3% in pL0N1 patients vs 86.6% pL1N1 patients. LVI was an independent predictor of OS (hazard ratio [HR]:1.28). LVI showed interaction with LNI, as LVI was associated with a higher overall-mortality in patients with LNI (HR:1.66), than in patients without LNI (HR:1.22). (all P<0.0001) CONCLUSIONS: Our report highlights the detrimental impact of LVI on OS. Patients with LVI alone fared similarly to patients with LNI alone. Patients with both LVI and LNI had worse OS than those with only LVI or LNI, implying a synergetic detrimental interaction. Our findings demonstrate an important utility that LVI can provide in deciding patients' prognoses.

Impact of treatment modality on overall survival in localized ductal prostate adenocarcinoma: A national cancer database analysis.

PURPOSE: Ductal adenocarcinoma is considered a rare histological variant of prostate adenocarcinoma (PCa). Given the rarity of this subtype, optimal treatment strategies for men with nonmetastatic ductal PCa is largely unknown. We aimed to describe the impact of surgery, radiotherapy, systemic therapy, and observation on overall survival (OS) in men with nonmetastatic ductal PCa. MATERIALS AND METHODS: We selected 1,656 cases of nonmetastatic ductal PCa, diagnosed between 2004 and 2015, within the National Cancer Database. Covariates included age, race, Charlson comorbidity score, clinical T stage, clinical lymph node stage, serum prostate specific antigen (PSA), income, hospital type, insurance status, year of diagnosis, and location of residence. Cox regression analysis tested the impact of treatment (surgery, radiotherapy, systemic therapy, and observation) on OS. RESULTS: In men with nonmetastatic ductal PCa, median (interquartile range [IQR]) age and PSA were 67 (60-73) years and 6.2 (4.2-10.7) ng/ml, respectively. Advanced local stage (≥cT3a) was most frequently observed in patients initially treated with systemic therapy (34.8%), followed by those treated with radiotherapy (18.1%), surgery (7.1%) and observation (6.4%, P< 0.001). Serum PSA at presentation was highest in the systemic therapy cohort (median 16.0 ng/ml, IQR: 4.9-37.7), followed by the radiotherapy cohort (median 7.2 ng/ml, IQR: 4.1-12.2), observation cohort (median 7.0 ng/ml, IQR: 4.3-13.3) and surgery cohort (median 5.9 ng/ml, IQR: 4.3-9.2, P< 0.001). Multivariable analysis showed that in comparison to men treated surgically, OS was significantly lower for patients receiving radiotherapy (HR 2.2; 95% CI: 1.5-3.2), under observation (HR 4.6; 95% CI: 2.8-7.6) and receiving systemic therapy (HR 5.2; 95% CI: 3.0-9.1) as an initial course of treatment. CONCLUSIONS: While limited by its retrospective nature, our study shows that starting treatment with surgery is associated with more favorable long-term OS outcomes than radiotherapy, systemic therapy or observation.

A Nationwide Persistent Underutilization of Adjuvant Radiotherapy in North American Prostate Cancer Patients.

OBJECTIVE: To examine the utilization of adjuvant radiotherapy (aRT) in contemporary prostate cancer patients with adverse pathological features at radical prostatectomy (RP). METHODS: We identified 189,240 patients with adverse features at RP (positive margin, stage ≥pT3a, and/or pN1 disease), from 2004 to 2015, within the National Cancer Database, and validated our findings within Surveillance, Epidemiology, and End Results (SEER) program. We examined the utilization of patients with aRT with adverse features at RP and patients with very aggressive disease (at least 2 of the following: ≥pT3b, pathological Gleason 8-10, and pN1). Regression analysis examined the relationship of various predictors of utilization adjusting to confounders. Pseudo R2 analysis examined the magnitude of influence that each variable had on the decision to use aRT. RESULTS: Within the National Cancer Database cohort, only 11.7% of our patients received aRT. In patients with very aggressive disease, aRT utilization rate was 28.9%. Within the SEER cohort, 16.3% of patients with any adverse features at time of RP received aRT. In patients with very aggressive disease, only 30% of patients received aRT. Further, year of diagnosis, Gleason grade, pathologic stage, and positive surgical margin were the variables that had the greatest influence on the decision to use aRT, and that positive surgical margin, type of institution at which care was received, and lymph node involvement were the most influential variables in patients with very aggressive disease. CONCLUSIONS: The current standard of care in the United States represents a significant underutilization of aRT in eligible patients with prostate cancer. Urgent efforts are necessary to address this quality-of-care concern.