Comparison of Work Relative Value Units Assigned to Urological and Gynecological Surgical Procedures.

INTRODUCTION: We sought to determine if work relative value unit differences exist between analogous, sex-specific procedures. METHODS: Representatives from the AUA and the American College of Obstetricians and Gynecologists independently reviewed the entire procedural code set and identified sex-specific procedures that had an analogous procedure in the opposite sex. These pairs were then evaluated and compared using current American Medical Association Relative Value Scale Update Committee methodology. Comparable code pair values were then examined to determine any systemic bias in the work relative value units assigned between the procedures. Mean differences and 95% confidence intervals were used to determine any differences in procedure or physician time values. The methodology used considered global period, intraservice time, total time, hospital days, postoperative office visits, and the date of the committee review. RESULTS: Of the 10 directly analogous code pairs reviewed, 7 of the female procedures had higher work relative value unit differences (range 0.29-6.47), and 3 of the male procedures had higher work relative value unit differences (range 1.23-2.34). There was no statistical difference between the code pair work relative value units. The work relative value unit per minute of intraservice time and total time were not statistically different. CONCLUSIONS: In this study, we compared operative procedures performed in women with clinically comparable operative procedures performed in men that had similar surgical approaches, global periods, and valuation methodologies. Overall, no statistical differences in work relative value units were demonstrated.

Shorter Ureters Lead to Fewer Strictures Following Cystectomy and Urinary Diversion.

OBJECTIVE: To identify the impact of length of distal ureteral resection on the risk of benign uretero-enteric anastomotic stricture (UEAS) formation following cystectomy and urinary diversion. METHODS: A database of patients who underwent cystectomy and urinary diversion from 2015 to 2022 was analyzed. Distal ureteral resections were sent for final pathology. The length of resected ureter was collected from pathology reports. Benign UEAS were confirmed with renal scintigraphy, antegrade nephrostogram, or endoscopic evaluation. The relationship between stricture formation and clinical parameters were assessed using T-tests, chi-square tests, and multivariable analysis. RESULTS: A total of 366 patients underwent cystectomy and urinary diversion. Of the cohort, 35 (9.5%) patients developed UEAS. Median time to stricture formation was 12.5months (IQR 4-30). Of the 711 uretero-enteric anastomoses, 40 (5.6%) ultimately formed a UEAS. Median distal ureteral resection was significantly longer among ureteral anastomoses which did not form a UEAS (2.3 cm vs 1.65 cm, P = .028). Multivariable logistic regression adjusting for surgical approach, prior radiation, ureteral side, and urinary diversion type demonstrated that longer distal ureteral resections were inversely associated with odds of UEAS formation (OR 0.73, 95% CI 0.58-0.92). Multivariable Cox regression analysis similarly showed that length of distal ureteral resection was inversely associated with time to stricture formation (HR 0.78, 95% CI 0.62-0.98). CONCLUSION: The etiology of benign UIA strictures is multifactorial. Vascular compromise is a critical hypothesis. We found that longer distal ureteral resections (and thus shorter ureters) were associated with a significantly lower risk of stricture formation in cystectomy patients.

Impact of Agent Orange Exposure on Non-muscle Invasive Bladder Cancer Outcomes.

OBJECTIVE: To explore the effect of Agent Orange (AO) exposure on bladder cancer (BCa) outcomes in patients receiving Bacillus Calmette-Guérin (BCG) for non-muscle invasive BCa (NMIBC). METHODS: We retrospectively examined the association between AO exposure in patients with NMIBC in national veterans affairs databases who were being treated with BCG. Patients were diagnosed with NMIBC from 2000 to 2010 with follow-up through 2018. Clinical, pathological, and demographic variables were compared by AO exposure. Associations of AO exposure with recurrence, progression, and cancer-specific survival were performed using Cox proportional hazard models after inverse propensity score weighting and competing risks adjustments. We also assessed the association of AO exposure on grade and stage via multivariable logistic regression models. RESULTS: A total of 7651 patients were identified of which 753 (9.8%) were exposed to AO. The median follow-up time was 130 months. The AO-exposed patients were younger (age 61 vs 71 years, P <.001), but had similar Charlson comorbidity scores and stage/grade distribution as the non-AO exposed patients. AO exposure was not associated with higher grade or stage. In our Cox multivariable analyses, AO exposure was not associated with worse recurrence (hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.72-1.10, P = .29), progression (HR 1.08, 95% CI 0.86-1.36, P = .51), or cancer-specific survival (HR 1.31, 95% CI 0.92-1.87, P = .13). CONCLUSION: AO exposure was not associated with worse oncologic outcomes in patients receiving BCG for NMIBC. While this is reassuring, additional research is needed in other patient populations and disease states to determine if the effect is consistent.

Lipid biosynthesis perturbation impairs endoplasmic reticulum-associated degradation.

The relationship between lipid homeostasis and protein homeostasis (proteostasis) is complex and remains incompletely understood. We conducted a screen for genes required for efficient degradation of Deg1-Sec62, a model aberrant translocon-associated substrate of the endoplasmic reticulum (ER) ubiquitin ligase Hrd1, in Saccharomyces cerevisiae. This screen revealed that INO4 is required for efficient Deg1-Sec62 degradation. INO4 encodes one subunit of the Ino2/Ino4 heterodimeric transcription factor, which regulates expression of genes required for lipid biosynthesis. Deg1-Sec62 degradation was also impaired by mutation of genes encoding several enzymes mediating phospholipid and sterol biosynthesis. The degradation defect in ino4Δ yeast was rescued by supplementation with metabolites whose synthesis and uptake are mediated by Ino2/Ino4 targets. Stabilization of a panel of substrates of the Hrd1 and Doa10 ER ubiquitin ligases by INO4 deletion indicates ER protein quality control is generally sensitive to perturbed lipid homeostasis. Loss of INO4 sensitized yeast to proteotoxic stress, suggesting a broad requirement for lipid homeostasis in maintaining proteostasis. A better understanding of the dynamic relationship between lipid homeostasis and proteostasis may lead to improved understanding and treatment of several human diseases associated with altered lipid biosynthesis.

Epitaxial Growth of a Thin Layer of Putative Cancer Cells under Limited Resources and in the Presence of an Alkylating Agent.

The dynamics of the Eden cluster in a 32x32 lattice is implemented using a stochastic model. A single-type of cells solid tumor is assumed. Duplication is probabilistic, and occurs when there is room in the immediate surroundings of a cell, otherwise the cell is inhibited by contact. The growth is epitaxial, the shape of the cluster is disk-like; the ratio between the numbers of perimeter cells; and bulk cells decreases as the cluster grows. Percolation is flagged by an inflection in the rate of growth. We assume that the inflection point actually flags a shortage of nutrients, thereafter the rate of growth decreases to zero. Cancer cells in culture, when deprived of nutrients, actually exhibit a similar behavior. Under the logistic hypothesis, the lattice contains nutrients to sustain the growth up to 1024 cells. The model is expanded to include a drug that pollutes the environment. The drug is an alkylating agent that hinders duplication, eventually causing the death of the cell. The logistic equation accounts for drug consumption. The probability of duplication with the drug decreases as the drug is consumed, eventually leading to relapse. Relapses and survival times are investigated as a function of the dose injected.

Gender and Racial Diversity among U.S. Urology Residency Programs and Efforts to Improve It: You Can't Be What You Can't See.

INTRODUCTION: The U.S. urology workforce lacks ethnic and gender diversity. Few programs exist to increase diversity, and little is known on their effectiveness. We assessed the landscape of specific programs designed to increase underrepresented in medicine (URiM) and female student participation in the U.S. Urology Match, and understand the concerns and attitudes of those students. METHODS: To better understand urology-specific programs, we sent an 11-item survey to all 143 urology residency programs. To better understand the concerns and attitudes of URiM and female students participating in the U.S. Urology Match, we sent a 12-item survey to the students who participated in the Match from 2017 to 2021. Lastly, we evaluated trends in match rate using Match data from 2019 to 2021. RESULTS: Among programs, 43% responded to our survey. Most residency programs offer a wide array of initiatives to increase their diversity, with unconscious bias training being the most frequent (78.7%). Programs with at least 1 female faculty member were associated with increased recruitment of female residents over time (p=0.047). A similar trend was seen in programs with URiM faculty. Among students, 10.5% responded to our survey, of whom 79.2% were unaware of any programs at their institution geared toward URiM or female students. Match data revealed that women were more likely to match (p=0.002), and URiM students were less likely to match (p <0.001) compared to the overall Match rate. CONCLUSIONS: Urology programs are making substantial efforts to improve diversity, but the message is lacking reach. Having a diverse faculty did make a difference in programs' ability to diversify.

Inner Nuclear Membrane Asi Ubiquitin Ligase Catalytic Subunits Asi1p and Asi3p, but not Asi2p, confer resistance to aminoglycoside hygromycin B in Saccharomyces cerevisiae.

The heterotrimeric Asi ubiquitin ligase (encoded by ASI1, ASI2, and ASI3) mediates protein degradation in the inner nuclear membrane in Saccharomyces cerevisiae. Asi1p and Asi3p possess catalytic domains, while Asi2p functions as an adaptor for a subset of Asi substrates. We hypothesized the Asi complex is an important mediator of protein quality control, and we predicted that Asi would be required for optimal growth in conditions associated with elevated abundance of aberrant proteins. Loss of Asi1p or Asi3p, but not Asi2p, sensitized yeast to hygromycin B, which promotes translational infidelity by distorting the ribosome A site. Surprisingly, loss of quality control ubiquitin ligase Hul5p did not sensitize yeast to hygromycin B. Our results are consistent with a prominent role for an Asi subcomplex that includes Asi1p and Asi3p (but not Asi2p) in protein quality control.

Transrectal ultrasound guided prostate biopsy performed by supervised junior and senior residents is safe and does not result in inferior outcomes.

PURPOSE: To compare transrectal ultrasound guided prostate biopsy (TRUSBx) cancer detection and complication rates between residents at different levels of training and attending physicians at a single academic center. METHODS: We performed a retrospective review of consecutive series of 623 men undergoing TRUSBx from June 2014 to February 2017. The procedure was performed either by resident physicians under direct supervision by an attending physician or by an attending physician. In total, junior residents, senior residents and attending physicians performed 244, 212, and 167 biopsies, respectively. Prostate cancer detection, 30-day complications, and 30-day hospitalizations rates were the outcomes of interest. We performed multivariable logistic regression analysis to identify predictors of these outcomes and examined the hypothesis that TRUSBx performed by trainees would not be associated with inferior outcomes. RESULTS: There was no statistically significant difference in patient populations between the three groups when stratified by age, BMI, Charleston co-morbidity index, aspirin use, PSA level and palpable nodule on DRE. Prostate cancer was detected in 43.8% of the biopsies and there was no difference in detection rates (P = 0.53), Gleason score (P = 0.11), number of positive cores (P = 0.95), 30-day hospitalization (P = 0.86), and 30-day complication rates (P = 0.67) between TRUSBx performed by trainees and attending physicians. CONCLUSIONS: TRUSBx performed by residents and attending physicians yielded equivalent rates of cancer detection with no significant difference in 30-day complications or 30-day hospitalizations rates. There was no difference in outcomes between junior and senior residents suggesting that with adequate faculty supervision, it is safe for trainees at all levels to perform prostate biopsies.

Beta-Adrenergic Antagonists and Cancer Specific Survival in Patients With Advanced Prostate Cancer: A Veterans Administration Cohort Study.

OBJECTIVE: To interrogate the National Veterans Health Administration (VA) database to determine if beta-blocker use at time of initiation of androgen therapy deprivation (ADT) would result in improved oncological outcomes in advanced prostate cancer (PCa). METHODS: All men diagnosed with high risk PCa (PSA >20) from 2000-2008 who were on ADT ≥ 6 months were identified. Patients receiving ADT concurrently with primary radiation therapy were excluded. Pharmacy data was interrogated for all beta-blockers, but then focused on the selective beta-1 blocker metoprolol. Cox proportional hazards ratios were calculated for overall survival (OS), PCa specific survival (CSS) and skeletal related events (SREs). RESULTS: In 39,198 patients with high risk PCa on ADT, use of any beta-blocker was not associated with improvement in OS, CSS, or SREs. Further analyses focusing on metoprolol found that 10,224 (31.9%) had used metoprolol while 21,834 had no beta-blocker use. Multivariable analysis with Inverse Propensity Score Weighting, adjusted for factors including PSA, Gleason score, and duration ADT, found that utilization of metoprolol was not associated with improvement in OS (hazard ratio [HR] 0.97, P = .19), CSS (HR 0.94, P = .23) or SREs (HR 0.98, P = .79). CONCLUSION: In this large cohort, metoprolol use in conjunction with ADT in high risk PCa was not associated with improvement in OS, CSS, or risk of SRE. In contrast to a recent smaller clinical study, our data strongly suggests no cancer specific benefit to beta-blocker use in advanced PCa.

Epigenetic field alterations in non-tumor prostate tissues detect prostate cancer in urine.

Prostate cancer (PC) development involves epigenetic DNA methylation changes that occur in the tumor. However, distinct DNA methylation changes have been previously found to encompass a widespread cancer field defect involving normal prostate tissue. In the current study, we analyzed a series of DNA methylation field markers to determine if they predict the presence of PC in urine. Urine samples were collected from patients undergoing prostate biopsy with biopsy-proven PC (90), and without PC (77). From the urine pellet, methylated DNA was quantified across several previously identified CpG island regions near the caveolin 1 (CAV1), even-skipped homeobox 1 (EVX1), fibroblast growth factor 1 (FGF1), natural cytotoxicity triggering receptor 2 (NCR2) and phospholipase A and acyltransferase 3 (PLA2G16) genes using bisulfite pyrosequencing. Univariate and multivariate analyses were performed. Urine cell pellets show significant increases in methylation in four of the markers from patients with PC compared to those without PC including EVX1 12.2 vs. 7.7%, CAV1 15.7 vs. 10.36%, FGF1 12.0 vs. 7.1%, and PLA2G16 12.2 vs. 8.3% [all P<0.01]. Area under the ROC Curve (AUCs) were generated for EXV1 (0.74, Odds ratios (OR) 1.09; 95% confidence intervals (CI) 0.94-1.25, CAV1 (0.72, OR 1.18; 95% CI 1.09-1.28) and PLA2G16 (0.76, OR 1.35; 95% CI 1.199-1.51). In combination, a two-marker assay performs better than prostate specific antigen (PSA), AUC 0.77 vs. PSA AUC of 0.6 (P = 0.01) with the lowest error. In addition, FGF1 distinguished between grade group 1 (GG1) and higher grade cancers (P<0.03). In conclusion, applying methylation of field defect loci to urine samples provides a novel approach to distinguish patients with and without cancer.

Overlapping function of Hrd1 and Ste24 in translocon quality control provides robust channel surveillance.

Translocation of proteins across biological membranes is essential for life. Proteins that clog the endoplasmic reticulum (ER) translocon prevent the movement of other proteins into the ER. Eukaryotes have multiple translocon quality control (TQC) mechanisms to detect and destroy proteins that persistently engage the translocon. TQC mechanisms have been defined using a limited panel of substrates that aberrantly occupy the channel. The extent of substrate overlap among TQC pathways is unknown. In this study, we found that two TQC enzymes, the ER-associated degradation ubiquitin ligase Hrd1 and zinc metalloprotease Ste24, promote degradation of characterized translocon-associated substrates of the other enzyme in Saccharomyces cerevisiae Although both enzymes contribute to substrate turnover, our results suggest a prominent role for Hrd1 in TQC. Yeast lacking both Hrd1 and Ste24 exhibit a profound growth defect, consistent with overlapping function. Remarkably, two mutations that mildly perturb post-translational translocation and reduce the extent of aberrant translocon engagement by a model substrate diminish cellular dependence on TQC enzymes. Our data reveal previously unappreciated mechanistic complexity in TQC substrate detection and suggest that a robust translocon surveillance infrastructure maintains functional and efficient translocation machinery.

Synthetic Lethal Metabolic Targeting of Androgen-Deprived Prostate Cancer Cells with Metformin.

The initiation of androgen-deprivation therapy (ADT) induces susceptibilities in prostate cancer cells that make them vulnerable to synergistic treatment and enhanced cell death. Senescence results in cell-cycle arrest, but cells remain viable. In this study, we investigated the mechanisms by which prostate cancer cells undergo senescence in response to ADT, and determined whether an FDA-approved antidiabetic drug metformin has a synergistic effect with ADT in prostate cancer both in vitro and in vivo Our results show that longer term exposure to ADT induced senescence associated with p16INK4a and/or p27kip2 induction. The activation of PI3K/AKT and inactivation of AMPK in senescent cells resulted in mTORC1 activation. In addition, the antiapoptotic protein XIAP expression was increased in response to ADT. The addition of metformin following ADT induced apoptosis, attenuated mTOR activation, reduced senescent cell number in vitro, and inhibited tumor growth in prostate cancer patient-derived xenograft models. This study suggests that combining ADT and metformin may be a feasible therapeutic approach to remove persistent prostate cancer cells after ADT.

Increased Bacillus Calmette-Guérin Treatment Intensity Associated With Improved Outcomes in Elderly Patients With Non-Muscle-invasive Bladder Cancer in United States Clinical Practice.

OBJECTIVE: To characterize Bacillus Calmette-Guérin (BCG) treatment patterns and associated outcomes in a large cohort of patients with non-muscle-invasive bladder cancer (NMIBC). METHODS: Our retrospective analysis of patients aged ≥66 years with stage 0-1 urothelial bladder carcinoma diagnosed between 2000 and 2012 in the United States Surveillance, Epidemiology, and End Results-Medicare database estimated proxies for recurrence and secondary events and both all-cause and bladder cancer-specific mortality. Proportional hazards models were used in conditional landmark analyses to compare adequate (≥5 induction instillations and ≥2 maintenance instillations) and inadequate BCG, stratified by National Comprehensive Cancer Network risk group. RESULTS: Of 39,532 patients who met the selection criteria, 16,225 (41.0%) received BCG; of them, 4602 (28.4%; 11.6% overall) received adequate treatment. Adequately treated patients were slightly younger and healthier than inadequately treated patients. Half of patients with intermediate- and high-risk NMIBC did not receive BCG; few received adequate treatment. At the 12-month landmark, adequate BCG treatment was associated with decreased risks of recurrence and of cancer-specific and all-cause mortality in patients with intermediate- and high-risk disease. CONCLUSION: We observed lower than expected use of adequate BCG treatment in patients with intermediate- to high-risk NMIBC despite evidence of improved outcomes, which suggested that practice patterns may not be in line with management recommendations in this population.

Trends in epidural anesthesia use at the time of radical cystectomy and its association with perioperative and survival outcomes: a population-based analysis.

Epidural anesthesia is used to improve pain control after major surgeries. Few data describe the impact of epidural use for bladder cancer patients treated with radical cystectomy (RC). Here, we evaluate epidural use on perioperative and long-term outcomes for patients treated with radical cystectomy for bladder cancer. Patients who received radical cystectomy for non-metastatic bladder urothelial carcinoma with epidural (n=1,748) and without epidural (n=6,109) anesthesia from 2002-2014 were identified using Surveillance, Epidemiology and End Results-Medicare data. Radical cystectomy outcomes with and without epidural anesthesia were compared using propensity score weighting. Epidural use at time of radical cystectomy was identified in 1,748 (22.2%) of 7,857 patients who met inclusion criteria. After propensity score weighted adjustment, epidural use was associated with increased 30-day readmission (29.6% vs. 26.2%, P<0.001), increased median length of stay in days (9.0, IQR 7.0-12.0 vs 8.0, IQR 6.0-12.0, P<0.01), and decreased likelihood of being discharged directly to home without need for home health or skilled nursing care (21.6% vs 29.1%, P<0.001). Post-operative MI (2.6% vs 1.3%, P<0.001) in the first 30 days after radical cystectomy was more common in the epidural group, but perioperative 30-day mortality was similar (3.3% vs 2.9%, P=0.21). Epidural use was not associated with increased cancer specific (HR 0.96, 0.90-1.02, P=0.20) or overall survival (HR 0.99, 0.95-1.04, P=0.73). Epidural use at time of radical cystectomy is associated with increased risk of perioperative complications, hospital readmission, and longer hospitalization without improving disease specific survival. Prospective studies are needed to confirm these findings.

Comparing Outcomes for Patients with Clinical T1b Renal Cell Carcinoma Treated With Either Percutaneous Microwave Ablation or Surgery.

OBJECTIVE: To compare perioperative and oncologic outcomes for patients with clinical T1b renal cell carcinoma following treatment with microwave ablation (MW), partial nephrectomy (PN), or radical nephrectomy (RN). METHODS: Comprehensive clinical and pathologic data were collected for nonmetastatic renal cell carcinoma patients with cT1b tumors following MW, PN, or RN from 2000 to 2018. Local recurrence-free, metastasis-free, cancer-specific and overall survival were estimated using Kaplan-Meier method. Prognostic factors for complications and survival were determined using logistic regression and Cox hazard models, respectively. RESULTS: A total of 325 patients (40 MW, 74 PN, and 211 RN) were identified. Patients treated with MW were older with higher Charlson comorbidity indices compared to surgical patients. Median length of hospitalization was shorter for MW compared to surgical patients (1 day vs 4 days, P <.0001). Post-treatment estimated glomerular filtration rate decreased by median 4.5% for MW compared to 3.2% for PN (P = .58) and 29% for RN (P <.001). Median follow-up was 34, 35, and 49 months following MW, PN, and RN, respectively. Estimated 5-year local recurrence-free survival was 94.5% for MW vs 97.9% for PN (P = .34) and 99.2% for RN (P = .02). Two patients recurred after MW and underwent repeat ablation without subsequent recurrence. No difference in 5-year metastasis-free survival or cancer-specific survival was found among MW, PN, or RN. Four (10%) MW patients had high-grade complication. Only prior abdominal surgery predicted high-grade complication (OR 6.29, P = .017). CONCLUSION: Microwave ablation is a feasible alternative to surgery in select comorbid patients with clinical T1b renal cell carcinoma.

Impact of bilateral biopsy-detected prostate cancer on an active surveillance population.

BACKGROUND: To assess factors that can predict active surveillance (AS) failure on serial transrectal ultrasound guided biopsies in patients with low-risk prostate cancer. METHODS: We evaluated the records of 144 consecutive patients enrolled in AS between 2007 and 2014 at a single academic institution. Low risk inclusion criteria included PSA < 10 ng/ml, cT1c or cT2a, Grade Group (GG) 1, < 3 positive cores, and < 50% tumor in a single core with the majority having a PSA density of < 0.15. AS reclassification was defined as progression to GG ≥2, 3 or more cores, or core tumor volume ≥ 50%. Univariate and multivariate Cox proportional hazards regression analysis was used to determine predictors of reclassification and a match-pair analysis performed on a control group of patients choosing surgery. RESULTS: Inclusion criteria were met by 130 men with a median follow-up of 52 months. The reclassification or AS failure rate was 38.5%, with the majority 41/50 (82%) finding GG ≥ 2 cancer. Most patients had unilateral disease on diagnostic biopsy (94.6%), but 40.7% had bilateral cancer detected during follow-up. Men with bilateral detected tumor were more likely to ultimately fail AS than patients with unilateral tumors (HR 4.089; P < 0.0001) and failed earlier with a reclassification-free survival of 32 vs 119 months respectively. In a matched-pair analysis using a population of 211 concurrent patients that chose radical prostatectomy rather than AS, 76% of patients with unilateral cancer on biopsy had bilateral cancer on final pathology. CONCLUSIONS: The finding of bilateral prostate cancer on biopsy is associated with earlier AS reclassification. Finding bilateral disease may not represent disease progression, but rather enhanced detection of more extensive disease highlighting the importance of confirmatory biopsy.

Combination therapy with androgen deprivation for hormone sensitive prostate cancer: A new frontier.

Androgen deprivation therapy (ADT) has been the standard of care for the last 75 years in metastatic hormone sensitive prostate cancer (PCa). However, this approach is rarely curative. Recent clinical trials have demonstrated that ADT combined with other agents, notably docetaxel and abiraterone, lead to improved survival. The mechanisms surrounding this improved cancer outcomes are incompletely defined. The response of cancer cells to ADT includes apoptosis and cell death, but a significant fraction remains viable. Our laboratory has demonstrated both in vitro and in vivo that cellular senescence occurs in a subset of these cells. Cellular senescence is a phenotype characterized by cell cycle arrest, senescence-associated ß-galactosidase (SA-ß-gal), and a hypermetabolic state. Positive features of cellular senescence include growth arrest and immune stimulation, although persistence may release cytokines and growth factors that are detrimental. Senescent tumor cells generate a catabolic state with increased glycolysis, protein turnover and other metabolic changes that represent targets for drugs, like metformin, to be applied in a synthetic lethal approach. This review examines the response to ADT and the putative role of cellular senescence as a biomarker and therapeutic target in this context.

The Impact of Agent Orange Exposure on Prostate Cancer Outcomes.

PURPOSE: In this study we explored the effect of Agent Orange exposure on prostate cancer survival in VA (Veterans Affairs) patients receiving androgen deprivation therapy for advanced prostate cancer. MATERIALS AND METHODS: We retrospectively examined the association between Agent Orange exposure in men with prostate cancer in national VA databases who were being treated with androgen deprivation therapy. Patients were diagnosed with prostate cancer from 2000 to 2008 with followup through May 2016. Clinical, pathological and demographic variables were compared by Agent Orange exposure. Associations of Agent Orange with overall survival, skeletal related events and cancer specific survival were performed using adjusted Cox proportional hazard models after IPSW (inverse propensity score weighted) adjustment. RESULTS: Overall 87,344 patients were identified. The 3,475 Agent Orange exposed patients were younger (p <0.001), had lower prostate specific antigen (p = 0.002) and were more likely to receive local therapy and chemotherapy (p <0.001) than the 83,869 nonexposed patients. The Charlson comorbidity index was similar in the groups (p = 0.40). After IPSW adjustment Agent Orange exposure was associated with improved overall survival (HR 0.84, 95% CI 0.73-0.97, p = 0.02). However, no difference was observed in the risk of skeletal related events (HR 1.04, 95% CI 0.80-1.35, p = 0.77) or cancer specific survival (HR 0.79, 95% CI 0.60-1.03, p = 0.08). CONCLUSIONS: Agent Orange exposure was associated with a decreased risk of death in men receiving androgen deprivation therapy for advanced prostate cancer. It does not appear to be associated with worse oncologic outcomes.