Distance to Treatment With Radical Cystectomy in a Rural State: Long Car Rides, Equivalent Outcomes.

INTRODUCTION: Radical cystectomy is a complex surgery with better outcomes reported when performed at high-volume centers. This may lead to patients traveling farther for care. We examined the impact of travel distance on clinical outcomes. METHODS: A total of 220 patients undergoing radical cystectomy from 2015-2021 were retrospectively reviewed. Distance traveled to the treatment center by patient zip codes was classified as <12.5 miles, 12.5-49.9 miles, and ≥50 miles. Multivariable logistic regression was used to assess complications, readmissions, 90-day mortality, and length of stay by distance traveled. Time to treatment based on distance traveled was compared. RESULTS: A total of 220 patients underwent radical cystectomy with complete 90-day follow-up. Of the patients 38.6% (85/220) were readmitted; 62.5% (53/85) presented to the treatment center or were transferred. All patients readmitted to an outside hospital traveled ≥12.5 miles (P < .001). Patients with high-grade complications were likely to be transferred to the treatment center with only 23.7% (9/38) definitively managed by outside hospital. Patients traveling >12.5 miles with low-grade complications were more likely to be managed at an outside hospital (57.5%, P = .01). There was no difference in time to initiation of neoadjuvant chemotherapy (P = .99) or time to radical cystectomy following neoadjuvant chemotherapy (P = .23) by distance traveled. For 49 muscle-invasive bladder cancer patients proceeding directly to surgery without neoadjuvant chemotherapy, time from diagnosis to radical cystectomy was increased if traveling >12.5 miles (P = .04). CONCLUSIONS: Increased travel distance did not impact early postoperative outcomes. Distance traveled may impact access to care, such as time to surgery or location of readmission to the treatment center postoperatively.

PRState: Incorporating genetic ancestry in prostate cancer risk scores for men of African ancestry.

BACKGROUND: Prostate cancer (PrCa) is one of the most genetically driven solid cancers with heritability estimates as high as 57%. Men of African ancestry are at an increased risk of PrCa; however, current polygenic risk score (PRS) models are based on European ancestry groups and may not be broadly applicable. The objective of this study was to construct an African ancestry-specific PrCa PRS (PRState) and evaluate its performance. METHODS: African ancestry group of 4,533 individuals in ELLIPSE consortium was used for discovery of African ancestry-specific PrCa SNPs. PRState was constructed as weighted sum of genotypes and effect sizes from genome-wide association study (GWAS) of PrCa in African ancestry group. Performance was evaluated using ROC-AUC analysis. RESULTS: We identified African ancestry-specific PrCa risk loci on chromosomes 3, 8, and 11 and constructed a polygenic risk score (PRS) from 10 African ancestry-specific PrCa risk SNPs, achieving an AUC of 0.61 [0.60-0.63] and 0.65 [0.64-0.67], when combined with age and family history. Performance dropped significantly when using ancestry-mismatched PRS models but remained comparable when using trans-ancestry models. Importantly, we validated the PRState score in the Million Veteran Program (MVP), demonstrating improved prediction of PrCa and metastatic PrCa in individuals of African ancestry. CONCLUSIONS: African ancestry-specific PRState improves PrCa prediction in African ancestry groups in ELLIPSE consortium and MVP. This study underscores the need for inclusion of individuals of African ancestry in gene variant discovery to optimize PRSs and identifies African ancestry-specific variants for use in future studies.

Total Synthesis of Mutanobactins†A, B from the Human Microbiome: Macrocyclization and Thiazepanone Assembly in a Single Step.

We report the first total syntheses of tricyclic mutanobactins A and B, lipopeptides incorporating a thiazepanone, isolated from Streptococcus mutans, a member of the human oral microbiome. A rapid, solid-phase peptide synthesis (SPPS) based route delivers these natural products from a cascade of cyclization reactions. This versatile process was also employed in a streamlined synthesis of mutanobactin D. Additionally, we provide an independent synthesis of a truncated mutanobactin A analog, utilizing a novel thiazepanone amino acid building block.

Mutanobactin D from the Human Microbiome: Total Synthesis, Configurational Assignment, and Biological Evaluation.

Mutanobactin D is a non-ribosomal, cyclic peptide isolated from Streptococcus mutans and shows activity reducing yeast-to-hyphae transition as well as biofilm formation of the pathogenic yeast Candida albicans. We report the first total synthesis of this natural product, which relies on enantioselective, zinc-mediated 1,3-dipolar cycloaddition and a sequence of cascading reactions, providing the key lipidated γ-amino acid found in mutanobactin D. The synthesis enables configurational assignment, determination of the dominant solution-state structure, and studies to assess the stability of the lipopeptide substructure found in the natural product. The information stored in the fingerprint region of the IR spectra in combination with quantum chemical calculations proved key to distinguishing between epimers of the α-substituted ß-keto amide. Synthetic mutanobactin D drives discovery and analysis of its effect on growth of other members of the human oral consortium. Our results showcase how total synthesis is central for elucidating the complex network of interspecies communications of human colonizers.

National Recommendations against Prostate Specific Antigen Screening versus Statewide Medicaid Expansion Initiatives: A Battle of the Titans.

PURPOSE: Medicaid expansion under the Patient Protection and Affordable Care Act occurred almost concurrently with 2012 U.S. Preventive Services Task Force recommendations against prostate specific antigen screening. Here the relative influence on prostate specific antigen screening rates by 2 concurrent and opposing system-level policy initiatives is investigated: improved access to care and change in clinical practice guidelines. MATERIALS AND METHODS: Behavioral Risk Factor Surveillance System data from years 2012 to 2018 were analyzed for trends in self-reported prostate specific antigen screening and insurance coverage. Subanalyses included state Medicaid expansion status and respondent federal poverty level. Multivariable logistic regression was performed to evaluate factors associated with prostate specific antigen screening. RESULTS: From 2012 to 2018 prostate specific antigen screening predominantly declined with a notable exception of an increase of 7.3% for men at <138% federal poverty level between 2011 and 2013 in early expansion states. Initial increases did not continue, and screening trends mirrored those of nonexpansion states by 2018. Notably, 2014 planned expansions states did not follow this trend with minimal change between 2015 and 2017 compared to declines in early expansion states and nonexpansion states (-0.4% vs -6.7% and -8.6%, respectively). CONCLUSIONS: Medicaid expansion was associated with increased rates of insured men at <138% federal poverty level from 2012 to 2018 in early expansion states. In this group, initial increases in prostate specific antigen screening were not durable and followed the trend of reduced screening seen across the United States. In planned expansions states the global drop in prostate specific antigen screening from 2016 to 2018 was offset in men at <138% federal poverty level by expanding access to care. Nonexpansion states showed a steady decline in prostate specific antigen screening rates. This suggests that policy such as U.S. Preventive Services Task Force recommendations against screening competes with and often outmatches access to care.

Meditative and mind-body practice among patients with genitourinary malignancy.

INTRODUCTION AND OBJECTIVE: Research on the utility of meditative and mind-body (MB) practices has increased dramatically in the last two decades and both have been suggested as useful adjuncts in coping with stressors associated with cancer survivorship. There exists little data on use among genitourinary (GU) cancer survivors. This study seeks to describe meditative and MB utilization among GU cancer survivors. METHODS: Analysis of data from the 2012 and 2017 National Health Interview Survey was conducted. Patients aged 40 and older reporting a history of any cancer diagnosis (including 3 GU cancers) were included in the analysis. We explored questions about meditative and MB practices in the past 12 months. Complex Samples Logistic regression was performed to compare the relationship between cancer status and use of these practices. RESULTS: Self-reported meditative practices were more prevalent in 2017 (17%) than in 2012 (5%). Patients who self-reported a cancer diagnosis of any kind were significantly more likely to utilize meditative practices. Patients with kidney cancer were significantly more likely to meditate and trended towards higher MB utilization. In contrast, bladder cancer patients were less likely to meditate and use MB practices. Increases in meditation were greater than those seen for MB in all groups. CONCLUSIONS: Meditative and MB practices increased in prevalence between 2012 and 2017 with notable heterogeneity between cancer types. Given the potential benefit, more broad incorporation into survivorship programs may be warranted. Future work should explore the significance of this heterogeneity and the utility of these practices to patients with urologic malignancy.

Impact of health literacy on shared decision making for prostate-specific antigen screening in the United States.

BACKGROUND: Current guidelines endorse shared decision making (SDM) for prostate-specific antigen (PSA) screening. The relationship between a patient's health literacy (HL) and SDM remains unclear. In the current study, the authors sought to identify the impact of HL on the rates of PSA screening and on the relationship between HL and SDM following the 2012 US Preventive Services Task Force recommendations against PSA screening. METHODS: Using data from the 2016 Behavioral Risk Factor Surveillance System, the authors examined PSA screening in the 13 states that administered the optional "Health Literacy" module. Men aged ≥50 years were examined. Complex samples multivariable logistic regression models were computed to assess the odds of undergoing PSA screening. The interactions between HL and SDM were also examined. RESULTS: A weighted sample of 12.249 million men with a rate of PSA screening of 33.4% were identified. Approximately one-third self-identified as having optimal HL. Rates of PSA screening were found to be highest amongst the highest HL group (42.2%). Being in this group was a significant predictor of undergoing PSA screening (odds ratio, 1.214; 95% confidence interval, 1.051-1.403). There was a significant interaction observed between HL and SDM (P for interaction, <.001) such that higher HL was associated with a lower likelihood of undergoing PSA screening when SDM was present. CONCLUSIONS: In the uncertain environment of multiple contradictory screening guidelines, men who reported higher levels of HL were found to have higher levels of screening. The authors demonstrated that increased HL may reduce the screening-promoting effect of SDM. These findings highlight the dynamic interplay between HL and SDM that should inform the creation and promulgation of SDM guidelines, specifically when considering patients with low HL.

Pathologic nodal downstaging in men with clinically involved lymph nodes undergoing radical prostatectomy: Implications for definitive locoregional therapy.

A prostate cancer (CaP) patient with nonmetastatic but clinical positive lymph nodes (cN+) represents a difficult clinical scenario. We compare overall survival (OS) between cN+ men that underwent radical prostatectomy (RP) and were found to have negative node status (pN) with those found to have positive nodal status (pN+), and assess predictors of discordant nodal status. We queried the National Cancer Data Base between 2004 and 2015 for patients that were cT1-3 cN+ cM0 CaP treated with RP. Patients with 0 nodes, cT4, or cM1 disease were excluded. We compared groups based on pathologic nodal status: Discordant (cN+ -> pN) & Concordant (cN+ -> pN+). Kaplan Meier estimations were used to compare OS. Logistic regression was used to determine possible predictors of nodal status. We find that of 6470 cN+ patients, 1,367 (21.1%) underwent RP, 866 (13.4%) had confirmed nodal status. Discordant status was found in 159 (18.4%) and concordant staging in 707 (81.6%). Differences exist in PSA at diagnosis (7.3 vs. 11.2), biopsy group, # of nodes examined (7 vs. 10), race, and Charlson index. Discordant staging had longer OS compared to Concordant staging (P = 0.007) and similar OS to a 3:1 matched cohort of high risk localized CaP patients used as reference (P = 0.46). Lower Gleason Score (GG1-3) was associated with an increased likelihood of discordant staging. Clinical nodal staging is associated with a substantial false positive rate. Discordant status had better OS than Concordant status and similar OS to matched patients with localized CaP. Clinical nodal staging may inappropriately lead to noncurative therapy in a substantial number of men with potentially curable disease.

Receipt of Survivorship Care Plans and Self-Reported Health Status among Patients with Genitourinary Malignancy.

PURPOSE: Implementation of survivorship care plans has been emphasized as a key component to improving care for cancer survivors. Our objective was to determine the prevalence of survivorship care plan receipt for survivors of genitourinary malignancy including kidney, prostate and bladder cancer, and evaluate whether receipt was associated with a measurable health benefit. MATERIALS AND METHODS: Data from the Behavioral Risk Factor Surveillance System Cancer Survivorship modules in 2012, 2014, 2016 and 2017 were analyzed. The proportion of patients with bladder, kidney or prostate cancer receiving a survivorship care plan was calculated. Complex samples multivariable logistic regressions were performed to determine the association of survivorship care plan receipt with sociodemographic variables, and assess the relationship between survivorship care plan receipt and self-reported health status (general, physical and mental). RESULTS: Survivorship care plan distribution increased from 27.5% in 2012 to 39.5% in 2017. Patients with low income, less formal education and extremes of age were less likely to receive a survivorship care plan. Those receiving a survivorship care plan were less likely to report poor physical health (OR 0.70, CI 0.52-0.96, p=0.026). Subanalysis showed a similar result for physical health of patients with prostate cancer (OR 0.68, CI 0.48-0.96, p=0.030) and general health of patients with kidney cancer (OR 0.37, CI 0.19-0.75, p=0.006). CONCLUSIONS: Distribution of survivorship care plans to genitourinary malignancy survivors has increased since 2012 in response to advocacy from national organizations. Nonetheless, utilization is low and there is heterogeneity in the populations likely to receive a survivorship care plan. There is a measurable association between survivorship care plans and improved health status but further study is needed to determine causality.

Prostate cancer navigation: initial experience and association with time to care.

OBJECTIVE: To evaluate factors associated with use of patient navigation in a prostate cancer population and identify whether navigation is associated with prolonged time to care. Cancer patient navigation has been shown to improve access to cancer screening, diagnosis, and treatment, but little is known about patient navigation in prostate cancer care. METHODS: All men diagnosed with localized prostate cancer between 2009 and 2015 were abstracted from the MaineHealth multi-specialty tumor registry. Regression analyses controlling for patient-, disease-, and system-level factors evaluated characteristics associated with navigation utilization. The association between navigation utilization, barriers to care, and longer time to treatment was assessed with Cox proportional hazards regression. RESULTS: Of the patient population (n = 1587), 85% of men were navigated. Navigation use was associated with earlier year of diagnosis, treatment by a high-volume urologist, and lower risk disease (p < 0.05). Treatment delay was associated with low-risk disease (vs: intermediate OR 0.62, 95% CI 0.46-0.85 and high OR 0.16, 95% CI 0.1-0.25) and receipt of navigation services (OR 1.65, 95% CI 1.12-2.45) but not distance to care, insurance, or treatment choice. CONCLUSIONS: We observed that patients with low-risk prostate cancer were more likely to utilize navigation, but traditional barriers to care were not associated with utilization. Navigation was associated with longer time to treatment, which likely reflects clinically appropriate delays associated with greater shared decision making. Time to treatment may not be the ideal metric for evaluating navigation in prostate cancer; shared decision making, patient satisfaction, and psychosocial outcomes may be more appropriate.

Impact of Volume and Type of Overnight Pages on Resident Sleep During Home Call.

BACKGROUND: Little research exists regarding factors that contribute to resident fatigue during home call. OBJECTIVE: We objectively tracked the number and type of pages received, as well as residents' sleep time, during home call. We then examined the relationship between paging volume, resident sleep, and resident fatigue. METHODS: A total of 4 of 4 urology residents (100%) at a single institution wore a FitBit Charge HR device from July 2015 to July 2016 to track sleep. Between January and July 2016, pages received by the on-call resident were counted as either floor (urology inpatient unit), clinic (after-hours answering service), or other. Postcall residents were defined as fatigued and excused at noon if they reported they were too tired to safely perform clinical duties. RESULTS: Residents slept an average of 408 minutes per night while not on call, versus 368 minutes while on call but not fatigued, and 181 minutes while on call and fatigued (P < .05). The most senior resident received fewer pages per night on average than the most junior resident. Each page was associated with 4.71 fewer minutes asleep on average for all residents. Pages in the other category were associated with 7.74 fewer minutes asleep per page for all residents, but only the most junior resident had significantly less sleep, 9.02 minutes, per floor page. CONCLUSIONS: Objective sleep data correlate with subjective assessment of resident fatigue and with volume and type of pages received. Senior residents spent less time awake per page and received fewer pages.

Prostate Cancer Screening in Early Medicaid Expansion States.

PURPOSE: The PPACA (Patient Protection and Affordable Care Act) of 2010 included a provision to expand Medicaid by 2014. Six states and jurisdictions elected to expand Medicaid early before 2012. This provided a natural experiment to test the association between expanded insurance coverage and preventive service utilization, including prostate cancer screening. MATERIALS AND METHODS: Using the 2012 and 2014 BRFSS (Behavioral Risk Factor Surveillance System) surveys we identified men 40 to 64 years old who reported prostate specific antigen testing in the preceding 12 months. Sociodemographic and access to care variables were extracted. Income was stratified by the relationship to Medicaid eligibility and the federal poverty level (less than 138%, 138% to 400% and greater than 400%). The weighted prevalence of prostate specific antigen was estimated. Multivariable logistic regression models were used to evaluate factors associated with prostate specific antigen screening. Interaction analysis for Medicaid expansion was performed. RESULTS: Among 158,103 respondents individuals in nonexpansion states had the highest incidence of prostate specific antigen screening. Nationally screening decreased between 2011 and 2013 (OR 0.87, 95% CI 0.83-0.91). In only early expansion states there was a 3% absolute increase in screening among men in the less than 138% federal poverty level, which was associated with expansion status (pinteraction = 0.04). Increased screening in early expansion states was also seen in men who were 55 to 59 years old, nonHispanic African American, Hispanic, previously married, not high school graduates and current smokers. CONCLUSIONS: Between 2011 and 2013 there were national declines in prostate cancer screening. However, there was significant narrowing of the gap in prostate specific antigen screening between higher and low income men in Medicaid early expansion states. This may reflect improved access to preventive services among populations with historic barriers to care.

Review of the comparative effectiveness of radical prostatectomy, radiation therapy, or expectant management of localized prostate cancer in registry data.

Evidence regarding the effectiveness of treatment for prostate cancer is primarily based on randomized controlled trials. Long-term outcomes are generally difficult to evaluate within experimental studies and may benefit from large pools of observational data. We conducted a systematic review of administrative and registry studies to evaluate the comparative effectiveness of treatment for clinically localized prostate cancer on overall and prostate-cancer specific mortality. MATERIALS AND METHODS: In accordance with the preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P, 2015), we conducted a systematic search of Ovid Medline and Embase (1946-February 2017) and identified studies that evaluated the relationship between types of treatment for localized prostate cancer and mortality. Additional articles were identified through manual search. Randomized, prospective, and single institution studies were excluded. The risk of bias for each study was evaluated with the Newcastle Ottawa scale. Multivariable adjusted hazard ratios were reported to evaluate overall and cancer-specific mortality. RESULTS: We screened 4,721 studies and included for review, 19 that were published between 2001 and 2015. The pooled population included 228,444 patients. Countries of origin included the United States, Canada, China, Switzerland, the Netherlands, and Sweden, and the sources included administrative (n = 6) and cancer registry or prostate databases (n = 11). Overall and cancer-specific mortality were lowest among definitive treatment arms as compared to conservative therapy with no treatment, observation, or active surveillance. Radiotherapy was associated with worse overall and cancer-specific mortality than radical prostatectomy. CONCLUSION: Although observational studies using large, population-based cohorts have the potential for bias, we found consistent evidence that high-quality observational studies may be used to evaluate the comparative effectiveness of prostate cancer treatment. Methodologic limitations of observational data should be considered.

The Association between Mortality and Distance to Treatment Facility in Patients with Muscle Invasive Bladder Cancer.

PURPOSE: Regionalization of bladder cancer treatment is suggested to improve quality of care. As an unintended consequence some patients travel farther for care with unknown implications on outcomes. We characterized the relationship between distance and overall mortality in patients with invasive bladder cancer and those who underwent radical cystectomy. MATERIALS AND METHODS: We performed a retrospective cohort study using NCDB (National Cancer Database) from 2004 to 2012 to identify patients with muscle invasive bladder cancer (cT2a-T4 N0 M0). We also extracted a subgroup of patients who underwent radical cystectomy. Multivariate Cox proportional hazards and multinomial logistic regression analyses were performed in each group, controlling for demographic, clinical, hospital and geographic factors. RESULTS: For 34,729 patients with muscle invasive bladder cancer traveling farther for treatment was associated with a lower probability of overall mortality (referent less than 12.5 miles, 12.5 to 49.9 miles HR 0.96, 95% CI 0.92-0.99 and 50 to 249.9 miles HR 0.91, 95% CI 0.86-0.96). This was significant for patients with cT2 disease and those treated at academic centers (p ≤0.05). For 11,059 patients who underwent radical cystectomy this trend did not reach significance. However, longer distance was associated with surgery at a high volume institution and receipt of neoadjuvant chemotherapy (each p <0.001). CONCLUSIONS: Patients who traveled farther for bladder cancer treatment did not experience inferior survival outcomes and traveling to academic institutions was associated with reduced mortality. For patients who undergo cystectomy this relationship was equivocal, although longer distance was associated with receiving neoadjuvant chemotherapy or surgery at a high volume facility. These findings may reflect a complex association of regionalization of bladder cancer care with patient individual health and health care seeking behavior.

The evolution of uncertainty in second opinions about prostate cancer treatment.

BACKGROUND: People who have cancer increasingly seek second opinions. Yet, we know little about what motivates patients to seek them and how beneficial they are. Uncertainty-experienced by patients or communicated by physician and patient-may be crucial throughout the second opinion process. OBJECTIVE: This study sought to investigate (1) how uncertainty influences men with prostate cancer to seek second opinions and (2) how second opinions may affect these patients' sense of uncertainty and subsequent experiences with their care. METHODS: A qualitative study using semi-structured interviews was performed. Men with localized or advanced prostate cancer (n=23) were interviewed by telephone about their motivations and experiences with seeking second opinions and the uncertainties they experienced. Analysis was performed using the constant comparative method. RESULTS: Patients sought second opinions because they were uncertain about receiving too little or biased information, experienced insufficient support in coming to a treatment decision, or because physicians expressed different levels of uncertainty than they did ("unshared uncertainty"). Uncertainty was reduced by the second opinion process for most patients, whereas for others, it increased or was sustained. This evolution depended on the way uncertainty was addressed during the second opinion consultation. CONCLUSIONS: Second opinions may be a useful tool for some but not all patients. They should be used judiciously and not be viewed as a solution for current limitations to health-care organization. An important yet challenging task for physicians is to focus less on information per se and more on how to assist patients manage irreducible uncertainty.

The Use of Bowel in Urologic Reconstructive Surgery.

Intestinal surgery involves an operative space shared by both general surgeons and urologists and is a border region where these 2 surgical disciplines often intersect. Urologists routinely use both small and large bowel for reconstructive procedures and surgeons often encounter such reconstructions of the urinary tract. It is essential for surgeons to understand the urologic indications for using intestinal segments for reconstructive procedures, the variety of such reconstructions, the anatomic landmarks and potential pitfalls that should be considered when intraoperatively encountering such reconstructions, and the potential metabolic consequences of the incorporation of bowel segments into the urinary collecting system.

Use of percutaneous nephrostomy and ureteral stenting in management of ureteral obstruction.

The management options for ureteral obstruction are diverse, including retrograde ureteral stent insertion or antegrade nephrostomy placement, with or without eventual antegrade stent insertion. There is currently no consensus on the ideal treatment or treatment pathway for ureteral obstruction owing, in part, to the varied etiologies of obstruction and diversity of institutional practices. Additionally, different clinicians such as internists, urologists, oncologists and radiologists are often involved in the care of patients with ureteral obstruction and may have differing opinions concerning the best management strategy. The purpose of this manuscript was to review available literature that compares percutaneous nephrostomy placement vs ureteral stenting in the management of ureteral obstruction from both benign and malignant etiologies.