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Objective: To assess whether patient factors, such as age and preoperative kidney function, were associated with receipt of partial nephrectomy in a national integrated healthcare system.Materials and Methods: We identified patients treated with a radical or partial nephrectomy from 2002 to 2014 in the Veterans Health Administration. We examined associations among patient age, sex, race or ethnicity, multimorbidity, baseline kidney function, tumor characteristics, and receipt of partial nephrectomy. We estimated the odds of receiving a partial nephrectomy and assessed interactions between covariates and the year of surgery to explore whether patient factors associated with partial nephrectomy changed over time.Results: In our cohort of 14,186 patients, 4508 (31.2%) received a partial nephrectomy. Use of partial nephrectomy increased from 17% in 2002 to 32% in 2008 and to 38% in 2014. Patient race or ethnicity, age, tumor stage, and year of surgery were independently associated with receipt of partial nephrectomy. Black veterans had significantly increased odds of receipt of partial nephrectomy, whereas older patients had significantly reduced odds. Partial nephrectomy utilization increased for all groups over time, but older patients and patients with worse baseline kidney function showed the least increase in odds of partial nephrectomy.Conclusion: Although the utilization of partial nephrectomy increased for all groups, the greatest increase occurred in the youngest patients and those with the highest baseline kidney function. These trends warrant further investigation to ensure that patients at the highest risk of impaired kidney function are considered for partial nephrectomy whenever possible. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: We sought to examine the trends in perioperative outcomes of kidney cancer surgery stratified by type (radical nephrectomy [RN] vs. partial nephrectomy [PN]) and approach (open vs. minimally invasive). Methods: We queried the National Surgical Quality Improvement Program database to identify kidney cancer operations performed from 2005 to 2011. We examined 30-day perioperative outcomes including operative time, transfusion rate, length of stay, major morbidity (cardiovascular, pulmonary, renal, and infectious), and mortality. Results: A total of 2,902 PN and 5,459 RN cases were identified. The use of PN increased over time, accounting for 39% of all nephrectomies in 2011. Minimally invasive approaches also increased over time for both RN and PN. Open surgery was associated with increased length of stay, receipt of transfusion, major complications, and perioperative mortality. Resident involvement and open approach were independent predictors of major complications for both PN and RN. Additionally, the presence of a medical comorbidity was also a risk factor for complications after RN. The overall complication rates decreased for all approaches over the study period. Conclusions: Minimally invasive approaches to kidney cancer renal surgery have increased with favorable outcomes. The safety of open and minimally invasive PN improved significantly over the study period. Although pathologic features cannot be determined from this data set, these data show that complications from renal surgical procedures are decreasing in an era of increasing use. [Copyright &y& Elsevier]

Objective: To examine the patient, tumor, and temporal factors associated with receipt of renal mass biopsy (RMB) in a contemporary nationally representative sample. Methods: We queried the Surveillance, Epidemiology, and End Results-Medicare data set for incident cases of renal cell carcinoma diagnosed between 1992 and 2007. We tested for associations among receipt of RMB and patient and tumor characteristics, type of therapy, and procedure type. Temporal trends in receipt of RMB were characterized over the study period. Results: Approximately 1 in 5 (20.7%) patients diagnosed with renal cell carcinoma (n = 24,702) underwent RMB before instituting therapy. There was a steady and modest increase in RMB utilization, with the highest utilization (30%) occurring in the final study year. Of patients who underwent radical (n = 15,666) or partial (n = 2211) nephrectomy, 17% and 20%, respectively, underwent RMB in advance of surgery. Sixty-five percent of patients who underwent ablation (n = 314) underwent RMB before or in conjunction with the procedure. Roughly half of patients (50.4%) treated with systemic therapy alone underwent RMB. Factors independently associated with use of RMB included younger age, black race, Hispanic ethnicity, tumor size <7 cm, and metastatic disease at presentation. Conclusion: At present, most patients who eventually undergo radical or partial nephrectomy do not undergo RMB, whereas most patients who eventually undergo ablation or systemic therapy do. The optimal use of RMB in the evaluation of kidney tumors has yet to be determined. [Copyright &y& Elsevier]

Abstract: Objectives: To explore the underlying mechanism of tumor regrowth in cases of noninvasive urothelial carcinoma that recur in unusual anatomic locations. Methods: The pathology files of our institution and the consult service of one of us were searched for cases of noninvasive nonmetastatic urothelial carcinoma with involvement of unusual anatomic sites. Cases in which the mode of spread included direct spread to the adjacent tissue and lymphovascular metastases were excluded. Medical history, including presenting symptoms, and follow-up data were obtained. Results: Two cases of noninvasive urothelial carcinoma were identified. One had presented as an implant in the peritoneal investment of the bladder dome and the other as multiple implants growing on the benign surface of the colonic mucosa of an orthotopic neobladder distant from the anastomosis site. Both cases had initially presented as noninvasive papillary urothelial carcinoma of the renal pelvis. Although the urinary bladder was free of neoplastic changes at nephroureterectomy, both patients also developed several papillary tumors within the bladder shortly after the removal of the kidney. Conclusions: After clinicopathologic correlation, the mode of tumor spread in these cases was best explained by the “seeding/implantation” theory. The urothelial tumor cells in each of these cases demonstrated the ability to implant themselves not only in the urothelium of the bladder but also in the colonic mucosa of a constructed neobladder and on the peritoneal surface. [Copyright &y& Elsevier]

Abstract: Recent advances in the understanding of the pathogenesis, behavior, and molecular biology of renal cell carcinoma (RCC) have paved the way for developments that may enhance early diagnosis, better predict prognosis, and improve survival. Reliable predictive factors are essential for the stratification of patients into clinically meaningful categories that can be used to provide patients with counseling regarding prognosis, select treatment modalities, and determine eligibility for clinical trials. The TNM (tumor, nodes, metastasis) staging system is currently the most extensively used staging system for RCC, but it has undergone systematic revisions as a result of emerging data. Comprehensive integrated staging systems that combine important clinical and pathological variables have been created in an attempt to improve prognostication. Although staging has improved with the development of integrated systems, the incorporation of molecular tumor markers are expected to revolutionize the staging of RCC. This article reviews the important molecular markers in RCC to date and discusses their role in the diagnosis, prognostication, and therapy of patients with RCC. [Copyright &y& Elsevier]

1. Identify opportunities to improve perioperative communication about goals for patients with urologic serious illness. 2. Understand the value of having both Palliative Care Specialists and Urologists involved in preoperative conversations about patient goals. A joint Urology-Palliative Care team approach to navigating patient goals is warranted in advance of surgery for patients with urologic serious illness. In coordination, Urologists and PC can offer complementary contributions to different parts of a goals of care conversations, covering both goals of care generally and developing shared understanding of risks and realistic expectations of what surgery can achieve. Care for urologic serious illness often includes surgery; preoperative shared decision making about patient goals is often inadequately implemented in surgical settings. To understand perspectives on improving perioperative communication about goals for patients facing urologic serious illness. We conducted 37 semi-structured interviews with Palliative Care Physicians (PC) (11), Urologists (13) and interdisciplinary clinicians (13) at fourteen geographically distributed Veteran Health Administration (VHA) sites. The analytic approach relied on content analysis with dual review; analysis is conducted separately by provider type and triangulated. 1) In existing pre-operative workflows: "patients are not [always] aware that we might be able to palliate their symptoms without surgery" (URO). 2) Goal of surgery is often something patients really need help understanding, e.g. "It's gonna help temporarily, but it's not gonna help long term" (PC). 3) PC is not in the position to have the part of the goal of care conversation that clarifies the goal of the surgery: "it's very hard for non-surgeon to have a robust goals of care discussion with the patient who's co-managed with surgery unless surgery is able to give you a sense of what to expect." (PC) 4) A team approach to clarifying and navigating patient goals is warranted: "how do we work together to sort of think about prognosis, how to plan ahead for care after the surgery and then setting sort of real realistic expectations and goals for after the surgery?"(PC). 5) In coordination, Urologists and PC can offer complementary contributions to different parts of a goals of care conversation: "the interventionists would better know how effective the intervention is going to be, but PC probably has much better perspective on how the patient is doing overall." (URO) Patients will benefit from a urology-PC team approach to clarifying goals of care and surgery. Shared Decision Making / Advance Care Planning / Surgical / Palliative Care [ABSTRACT FROM AUTHOR]

Equations estimating the glomerular filtration rate are important clinical tools in detecting and managing kidney disease. Urologists extensively use these equations in clinical decision making. For example, the estimated glomerular function rate is used when considering the type of urinary diversion following cystectomy, selecting systemic chemotherapy in managing urologic cancers, and deciding the type of cross-sectional imaging in diagnosing or staging urologic conditions. However, these equations, while widely accepted, are imprecise and adjust for race which is a social, not a biologic construct. The recent killings of unarmed Black Americans in the US have amplified the discussion of racism in healthcare and has prompted institutions to reconsider the role of race in estimation of glomerular filtration rate equations and raced-based medicine. Urologist should be aware of the consequences of removing race from these equations, potential alternatives, and how these changes may affect Black patients receiving urologic care. [ABSTRACT FROM AUTHOR]

1. Identify time points along the perioperative continuum where PC and Urology can be better integrated. 2. Understand the importance of the perioperative period as a focus for future interventions to improve quality of care in patients facing urologic serious illness. Stakeholder interviews reveal a general overall need to create a culture change so that palliative care is integrated appropriately for patients with urologic serious illness. Many urologic serious illnesses are treated with surgical procedures, which may put patients at a further risk of diminished quality of life. To understand stakeholder perceptions on integrating perioperative Palliative Care (PC) for patients with serious urologic illness. We conducted semi-structured interviews with purposefully sampled palliative care physicians (11), urologists (13), and clinical team members (13) at eleven geographically distributed Veteran Health Administration sites. Team-based thematic analysis was conducted to consensus with a dual review in Atlas.ti. We identified one general overall theme and three themes representing needs along the perioperative continuum as opportunities for integrating PC and urology. The general overall need was to "change culture" so that PC is not a "last resort" and "ideally, we would be starting palliative [care], when [we] start curative [treatment]." Opportunity 1: Utilizing telehealth and team member role expansion when discussing diagnosis and treatment options, with urologic surgery as a potential treatment, allows for multiple conversations "so they're not rushed in 15 minutes to mentally deal with the new diagnosis of cancer." Opportunity 2: Creating a process to ensure goal of surgery conversations occur with both urologists and PC, since "urologic procedures can have complications that significantly impact quality of life," which "would require changing how our workflow is structured." Opportunity 3: During the pre-operative visits, there can be interdisciplinary input and evaluation of the patient prior to surgery, so that the patient can "have a sort of joint meeting with us and the urologist." This represented the last point in time to de-escalate and offer non-surgical options prior to surgery. The study informs future interventions to improve the quality of care by integrating palliative care with urology. Future work can build on these findings by implementing the opportunities and determining how it impacts patient outcomes. Interdisciplinary Teamwork/Professionalism/Qualitative and Mixed Methods Research [ABSTRACT FROM AUTHOR]

Objective: To determine whether 24-hour urine testing in Veterans with USD (urinary stone disease) reduces or delays urinary stone recurrence.Methods: Cohort study of national health record data from Veterans Health Administration from 2007 through 2013. We utilized a study population of 130,129 Veterans with USD based on diagnostic or procedural codes and excluded those with USD claims in the 2 years before cohort entry. We then created a propensity-score matched cohort of 14,854 Veterans based on completion of 24-hour urine testing within 6 months of stone diagnosis. Primary outcome was time-to-next clinically significant stone event, defined as an emergency department visit, inpatient admission related to a urinary stone, or urologic stone procedure with 5-year follow up.Results: Of 14,854 Veterans in the propensity-score matched cohort, 8560 (57.6%) experienced a recurrent USD event. Completion of 24-hour urine testing was associated with a higher risk of developing a second stone event (hazard ratio [HR] 1.17, 95% confidence interval [95% CI] 1.12-1.22). Among Veterans with known recurrent disease, we examined time to a third stone event. In this cohort of 4736 patients, completion of 24-hour urine testing was not associated with a higher risk of developing a third stone event (HR 1.06, 95% CI 0.99-1.12).Conclusion: Completion of 24-hour urine testing was not associated with a reduction in urinary stone recurrence. These findings challenge the validity of a longstanding recommendation in general medicine, nephrology, and urology practice. [ABSTRACT FROM AUTHOR]

Abstract: Background: External shock wave lithotripsy (ESWL) and percutaneous nephrolithotomy (PNL) have been the standard of care for the treatment of intrarenal calculi. Objective: We sought to determine the safety and efficacy of flexible ureteroscopy and holmium laser lithotripsy for the treatment of multiple intrarenal calculi and further stratify the efficacy by stone burden less than and greater than 20mm. Design, setting, and participants: Patients with multiple unilateral renal calculi treated between 2000 and 2006 at a single tertiary academic center were retrospectively evaluated. Intervention: All patients underwent retrograde flexible ureteroscopy and holmium laser lithotripsy. Measurements: Stone-free status was determined by ureteroscopy 15 d after the last procedure and was defined as the absence of stones in the kidney or residual fragments <1mm. A renal ultrasound was performed 30 d after the last treatment to confirm the absence of stones and hydronephrosis. Results and Limitations: Fifty-one patients were identified for a total of 161 intrarenal calculi with a mean stone size per patient of 6.6±3mm (range: 2–15). The mean number of stones per patient was 3.1±1 (range: 2–6). The mean number of primary procedures was 1.4±0.6 (range: 1–3). The overall stone-free rates after one and two procedures were 64.7% and 92.2%, respectively. The stone-free rates for patients with a stone burden greater than and less than 20mm were 85.1% and 100%, respectively. The overall complication rate was 13.6%; 97.6% of cases were performed as outpatient procedures. There are some limitations to this study, however: This is a retrospective review from a single institution, and our results are based on a relatively small sample size. Conclusions: For select patients with multiple intrarenal calculi, flexible ureteroscopy with holmium laser lithotripsy may represent an alternative therapy to ESWL or PNL, with acceptable efficacy and low morbidity. [Copyright &y& Elsevier]

Unlabelled Image • The optimal anesthetic technique for transurethral resection surgery is not known. • Spinal and general anesthesia are commonly performed for these surgeries. • Spinal anesthesia is associated with a higher-rate of opioid-free recovery. • There are no major outcome differences between anesthetic techniques. [ABSTRACT FROM AUTHOR]

Objectives: To determine if an automatically calculated electronic health record score can estimate intermediate-term life expectancy in men with prostate cancer to provide guideline concordant care.Methods: We identified all men (n = 36,591) diagnosed with prostate cancer in 2013-2015 in the VHA. Of the 36,591, 35,364 (96.6%) had an available Care Assessment Needs (CAN) score (range: 0-99) automatically calculated in the 30 days prior to the date of diagnosis. It was designed to estimate short-term risks of hospitalization and mortality. We fit unadjusted and multivariable Cox proportional hazards regression models to determine the association between the CAN score and overall survival among men with prostate cancer. We compared CAN score performance to two established comorbidity measures: The Charlson Comorbidity Index and Prostate Cancer Comorbidity Index (PCCI).Results: Among 35,364 men, the CAN score correlated with overall stage, with mean scores of 46.5 ( ± 22.4), 58.0 ( ± 24.4), and 68.1 ( ± 24.3) in localized, locally advanced, and metastatic disease, respectively. In both unadjusted and adjusted models for prostate cancer risk, the CAN score was independently associated with survival (HR = 1.23 95%CI 1.22-1.24 & adjusted HR = 1.17 95%CI 1.16-1.18 per 5-unit change, respectively). The CAN score (overall C-Index 0.74) yielded better discrimination (AUC = 0.76) than PCCI (AUC = 0.65) or Charlson Comorbidity Index (AUC = 0.66) for 5-year survival.Conclusion: The CAN score is strongly associated with intermediate-term survival following a prostate cancer diagnosis. The CAN score is an example of how learning health care systems can implement multi-dimensional tools to provide fully automated life expectancy estimates to facilitate patient-centered cancer care. [ABSTRACT FROM AUTHOR]

Objective: To define current national practice patterns of imaging modalities and urologic procedures in pregnant women with urinary stone disease.Methods: Using the IBM MarketScan national insurance claims database, we identified pregnant women with urinary stone disease and their corresponding gestational age between 2011 and 2016 using administrative claims data. We then assessed each encounter for urinary stone disease or stone-related urologic procedure during their pregnancy. We abstracted demographic information as well as codes for stone procedures and imaging.Results: We identified 14,298 pregnant women with urinary stone disease during the study period. Of the 12,315 undergoing abdominal imaging (86.1%), magnetic resonance imaging was used in 2.8%, x-ray in 9%, and ultrasound in 74.3%. Computed tomography was not used as a diagnostic modality during pregnancy. Procedural intervention was performed in 749 women (5.2%): 476 (3.3%) ureteral stent placement without definitive stone treatment, 93 (0.6%) percutaneous nephrostomy placement, and 180 (1.3%) ureteroscopy (URS) for definitive stone treatment. URS was most commonly performed before 34 weeks gestation with only 27 cases (15%) performed after.Conclusion: This large national cohort reveals the current imaging and procedural practice patterns for urinary stone disease during pregnancy and provides a critical baseline as these practice patterns evolve in the future. [ABSTRACT FROM AUTHOR]

Objective: To evaluate unplanned medical visits within the early postoperative period after ureteroscopy in patients with and without ureteral stent placement.Materials and Methods: We identified all ureteroscopic procedures for urinary stone disease in the California Office of Statewide Health Planning and Development database from 2010 to 2012. The primary outcome was any emergency department visit or inpatient hospital admission in the first 7 days following ureteroscopy. Patients were subcategorized by type of ureteroscopy (ie, laser lithotripsy vs basket retrieval) and were analyzed for significant differences between stented and unstented patients. Multivariable logistic regression was performed to determine if ureteral stent placement was independently associated with unplanned visits.Results: Our analytic cohort included 16,060 patients undergoing 17,716 ureteroscopy procedures. A ureteral stent was placed in 86.2% of patients undergoing laser lithotripsy and in 70.5% of patients receiving basket retrieval. In the 7 days following ureteroscopy, 6.6% of patients were seen in the emergency department and 2.2% of patients were admitted to a hospital. In a fully adjusted model, the utilization of a ureteral stent was not associated with emergency department visits or inpatient admissions.Conclusion: Ureteral stent placement during ureteroscopy is not associated with an increased odds of emergency department visits and inpatient admissions in the early postoperative period. [ABSTRACT FROM AUTHOR]

• Cost-effectiveness analysis of therapies for low/intermediate-risk prostate cancer across range of life expectancies. • Active surveillance dominates surgery/radiation (more effective and less costly) when life expectancy is <10 years in both low and intermediate-risk prostate cancer. • For longer life expectancy, active surveillance fails to dominate primarily due to its high cost. • Active surveillance costs for men with longer life expectancy must be reduced. Life expectancy (LE) impacts effectiveness and morbidity of prostate cancer (CaP) treatment, but its impact on cost-effectiveness is unknown. We sought to evaluate the impact of LE on the cost-effectiveness of radical prostatectomy (RP), radiation therapy (RT), and active surveillance (AS) for clinically localized disease. We created a Markov model to calculate incremental cost-effectiveness ratios (ICERs) for RP, RT, and AS over a 20-year time horizon from a Medicare payer perspective for low- and intermediate-risk CaP. Mortality outcomes varied by tumor risk and PCCI score, a validated proxy for LE. We performed 1,000 Monte Carlo simulations with 1-way sensitivity analyses of PCCI within each tumor risk subgroup to compare cost/quality-adjusted life years (QALYs) between treatments. AS dominated RP and RT for low- and intermediate-risk disease in men with LE ≤10 years (PCCI ≥7 and ≥9, respectively). However, AS failed to dominate RP and RT for men with longer LE. For men with low-risk cancer and LE>10 years (PCCI 0–6), AS had the greatest effectiveness, but failed to dominate due to higher cost relative to RP. For men with intermediate-risk cancer with LE>10 years, AS failed to dominate due to higher cost relative to RP (PCCI 0–8) and lower effectiveness relative to RT (PCCI 0–3). The range of QALYs between RP, RT, and AS varied <13% (range: 0%–12.9%) while costs varied up to 521% (range 0.5%–521%) across PCCI scores. LE strongly modulates the cost of CaP treatments. This results in AS dominating RP and RT in men with LE ≤10 years. However, in men with longer LE, AS fails to dominate primarily due to its high cumulative costs, underscoring the need for risk-adjusted AS protocols. [ABSTRACT FROM AUTHOR]

A better understanding of overall survival among patients with clinically localized prostate cancer (PCa) in the US Veterans Health Administration (VHA) is critical to inform PCa treatment decisions, especially in light of data from the Prostate Intervention Versus Observation Trial (PIVOT). We sought to describe patterns of survival for all patients with clinically localized PCa treated by the VHA. We created an analytic cohort of 35 954 patients with clinically localized PCa diagnosed from 1995 to 2001, approximating the PIVOT inclusion criteria (age of diagnosis ≤75 yr and clinical stage T2 or lower). Mean patient age was 65.9 yr, and median follow-up was 161 mo. Overall, 22.5% of patients were treated with surgery, 16.6% were treated with radiotherapy, and 23.1% were treated with androgen deprivation. Median survival of the entire cohort was 14 yr (25th, 75th percentiles, range: 7.9–20 yr). Among patients who received treatment with curative intent, median survival was 17.9 yr following surgery and 12.9 yr following radiotherapy. One-third of patients died within 10 yr of diagnosis compared with nearly half of the participants in PIVOT. This finding sounds a note of caution when generalizing the mortality data from PIVOT to VHA patients and those in the community. Patient summary More than one-third of patients diagnosed with clinically localized prostate cancer treated through the US Veterans Health Administration from 1995 to 2001 died within 10 yr of their diagnosis. Caution should be used when generalizing the estimates of competing mortality data from PIVOT. [ABSTRACT FROM AUTHOR]

Abstract: Background: The prevalence of kidney stone disease is rising along with increasing rates of obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome. Objective: To investigate the associations among the presence and severity of T2DM, glycemic control, and insulin resistance with kidney stone disease. Design, setting, and participants: We performed a cross-sectional analysis of all adult participants in the 2007–2010 National Health and Nutrition Examination Survey (NHANES). A history of kidney stone disease was obtained by self-report. T2DM was defined by self-reported history, T2DM-related medication usage, and reported diabetic comorbidity. Insulin resistance was estimated using fasting plasma insulin (FPI) levels and the homeostasis model assessment of insulin resistance (HOMA-IR) definition. We classified glycemic control using glycosylated hemoglobin A1c (HbA1c) and fasting plasma-glucose levels (FPG). Outcome measurements and statistical analysis: Odds ratios (OR) for having kidney stone disease were calculated for each individual measure of T2DM severity. Logistic regression models were fitted adjusting for age, sex, race/ethnicity, smoking history, and the Quételet index (body mass index), as well as laboratory values and components of metabolic syndrome. Results and limitations: Correlates of kidney stone disease included a self-reported history of T2DM (OR: 2.44; 95% confidence interval [CI], 1.84–3.25) and history of insulin use (OR: 3.31; 95% CI, 2.02–5.45). Persons with FPG levels 100–126mg/dl and >126mg/dl had increased odds of having kidney stone disease (OR 1.28; 95% CI, 0.95–1.72; and OR 2.29; 95% CI, 1.68–3.12, respectively). Corresponding results for persons with HbA1c 5.7–6.4% and ≥6.5% were OR 1.68 (95% CI, 1.17–2.42) and OR 2.82 (95% CI, 1.98–4.02), respectively. When adjusting for patient factors, a history of T2DM, the use of insulin, FPI, and HbA1c remained significantly associated with kidney stone disease. The cross-sectional design limits causal inference. Conclusions: Among persons with T2DM, more-severe disease is associated with a heightened risk of kidney stones. [Copyright &y& Elsevier]

Background: Prognostic models for patients with metastatic renal cell carcinoma (mRCC) include select laboratory values. These models have important limitations, including reliance on a limited array of laboratory tests, and use of dichotomous ("high-low") cutoffs. We applied a Laboratory-Wide Association Study (LWAS) framework to systematically evaluate common clinical laboratory results associated with survival for patients diagnosed with mRCC.Methods: We used laboratory data for 3,385 patients diagnosed with mRCC from 2002 to 2017. We developed a LWAS framework, to examine the association with 53 common clinical laboratory tests results (641,712 measurements) and overall survival. We employed false-discovery rate to test the association of multiple laboratory tests with survival, and validated these results using 3 separate cohorts to generate a standardized hazard ratio (sHR), reported for a 1 standard deviation unit change in each laboratory test.Results: The LWAS approach confirmed the association of laboratory values currently used in prognostic models with survival, including calcium (HR 1.35, 95%CI 1.24-1.48), leukocyte count (HR 1.40, 95%CI 1.30-1.51), platelet count (HR 1.36, 95%CI 1.27-1.51), and hemoglobin (HR 0.79, 95%CI 0.72-0.86). Use of these tests as continuous variables improved model performance. LWAS also identified acute phase reactants associated with survival not typically included in prognostic models, including serum albumin (HR 0.66, 95%CI 0.61-0.72), ferritin (HR 1.25, 95%CI 1.08-1.45), alkaline phosphatase (HR 1.31, 95%CI 1.23-1.40), and C-reactive protein (HR 1.70, 95%CI 1.14-2.53).Conclusions: Routinely measured laboratory tests can refine current prognostic models, facilitate comparisons across clinical trial cohorts, and match patients with specific systemic therapies. [ABSTRACT FROM AUTHOR]

OBJECTIVE To determine the extent to which the year of diagnosis, year of birth, and age at diagnosis influence the incidence trends of kidney cancer in the United States. METHODS Cancer registry data from the National Cancer Institute's Surveillance, Epidemiology, and End- Results (SEER) program were obtained for 64,041 patients with kidney cancer diagnosed between 1973 and 2008. Overall and age-specific incidence rates were calculated and adjustments were made for birth cohort and period effects. Results were stratified by race and sex. Age-period-cohort analysis was used to examine the effects of age, year of diagnosis (period), and year of birth (cohort) on incidence trends. RESULTS The overall age-standardized annual incidence per 100,000 increased during the study period (1973 to 2008) by race, from 6.75 (95% confidence interval, 6.18-7.36) to 19.56 (18.85-20.20) among whites, from 5.31 (3.50-7.71) to 25.38 (23.00-27.92) among blacks, and from 5.61 (3.50-8.50) to 13.98 (12.41-15.71) among other races; and by sex, from 9.44 (8.49-10.47) to 26.48 (25.39-27.60) among men and from 4.21 (3.65-4.84) to 13.38 (12.64-14.11) among women. Age-period-cohort analysis revealed a strong influence from period and cohort effects. The 1983 birth cohort, for example, had a 2-fold increase in kidney cancer (incidence rate ratio, 1.93 [1.63-2.25]) compared with the referent 1948 cohort. CONCLUSION From 1973 to 2008, the incidence rate of kidney cancer increased for each sex and race across all age groups. Age-period-cohort models revealed that period-related factors, although significant, cannot alone account for these unfavorable temporal trends. [ABSTRACT FROM AUTHOR]

Abstract: Background: While it is well known that clear cell renal cell carcinoma (ccRCC) that presents with lymphatic spread is associated with an extremely poor prognosis, its molecular and genetic biology is poorly understood. Objective: Define the clinicopathologic, molecular, and genetic biological characteristics of these tumors in comparison to nonmetastatic (N0M0) renal cell carcinomas. Design, setting, and participants: A retrospective study defined clinicopathologic features, expression of 28 molecular markers, and occurrence of chromosomal aberrations for their correlation with lymphatic spread in three cohorts of 502, 196, and 272 patients, respectively. Measurements: Fisher exact test or the χ2 test were used to compare categorical variables; continuous variables were compared with the Mann-Whitney U test or student t test. Cut-off values were calculated based on receiver operating characteristic curves and the Youden Index. Uni- and multivariate regression analyses were used to investigate the correlation with lymphatic spread. Results and limitations: In clinical analyses, a predictive model consisting of smoking history (p =0.040), T stage (p <0.0001), Fuhrman grade (p <0.0001), Eastern Cooperative Oncology Group performance status (p <0.0001), and microvascular invasion (p <0.0001) was independently associated with lymphatic spread. After adjustment with these clinical variables, low carbonic anhydrase IX (CAIX) (p =0.043) and high epithelial vascular endothelial growth factor receptor 2 (p =0.033) protein expression were associated with a higher risk of lymphatic spread, and loss of chromosome 3p (p <0.0001) with a lower risk. The current study is limited by its retrospective design, small sample size, and single-center experience. Conclusions: The low rates of CAIX expression and loss of chromosome 3p suggest that lymphatic spread in ccRCC occurs independently of von Hippel-Lindau tumor suppressor inactivation. [Copyright &y& Elsevier]

Objectives: Carbonic anhydrase-IX (CA-IX) is a cell surface tumor-associated antigen expressed by most clear cell renal cell carcinomas (RCCs). The specificity and the prognostic value of CA-IX provide impetus to create a mouse model of CA-IX-expressing RCC for testing CA-IX-targeted therapies against RCC. Methods: A retrovirus encoding the human CA-IX gene was used to transduce the murine RCC line, RENCA. In vivo growth kinetics and CA-IX expression were compared between RENCA and RENCA/CA-IX using heterotopic, metastatic, and orthotopic models. Results: Transduction of RENCA created the RENCA/CA-IX line with nearly 100% CA-IX surface expression. In the heterotopic model, subcutaneous injection of 500,000 and 50,000 cells led to tumor formation at 2 to 2.5 weeks after injection, with similar growth kinetics between the two cell lines at either cell number. In the pulmonary metastatic model, a similar number of metastases was noted after inoculation of RENCA and RENCA/CA-IX. In the orthotopic model, autopsy revealed a CA-IX-expressing renal tumor, as well as CA-IX-expressing metastases to the lungs, liver, contralateral kidney, intestines, and lymph nodes. In all the above models, the RENCA/CA-IX tumors retained expression of CA-IX, as demonstrated by immunohistochemistry staining. Conclusions: RENCA/CA-IX is the first tumor model that manifests in immunocompetent Balb/c mice and stably expresses a defined kidney cancer-associated antigen. It maintains antigen expression, forms metastases, and produces reliable tumor growth kinetics equivalent to that of its parental cell line. [ABSTRACT FROM AUTHOR]

Purpose: Accurate life expectancy estimates are required to inform prostate cancer treatment decisions. However, few models are specific to the population served or easily implemented in a clinical setting. We sought to create life expectancy estimates specific to Veterans diagnosed with prostate cancer.Materials and Methods: Using national Veterans Health Administration electronic health records, we identified Veterans diagnosed with prostate cancer between 2000 and 2015. We abstracted demographics, comorbidities, oncologic staging, and treatment information. We fit Cox Proportional Hazards models to determine the impact of age, comorbidity, cancer risk, and race on survival. We stratified life expectancy estimates by age, comorbidity and cancer stage.Results: Our analytic cohort included 145,678 patients. Survival modeling demonstrated the importance of age and comorbidity across all cancer risk categories. Life expectancy estimates generated from age and comorbidity data were predictive of overall survival (C-index 0.676, 95% CI 0.674-0.679) and visualized using Kaplan-Meier plots and heatmaps stratified by age and comorbidity. Separate life expectancy estimates were generated for patients with localized or advanced disease. These life expectancy estimates calibrate well across prostate cancer risk categories.Conclusions: Life expectancy estimates are essential to providing patient-centered prostate cancer care. We developed accessible life expectancy estimation tools for Veterans diagnosed with prostate cancer that can be used in routine clinical practice to inform medical-decision making. [ABSTRACT FROM AUTHOR]

Introduction: Surgical management of penile cancer depends on accurate margin assessment and staging. Advanced optical imaging technologies may improve penile biopsy and organ-sparing treatment. We evaluated the feasibility of confocal laser endomicroscopy for intraoperative assessment of benign and malignant penile tissue.Patients and Methods: With institutional review board approval, 11 patients were recruited, 9 with suspected penile cancer, and 2 healthy controls. Confocal laser endomicroscopy using a 2.6-mm fiber-optic probe was performed at 1 or 2 procedures on all subjects, for 13 imaging procedures. Fluorescein was administered intravenously approximately 3 minutes prior to imaging for contrast. Video sequences from in vivo (n = 12) and ex vivo (n = 6) imaging were obtained of normal glans, suspicious lesions, and surgical margins. Images were processed, annotated, characterized, and correlated with standard hematoxylin and eosin histopathology.Results: No adverse events related to imaging were reported. Distinguishing features of benign and malignant penile tissue could be identified by confocal laser endomicroscopy. Normal skin had cells of uniform size and shape, with distinct cytoplasmic membranes consistent with squamous epithelium. Malignant lesions were characterized by disorganized, crowded cells of various size and shape, lack of distinct cytoplasmic membranes, and hazy, moth-eaten appearance. The transition from normal to abnormal squamous epithelium could be identified.Conclusions: We report the initial feasibility of intraoperative confocal laser endomicroscopy for penile cancer optical biopsy. Pending further evaluation, confocal laser endomicroscopy could serve as an adjunct or replacement to conventional frozen section pathology for management of penile cancer. [ABSTRACT FROM AUTHOR]

Objectives: The PRECISION trial provides level 1 evidence supporting prebiopsy multiparametric magnetic resonance imaging (mpMRI) followed by targeted biopsy only when mpMRI is abnormal [1]. This approach reduced over-detection of low-grade cancer while increasing detection of clinically significant cancer (CSC). Still, important questions remain regarding the reproducibility of these findings outside of a clinical trial and quantifying missed CSC diagnoses using this approach. To address these issues, we retrospectively applied the PRECISION strategy in men who each underwent prebiopsy mpMRI followed by systematic and targeted biopsy.Methods and Materials: Clinical, imaging, and pathology data were prospectively collected from 358 biopsy naïve men and 202 men with previous negative biopsies. To apply the PRECISION approach, a retrospective analysis was done comparing the cancer yield from 2 diagnostic strategies: (1) mpMRI followed by targeted biopsy alone for men with Prostate Imaging Reporting and Data System ≥ 3 lesions and (2) systematic biopsy alone for all men. Primary outcomes were biopsies avoided and the proportion of CSC cancer (Grade Group 2-5) and non-CSC (Grade Group 1).Results: In biopsy naïve patients, the mpMRI diagnostic strategy would have avoided 19% of biopsies while detecting 2.5% more CSC (P= 0.480) and 12% less non-CSC (P< 0.001). Thirteen percent (n= 9) of men with normal mpMRI had CSC on systematic biopsy. For previous negative biopsy patients, the mpMRI diagnostic strategy avoided 21% of biopsies, while detecting 1.5% more CSC (P= 0.737) and 13% less non-CSC (P< 0.001). Seven percent (n= 3) of men with normal mpMRI had CSC on systematic biopsy.Conclusions: Our results provide external validation of the PRECISION finding that mpMRI followed by targeted biopsy of suspicious lesions reduces biopsies and over-diagnosis of low-grade cancer. Unlike PRECISION, we did not find increased diagnosis of CSC. This was true in both biopsy naïve and previously negative biopsy cohorts. We have incorporated this information into shared decision making, which has led some men to choose to avoid biopsy. However, we continue to recommend targeted and systematic biopsy in men with abnormal MRI. [ABSTRACT FROM AUTHOR]