Personalizing approaches to the management of metastatic hormone sensitive prostate cancer: role of advanced imaging, genetics and therapeutics.

PURPOSE: To summarize contemporary and emerging strategies for the diagnosis and management of metastatic hormone sensitive prostate cancer (mHSPC), focusing on diagnostic testing and therapeutics. METHODS: Literature review using PUBMED-Medline databases as well as clinicaltrials.gov to include reported or ongoing clinical trials on treatment for mHSPC. We prioritized the findings from phase III randomized clinical trials, systematic reviews, meta-analyses and clinical practice guidelines. RESULTS: There have been significant changes to the diagnosis and staging evaluation of mHSPC with the integration of increasingly accurate positron emission tomography (PET) imaging tracers that exceed the performance of conventional computerized tomography (CT) and bone scan. Germline multigene testing is recommended for the evaluation of patients newly diagnosed with mHSPC given the prevalence of actionable alterations that may create candidacy for specific therapies. Although androgen deprivation therapy (ADT) remains the backbone of treatment for mHSPC, approaches to first-line treatment include the integration of multiple agents including androgen receptor synthesis inhibitors (ARSI; abiraterone) Androgen Receptor antagonists (enzalutamide, darolutamide, apalautamide), and docetaxel chemotherapy. The combination of ADT, ARSI, and docetaxel chemotherapy has recently been evaluated in a randomized trial and was associated with significantly improved overall survival including in patients with a high burden of disease. The role of local treatment to the prostate with radiation has been evaluated in randomized trials with additional studies underway evaluating the role of cytoreductive radical prostatectomy. CONCLUSION: The staging and initial management of patients with mHSPC has undergone significant advances in the last decade with advancements in the diagnosis, treatment and sequencing of therapies.

Optimal Use of Tumor-Based Molecular Assays for Localized Prostate Cancer.

PURPOSEOF REVIEW: The use of genomic testing for prostate cancer continues to grow; however, utilization remains institutionally dependent. Herein, we review current tissue-based markers and comment on current use with active surveillance and prostate MRI. RECENT FINDINGS: While data continues to emerge, several studies have shown a role for genomic testing for treatment selection. Novel testing options include ConfirmMDx, ProMark, Prolaris, and Decipher, which have shown utility in select patients. The current body of literature on this specific topic remains very limited; prospective trials with long-term follow-up are needed to improve our understanding on how these genomic tests fit when combined with our current clinical tools. As the literature matures, it is likely that newer risk calculators that combine our classic clinical variables with genomic and imaging data will be developed to bring about standard protocols for prostate cancer decision-making.

Outcomes for urologic oncology procedures: are there differences between academic and community hospitals?

OBJECTIVE: To compare the rate of hospital-based outcomes including costs, 30-day readmission, mortality, and length of stay in patients who underwent major urologic oncologic procedures in academic and community hospitals. METHODS: We retrospectively reviewed the Vizient Database (Irving, Texas) from September 2014 to December 2017. Vizient includes ~ 97% of academic hospitals (AH) and more than 60 community hospitals (CH). Patients aged ≥ 18 with urologic malignancies who underwent surgical treatment were included. Chi square and Student t tests were used to compare categorical and continuous variables, respectively. RESULTS: We identified a total of 37,628 cases. There were 33,290 (88%) procedures performed in AH and 4330 (12%) in CH. These included prostatectomy (18,540), radical nephrectomy (rNx) 8059, partial nephrectomy (pNx) (5287), radical cystectomy (4421), radical nephroureterectomy (rNu) (1006), and partial cystectomy (321). There were no significant differences in 30-day readmission rates or mortality for any procedure between academic and community hospitals (Table 1), p > 0.05 for all. Length of stay was significantly lower for radical cystectomy and prostatectomy in AH (p < 0.01 for both) and lower for rNx in CH (p = 0.03). The mean direct cost for index admission was significantly higher in AH for rNx, pNx, rNu, and prostatectomy. Case mix index was similar between the community and academic hospitals. CONCLUSION: Despite academic and community hospitals having similar case complexity, direct costs were lower in community hospitals without an associated increase in readmission rates or deaths. Length of stay was shorter for cystectomy in academic centers.

Risk factors for metachronous bilateral renal cell carcinoma: A surveillance, epidemiology, and end results analysis.

BACKGROUND: Patients treated for renal cell carcinoma (RCC) may be diagnosed with a metachronous, contralateral tumor. We evaluated the risks of contralateral tumor development using the Surveillance, Epidemiology, and End Results database. METHODS: Among RCC patients, we identified those with a metachronous, contralateral RCC diagnosed ≥1 year after primary diagnosis. We performed a competing risks analysis to evaluate associations between clinicopathologic factors and metachronous, bilateral RCC. Cumulative incidence and standardized incidence ratios (SIRs) were calculated. RESULTS: There were 80,403 cases of RCC identified, with a median follow-up of 8.3 years; of these, 1063 (1.3%) developed metachronous, contralateral RCC (median of 6 years after diagnosis). The cumulative incidence at 10, 20, and 30 years of follow-up was 1.5%, 3.1%, and 4.7%, respectively. An increased risk was observed among men (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.20-1.55), blacks (HR, 2.00; 95% CI, 1.71-2.33), and those with papillary histology (HR, 1.72; 95% CI, 1.41-2.10). Risk of metachronous disease decreased with increasing age at primary diagnosis (HR per 1-year increase, 0.97; 95% CI, 0.96-0.97). The SIRs were highest among those diagnosed at a younger age and remained elevated even after extended follow-up (>10 years). CONCLUSIONS: Our findings suggest that the cumulative incidence of metachronous, contralateral RCC may be higher than previously reported. Younger age, black race, papillary histology, and male sex increase the risk of metachronous, contralateral RCC development. The high SIRs seen in all demographic groups may support a rationale for lifelong surveillance, especially in high-risk subgroups with early disease onset.

Outcomes of upper tract urothelial cancer managed non-surgically.

INTRODUCTION: Approximately 7% of patients with localized upper tract urothelial cancer (UTUC) are treated without definitive therapy. Understanding outcomes and alternative therapy would aid in counseling older patients with comorbidities. MATERIALS AND METHODS: We utilized the National Cancer Database to identify patients with localized UTUC managed non-surgically between 2004 and 2013. Patient demographics, comorbidity, tumor grade, and chemotherapy and radiation utilization were recorded. Survival analyses were performed with the Kaplan-Meier method and a cox proportional hazard regression model. RESULTS: We identified 3157 (10.9%) patients with localized UTUC who did not receive definitive surgery. Median age was 79 years, 55% were males, 79% had government health insurance, and 68% had a Charlson-Deyo Score (CDS) of 0. Tumor grade was low (grade 1 or 2) in 632 (36.4%) and high (grade 3 or 4) in 1104 (63.6%). Median overall survival (OS) for the cohort was 2.2 years, significantly shorter for patients with greater comorbidities. Chemotherapy or radiation was performed in 294 (9.3%) and 197 (6.3%) patients respectively. There were no OS differences for individuals receiving chemotherapy. Of patients who received radiation therapy, the median OS was 1.4 versus 2.0 years, (p < 0.001) favoring no radiation. Those with high grade tumors had worse survival (1.9 versus 3.8 years (p < 0.001). Significant predictors of shorter OS included older age, male gender, higher CDS, and government insurance. CONCLUSIONS: In this population-based cohort, 10.9% of patients with localized UTUC were managed non-surgically. There was no OS advantage noted in cohorts receiving chemotherapy and radiation therapy. Median OS was significantly shorter for those with higher grade disease, increasing comorbidity profile, male gender, and those with government insurance status.

Genetic testing for hereditary prostate cancer: Current status and limitations.

A significant proportion of prostate cancer diagnoses may be associated with a strong hereditary component. Men who have multiple single-gene polymorphisms and a family history of prostate cancer have a significantly greater risk of developing prostate cancer. Numerous single-gene alterations have been confirmed to increase the risk of prostate cancer. These include breast cancer genes 1 and 2 (BRCA1 and BRCA2, respectively), mutL homolog 1 (MLH1), mutS homologs 2 and 6 (MSH2 and MSH6, respectively), postmeiotic segregation increased 2 (PMS2), homeobox B13 (HOXB13), checkpoint kinase 2 (CHEK2), nibrin (NBN), BRCA1-interacting protein C-terminal helicase 1 (BRIP1), and ataxia telangiectasia mutated (ATM). Currently, there are no uniform guidelines on the definition of hereditary prostate cancer and genetic testing. With the advent of next-generation sequencing, which is capable of testing multiple genes simultaneously, and the approval of olaparib for BRCA1/BRCA2 or ATM-mutated, metastatic, castrate-resistant prostate cancer, it is being recognized that the results of genetic testing have an impact on therapeutic strategies. In this review, the authors examine the role of genetic counseling and testing, the challenges of insurance coverage for testing, the available germline and somatic testing panels, and the complexity of each testing method and its implications. Cancer 2018. © 2018 American Cancer Society.

The Effect of Continued Low Dose Aspirin Therapy in Patients Undergoing Percutaneous Nephrolithotomy.

PURPOSE: Aspirin is often stopped prior to percutaneous nephrolithotomy due to concern about the surgical bleeding risk. There is evidence that discontinuing aspirin perioperatively increases thromboembolic events and continuing it may be safe. We assessed the effect of continuing low dose aspirin through percutaneous nephrolithotomy and its effect on surgical and safety outcomes. MATERIALS AND METHODS: We retrospectively reviewed the records of 285 consecutive percutaneous nephrolithotomies performed between 2012 and 2015 at our institution. We compared outcomes and complications in patients who continued 81 mg aspirin daily to those in patients not receiving aspirin. RESULTS: A total of 67 patients (24.5%) were maintained on low dose aspirin and 207 (75.5%) were not on aspirin. The aspirin group was older (66 vs 52 years), included more tobacco users (58.2% vs 31.4%) and had a higher ASA® (American Society of Anesthesiologists®) score (2.9 vs 2.5, all p <0.001). There was no difference in mean S.T.O.N.E. (size, topography [stone location], obstruction, number of stones and evaluation of HU) score (7.6 vs 7.7, p = 0.71) or blood loss (44 vs 54 ml, p = 0.151). There was no difference in residual stone fragment size, including 0 to 2 mm in 65.3% vs 61.4% of aspirin vs no aspirin cases, 3 to 4 mm in 19.4% vs 16.2% and greater than 4 mm in 15.3% vs 22.4% (p = 0.407). Length of stay and the change in hemoglobin, hematocrit and creatinine were similar. There was no difference in the readmission rate (14.9% vs 12.6%, p = 0.618) or the total complication rate (34.4% vs 26.6%, p = 0.221). There was also no difference in the number of major complications (10.4% vs 5.8%, p = 0.193), bleeding complications (3.0% vs 2.9%, p = 0.971) and the transfusion rate (1.5% vs 1.0%, p = 0.57). CONCLUSIONS: Percutaneous nephrolithotomy appears effective and safe in patients who continue low dose aspirin perioperatively.

Survival outcomes for patients with localised upper tract urothelial carcinoma managed with non-definitive treatment.

OBJECTIVE: To investigate the outcomes of patients with upper tract urothelial carcinoma (UTUC) with non-definitive therapy, which currently remains unknown. PATIENTS AND METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database to identify individuals with a localised, histologically confirmed kidney/renal pelvis and ureteric UC. Survival analysis using the Kaplan-Meier method was performed. A competing risk model evaluated the cumulative incidence and predictors of cancer-specific mortality (CSM). RESULTS: We identified 633 (7.6%) individuals who did not receive surgery. These individuals were significantly older (median age 81 vs 71 years, P < 0.001) than surgically managed patients. The median overall survival (OS) was significantly shorter compared to the surgical cohort (1.9 vs 7.8 years, P < 0.001). The 3-year disease-specific survival (DSS) for patients without surgery was significantly lower compared to those with surgery, at 73.7% vs 92.4%, respectively (P < 0.001). The 3-year DSS for patients with high-grade tumours was worse when compared to patients with low-grade tumours, at 65.1% vs 82.9%, respectively (P < 0.001). The 3-year cumulative CSM was 26.3%. On multivariable analysis, older age (hazard ratio [HR] 1.05, P < 0.001) and high tumour grade (HR 1.88, P < 0.001) were predictors of worse outcomes. CONCLUSIONS: In this population-based cohort, 7.6% of patients with UTUC were managed with a non-definitive approach. The median OS for the untreated cohort was significantly shorter compared to the surgical cohort (1.9 vs 7.8 years, respectively). These data may be helpful in counselling patients who are poor surgical candidates, as non-definitive therapy may provide reasonable oncological outcomes.

Risk of Clinically Significant Prostate Cancer Associated With Prostate Imaging Reporting and Data System Category 3 (Equivocal) Lesions Identified on Multiparametric Prostate MRI.

OBJECTIVE: The objective of this study is to determine the frequency of clinically significant cancer (CSC) in Prostate Imaging Reporting and Data System (PI-RADS) category 3 (equivocal) lesions prospectively identified on multiparametric prostate MRI and to identify risk factors (RFs) for CSC that may aid in decision making. MATERIALS AND METHODS: Between January 2015 and July 2016, a total of 977 consecutively seen men underwent multiparametric prostate MRI, and 342 underwent MRI-ultrasound (US) fusion targeted biopsy. A total of 474 lesions were retrospectively reviewed, and 111 were scored as PI-RADS category 3 and were visualized using a 3-T MRI scanner. Multiparametric prostate MR images were prospectively interpreted by body subspecialty radiologists trained to use PI-RADS version 2. CSC was defined as a Gleason score of at least 7 on targeted biopsy. A multivariate logistic regression model was constructed to identify the RFs associated with CSC. RESULTS: Of the 111 PI-RADS category 3 lesions, 81 (73.0%) were benign, 11 (9.9%) were clinically insignificant (Gleason score, 6), and 19 (17.1%) were clinically significant. On multivariate analysis, three RFs were identified as significant predictors of CSC: older patient age (odds ratio [OR], 1.13; p = 0.002), smaller prostate volume (OR, 0.94; p = 0.008), and abnormal digital rectal examination (DRE) findings (OR, 3.92; p = 0.03). For PI-RADS category 3 lesions associated with zero, one, two, or three RFs, the risk of CSC was 4%, 16%, 62%, and 100%, respectively. PI-RADS category 3 lesions for which two or more RFs were noted (e.g., age ≥ 70 years, gland size ≤ 36 mL, or abnormal DRE findings) had a CSC detection rate of 67% with a sensitivity of 53%, a specificity of 95%, a positive predictive value of 67%, and a negative predictive value of 91%. CONCLUSION: Incorporating clinical parameters into risk stratification algorithms may improve the ability to detect clinically significant disease among PI-RADS category 3 lesions and may aid in the decision to perform biopsy.

MRI-Ultrasound Fusion Targeted Biopsy of Prostate Imaging Reporting and Data System Version 2 Category 5 Lesions Found False-Positive at Multiparametric Prostate MRI.

OBJECTIVE: The purpose of this study was to determine imaging and clinical features associated with Prostate Imaging Reporting and Data System (PI-RADS) category 5 lesions identified prospectively at multiparametric MRI (mpMRI) that were found benign at MRI-ultrasound fusion targeted biopsy. MATERIALS AND METHODS: Between January 2015 and July 2016, 325 men underwent prostate mpMRI followed by MRI-ultrasound fusion targeted biopsy of 420 lesions prospectively identified and assessed with PI-RADS version 2. The frequency of clinically significant prostate cancer (defined as Gleason score ≥ 7) among PI-RADS 5 lesions was determined. Lesions with benign pathologic results were retrospectively reassessed by three abdominal radiologists and categorized as concordant or discordant between mpMRI and biopsy results. Multivariate logistic regression was used to identify factors associated with benign disease. Bonferroni correction was used. RESULTS: Of the 98 PI-RADS 5 lesions identified in 89 patients, 18% (18/98) were benign, 10% (10/98) were Gleason 6 disease, and 71% (70/98) were clinically significant prostate cancer. Factors associated with benign disease at multivariate analysis were lower prostate-specific antigen density (odds ratio [OR], 0.88; p < 0.001) and apex (OR, 3.54; p = 0.001) or base (OR, 7.11; p = 0.012) location. On secondary review of the 18 lesions with benign pathologic results, 39% (7/18) were scored as benign prostatic hyperplasia nodules, 28% (5/18) as inflammatory changes, 5% (1/18) as normal anatomic structures, and 28% (5/18) as discordant with imaging findings. CONCLUSION: PI-RADS 5 lesions identified during routine clinical interpretation are associated with a high risk of clinically significant prostate cancer. A benign pathologic result was significantly correlated with lower prostate-specific antigen density and apex or base location and most commonly attributed to a benign prostatic hyperplasia nodule. Integration of these clinical features may improve the interpretation of high-risk lesions identified with mpMRI.

Advances in the diagnosis of hereditary kidney cancer: Initial results of a multigene panel test.

BACKGROUND: Panel testing has been recently introduced to evaluate hereditary cancer; however, limited information is available regarding its use in kidney cancer. METHODS: The authors retrospectively reviewed test results and clinical data from patients who underwent targeted multigene panel testing of up to 19 genes associated with hereditary kidney cancer from 2013 to 2016. The frequency of positive (mutation/variant likely pathogenic), inconclusive (variant of unknown significance), and negative results was evaluated. A logistic regression analysis evaluated predictive factors for a positive test. RESULTS: Patients (n = 1235) had a median age at diagnosis of 46 years, which was significantly younger than the US population of individuals with kidney cancer (P < .0001). Overall, 6.1%, 75.5%, and 18.4% of individuals had positive, negative, and inconclusive results, respectively. The most commonly altered genes included folliculin (FLCN) and fumarate hydratase (FH), which were altered in 1.8% and 1.3% of patients, respectively. Tuberous Sclerosis Complex 2 (TSC2), mesenchymal epithelial transition factor proto-oncogene (MET), and PMS1 homolog 2 (PMS2) had the highest rates of variants of unknown significance, which were identified in 2.7%, 2.2%, and 1.7% of patients, respectively. Early age of onset was the only factor that was identified as predictive of a positive test on multivariate analysis (odds ratio, 0.975; P = .0052) and may be the only identifying characteristic of low-penetrant syndromes, such as those associated with MITF (melanogenesis-associated transcription factor) mutations, which do not have singular histology or a family history of kidney cancer. CONCLUSIONS: Panel tests may be particularly useful for patients who lack distinguishing clinical characteristics of known hereditary kidney cancer syndromes. The current results support the use of early age of onset for genetic counseling and/or testing. Cancer 2017;123:4363-71. © 2017 American Cancer Society.

Optimizing waiting duration for renal transplants in the setting of renal malignancy: is 2 years too long to wait?

BACKGROUND: For potential transplant recipients with a prior history of renal malignancy, no evidence-based recommendations currently exist with regard to waiting duration on dialysis. We aim to improve decision making by evaluating the impact of waiting duration on the outcomes of kidney cancer patients awaiting renal transplantation. METHODS: The United States Renal Data System was used to identify patients with a known cause of end-stage renal disease (ESRD) from 1983 to 2007. Evaluation of overall survival (OS) was performed with Kaplan-Meier estimates and Cox proportional hazards models. Fine-Gray competing risk models were used to assess cancer-specific mortality (CSM) and non-cancer-specific mortality (NCSM). RESULTS: Of 1 374 175 patients with ESRD, 228 984 (16.7%) received transplantation. Transplant recipients with renal malignancy-associated ESRD (RM-ESRD) had longer waiting durations than those with other known causes of ESRD (2.4 versus 1.3 years; P < 0.0001). RM-ESRD patients who had shorter waiting durations (0-2 years) had better OS than those who waited longer (2+ years) (10-year OS 69.0 versus 46.7%, respectively; P < 0.0001), with similar CSM (10-year CSM 10.3 versus 10.2%, respectively; P = 0.883), whereas NCSM was worse for those with longer waiting durations (10-year NCSM 20.7 versus 44.3%, respectively; P < 0.0001). On Cox modeling, the status of RM-ESRD was not a significant predictor (P = 0.07), while longer waiting duration remained significant (P < 0.0001). CONCLUSION: We found that CSM was not affected by waiting duration, while NCSM significantly improved with shorter wait times. These findings suggest that the OS of potential transplant recipients with RM-ESRD may be improved by reducing waiting duration.

Distinguishing pediatric and adolescent renal cell carcinoma from other renal malignancies.

PURPOSE: Renal cell carcinoma (RCC) represents a small proportion of renal malignancies early in life. Distinguishing RCC from other malignancies is important as treatment strategies may differ. We analyze the Surveillance Epidemiology, and End Results (SEER) database to identify predictive factors of RCC in the pediatric population with renal tumors. METHODS: We queried SEER to identify patients from ages 0 to 19 diagnosed with a renal malignancy between 1973 and 2013. Cases were sorted using histology and site codes. Age-adjusted standardized incidence rates (SIR) were calculated. We compared differences in characteristics between cancer types. A logistic regression model and a nomogram were created to identify predictors of RCC. RESULTS: A total of 3,670 patients were identified, of which 281 (7.7%) were diagnosed with RCC. The SIR of RCC increased with age. After age 12, RCC was found in >50% of all newly diagnosed cases. On multivariate analysis, RCC was associated with smaller tumor size (P < 0.001), increasing age (P < 0.001), black race (P < 0.001), and localized stage (P < 0.001). The nomogram predicted RCC pathology with a concordance index of 0.965. CONCLUSIONS: RCC in childhood and adolescence is relatively uncommon; however, it accounts for >50% of renal malignancies after age 12. For every year of increasing age, the odds of having an RCC diagnosis are increased by 50%. The odds of a renal tumor being RCC are increased in black children, those with localized disease, and those with smaller tumors. In these specific populations, RCC should be favored in the differential diagnosis of the renal mass.

Current Management Strategy for Active Surveillance in Prostate Cancer.

PURPOSE OF REVIEW: Active surveillance has been increasingly utilized as a strategy for the management of favorable-risk, localized prostate cancer. In this review, we describe contemporary management strategies of active surveillance, with a focus on traditional stratification schemes, new prognostic tools, and patient outcomes. RECENT FINDINGS: Patient selection, follow-up strategy, and indication for delayed intervention for active surveillance remain centered around PSA, digital rectal exam, and biopsy findings. Novel tools which include imaging, biomarkers, and genetic assays have been investigated as potential prognostic adjuncts; however, their role in active surveillance remains institutionally dependent. Although 30-50% of patients on active surveillance ultimately undergo delayed treatment, the vast majority will remain free of metastasis with a low risk of dying from prostate cancer. The optimal method for patient selection into active surveillance is unknown; however, cancer-specific mortality rates remain excellent. New prognostication tools are promising, and long-term prospective, randomized data regarding their use in active surveillance will be beneficial.

Adverse pathologic characteristics in the small renal mass: implications for active surveillance.

INTRODUCTION: Evidence has demonstrated that tumor size is related to adverse oncologic outcomes in small renal tumors (≤ 4 cm). We evaluated the association of adverse pathologic features (APF) with tumor size and survival in patients with a small renal mass (SRM). MATERIALS AND METHODS: We retrospectively reviewed the pathologic characteristics of 380 surgically resected SRMs from a single institution. APFs included lymphovascular invasion, coagulative necrosis, sarcomatoid/rhabdoid features, papillary type II histology, and perinephric fat/renal sinus invasion. The number and type of APFs were compared with tumor size. Survival analysis was performed using the Kaplan-Meier method. RESULTS: There were 244 (64.2%) males and 136 (35.8%) females. The median age was 61 years, and median tumor size was 2.7 cm. The median follow up time was 65 months. A significant association was found between tumor size and presence of APFs (p = 0.018). At least 1 APF could be found in 22%, 32%, 36%, and 49% of tumors ≤ 1 cm, 1 cm-2 cm, 2 cm-3 cm, and 3 cm-4 cm, respectively. There were no differences in overall survival or recurrence free survival when compared by tumor size at diagnosis (p = 0.22 and 0.15 respectively). Compared to patients with ≤ 1 APFs, disease specific survival was worse for patients with ≥ 2 APFs (p < 0.002). CONCLUSION: Our data support that aggressive tumor biology in a SRM is associated with greater size. In patients with a SRM, the decision to pursue active surveillance and the trigger for intervention should take tumor size and APFs into consideration as this may have future oncologic implications.

Ethnic disparities in renal cell carcinoma: An analysis of Hispanic patients in a single-payer healthcare system.

OBJECTIVE: To investigate differences between Hispanics and non-Hispanic whites diagnosed with and treated for renal cell carcinoma in an equal access healthcare system. METHODS: We carried out a retrospective cohort study within the Kaiser Permanente healthcare system using records from renal cell carcinoma cases. Ethnicity was identified as Hispanic or non-Hispanic whites. Patient characteristics, comorbidities, tumor characteristics and treatment were compared. Overall and disease-specific survival was calculated, and a Cox proportion hazard model estimated the association of ethnicity and survival. RESULTS: A total of 2577 patients (2152 non-Hispanic whites, 425 Hispanic) were evaluated. Hispanics were diagnosed at a younger age (59.6 years vs 65.3 years). Clear cell renal cell carcinoma was more prevalent, whereas papillary renal cell carcinoma was less common among Hispanics. Hispanics had a lower American Joint Committee on Cancer stage (I/II vs III/IV) than non-Hispanic whites (67.4% vs 62.2%). Hispanics were found to have a greater frequency of comorbidities, such as chronic kidney disease and diabetes, but were more likely to receive surgery. The presence of metastases, nodal involvement, increased tumor size, non-surgical management, increasing age and Hispanic ethnicity were independent predictors of worse cancer-specific outcome. CONCLUSIONS: Within an equal access healthcare system, Hispanics seem to be diagnosed at younger ages, to have greater comorbidities and to present more frequently with clear cell renal cell carcinoma compared with non-Hispanic white patients. Despite lower stage and greater receipt of surgery, Hispanic ethnicity seems to be an independent predictor of mortality. Further work is necessary to confirm these findings.

Non-alcoholic Fatty Liver in Children and Adolescents in Saudi Arabia.

Objectives This study aims to describe the disease parameters of children and adolescents diagnosed with non-alcoholic fatty liver disease (NAFLD) in Saudi Arabia. It also investigates the disease's progression and compares clinical, biochemical, and radiological parameters at baseline and follow-up of patients with NAFLD. This study was done between two groups of patients: obese and those of average body weight.  Methods A retrospective cohort study was conducted between 2014 and 2018 through retrieved data from medical records. It included all children aged between six to 18 years diagnosed with NAFLD. Medical history was taken from each medical record, liver function test results, cholesterol, blood pressure readings, and body weight. Data have been restored from King Abdullah Specialist Children's Hospital (KASCH)​, Security Forces Hospital (SFH), and King Khalid University Hospital (KKUH). Results A total of 116 subjects met the inclusion criteria; 65 (56%) were male, and 81 (70%) were obese. The majority of subjects (n=112) had mild NAFLD, with (71%) obese and (29%) non-obese, followed by moderate NAFLD with 50% among obese and non-obese (N=2), and non-alcoholic steatohepatitis (NASH) with 100% non-obese (N=2). Data showed that patients' proportion of obese to non-obese is 70% (N=81) to 30% (N=35), respectively.  Conclusion NAFLD was found to affect obese children and adolescents more than non-obese, and male patients had a higher proportion of NAFLD than females. Also, obese patients had more advanced stages of NAFLD than non-obese patients. Finally, most subjects had been diagnosed with mild stage while a few had developed NASH.

Oncologic outcomes of neoadjuvant chemotherapy in patients with micropapillary variant urothelial carcinoma of the bladder.

BACKGROUND: There is lack of consensus about the effectiveness of neoadjuvant platinum-based chemotherapy in patients with micropapillary variant urothelial carcinoma (MVUC) prior to radical cystectomy. We studied the association between neoadjuvant chemotherapy (NAC) and pathologic response (PR) among patients with micropapillary versus non-variant bladder urothelial carcinoma (UC). METHODS: We queried the National Cancer Database to identify patients with localized UC and MVUC from 2004 to 2017. We restricted our analysis to patients who underwent radical cystectomy with or without NAC. We compared clinical, demographic, and pathologic characteristics associated with NAC. We used multivariable logistic regression and propensity score matching to examine the association between NAC and the occurrence of a pathologic complete response (pT0) and pathologic lymph node positivity (pN+). Kaplan Meier analyses and Cox proportional hazards models were used to assess overall survival (OS). We performed analyses among subsets of patients with clinical stage II (cT2) disease, as well as the entire cohort (cT2-T4). RESULTS: We identified 18,761 patients, including 18,027 with non-variant UC and 734 patients with MVUC. Multivariable analysis revealed that NAC use was associated with greater odds of pT0 (9.64[7.62-12.82], P<0.001), and the association did not differ significantly between MVUC and non-variant UC. In a propensity matched analysis of patients with MVUC, NAC use was associated with higher odds of pT0 (OR 4.93 [2.43-13.18] P<0.001), lower odds of pN+ (OR 0.52 [0.26-0.92] P=0.047) and pathologic upstaging (OR 0.63 [0.34-0.97] P=0.042) in all stages. Similar findings were observed with cT2 disease. No significant association was seen between NAC and OS with MVUC (HR 0.89 [0.46-1.10] P=0.63), including the subset of patients with cT2 (HR 0.83 [0.49-1.06] P=0.58). CONCLUSIONS: NAC is associated with similar pathologic and nodal responses in patients with localized MVUC and non-variant UC. Improvements in pathologic findings did not translate into OS in this retrospective hospital-based registry study.

Graduate and postgraduate educational challenges during the COVID-19 pandemic period: its impact and innovations-a scoping review.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has transformed the global view of education, including graduate and postgraduate education making the development of an alternative approach in times of social isolation an academic imperative. The present review aims to investigate the challenges experienced among undergraduate and postgraduate education and the strategies adopted to address these challenges during the pandemic. METHOD: The preferred reporting items for the systematic review and meta-analyses extension for Scoping Reviews (PRISMA-ScR) were followed. The aim was to include journal articles published in the English language that discussed the influence of the pandemic on educational processes and applied innovative approaches as a solution to educational challenges. From January to August 2020, PubMed, EMBASE, and Google Scholar were searched for articles, yielding 10,019 articles. Two groups of authors examined the retrieved articles separately to avoid any risk of bias. The title and abstract of the articles were used for scrutiny, followed by full-text screening based on the established inclusion and exclusion criteria. The facts and findings of the studies were also discussed based on per capita income, literacy rate, and Internet accessibility. RESULTS: Thirty of the obtained articles were included in the study. The selected articles were from North and South/Latin America, Asia & Pacific, South Africa, and Europe regions. Nineteen of the selected articles dealt with undergraduate education, ten with postgraduate, and one with both groups. The affordability of digital devices and the availability of Internet services were the major challenges for low- and middle-income economies. The ZOOM platform has been adopted by more than 90% of the education systems. CONCLUSION: Means of communication, including visual media, digitized content, and other web-based platforms, have been recognized as efficient learning and training tools, but have not been fully accessible for mass application and use due to the lack of availability of resources, their cost, and insufficient training among the users. In light of this review, it is suggested that harmonized and collaborative efforts should be made to develop cost-effective and user-friendly tools to overcome the current challenges and prevent future educational crises. SYSTEMIC REVIEW REGISTRATION: The review was not registered.