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1.
J Urol ; 205(5): 1387-1393, 2021 May.
Article in English | MEDLINE | ID: mdl-33356483

ABSTRACT

PURPOSE: Microhematuria is a prevalent condition and the American Urological Association has developed a new risk-stratified approach for the evaluation of patients with microhematuria. Our objective was to provide the first evaluation of this important guideline. MATERIALS AND METHODS: This multinational cohort study combines contemporary patients from 5 clinical trials and 2 prospective registries who underwent urological evaluation for hematuria. Patients were stratified into American Urological Association risk strata (low, intermediate or high risk) based on sex, age, degree of hematuria, and smoking history. The primary end point was the incidence of bladder cancer within each risk stratum. RESULTS: A total of 15,779 patients were included in the analysis. Overall, 727 patients (4.6%) were classified as low risk, 1,863 patients (11.8%) were classified as intermediate risk, and 13,189 patients (83.6%) were classified as high risk. The predominance of high risk patients was consistent across all cohorts. A total of 857 bladder cancers were diagnosed with a bladder cancer incidence of 5.4%. Bladder cancer was more prevalent in men, smokers, older patients and patients with gross hematuria. The cancer incidence for low, intermediate and high risk groups was 0.4% (3 patients), 1.0% (18 patients) and 6.3% (836 patients), respectively. CONCLUSIONS: The new risk stratification system separates hematuria patients into clinically meaningful categories with differing likelihoods of bladder cancer that would justify evaluating the low, intermediate and high risk groups with incremental intensity. Furthermore, it provides the relative incidence of bladder cancer in each risk group which should facilitate patient counseling regarding the risks and benefits of evaluation for bladder cancer.


Subject(s)
Hematuria/classification , Hematuria/etiology , Urinary Bladder Neoplasms/complications , Adult , Aged , Cohort Studies , Female , Humans , Incidence , Male , Middle Aged , Practice Guidelines as Topic , Prospective Studies , Risk Assessment , Societies, Medical , United States , Urinary Bladder Neoplasms/epidemiology , Urology
2.
J Urol ; 205(1): 137-144, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32856980

ABSTRACT

PURPOSE: Current serum tumor markers for testicular germ cell tumor are limited by low sensitivity. Growing evidence supports the use of circulating miR-371a-3p as a superior marker for malignant (viable) germ cell tumor management. We evaluated the real-world application of serum miR-371a-3p levels in detecting viable germ cell tumor among patients undergoing partial or radical orchiectomy. MATERIALS AND METHODS: Serum samples were collected from 69 consecutive patients before orchiectomy. Performance characteristics of serum miR-371a-3p were compared with conventional serum tumor markers (⍺-fetoprotein/ß-human chorionic gonadotropin/lactate dehydrogenase) between patients with viable germ cell tumor and those without viable germ cell tumor on orchiectomy pathology. Relative miR-371a-3p levels were correlated with clinical course. The Kruskal-Wallis test and linear and ordinal regression models were used for analysis. RESULTS: For detecting viable germ cell tumor, combined conventional serum tumor markers had a specificity of 100%, sensitivity of 58% and AUC of 0.79. The miR-371a-3p test showed a specificity of 100%, sensitivity of 93% and AUC of 0.978. Median relative expression of miR-371a-3p in viable germ cell tumor cases was more than 6,800-fold higher than in those lacking viable germ cell tumor. miR-371a-3p levels correlated with composite stage (p=0.006) and, among composite stage I cases, independently associated with embryonal carcinoma percentage (p=0.0012) and tumor diameter (p <0.0001). Six patients underwent orchiectomy after chemotherapy and were correctly predicted to have presence or absence of viable germ cell tumor by the miR-371a-3p test. CONCLUSIONS: If validated, the miR-371a-3p test can be used in conjunction with conventional serum tumor markers to aid clinical decision making. A positive miR-371a-3p test in patients after preoperative chemotherapy or with solitary testes could potentially guide subsequent orchiectomy or observation.


Subject(s)
Biomarkers, Tumor/blood , Circulating MicroRNA/blood , MicroRNAs/blood , Neoplasms, Germ Cell and Embryonal/diagnosis , Orchiectomy , Testicular Neoplasms/diagnosis , Adult , Case-Control Studies , Chemotherapy, Adjuvant , Clinical Decision-Making/methods , Feasibility Studies , Humans , Male , Middle Aged , Neoadjuvant Therapy/methods , Neoplasm Staging , Neoplasms, Germ Cell and Embryonal/blood , Neoplasms, Germ Cell and Embryonal/pathology , Neoplasms, Germ Cell and Embryonal/therapy , Preoperative Period , Testicular Neoplasms/blood , Testicular Neoplasms/pathology , Testicular Neoplasms/therapy , Testis/pathology , Testis/surgery , Watchful Waiting
3.
BJU Int ; 128(1): 57-64, 2021 07.
Article in English | MEDLINE | ID: mdl-33124175

ABSTRACT

OBJECTIVES: To determine whether utilisation of a serum microRNA (miRNA) test could improve treatment appropriateness and cost-effectiveness for patients with Stage I non-seminomatous germ cell tumours (NSGCTs). PATIENTS AND METHODS: A decision tree model was built to investigate treatment course, clinical and cost outcomes for patients with Stage IA (T1N0M0S0) and IB (T2-4N0M0S0) NSGCT. The model compared outcomes and cost of standard approach using histopathology, conventional serum tumour markers and radiographic staging (standard model) to a miRNA-based approach using the standard model + post-orchidectomy serum miR-371a-3p (marker model). Probabilities of expected treatment and outcomes were based on presence/absence of cancer upon entering into the model. Overtreatment was defined as adjuvant chemotherapy or primary retroperitoneal lymph node dissection in a patient without cancer. Undertreatment was defined as initial surveillance for a patient with cancer. RESULTS: Utilising the miRNA marker-based approach, 26% of patients avoid overtreatment and 8% avoid undertreatment in Stage IA NSGCT; 27% avoid overtreatment and 23% avoid undertreatment in Stage IB disease. Appropriate treatment decision-making increased from 65% to 94% and 50% to 92% for Stage IA and IB, respectively. The miRNA-based approach remained cost-effective over a wide range of performance characteristics with savings of ~$1400 (American dollars)/patient for both Stage IA and IB disease. CONCLUSION: A miRNA-based approach may potentially select patients with Stage I NSGCT for correct treatment in a cost-effective manner. Identification of residual teratoma-only remains an issue. Prospective studies are necessary to validate these findings.


Subject(s)
Circulating MicroRNA/blood , MicroRNAs/blood , Neoplasms, Germ Cell and Embryonal/blood , Testicular Neoplasms/blood , Costs and Cost Analysis , Decision Trees , Humans , Male , Neoplasm Staging , Neoplasms, Germ Cell and Embryonal/economics , Neoplasms, Germ Cell and Embryonal/pathology , Neoplasms, Germ Cell and Embryonal/therapy , Testicular Neoplasms/economics , Testicular Neoplasms/pathology , Testicular Neoplasms/therapy , Treatment Outcome
4.
World J Urol ; 39(2): 491-500, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32318857

ABSTRACT

PURPOSE: Inconsistent prognostic implications of body mass index (BMI) in upper tract urothelial carcinoma (UTUC) have been reported across different ethnicities. In this study, we aimed to analyze the oncologic role of BMI in Asian and Caucasian patients with UTUC. METHODS: We retrospectively collected data from 648 Asian Taiwanese and 213 Caucasian American patients who underwent radical nephroureterectomy for UTUC. We compared clinicopathologic features among groups categorized by different BMI. Kaplan-Meier method and Cox regression model were used to examine the impact of BMI on recurrence and survival by ethnicity. RESULTS: According to ethnicity-specific criteria, overweight and obesity were found in 151 (23.2%) and 215 (33.2%) Asians, and 79 (37.1%) and 78 (36.6%) Caucasians, respectively. No significant association between BMI and disease characteristics was detected in both ethnicities. On multivariate analysis, overweight and obese Asians had significantly lower recurrence than those with normal weight (HR 0.631, 95% CI 0.413-0.966; HR 0.695, 95% CI 0.493-0.981, respectively), and obesity was an independent prognostic factor for favorable cancer-specific and overall survival (HR 0.521, 95% CI 0.342-0.794; HR 0.545, 95% CI 0.386-0.769, respectively). There was no significant difference in outcomes among normal, overweight and obese Caucasians, but obese patients had a relatively poorer 5-year RFS, CSS, and OS rates of 52.8%, 60.5%, and 47.2%, compared to 54.9%, 69.1%, and 54.9% for normal weight patients. CONCLUSION: Higher BMI was associated with improved outcomes in Asian patients with UTUC. Interethnic differences could influence preoperative counseling or prediction modeling in patients with UTUC.


Subject(s)
Asian , Body Mass Index , Carcinoma, Transitional Cell/complications , Carcinoma, Transitional Cell/surgery , Kidney Neoplasms/complications , Kidney Neoplasms/surgery , Nephroureterectomy , Obesity/complications , Ureteral Neoplasms/complications , Ureteral Neoplasms/surgery , White People , Aged , Carcinoma, Transitional Cell/mortality , Female , Humans , Kidney Neoplasms/mortality , Male , Middle Aged , Retrospective Studies , Survival Rate , Treatment Outcome , Ureteral Neoplasms/mortality
5.
Cancer ; 126(19): 4362-4370, 2020 10 01.
Article in English | MEDLINE | ID: mdl-32776520

ABSTRACT

BACKGROUND: The objective of this study was to determine whether standardized treatment of germ cell tumors (GCTs) could overcome sociodemographic factors limiting patient care. METHODS: The records of all patients undergoing primary treatment for GCTs at both a public safety net hospital and an academic tertiary care center in the same metropolitan area were analyzed. Both institutions were managed by the same group of physicians in the context of multidisciplinary cancer care. Patients were grouped by care center; clinicopathologic features and outcomes were analyzed. RESULTS: Between 2006 and 2018, 106 and 95 patients underwent initial treatment for GCTs at the safety net hospital and the tertiary care center, respectively. Safety net patients were younger (29 vs 33 years; P = .005) and were more likely to be Hispanic (79% vs 11%), to be uninsured (80% vs 12%; P < .001), to present via the emergency department (76% vs 8%; P < .001), and to have metastatic (stage II/III) disease (42% vs 26%; P = .025). In a multivariable analysis, an absence of lymphovascular invasion (odds ratio [OR], 0.30; P = .008) and an embryonal carcinoma component (OR, 0.36; P = .02) were associated with decreased use of adjuvant treatment for stage I patients; hospital setting was not (OR, 0.67; P = .55). For patients with stage II/III nonseminomatous GCTs, there was no difference in the performance of postchemotherapy retroperitoneal lymph node dissection between the safety net hospital and the tertiary care center (52% vs 64%; P = .53). No difference in recurrence rates was observed between the cohorts (5% vs 6%; P = .76). CONCLUSIONS: Sociodemographic factors are often associated with adverse clinical outcomes in the treatment of GCTs; they may be overcome with integrated, standardized management of testicular cancer.


Subject(s)
Testicular Neoplasms/epidemiology , Adult , Humans , Male , Safety-net Providers , Socioeconomic Factors
6.
Cancer ; 125(2): 223-231, 2019 01 15.
Article in English | MEDLINE | ID: mdl-30291813

ABSTRACT

BACKGROUND: An assessment of surgical risk is essential for patient counseling and decision making, and it can provide rationale adjustment for patient populations as health care moves from a fee-for-service to a value-based reimbursement model. The modified Frailty Index (mFI) has been proposed as a risk-stratification tool for radical cystectomy (RC), and the objective of the current study was to validate this potential use of the mFI using an institutional cohort. METHODS: A retrospective review of all patients who underwent RC for bladder cancer was conducted at the authors' institution from 2012 to 2016. In addition to detailed clinicopathologic and treatment parameters, patients were categorized according to the mFI, the Charlson Comorbidity Index (CCI), and the American Society of Anesthesiologists (ASA) classification. Covariates were analyzed to determine associations with 1-month complication rates (according to the Clavien-Dindo system), 3-month readmission rates, hospitalization length, and hospitalization costs. RESULTS: In total, 346 patients were included in the analysis. The overall complication rate was 56.6%, the major (Clavien grade ≥3) complication rate was 19.4%, and the readmission rate was 27.9%. Receiver operating curve analysis demonstrated a weak association of all indices with major complications after RC: the area under the curve was 0.535 (95% confidence interval [CI], 0.460-0.611) for the ASA classification; 0.565 (95% CI, 0.485-0.645) for the CCI score; and 0.551 (95% CI, 0.471-0.631) for the mFI. There were no significant differences in the rate of major complications when stratifying the results according to the mFI, CCI, or ASA class. Length of hospitalization and associated costs were correlated with mFI. CONCLUSIONS: Frailty was not associated with postoperative complications and provided little additional predictive ability over the ASA classification and the CCI score. Further research is required to identify patients who are likely to suffer significant complications after RC.


Subject(s)
Cystectomy/methods , Frailty , Postoperative Complications/etiology , Urinary Bladder Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Area Under Curve , Comorbidity , Cystectomy/adverse effects , Cystectomy/economics , Female , Health Status Indicators , Humans , Length of Stay/economics , Male , Middle Aged , Patient Readmission/statistics & numerical data , Retrospective Studies , Treatment Outcome , Urinary Bladder Neoplasms/epidemiology , Urinary Bladder Neoplasms/pathology
7.
Cancer ; 125(22): 3947-3952, 2019 11 15.
Article in English | MEDLINE | ID: mdl-31355922

ABSTRACT

BACKGROUND: Using a large, nationally representative, population-based cancer registry, this study systematically evaluated the impact of the location and burden of extranodal testicular germ cell tumor (TGCT) metastases on survival. METHODS: Men with stage III TGCTs captured by the Surveillance, Epidemiology, and End Results registry from 2010 to 2015 with distant extranodal metastases were identified. Clinicopathologic information was collected, and patients were subdivided according to the specific organ site or sites of metastatic involvement (lung, liver, bone, and/or brain). Kaplan-Meier analysis and multivariable Cox regression were used to evaluate cancer-specific survival (CSS), and model performance was assessed with Harrell's C statistic. RESULTS: Nine hundred sixty-nine patients with stage III TGCTs were included with predominantly nonseminomatous histology (84%). Most patients (91%) had pulmonary metastases, whereas 20%, 10%, and 10% had liver, bone, and brain metastases, respectively. Over a median follow-up of 21 months, 19% of these men died of TGCTs. When they were grouped by the primary site of metastasis, patients with more than 1 extrapulmonary metastasis exhibited the worst CSS (hazard ratio [HR] vs isolated pulmonary involvement, 4.27; 95% confidence interval [CI], 2.60-7.00; P < .01). Among patients with isolated extrapulmonary involvement, those with brain metastases had the poorest survival (HR, 3.24; 95% CI, 1.98-5.28; P < .01), and they were followed by patients with liver (HR, 2.29; 95% CI, 1.56-3.35; P < .01) and bone metastases (HR, 1.97; 95% CI, 1.11-3.50; P = .02). Harrell's C statistic (multivariable) was 0.71. CONCLUSIONS: The site of metastatic involvement affects survival outcomes for patients with TGCTs, and this may reflect both the aggressive biology and the challenging treatment of these tumors. Further incorporation of organotropism into current prognostic models for metastatic TGCTs warrants attention.


Subject(s)
Neoplasms, Germ Cell and Embryonal/mortality , Neoplasms, Germ Cell and Embryonal/pathology , Testicular Neoplasms/mortality , Testicular Neoplasms/pathology , Adult , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Prognosis , Proportional Hazards Models , SEER Program , Young Adult
8.
World J Urol ; 37(11): 2419-2427, 2019 Nov.
Article in English | MEDLINE | ID: mdl-30759271

ABSTRACT

PURPOSE: To evaluate the prognostic value of BRCA1-associated protein-1 (BAP1) expression in upper tract urothelial carcinoma (UTUC), as BAP1 mutations have been associated with prognostic implications in urologic and non-urologic malignancies. METHODS: We reviewed a multi-institutional cohort of patients who underwent radical nephroureterectomy (RNU) for high-grade UTUC from 1990-2008. Immunohistochemistry (IHC) for BAP1 was performed on tissue microarrays. Staining intensity was graded from 0-3, with BAP1 loss defined as an average intensity of < 1. Clinicopathologic characteristics and oncologic outcomes [recurrencefree (RFS), cancer-specific (CSS), and overall survival (OS)] were stratified by BAP1 status. The prognostic role of BAP1 was assessed using Kaplan-Meier (KM) and Cox regression analysis. Significance was defined as p < 0.05. RESULTS: 348 patients were included for analysis and 173 (49.7%) showed BAP1 loss. Median follow-up was 36.0 months. BAP1 loss was associated with papillary architecture and absence of tumor necrosis or CIS. On univariable analysis, BAP1 loss was associated with improved RFS (HR 0.60, p = 0.013) and CSS (HR 0.55, p = 0.007), although significance was lost on multivariable analysis (HR 0.71, p = 0.115 and HR 0.65, p = 0.071; respectively) after adjusting for other significant parameters. BAP1 expression was not significantly associated with OS. CONCLUSIONS: BAP1 loss was associated with favorable pathologic features and better oncologic outcomes in univariate but not multivariate analysis in patients with high-grade UTUC. In contrast to renal cell carcinoma, loss of BAP1 expression appears to confer a better prognosis in high-grade UTUC. The role of the BAP1 pathway in UTUC pathogenesis remains to be further elucidated.


Subject(s)
Carcinoma, Transitional Cell/metabolism , Carcinoma, Transitional Cell/mortality , Kidney Neoplasms/metabolism , Kidney Neoplasms/mortality , Tumor Suppressor Proteins/biosynthesis , Ubiquitin Thiolesterase/biosynthesis , Ureteral Neoplasms/metabolism , Ureteral Neoplasms/mortality , Aged , Carcinoma, Transitional Cell/chemistry , Carcinoma, Transitional Cell/pathology , Female , Humans , Kidney Neoplasms/chemistry , Kidney Neoplasms/pathology , Male , Middle Aged , Neoplasm Grading , Prognosis , Retrospective Studies , Survival Rate , Tumor Suppressor Proteins/analysis , Ubiquitin Thiolesterase/analysis , Ureteral Neoplasms/chemistry , Ureteral Neoplasms/pathology
9.
Can J Urol ; 26(1): 9634-9643, 2019 02.
Article in English | MEDLINE | ID: mdl-30797246

ABSTRACT

INTRODUCTION: To determine whether quantifying the proximity of positive prostate biopsy cores to the capsular edge may aid in identifying patients at risk for extracapsular extension (ECE) at the time of radical prostatectomy (RP). MATERIALS AND METHODS: We reviewed a single-surgeon experience of 429 systematic transrectal prostate biopsies from 2010-2014. Marking ink was applied to the capsular edge ex vivo following specimen acquisition, and the proximity of cancer to the stained capsular edge was measured. Primary outcome was ECE at RP. Demographics, PSA, DRE findings, Gleason score, core location and involvement, and RP pathology were recorded. Predictors of ECE were identified using multivariable logistic regression. Receiver operating characteristic (ROC) analyses were performed to assess the predictive value of variables alone and in combination. RESULTS: One hundred and one patients who underwent staining during biopsy received RP (202 hemiprostates). Thirty-three patients (40 hemiprostates) exhibited ECE. There were 343 positive stained biopsy cores. Mean proximity of carcinoma to capsule was 4.7 mm. On univariable analysis, proximity of positive core ≤ 1 mm to capsule was predictive of side-specific ECE (OR 2.86, p = 0.013), though significance was lost in multivariable models. Area under the curve (AUC) for proximity was 0.571 alone and 0.804 in combination with PSA, cT stage, and total biopsy Gleason score. CONCLUSION: Proximity of positive biopsy core to capsular margin may supply additional information in predicting ECE but requires validation in a larger cohort. Implementation of a staining technique at the time of systematic biopsy may be helpful in counseling patients and determining utility of nerve-sparing approaches.


Subject(s)
Extranodal Extension , Prostate/pathology , Prostate/surgery , Prostatectomy , Biopsy/methods , Humans , Male , Margins of Excision , Middle Aged , Neoplasm Staging , Pilot Projects , Predictive Value of Tests , Retrospective Studies
10.
J Urol ; 199(6): 1440-1445, 2018 06.
Article in English | MEDLINE | ID: mdl-29427584

ABSTRACT

PURPOSE: We evaluated the discordance between ureteroscopic biopsy and surgical pathology findings for grading and staging upper tract urothelial carcinoma. We also sought to establish preoperative predictors of aggressive tumors. MATERIALS AND METHODS: We retrospectively reviewed the records of 314 patients who underwent ureteroscopic biopsy followed by surgical management of upper tract urothelial carcinoma from 2000 to 2016 at a total of 3 institutions. Our primary outcomes were muscle invasive (pT2 or greater) disease at surgical pathology and upgrading of clinical low grade tumors to pathological high grade. RESULTS: At biopsy 61% of the patients had clinical high grade tumors and 21% had subepithelial connective tissue invasion (cT1+). On final pathology 79% of the patients had pathological high grade tumors and 45% had stage pT2 or greater. On multivariate analysis advanced patient age, clinical high grade and cT1+ were independently associated with pT2 or greater. The combined presence of clinical high grade and cT1+ had 86% positive predictive value for muscle invasion while the combined absence of clinical high grade and cT1+ had 80% negative predictive value. The likelihood of missing invasion on biopsy in patients with muscle invasive disease was increased when biopsy fragments were limited to 1 mm or less. Of clinical low grade cases on biopsy 51% were upgraded at surgery. The presence of positive urine cytology was associated with an increased risk of upgrading but this was not statistically significant. CONCLUSIONS: Clinical high grade, cT1+ on biopsy and advanced patient age are independent risk factors for muscle invasive upper tract urothelial carcinoma. There is a significant risk of upgrading in patients with clinical low grade tumors on biopsy, especially when urine cytology is positive. The predictive value of biopsy can likely be improved by more extensive ureteroscopic sampling.


Subject(s)
Carcinoma, Transitional Cell/pathology , Kidney Neoplasms/pathology , Kidney Pelvis , Ureteral Neoplasms/pathology , Ureteroscopy , Aged , Carcinoma, Transitional Cell/surgery , Female , Humans , Image-Guided Biopsy , Kidney Neoplasms/surgery , Male , Neoplasm Grading , Neoplasm Staging , Retrospective Studies , Ureteral Neoplasms/surgery
11.
BJU Int ; 122(3): 434-440, 2018 09.
Article in English | MEDLINE | ID: mdl-29603871

ABSTRACT

OBJECTIVES: To model the cost-effectiveness of a biomarker-based approach to select patients for neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) in muscle-invasive bladder cancer (MIBC). PATIENTS AND METHODS: We obtained data from the most recent clinical studies on patients with locally advanced MIBC treated by RC, including stage distributions, overall survival (OS) estimates, associated costs, and utilisation/response to NAC. Additionally, we estimated the putative efficacy of three biomarkers to select patients for NAC: DNA-repair gene panel [ataxia telangiectasia mutated (ATM), retinoblastoma 1 (RB1), and Fanconi anaemia complementation group C (FANCC)], excision repair cross-complementation group 2 (ERCC2), and ribonucleic acid (RNA) subtypes. A decision analysis model was developed to evaluate the cost-effectiveness of biomarker-based approaches to select patients with MIBC for NAC. Comparison of cost-effectiveness included RC alone, unselected NAC plus RC, and NAC based on the three aforementioned biomarkers. RESULTS: The DNA-repair gene panel-based approach to NAC was the most cost-effective strategy (mean OS of 3.14 years, $31 482/life year). Under this approach, 38% would undergo NAC, about twice the number of patients who are currently receiving NAC for MIBC. Such an approach would improve mean OS by 5.2, 1.6, and 4.4 months compared to RC alone, a hypothetical scenario where all patients received NAC, and compared to current estimates of NAC utilisation, respectively. CONCLUSIONS: A biomarker-based strategy to identify patients with MIBC who should undergo NAC was more cost-effective than unselected use of NAC or RC alone. As further data becomes available, such a model may serve as a basis for incorporating biomarkers into clinical decision making.


Subject(s)
Biomarkers, Tumor/genetics , Health Care Costs/statistics & numerical data , Neoadjuvant Therapy/economics , Urinary Bladder Neoplasms/drug therapy , Biomarkers, Tumor/economics , Cost-Benefit Analysis , Cystectomy/economics , Cystectomy/methods , Databases, Factual , Decision Support Techniques , Humans , Mutation , Neoadjuvant Therapy/methods , Patient Selection , Survival Rate , Urinary Bladder/pathology , Urinary Bladder/surgery , Urinary Bladder Neoplasms/economics , Urinary Bladder Neoplasms/surgery
12.
Curr Opin Urol ; 28(5): 440-447, 2018 09.
Article in English | MEDLINE | ID: mdl-30004908

ABSTRACT

PURPOSE OF REVIEW: We aim to give an overview of the epidemiology and treatment trends of testicular germ cell tumors (TGCTs), with an emphasis on recent trends. RECENT FINDINGS: The incidence of TGCT appears to be increasing, particularly in developed countries, although the reasons are not well understood. There is evidence of racial differences in predisposition to TGCT, with white men having highest risk and men of African or Asian descent having lower risk. In the United States, the incidence of TGCT among Hispanics appears to be rising most quickly. A recent genomic analysis indicates there is no highly penetrant major TGCT susceptibility gene. Incorporation of multidisciplinary care has led to excellent long-term cure rates; however, access to care and insurance remains barriers in young men. Recent treatment trends have centered on maximizing oncologic outcomes while minimizing long-term morbidity. SUMMARY: Emerging population-level data provide critical insight into the evolving demographics of TGCT, which may allow for elucidation of biologic and environmental determinants of TGCT. Further, identification of socioeconomic barriers to excellent clinical outcomes will allow for targeted interventions to patients with unique demographic and socioeconomic considerations. Treatment trend analyses suggest that the field is moving toward minimizing treatment-related morbidity.


Subject(s)
Neoplasms, Germ Cell and Embryonal/epidemiology , Testicular Neoplasms/epidemiology , Chemotherapy, Adjuvant/trends , Ethnicity/statistics & numerical data , Genetic Predisposition to Disease , Health Services Accessibility , Humans , Incidence , Male , Neoplasms, Germ Cell and Embryonal/ethnology , Neoplasms, Germ Cell and Embryonal/genetics , Neoplasms, Germ Cell and Embryonal/therapy , Orchiectomy/trends , Population Growth , Radiotherapy, Adjuvant/trends , Testicular Neoplasms/ethnology , Testicular Neoplasms/genetics , Testicular Neoplasms/therapy , United States/epidemiology
13.
J Urol ; 198(6): 1253-1262, 2017 12.
Article in English | MEDLINE | ID: mdl-28668287

ABSTRACT

PURPOSE: We investigated the prognostic value of PD-1 and PD-L1 expression in patients with high grade upper tract urothelial carcinoma. MATERIALS AND METHODS: Tissue microarrays of 423 patients treated with extirpative surgery for high grade upper tract urothelial carcinoma from the International Upper Tract Urothelial Carcinoma collaboration were stained for PD-1 and PD-L1 using antibodies, including Cell Marque™ NAT105 diluted 1:250 and prediluted E1L3N® via immunohistochemistry. A 1% or greater staining rate of tumor infiltrating lymphocytes (PD-1) and tumor cells (PD-L1) was considered positive. Univariate and multivariate analyses were performed to assess independent prognosticators of survival outcomes. RESULTS: Median patient age was 70.0 years and median followup was 37.0 months. PD-1 and PD-L1 were positive in 37.2% and 26.2% of patients, respectively. PD-1 positivity was significantly associated with adverse pathological characteristics while PD-L1 positivity was associated with favorable pT stage. On univariate analysis PD-1 expression was associated with worse recurrence-free, cancer specific and overall survival. On multivariate analysis PD-1 expression was an independent prognosticator of cancer specific survival (HR 1.7, 95% CI 1.03-2.66, p = 0.039) and overall survival (HR 1.5, 95% CI 1.05-2.24, p = 0.029) but not recurrence-free survival (HR 1.4, 95% CI 0.9-2.16, p = 0.139). On univariate analysis PD-L1 expression was not significantly associated with survival outcomes. However, on multivariate analysis in patients with organ confined disease (pT2 or less, pN0/x and cM0), PD-L1 positivity was an independent prognosticator of recurrence-free survival (HR 0.2, 95% CI 0.06-0.98, p = 0.046) and overall survival (HR 0.3, 95% CI 0.11-0.63, p = 0.003). CONCLUSIONS: PD-1 positivity of tumor-infiltrating lymphocytes was associated with adverse pathological criteria and independent prognostication of worse survival outcomes. PD-L1 positivity of tumor cells was an independent prognosticator of favorable survival outcomes in cases of organ confined disease.


Subject(s)
B7-H1 Antigen/biosynthesis , Carcinoma, Transitional Cell/metabolism , Kidney Neoplasms/metabolism , Programmed Cell Death 1 Receptor/biosynthesis , Ureteral Neoplasms/metabolism , Aged , B7-H1 Antigen/analysis , Carcinoma, Transitional Cell/pathology , Female , Humans , Kidney Neoplasms/pathology , Male , Neoplasm Grading , Prognosis , Programmed Cell Death 1 Receptor/analysis , Retrospective Studies , Tissue Array Analysis , Ureteral Neoplasms/pathology
14.
BJU Int ; 119(3): 371-380, 2017 03.
Article in English | MEDLINE | ID: mdl-28058776

ABSTRACT

Non-muscle-invasive bladder cancer (NMIBC) represents the vast majority of bladder cancer diagnoses, but this definition represents a spectrum of disease with a variable clinical course, notable for significant risk of recurrence and potential for progression. Management involves risk-adapted strategies of cystoscopic surveillance and intravesical therapy with the goal of bladder preservation when safe to do so. Multiple organizational guidelines exist to help practitioners manage this complicated disease process, but adherence to management principles among practising urologists is reportedly low. We review four major organizational guidelines on NMIBC: the American Urological Association (AUA)/Society of Urologic Oncology (SUO), European Association of Urology (EAU), National Comprehensive Cancer Network (NCCN), and National Institute for Health and Care Excellence (NICE) guidelines.


Subject(s)
Urinary Bladder Neoplasms/therapy , Humans , Muscle, Smooth , Neoplasm Invasiveness , Practice Guidelines as Topic , Urinary Bladder Neoplasms/pathology
15.
Curr Opin Urol ; 27(1): 41-47, 2017 01.
Article in English | MEDLINE | ID: mdl-27584029

ABSTRACT

PURPOSE OF REVIEW: Testicular germ cell tumors (TGCTs) are a model for curable cancer because of exquisite chemosensitivity and incorporation of multimodal therapy. Nevertheless, our ability to predict metastases in early-stage disease and responders to chemotherapy in advanced disease is limited. Treatment options for cisplatin-resistant disease are sparse. A further understanding of TGCT biology may allow for more precise patient counseling and identify novel therapies in patients with cisplatin-resistant disease. RECENT FINDINGS: Adult TGCTs are characterized by frequent chromosomal anomalies and low rates of somatic mutations. Large-scale integrated molecular analysis of early-stage TGCT patients is actively underway. In addition to ubiquitous gain of isochromosome 12p, current molecular studies have confirmed mutations of previously described genes (i.e., KIT and KRAS) and described novel mutations. Analysis of cisplatin-resistant cases has identified high rates of alterations within the TP53-MDM2 axis and a high proportion of patients with potentially actionable targets, including TP53-MDM2, PI3 kinase, and MAPK signaling pathway alterations. The role of epigenetics in TGCT development and prognosis is also being further characterized. SUMMARY: Further molecular characterization of TGCT may allow for avoidance of unnecessary treatment in patients with early-stage disease and also provide new treatment options in patients with cisplatin-resistant disease.


Subject(s)
Genomics , Neoplasms, Germ Cell and Embryonal/genetics , Testicular Neoplasms/genetics , Cisplatin , Genetic Predisposition to Disease , Genomics/trends , Humans , Male
16.
J Urol ; 205(6): 1620, 2021 06.
Article in English | MEDLINE | ID: mdl-33734861
17.
Curr Urol Rep ; 17(1): 8, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26754033

ABSTRACT

Partial nephrectomy (PN) is the current standard of care for the management of small renal masses (SRM), providing comparable oncologic control with improved renal functional outcomes. Additionally, new technologies such as thermal ablation provide attractive alternatives to traditional extirpative surgery. The obvious benefit of these nephron sparing procedures (NSPs) is to the preservation of renal parenchymal volume (RPV), but the factors that influence postoperative renal function are complex and inter-related, and include non-modifiable factors such as baseline renal function and tumor size, complexity, and location as well as potentially modifiable factors such as ischemia time, ischemia type, and RPV preservation. Our review presents the most recent evidence analyzing the relationship between the modifiable factors in PN and renal outcomes, with a focus on RPV preservation. Furthermore, novel surgical techniques, imaging modalities, and NSPs are discussed, evaluating their efficacy in maximizing functional nephron mass and improving long-term renal outcomes.


Subject(s)
Kidney Diseases/physiopathology , Nephrons/physiopathology , Humans , Ischemia/physiopathology , Ischemia/surgery , Kidney Diseases/surgery , Kidney Function Tests , Nephrectomy/methods , Nephrons/surgery
18.
J Urol ; 194(3): 658-63, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25818030

ABSTRACT

PURPOSE: We analyze the relationship among various patient, operative and tumor characteristics to determine which factors correlate with renal parenchymal volume loss after nephron sparing surgery using a novel 3-dimensional volume assessment. MATERIALS AND METHODS: We conducted a retrospective review of an institutional database of patients who underwent nephron sparing surgery from 1992 to 2014 for a localized renal mass. Tumors were classified according to the R.E.N.A.L. nephrometry system. Using 3-dimensional reconstruction imaging software, preoperative and postoperative renal parenchymal volume was calculated for the ipsilateral and contralateral kidney. RESULTS: A total of 158 patients were analyzed. Mean patient age was 58.7 years and mean followup was 40.1 months. Mean preoperative tumor volume was 34.0 cc and mean tumor dimension was 3.4 cm. Mean R.E.N.A.L. nephrometry score was 6.2, with 60.1%, 34.2% and 5.7% of tumors classified as low, medium and high complexity, respectively. Mean change in renal parenchymal volume after nephron sparing surgery was -15.3% for the ipsilateral kidney and -6.8% for total kidney volume. On univariate analysis ischemia time, tumor size, R.E.N.A.L. nephrometry score, complexity grouping and the individual nephrometry components of tumor size, percent exophytic, anterior/posterior, depth and tumor proximity to the renal artery or vein were associated with greater renal parenchymal volume loss. On multivariate analysis only ischemia time, tumor size, posterior location and percent exophytic were independently associated with more renal parenchymal volume loss. CONCLUSIONS: Using precise 3-dimensional volumetric analysis we found that ischemia time, tumor size and endophytic/exophytic properties of a localized renal mass are the most important determinants of renal parenchymal volume loss.


Subject(s)
Carcinoma, Renal Cell/surgery , Kidney Neoplasms/surgery , Kidney/anatomy & histology , Kidney/surgery , Nephrectomy/methods , Female , Humans , Imaging, Three-Dimensional , Male , Middle Aged , Nephrons , Organ Size , Organ Sparing Treatments , Prognosis , Retrospective Studies
19.
Int Braz J Urol ; 41(3): 473-85, 2015.
Article in English | MEDLINE | ID: mdl-26200540

ABSTRACT

OBJECTIVE: To compare the utilization, perioperative complications and predictors of LCA versus RPN in the treatment of localized renal tumors. METHODS: From the Nationwide Inpatient Sample we identified patients undergoing RPN or LCA for the treatment of localized renal tumors from October 2008 through 2010. Patient and hospital-specific factors which predict postoperative complications and use of LCA were investigated. RESULTS: 14,275 patients with localized renal tumors were identified: 70.3% had RPN and 29.7% had LCA. LCA was more common in older patient and at hospitals without robotic consoles. No difference was identified in perioperative complications (0.2% vs. 0.2%), transfusion (5.1% vs. 6.2%), length of stay (2.9 vs. 3.0 days) or median cost ($41,753 vs. $44,618) between the groups, LCA vs. RPN. On multivariate analysis sicker patients were more likely to have LCA (OR 1.34, p=0.048) and sicker patients had greater postoperative complications (OR 3.30, p<0.001); LCA did not predict more complications (OR 1.63, p=0.138) and LCA was performed at hospitals without RCs (OR 0.02, p<0.001). Limitations include observational study design, inability to assess disease severity, operative time, or body mass index, which may affect patient selection and outcomes. CONCLUSIONS: More patients had RPN vs. LCA; surgical technique was not predictive of postoperative complications. As technology develops to treat localized renal tumors, it will be important to continue to track outcomes and costs for procedures including RPN and LCA.


Subject(s)
Cryosurgery/methods , Intraoperative Complications , Kidney Neoplasms/surgery , Laparoscopy/methods , Nephrectomy/methods , Robotic Surgical Procedures/methods , Age Factors , Aged , Aged, 80 and over , Cryosurgery/adverse effects , Female , Hospital Mortality , Humans , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Male , Middle Aged , Operative Time , Reference Values , Reproducibility of Results , Risk Factors , Robotic Surgical Procedures/adverse effects , Sex Factors , Treatment Outcome
20.
J Urol ; 201(5): 901, 2019 05.
Article in English | MEDLINE | ID: mdl-30822204
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