Interethnic differences in the impact of body mass index on upper tract urothelial carcinoma following radical nephroureterectomy.

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.

Overcoming sociodemographic factors in the care of patients with testicular cancer at a safety net hospital.

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.

Pathologic stage as a surrogate for oncologic outcomes after receipt of neoadjuvant chemotherapy for high-grade upper tract urothelial carcinoma.

OBJECTIVE: Whether pathologic stage at radical nephroureterectomy (RNU) can serve as an appropriate surrogate for oncologic outcomes in patients with high-grade (HG) upper tract urothelial carcinoma (UTUC) treated with neoadjuvant chemotherapy (NAC) is not defined. We sought to determine whether patients who achieve pathologically non-muscle-invasive (ypT0, ypTa, ypT1, ypTis) HG UTUC after receipt of NAC exhibit oncologic outcomes comparable to those who are inherently low stage without chemotherapy. METHODS: We identified 647 UTUC patients who underwent RNU among 3 institutions from 1993to2016. Patients with low or unknown grade, pathologic muscle invasion, or receipt of adjuvant chemotherapy were excluded. We compared clinicopathologic data and oncologic outcomes between pT0-1 and ypT0-1 patients. Kaplan-Meier analysis was used to assess overall (OS), cancer-specific (CSS), and systemic recurrence-free (RFS) survival. Predictors of these endpoints were identified using Cox regression. RESULTS: 234 (43 ypT0-1, 191 pT0-1) patients with HG UTUC were included. Two patients exhibited pathologic complete response after NAC. OS (P = 0.055), CSS (P = 0.152), and RFS (P = 0.098) were similar between ypT0-1 and pT0-1 patients. Predictors of worse outcomes included African-American race (RFS, CSS, and OS), Charlson score (OS), and systemic recurrence (OS and CSS). CONCLUSIONS: Patients with HG UTUC who achieve ypT0-1 stage after NAC exhibit favorable oncologic outcomes comparable to those inherently non-muscle-invasive who do not receive chemotherapy. Improvements in clinical staging will play an important role in better defining candidacy for NAC in treating HG UTUC while minimizing overtreatment. Furthermore, pathologic stage may serve as an appropriate early surrogate for oncologic endpoints in designing clinical trials.

Validation of Hyponatremia as a Prognostic Predictor in Multiregional Upper Tract Urothelial Carcinoma.

Hyponatremia has been shown to be associated with prognosis in various cancers, but its role in upper tract urothelial carcinoma (UTUC) is largely unidentified. We created an international multiregional cohort of UTUC, consisting of 524 and 213 patients from Taiwan and the U.S., to validate the significance of hyponatremia. Clinicopathologic characteristics were compared according to the presence of hyponatremia. Univariate and multivariate Cox regression models were used to investigate the association of hyponatremia with disease progression and survival. The impact of hyponatremia in patients from distinct regions was also analyzed. Hyponatremia was found in 143 (19.4%) patients. Hyponatremic patients had significantly worse Eastern Cooperative Oncology Group (ECOG) performance status (p = 0.00001) and higher pT stage (p = 0.002). In multivariate analysis, hyponatremia was an independent prognostic factor for progression (HR 1.585, 95% CI 1.115-2.253, p = 0.010), cancer-specific death (HR 2.225, 95% CI 1.457-3.397, p = 0.0002), and overall mortality (HR 1.819, 95% CI 1.299-2.545, p = 0.0005). Kaplan-Meier analysis showed the consistent adverse effect of hyponatremia on all outcomes in patients from Taiwan and the U.S. (all p < 0.05). Hyponatremia is commonly accessible and can serve as a negative marker for both the general health condition and disease severity of UTUC patients. A similar implication of hyponatremia in progression and survival despite patients' region of presentation suggests its general applicability across different ethnicities.

Improved survival after cytoreductive nephrectomy for metastatic renal cell carcinoma in the contemporary immunotherapy era: An analysis of the National Cancer Database.

OBJECTIVES: Despite immune checkpoint inhibitor (ICI) approval for metastatic renal cell carcinoma (mRCC) in 2015, cytoreductive nephrectomy (CN) is guided by extrapolation from earlier classes of therapy. We evaluated survival outcomes, timing, and safety of combining CN with modern immunotherapy (IO) for mRCC. METHODS: From 96,329 renal cancer cases reported to the NCDB between 2015 and 2016, we analyzed 391 surgical candidates diagnosed with clear cell mRCC treated with IO ± CN and no other systemic therapies. Primary outcome was overall survival (OS) stratified by the performance of CN (CN + IO vs. IO alone). Secondary outcomes included OS stratified by the timing of CN, pathologic findings, and perioperative outcomes. RESULTS: Of 391 patients, 221 (56.5%) received CN + IO and 170 (43.5%) received IO only. Across a median follow-up of 14.7 months, patients who underwent CN + IO had superior OS (median NR vs. 11.6 months; hazard ratio 0.23, P < 0.001), which was upheld on multivariable analyses. IO before CN resulted in lower pT stage, grade, tumor size, and lymphovascular invasion rates compared to upfront CN. Two of 20 patients (10%) undergoing CN post-IO achieved complete pathologic response in the primary tumor (pT0). There were no positive surgical margins, 30-day readmissions, or prolonged length of stay in patients undergoing delayed CN. CONCLUSION: Using a large, national, registry-based cohort, we provide the first report of survival outcomes in mRCC patients treated with CN combined with modern IO. Our findings support an oncologic role for CN in the ICI era and provide preliminary evidence regarding the timing and safety of CN relative to IO administration.

Prognostic significance of BAP1 expression in high-grade upper tract urothelial carcinoma: a multi-institutional study.

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.

Multi-institutional evaluation of the prognostic significance of EZH2 expression in high-grade upper tract urothelial carcinoma.

PURPOSE: Enhancer of zeste homolog 2 is a methyltransferase encoded by the EZH2 gene, whose role in upper tract urothelial carcinoma (UTUC) is poorly understood. We sought to evaluate the prognostic value of EZH2 expression in UTUC. METHODS: We reviewed a multi-institutional cohort of patients who underwent radical nephroureterectomy for high-grade UTUC from 1990 to 2008. Immunohistochemistry for EZH2 was performed on tissue microarrays. Percentage of staining was evaluated, and the discriminative value of EZH2 was tested, with EZH2 positivity defined as>20% staining present. Clinicopathologic characteristics and oncologic outcomes (recurrence-free (RFS), cancer-specific (CSS), and overall survival (OS)) were compared, stratified by EZH2 positivity. The prognostic role of EZH2 was assessed using Kaplan-Meier, univariate (UVA), and multivariate (MVA) Cox regression analyses. Significance was defined for P<0.05. RESULTS: A total of 376 patients were included for analysis, with median follow-up 36.0 months. Overall, 78 (20.7%) were EZH2-positive. EZH2 expression was more often associated with ureteral location, lymphovascular invasion, sessile architecture, necrosis, and concomitant carcinoma in situ. On UVA, increased EZH2 expression was a significant predictor for inferior RFS (HR 1.63, P = 0.033), CSS (HR 2.03, P = 0.003), and OS (HR 2.11, P<0.001). On MVA EZH2 remained a significant predictor of worse CSS (HR 1.99 [95% CI: 1.21-3.27], P = 0.007) and OS (HR 1.54 [95% CI: 1.06-2.24], P = 0.024), while significance was lost for RFS. CONCLUSION: Increased EZH2 expression is associated with adverse pathologic features and inferior oncologic outcomes in patients with high-grade UTUC. The role of EZH2 biology in UTUC pathogenesis remains to be further elucidated.

Usage and survival implications of surgical staging of inguinal lymph nodes in intermediate- to high-risk, clinical localized penile cancer: A propensity-score matched analysis.

OBJECTIVES: To evaluate the usage of surgical staging of inguinal lymph nodes (SSILNs) in the United States for intermediate to high-risk, clinically localized penile squamous cell cancer (SCC), to explore patient and hospital factors associated with omission of this staging, and to evaluate the effect on survival. PATIENTS AND METHODS: Retrospective, observational study using the National Cancer Database from 2004 to 2014 of 1,689 men diagnosed with pT1b-T3, cN0 penile SCC, who by current guidelines should receive SSILNs-either by inguinal lymph node (ILN) dissection or sentinel node biopsy. Binomial logistic regression analysis was performed to determine predictors of SSILNs. Multivariate Cox regression analysis was performed to determine the impact of SSILNs on survival in the overall and propensity-score matched patient populations. RESULTS: Only 25.3% of patients underwent SSILNs. Increasing patient age, higher comorbidity status, lower pathologic stage, Medicaid insurance, and treatment at a nonacademic facility were independent factors associated with the omission of SSILNs. Omission of SSILNs was an independent predictor of overall mortality, both in the overall patient population after multivariate adjustment, HR = 1.46 [(95% CI: 1.14-1.88), P = 0.003], and in the propensity-score matched adjusted population, HR = 1.59 [(95% CI: 1.20-2.13), P = 0.001]. Limitations include an inability to distinguish biopsy from ILN dissection and those inherent in observational study design. CONCLUSION: Utilization of SSILN for penile SCC is low and has not changed significantly since the publication of guidelines in the United States. In particular, nonacademic institutions were less likely to adhere to recommendations for performance of SSILNs. We found the omission of SSILNs is associated with a significant increase in mortality.

Differences at Presentation and Treatment of Testicular Cancer in Hispanic Men: Institutional and National Hospital-based Analyses.

OBJECTIVE: To describe epidemiologic patterns, stage at presentation, histology, and treatment differences associated with Hispanic men diagnosed with testicular germ cell tumor (TGCT). Hispanics are the fastest growing demographic in the United States and reports suggest that the incidence of TGCT is rising most rapidly in this demographic, yet little is known about TGCTs in Hispanic patients. MATERIALS AND METHODS: We compared patient factors, tumor characteristics, treatment patterns, and outcomes of non-Hispanic white (NHW) vs Hispanic patients at our own institution in North Texas from 2010 to 2016. The findings were corroborated by analyzing the National Cancer Database testicular cancer registry from 2004 to 2014. RESULTS: We identified 154 patients with TGCT at our institution, of which 89 were NHW (56.0%) and 65 were Hispanic (40.9%). A review of the National Cancer Database identified 49,607 NHW patients (81.5%) and 6724 Hispanic patients (11.0%) diagnosed with TGCT. At presentation, Hispanic patients were approximately 5 years younger than NHW patients, delay seeking care for testicular cancer, were more likely to have nonseminomatous histology, had a larger tumor size, and had a higher disease burden at presentation. Additionally, we identified differences in treatment patterns at the national level. CONCLUSION: Differences in outcomes and treatment patterns of Hispanic and NHW patients with TGCT may represent underlying socioeconomic issues and access to care; however, discrepancies in age of onset and histology of TGCT between Hispanic and NHW patients may signify differences in tumor biology or risk factors. We suggest that this possibility be explored further as we embark upon the genomic classification of TGCT.

Prognostic Value of PD-1 and PD-L1 Expression in Patients with High Grade Upper Tract Urothelial Carcinoma.

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.

Postoperative Nomogram for Relapse-Free Survival in Patients with High Grade Upper Tract Urothelial Carcinoma.

PURPOSE: We developed a prognostic nomogram for patients with high grade urothelial carcinoma of the upper urinary tract after extirpative surgery. MATERIALS AND METHODS: Clinical data were available for 2,926 patients diagnosed with high grade urothelial carcinoma of the upper urinary tract who underwent extirpative surgery. Cox proportional hazard regression models identified independent prognosticators of relapse in the development cohort (838). A backward step-down selection process was applied to achieve the most informative nomogram with the least number of variables. The L2-regularized logistic regression was applied to generate the novel nomogram. Harrell's concordance indices were calculated to estimate the discriminative accuracy of the model. Internal validation processes were performed using bootstrapping, random sampling, tenfold cross-validation, LOOCV, Brier score, information score and F1 score. External validation was performed on an external cohort (2,088). Decision tree analysis was used to develop a risk classification model. Kaplan-Meier curves were applied to estimate the relapse rate for each category. RESULTS: Overall 35.3% and 30.7% of patients experienced relapse in the development and external validation cohort. The final nomogram included age, pT stage, pN stage and architecture. It achieved a discriminative accuracy of 0.71 and 0.76, and the AUC was 0.78 and 0.77 in the development and external validation cohort, respectively. Rigorous testing showed constant results. The 5-year relapse-free survival rates were 88.6%, 68.1%, 40.2% and 12.5% for the patients with low risk, intermediate risk, high risk and very high risk disease, respectively. CONCLUSIONS: The current nomogram, consisting of only 4 variables, shows high prognostic accuracy and risk stratification for patients with high grade urothelial carcinoma of the upper urinary tract following extirpative surgery, thereby adding meaningful information for clinical decision making.

Cell-cycle markers do not improve discrimination of EORTC and CUETO risk models in predicting recurrence and progression of non-muscle-invasive high-grade bladder cancer.

PURPOSE: To assess if a panel of cell-cycle markers could improve the discrimination of European Organization for Research and Treatment of Cancer (EORTC) and Spanish Urological Club for Oncological Treatment (CUETO) models in predicting recurrence and progression of high-grade non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: Between January 2007 and January 2012, every patient with high-grade NMIBC treated with transurethral resection of bladder underwent immunohistochemical staining for 5 biomarkers (p21, p27, p53, KI-67, and cyclin E1). We excluded patients who had muscle-insvasive disease, underwent early cystectomy, and those with incomplete follow-up. Kaplan-Meier curves assessed recurrence and progression-free survival. Univariate and multivariate Cox regression analysis assessed the predictive ability of markers after correcting for EORTC or CUETO risk scores. Harrel concordance index assessed for discrimination. RESULTS: There were 131 patients with a median follow-up of 31.1 months. Stage was Ta (50%), T1 (44%), and Tis (8%). For 95 patients this was the primary tumor. Intravesical therapy was used in 76% of cases of which 45% had maintenance. Recurrence-free survival rates at 6, 12, and 24 months were 68.9%, 52.1%, and 33.2%, respectively, whereas progression-free survival rate at 6, 12, and 24 months were 93.8%, 88%, and 84.3%, respectively. No differences in survival based on number of altered markers were noted. Biomarker status was neither a significant predictor of recurrence nor progression. Marker alterations marginally improved discrimination of EORTC and CUETO models, which were confirmed to be mediocre. CONCLUSIONS: Markers were not significant predictors of recurrence nor progression in patients with high-grade NMIBC and their addition to prediction models is of little benefit.

Comparing Changes in Renal Function After Radical Surgery for Upper Tract Urothelial Carcinoma and Renal Cell Carcinoma.

OBJECTIVE: To compare changes in renal function after radical nephrectomy for renal cell carcinoma (RCC) and radical nephroureterectomy for upper tract urothelial carcinoma (UTUC), and assess their effects on non-cancer-specific mortality (CSM). METHODS: Clinicopathologic data from 1114 patients with RCC or UTUC treated surgically from 1997 to 2013 were compiled. Patients who underwent nephron-sparing surgeries, had bilateral disease, received chemotherapy, or had <1 month of follow-up were excluded. Renal function (estimated glomerular filtration rate [eGFR]) was calculated preoperatively, 3 months postoperatively, and at last follow-up. Events were defined as ≥25% decline in eGFR from baseline. Event-free survival and non-CSM were assessed using Kaplan-Meier analysis. Multivariable Cox regression was performed to identify predictors of events. RESULTS: Four hundred thirty-five patients were included (317 radical nephrectomy, 118 radical nephroureterectomy). Median follow-up was 38.2 months. UTUC patients were older (P < .001), had worse Charlson score (P < .001), and more frequently used tobacco (P = .006). Median baseline eGFR was lower in UTUC patients (58.4 vs 74.9, P < .001). RCC patients experienced a larger event rate following surgery at first (56.8% vs 31.4%, P < .001) and last (51.7% vs 35.6%, P = .003) follow-up than UTUC patients. On Kaplan-Meier analysis, UTUC patients exhibited worse non-CSM (P < .001). Postsurgical decline in renal function was a significant predictor of non-CSM in RCC patients at first (hazard ratio = 4.71, P = .041) and last (hazard ratio = 4.56, P = .018) follow-up, whereas this was not the case for UTUC patients. CONCLUSION: UTUC patients had worse baseline eGFR and overall health status than RCC patients. RCC patients experienced greater postsurgical declines in renal function. These results shed light on differences in patient characteristics between these forms of kidney cancer and guide expectations for postoperative renal function.

Concordance in Biomarker Status Between Bladder Tumors at Time of Transurethral Resection and Subsequent Radical Cystectomy: Results of a 5-year Prospective Study.

PURPOSE: To assess the concordance rate in alterations of molecular markers at the time of transurethral resection (TUR) and subsequent radical cystectomy (RC) among patients with high-grade urothelial carcinoma of the bladder (UCB). METHODS: We prospectively performed immunohistochemical staining p53, p21, p27, Ki-67 and cyclin E1 on TUR and on RC specimens from 102 patients treated with RC and bilateral lymphadenectomy for high-grade UCB. We analyzed the concordance rate of individual markers and of the number of altered markers. Concordant and discordant findings were reported in the overall population and according to clinical stage. RESULTS: Median patient age was 74 years (IQR 67-79) and mostly male (86%). Median time from TUR to RC was 1.5 months (IQR 1.0-2.4). Clinical stage at time of RC was cTa/Tis/T1 in 50% , cT2 in 47% , and cT4 in 1% of patients Nine (9%) patients received neoadjuvant chemotherapy. The concordance of biomarkers between TUR and RC specimens was 92.2% , 77.5% , 80.4% , 77.5% , and 83.3% for cyclin E1, p21, p27, p53 and Ki-67, respectively. The concordance between number of altered biomarkers was 51.0%. CONCLUSIONS: The rate of individual marker alterations at time of TUR closely approximates that found at RC specimens. However, the correlation of number of altered markers is lower. Molecular marker status at TUR could help predict the marker status at RC and may help guide multimodal therapeutic planning.

Prognostic serum markers in patients with high-grade upper tract urothelial carcinoma.

INTRODUCTION: The role of preoperative serum-based markers in predicting survival outcomes of patients has been reported for several cancer types; however, their association with upper tract urothelial carcinoma (UTUC) prognosis is unclear. We evaluated the role of systemic serum-based markers in predicting adverse pathological features and survival outcomes in patients surgically treated for high-grade (HG) UTUC. METHODS: We retrospectively reviewed all patients undergoing surgery for HG UTUC between June 2006 and July 2013 at our institution. Comprehensive clinicopathologic data and preoperative serum-based markers including hemoglobin, white blood cell count, platelet count, serum albumin, calcium, and liver function tests were recorded. Associations of serum markers with pathologic features and recurrence-free survival (RFS) were determined by logistic and Cox regression analyses, respectively. The concordance index for the oncologic outcomes model was determined. RESULTS: In total, 101 patients were identified with a median follow-up of 18.5 months (range: 1-74mo). In all, 60% of patients had pT2 or less and 11% had nodal metastases. Preoperative elevated alkaline phosphatase (ALP) (≥116IU/l) was associated with multiple adverse pathologic features including advanced T stage, lymphovascular invasion, and histologic necrosis. On univariate analysis, serum markers independently associated with RFS included hemoglobin≤12.9 (hazards ratio [HR] = 2.51; 95% CI: 1.17-5.36, P = 0.018), albumin≤4g/dl (HR = 4.4; 95% CI: 2.04-9.30; P<0.0001), ALP≥116U/l (HR = 13.3; 95% CI: 5.3-33.52, P<0.0001), alanine transaminase≥27 (HR = 2.63, 95% CI: 1.11-6.21, P = 0.028), serum aspartate transaminase≥20 (HR = 2.21, 95% CI: 1.04-4.69, P = 0.038), and corrected calcium≥9.3 (HR = 2.45, 95% CI: 1.01-5.93, P = 0.047). The 2 strongest predictors, albumin and ALP, were combined to form an AA score (range: 0-2), which improved the baseline preoperative clinical model concordance index for prediction of RFS from 0.626 to 0.799. CONCLUSION: In HG UTUC, elevated preoperative ALP was associated with adverse pathologic features. Additionally, elevated ALP and low albumin were independently associated with worse RFS and overall survival. These serum-based markers are often measured in the preoperative workup of UTUC, and thus they can be included in future prognostic models to risk stratify patients.

The Usefulness of Chest X-Rays for T1a Renal Cell Carcinoma Surveillance.

PURPOSE: The overall incidence of pulmonary metastasis of T1 renal cell carcinoma is low. We evaluated the usefulness of chest x-rays based on the current AUA (American Urological Association) guidelines and NCCN Guidelines® for T1a renal cell carcinoma surveillance. MATERIALS AND METHODS: Between 2006 and 2012, 258 patients with T1a renal cell carcinoma were treated with partial nephrectomy, radical nephrectomy or radio frequency ablation with surveillance followup at our institution. A retrospective chart review was performed to identify demographics, pathological findings and surveillance records. The primary outcome was the incidence of asymptomatic pulmonary recurrences diagnosed by chest x-ray in cases of T1a disease. Our secondary outcome was a comparison of diagnoses by treatment modality (partial nephrectomy, radical nephrectomy or radio frequency ablation). RESULTS: Pulmonary metastases developed in 3 of 258 patients (1.2%) but only 1 (0.4%) was diagnosed by standard chest x-ray surveillance. Median followup in the entire cohort was 36 months (range 6 to 152) and 193 of 258 patients (75%) had greater than 24 months of followup. A mean of 3.3 surveillance chest x-rays were completed per patient. When assessed by treatment type, there was no significant difference in the recurrence rate for partial nephrectomy (0 of 191 cases), radical nephrectomy (0 of 22) or radio frequency ablation (1 of 45 or 2.2%) (p = 0.09). CONCLUSIONS: Chest x-rays are a low yield diagnostic tool for detecting pulmonary metastasis in patients treated for T1a renal cel carcinoma. Treatment mode does not appear to influence the need for chest x-ray surveillance.

Do Referral Patterns in Adolescents and Young Adults with Testicular Cancer Impact Oncologic Outcomes?

PURPOSE: Oncologic outcomes in advanced testicular cancer (TC) depend on appropriate and timely care. Often this care is referred to tertiary academic medical centers (AMCs). The aim of this study was to compare oncologic outcomes of adolescent and young adult (AYA) patients with TC treated from the outset at an AMC to those whose care was initiated elsewhere with subsequent referral. METHODS: An institutional TC database was reviewed, and those AYA patients initiating TC care either inside or outside an AMC were compared. Patients were classified as initiating care outside if they had any non-orchiectomy surgery, chemotherapy, or radiotherapy for TC outside an AMC. RESULTS: A total of 183 patients were reviewed, of whom 59 initiated TC care outside and 124 were managed initially at an AMC. Patients initiating care outside were more likely to have non-seminoma histology and more often presented with metastatic disease (Stage II [30.5%] or III [35.6%] vs. Stage II [19.4%] or III [19.4%]; p = 0.007). Lower 3-year event-free survival (EFS) was observed in those initiating treatment outside an AMC (60.6% vs. 78.7%; p = 0.027). However, on multivariate analysis adjusting for stage and histology, the location of initiating TC care was no longer significant (hazard ratio = 1.5, 95% confidence interval 0.8-2.9). CONCLUSION: AYA patients initially treated for TC in the community and subsequently referred to an AMC were initially observed to experience worse EFS than those who were managed at an AMC from the outset. However, on multivariate analysis, these findings were largely explained by referral bias, where AYA patients with advanced disease were more likely to be referred to AMCs.

Molecular profile of urothelial carcinoma of the upper urinary tract: are pelvicalyceal and ureteral tumors different?

PURPOSE: To assess the potential biologic impact of tumor location on oncological outcomes for patients with upper tract urothelial carcinoma (UTUC), we used prospectively collected molecular signatures of high-grade UTUC. METHODS: Immunohistochemical staining for p21, p27, p53, cyclin E, and Ki-67 was prospectively performed on 96 UTUC specimens of patients with non-metastatic high-grade UTUC treated with extirpative surgery. Patients were grouped according to primary tumor location (pelvicalyceal vs. ureteral) where primary tumor was defined as the highest tumor stage and diameter. Primary outcome was assessment of differences in marker expression between groups. Secondary outcome was difference in survival according to marker status. RESULTS: Pelvicalyceal and ureteral tumors were found in 52.1 and 47.9 %, respectively, and 42.7 % of patients had non-organ-confined disease. Over a median follow-up of 22.0 months, 31.2 and 20.8 % of patients experienced disease recurrence and died of UTUC, respectively. The total number of altered markers stained for was 0-2 in 67.7 and 3-5 in 32.3 % of patients. The number of altered markers and alteration status of markers were not significantly different between patients with primary pelvicalyceal versus ureteral tumors when stratified by tumor stage and nodal status. There were no significant differences in survival outcomes between both groups when stratified by number of altered markers (0-2 and 3-5). CONCLUSIONS: The prospective assessment of selected cell cycle and proliferative markers suggests no molecular difference between UTUC of the pelvicalyceal system and that of the ureter. Our study is limited by its size and definition of location.

Statin Use and Serum Lipid Levels Are Associated With Survival Outcomes After Surgery for Renal Cell Carcinoma.

OBJECTIVE: To evaluate the association of statin use and preoperative serum lipid parameters with oncologic outcomes following surgery for renal cell carcinoma. METHODS: A total of 850 patients who underwent surgery for localized renal cell carcinoma at our institution from 2000 to 2012 were included. Use of statins, preoperative serum lipid profile, and comprehensive clinicopathologic features were retrospectively recorded. Kaplan-Meier analysis and multivariate Cox proportional hazards model were employed to compare survival outcomes. RESULTS: There were 342 statin users and 508 non-users. Median follow-up was 25.0 months. Statin users were older, had greater body mass index, and had worse performance status than non-users. Tumor pathologic characteristics were balanced between groups. Five-year recurrence free survival (RFS) was 77.9% for non-users compared with 87.6% for statin users (P = .004). After adjustment for clinicopathologic variables, statin use was independently associated with improved RFS (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.33-0.86, P = .011) and overall survival (HR 0.45, 95%CI 0.28-0.71, P = .001). In patients with available serum lipid parameters (n = 193), 5-year RFS was 83.8% for patients with triglycerides <250 mg/dL compared with 33.3% for those with triglycerides >250 mg/dL (P <.0001). Elevated serum triglycerides (>250 mg/dL) was independently associated with worse RFS (HR 2.69, 95%CI 1.22-5.93, P = .015) on multivariate analysis. CONCLUSION: Statin use was independently associated with improved survival, whereas elevated serum triglyceride levels correlated with worse oncologic outcomes in this cohort. These findings warrant validation in prospective studies.

Changing trends in utilization of neoadjuvant chemotherapy in muscle-invasive bladder cancer.

INTRODUCTION: To reassess use of perioperative chemotherapy in muscle-invasive bladder cancer (MIBC) following implementation of monthly multidisciplinary meetings to facilitate optimal oncologic treatment. We previously reported from 2003 to 2008 17% of eligible patients with bladder cancer received cisplatin-based neoadjuvant chemotherapy (NAC) at our institution. MATERIALS AND METHODS: A retrospective review of all patients who underwent radical cystectomy (RC) between 2008 and 2012 was performed. Information on clinical and pathologic stage, renal function, perioperative chemotherapy (CTX) use and oncologic outcomes was collected. Rationale for utilization decisions was obtained from physician encounter notes. Primary outcome was use of CTX among eligible patients. Secondary measures were type of CTX, pathologic and survival outcomes. RESULTS: Among 261 patients undergoing RC for bladder cancer, 162 were eligible for NAC. Overall 40.7% (n = 66) received NAC, and 86.4% were given platinum. Patients given NAC were younger and had more advanced clinical stage. The degree of chronic kidney disease (CKD) (0-3) did not impact likelihood of receiving NAC. NAC patients were more likely to be downstaged to non-muscle-invasive disease (21.2% versus 7.3% p < 0.01) or have a complete pathologic response (12.1% versus 3.1% p = 0.025). Receipt of NAC did not affect oncologic outcomes. Following RC 22.3% of high risk patients (n = 112) received adjuvant chemotherapy (AC). CONCLUSIONS: Our use of cisplatin-based NAC improved from 17% to 35% and overall utilization of NAC increased from 22% to 41%. NAC led to improved pT0 rates and increased pathologic downstaging. The degree of CKD (0-3) did not impact likelihood of receiving NAC. AC use decreased in part due to higher utilization of NAC.