Pathogenic Roles for RNASET2 in Clear Cell Renal Cell Carcinoma.

A specific splicing isoform of RNASET2 is associated with worse oncologic outcomes in clear cell renal cell carcinoma (ccRCC). However, the interplay between wild-type RNASET2 and its splice variant and how this might contribute to the pathogenesis of ccRCC remains poorly understood. We sought to better understand the relationship of RNASET2 in the pathogenesis of ccRCC and the interplay with a pathogenic splicing isoform (RNASET2-SV) and the tumor immune microenvironment. Using data from The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium, we correlated clinical variables to RNASET2 expression and the presence of a specific RNASET2-SV. Immunohistochemical staining with matched RNA sequencing of ccRCC patients was then utilized to understand the spatial relationships of RNASET2 with immune cells. Finally, in vitro studies were performed to demonstrate the oncogenic role of RNASET2 and highlight its potential mechanisms. RNASET2 gene expression is associated with higher grade tumors and worse overall survival in The Cancer Genome Atlas cohort. The presence of the RNASET2-SV was associated with increased expression of the wild-type RNASET2 protein and epigenetic modifications of the gene. Immunohistochemical staining revealed increased intracellular accumulation of RNASET2 in patients with increased RNA expression of RNASET2-SV. In vitro experiments reveal that this accumulation results in increased cell proliferation, potentially from altered metabolic pathways. RNASET2 exhibits a tumor-promoting role in the pathogenesis of ccRCC that is increased in the presence of a specific RNASET2-SV and associated with changes in the cellular localization of the protein.

NCCN Guidelines® Insights: Kidney Cancer, Version 2.2024.

The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients with renal cell carcinoma (RCC). These NCCN Guidelines Insights focus on the systemic therapy options for patients with advanced RCC and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Kidney Cancer.

Antegrade administration of mitomycin gel for upper tract urothelial carcinoma via percutaneous nephrostomy tube: a multi-institutional retrospective cohort study.

OBJECTIVES: To assess the safety profile of antegrade mitomycin gel instillation through a percutaneous nephrostomy tube (PCNT) for upper tract urothelial carcinoma (UTUC) with the aim of decreasing morbidity associated with therapy. PATIENTS AND METHODS: Patients undergoing antegrade administration of mitomycin gel via PCNT were retrospectively included for analysis from four tertiary referral centres between 2020 and 2022. The primary outcome was safety profile, as graded by Common Terminology Criteria for Adverse Events (v5.0). Post-therapy disease burden was assessed by primary disease evaluation (PDE) via ureteroscopy. RESULTS: Thirty-two patients received at least one dose of mitomycin gel via PCNT for UTUC, 29 of whom completed induction and underwent PDE. Thirteen patients (41%) had residual tumour present prior to induction therapy. At a median of 15.0 months following first dose of induction therapy, ureteric stenosis occurred in three patients (9%), all of whom were treated without later recurrence or chronic stenosis. Other adverse events included fatigue (27%), flank pain (19%), urinary tract infection (12%), sepsis (8%) and haematuria (8%). No patients had impaired renal function during follow-up and there were no treatment-related deaths. Seventeen patients (59%) had no evidence of disease at PDE and have not experienced recurrence at a median follow-up of 13.0 months post induction. CONCLUSIONS: Administration of mitomycin gel via a PCNT offers a low rate of ureteric stenosis, demonstrates a favourable safety profile, and is administered without general anaesthesia.

Detectable Lipidomes and Metabolomes by Different Plasma Exosome Isolation Methods in Healthy Controls and Patients with Advanced Prostate and Lung Cancer.

Circulating exosomes in the blood are promising tools for biomarker discovery in cancer. Due to their heterogeneity, different isolation methods may enrich distinct exosome cargos generating different omic profiles. In this study, we evaluated the effects of plasma exosome isolation methods on detectable multi-omic profiles in patients with non-small cell lung cancer (NSCLC), castration-resistant prostate cancer (CRPC), and healthy controls, and developed an algorithm to quantify exosome enrichment. Plasma exosomes were isolated from CRPC (n = 10), NSCLC (n = 14), and healthy controls (n = 10) using three different methods: size exclusion chromatography (SEC), lectin binding, and T-cell immunoglobulin domain and mucin domain-containing protein 4 (TIM4) binding. Molecular profiles were determined by mass spectrometry of extracted exosome fractions. Enrichment analysis of uniquely detected molecules was performed for each method with MetaboAnalyst. The exosome enrichment index (EEI) scores methods based on top differential molecules between patient groups. The lipidomic analysis detected 949 lipids using exosomes from SEC, followed by 246 from lectin binding and 226 from TIM4 binding. The detectable metabolites showed SEC identifying 191 while lectin binding and TIM4 binding identified 100 and 107, respectively. When comparing uniquely detected molecules, different methods showed preferential enrichment of different sets of molecules with SEC enriching the greatest diversity. Compared to controls, SEC identified 28 lipids showing significant difference in NSCLC, while only 1 metabolite in NSCLC and 5 metabolites in CRPC were considered statistically significant (FDR < 0.1). Neither lectin-binding- nor TIM4-binding-derived exosome lipids or metabolites demonstrated significant differences between patient groups. We observed the highest EEI from SEC in lipids (NSCLC: 871.33) which was also noted in metabolites. These results support that the size exclusion method of exosome extraction implemented by SBI captures more heterogeneous exosome populations. In contrast, lectin-binding and TIM4-binding methods bind surface glycans or phosphatidylserine moieties of the exosomes. Overall, these findings suggest that specific isolation methods select subpopulations which may significantly impact cancer biomarker discovery.

Contemporary Management of Chylous Ascites after Retroperitoneal Surgery: Development of an Evidence-Based Treatment Algorithm.

PURPOSE: Chylous ascites (CA) is an uncommon complication that occurs from traumatic disruption of lymphatic channels after retroperitoneal surgery. The purpose of this study was to generate an evidence-based management strategy for CA by reviewing the current literature and available treatment modalities. MATERIALS AND METHODS: A MEDLINE® literature review was performed for "chylous ascites." Individual patient data were extracted from case series and reports to create an efficacy analysis. Treatment modality, drain output, time to escalation of care and time to resolution were recorded. The efficacy analysis was utilized to generate a data-driven treatment algorithm. RESULTS: The literature review yielded 1,953 articles, from which 146 studies contributed data for 523 patients. The efficacy analysis included 245 patients, 168 (69%) of whom were managed successfully with conservative management (CM), at a median time to resolution of 11 days. Forty-eight patients underwent lymphangiography±embolization after CM, with a success rate of 85%. Thirty-one (12%) patients underwent surgical exploration. When treating CA, the patients who underwent stepwise management with CM followed by lymphangiography if CM failed experienced a resolution rate of 96.7%. An evidence-based treatment algorithm was created to guide treatment selection and duration of therapy before escalating to additional forms of therapy. CONCLUSIONS: In this report, we describe the largest conglomeration of iatrogenic CA cases from a literature review (523 cases) and efficacy analysis (245 cases), and created the first evidence-based treatment algorithm for this condition. Treatment success is substantial when using a stepwise combination of CM followed by lymphangiography±embolization.

Kidney Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Guidelines for Kidney Cancer focus on the screening, diagnosis, staging, treatment, and management of renal cell carcinoma (RCC). Patients with relapsed or stage IV RCC typically undergo surgery and/or receive systemic therapy. Tumor histology and risk stratification of patients is important in therapy selection. The NCCN Guidelines for Kidney Cancer stratify treatment recommendations by histology; recommendations for first-line treatment of ccRCC are also stratified by risk group. To further guide management of advanced RCC, the NCCN Kidney Cancer Panel has categorized all systemic kidney cancer therapy regimens as "Preferred," "Other Recommended Regimens," or "Useful in Certain Circumstances." This categorization provides guidance on treatment selection by considering the efficacy, safety, evidence, and other factors that play a role in treatment selection. These factors include pre-existing comorbidities, nature of the disease, and in some cases consideration of access to agents. This article summarizes surgical and systemic therapy recommendations for patients with relapsed or stage IV RCC.

Pathological and Survival Outcomes Associated with Variant Histology Bladder Cancers Managed by Cystectomy with or without Neoadjuvant Chemotherapy.

PURPOSE: Although neoadjuvant chemotherapy is associated with a survival advantage in pure urothelial, muscle invasive bladder cancer, the role of neoadjuvant chemotherapy is less clear in variant histology or urothelial carcinoma with divergent differentiation. We compared chemotherapy response and survival outcomes of patients with nonpure urothelial carcinoma histology who were managed with neoadjuvant chemotherapy followed by cystectomy vs cystectomy alone. MATERIALS AND METHODS: We analyzed 768 patients with clinical muscle invasive bladder cancer (cT2-4N0M0) who were treated with cystectomy at a tertiary care center from 2007 to 2017. Patients were stratified by histology and treatment strategy. Adjusted logistic and Cox regression models were used to evaluate pathological downstaging, cancer specific survival and overall survival. RESULTS: The cohort consisted of 410 patients (53%) with pure urothelial carcinoma, 185 (24%) with urothelial carcinoma with divergent differentiation and 173 (23%) with variant histology. Overall, 314 patients (41%) received neoadjuvant chemotherapy prior to cystectomy. There were similar rates of complete (18% to 30%) and partial (37% to 46%) pathological downstaging with neoadjuvant chemotherapy across all histological subgroups (p=0.30 and p=0.40, respectively). However, while patients with pure urothelial carcinoma experienced an overall survival benefit (HR 0.71, 95% CI 0.51-0.98, p=0.0013) and those with variant histology experienced a cancer specific survival benefit (HR 0.55, 95% CI 0.30-0.99, p=0.0495) with neoadjuvant chemotherapy, patients with urothelial carcinoma with divergent differentiation did not experience overall or cancer specific survival benefits with the use of neoadjuvant chemotherapy prior to cystectomy. CONCLUSIONS: Among patients with muscle invasive bladder cancer those with nonpure urothelial carcinoma histology with variant histology achieved nearly equivalent response rates and survival benefits with the use of neoadjuvant chemotherapy as those with pure urothelial carcinoma, while patients with urothelial carcinoma with divergent differentiation experienced significantly worse survival outcomes regardless of the use of neoadjuvant chemotherapy prior to cystectomy.

Pathological Downstaging and Survival Outcomes Associated with Neoadjuvant Chemotherapy for Variant Histology Muscle Invasive Bladder Cancer.

PURPOSE: Patients with muscle invasive bladder cancer (MIBC) of variant histology have a poor prognosis. It is unclear if neoadjuvant chemotherapy prior to radical cystectomy is associated with pathological downstaging or improved overall survival (OS) for patients with variant histology. Our objective was to assess for associations between receipt of neoadjuvant chemotherapy, pathological downstaging and OS for patients with variant histology MIBC. MATERIALS AND METHODS: Patients were identified in the National Cancer Database from 2004 to 2017 with MIBC, without metastases, who underwent radical cystectomy. Patients were stratified by histological subgroup, and receipt or nonreceipt of neoadjuvant chemotherapy. Pathological downstaging was defined as pT0N0 or pT ≤1N0, and OS from the time of diagnosis to date of death or censoring at last followup. Multivariable logistic regression analysis determined associations between neoadjuvant chemotherapy and pathological downstaging. Multivariable Cox regression analysis determined associations between neoadjuvant chemotherapy and OS. RESULTS: A total of 31,218 patients were included in the final study population (urothelial carcinoma [UC]: 27,779; sarcomatoid UC: 501; micropapillary UC: 418; squamous cell carcinoma: 1,141; neuroendocrine carcinoma: 629; adenocarcinoma: 750). Neoadjuvant chemotherapy was associated with pathological downstaging to pT0N0 in all histological subgroups (UC: OR 5.1 [4.6-5.6]; sarcomatoid UC: OR 13.8 [5.5-39.0]; micropapillary UC: OR 9.7 [2.8-46.8]; squamous cell carcinoma: OR 7.4 [2.1-24.5]; neuroendocrine: OR 4.7 [2.6-9.2]; adenocarcinoma: OR 23.3 [8.0-74.2]). Neoadjuvant chemotherapy was associated with improved OS for UC (HR 0.8 [0.77-0.84]), sarcomatoid UC (HR 0.64 [0.44-0.91]) and neuroendocrine carcinoma (HR 0.55 [0.43-0.70]). CONCLUSIONS: Neoadjuvant chemotherapy was associated with pathological downstaging for all MIBC histological variants, with improved OS for patients with UC, sarcomatoid variant UC and neuroendocrine carcinoma.

Retroperitoneal Lymph Node Dissection Versus Surveillance for Adult Early Stage Pure Testicular Teratoma: A Nationwide Analysis.

PURPOSE: Following radical orchiectomy, surveillance and primary retroperitoneal lymph node dissection (RPLND) are acceptable options for the management of early stage pure testicular teratoma in adult patients; however, there is no uniform consensus. The aim of this study was to investigate survival outcomes of adults with early stage pure testicular teratoma based on management strategy. METHODS: Data was extracted from the National Cancer Database (NCDB) from testicular cancer patients diagnosed with clinical stage (CS) I pure teratoma (pT1-4N0M0S0) between 2004 and 2014. Kaplan-Meier and Cox regression analyses were used to assess clinical outcomes based on management strategy. RESULTS: Of the 61,167 patients diagnosed with testicular cancer, 692 (1.1%) had pure teratoma. Only individuals with CS I disease were considered (n = 237). The median age was 28 (23-35) years. Overall, 43 (18%) patients underwent RPLND and 194 (82%) patients were managed with surveillance. There was an increase in surveillance for CS I teratoma during the study period. Increasing distance from residence to treatment facility was an unadjusted predictor for undergoing primary RPLND (p < 0.001). Median follow-up was 54 months and there was no significant difference in overall survival between CS I teratoma patients managed with RPLND and those managed with surveillance (p = 0.13). CONCLUSIONS: There has been a trend toward increasing adoption of surveillance for the management of early stage pure testicular teratoma in adults. Our findings suggest that surveillance provides comparable survival outcomes to primary retroperitoneal lymph node dissection in this setting.

Positive Ki-67 and PD-L1 expression in post-neoadjuvant chemotherapy muscle-invasive bladder cancer is associated with shorter overall survival: a retrospective study.

PURPOSE: There is an unmet need to develop prognostic biomarkers in post-neoadjuvant chemotherapy (NAC) muscle-invasive bladder cancer (MIBC) patients. We examine whether Ki-67 and PD-L1 expression can be used to guide adjuvant therapy. METHODS: Tissue microarrays were constructed from 130 post-NAC radical cystectomy samples. Up to 5 cores per sample were included. Expressions of Ki-67 and PD-L1 were evaluated using immunohistochemistry (IHC). RESULTS: Using a Cox regression model, positive Ki-67 expression in post-NAC radical cystectomy samples was associated with poorer overall survival (OS) (HR = 2.412, 95% CI, 1.076-5.408), independent of the pathological lymph node/N-stage. Positive Ki-67 expression was also associated with lack of tumor downstaging in a multivariable logistic regression model analysis (OR = 0.081, 95% CI, 0.014-0.464). PD-L1- and PD-L1+ expression was associated with a median OS of 49.8 months and 26.9 months, respectively, which did not reach statistical significance. Patients with Ki-67/PD-L1 double-negative tumors had a significantly longer median OS of 98.2 months versus 29.9 and 26.9 months in PD-L1-/Ki-67+ and PD-L1+/Ki-67+ tumors, respectively. Lack of tumor downstaging was significantly associated with positive Ki-67 and positive PD-L1 expression. CONCLUSION: Positive Ki-67 and PD-L1 expression in post-NAC radical cystectomy samples was associated with inferior OS and absence of tumor downstaging. IHC on Ki-67 and PD-L1 would help to select patients for adjuvant therapy in post-NAC muscle-invasive bladder cancer.

Effectiveness and Safety of Prostatic Artery Embolization for the Treatment of Lower Urinary Tract Symptoms from Benign Prostatic Hyperplasia in Men with Concurrent Localized Prostate Cancer.

PURPOSE: To assess the effectiveness and safety of prostatic artery embolization (PAE) on lower urinary tract symptoms (LUTS) in the setting of localized prostate cancer (PCa). MATERIALS AND METHODS: This was a retrospective, single-center, institutional review board-approved study from December 2016 to June 2020 of 21 patients (median age, 72; range, 63-83 years) with moderate LUTS and localized PCa. Clinical effectiveness was evaluated at 6 and 12 weeks using International Prostate Symptom Score (IPSS) and quality of life (QoL) improvement. Seventeen patients were scheduled to receive definitive radiotherapy (RT) after PAE; 13 patients completed RT. Short-term imaging signs of oncologic progression were evaluated at 6 and 12 weeks defined by at least one of the following on magnetic resonance imaging: increased Prostate Imaging-Reporting and Data System score of index lesion(s) to at least 4, new extracapsular extension, seminal vesicle involvement, or pelvic lymphadenopathy. Nonparametric Wilcoxon signed-rank test was used for analysis. RESULTS: IPSS improved by a median of 12 (n = 19, P < .0001) and 14 (n = 14, P < .0001) at 6 and 12 weeks, respectively. QoL improved by a median of 2 (n = 19, P < .0001) and 3 (n = 3, P < .0001) at 6 and 12 weeks. Prostate volume decreased by a median of 24% (n = 19, P < .0001) and 36% (n = 12, P = .015) at 6 and 12 weeks. No patients demonstrated disease progression at 6 (n = 16) or 12 (n = 8) weeks by imaging. No patients experienced increased prostate-specific antigen after RT, grade ≥3 adverse events, or greater genitourinary toxicity. CONCLUSIONS: PAE is effective and safe for the treatment of men with LUTS from benign prostatic hyperplasia in the setting of concomitant, localized, non-obstructive PCa.

NCCN Guidelines Insights: Kidney Cancer, Version 1.2021.

The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients with renal cell carcinoma (RCC). These NCCN Guidelines Insights focus on recent updates to the guidelines, including changes to certain systemic therapy recommendations for patients with relapsed or stage IV RCC. They also discuss the addition of a new section to the guidelines that identifies and describes the most common hereditary RCC syndromes and provides recommendations for genetic testing, surveillance, and/or treatment options for patients who are suspected or confirmed to have one of these syndromes.

Focal bipolar radiofrequency ablation for localized prostate cancer: Safety and feasibility.

OBJECTIVES: To evaluate the safety and feasibility of focal bipolar radiofrequency ablation in men with localized prostate cancer. METHODS: A review of 10 patients treated with a novel bipolar radiofrequency ablation probe integrated in a coil design (Encage; Trod Medical, Bradenton, FL, USA) between 2011 and 2017 in two prospective pilot trials. All men had clinical stage T1c prostate cancer, prostate-specific antigen <10 ng/mL and Gleason score ≤7. Ablation was carried out under general anesthesia, and bipolar probes were inserted transperineally under transrectal ultrasound guidance. Treatment-related adverse events, quality of life and negative biopsy rate were evaluated at 6 months after ablation. The Wilcoxon signed-rank test was used to compare baseline and post-treatment symptom scores. RESULTS: The median age was 58 years (range 50-64 years) and the median prostate volume was 49.65 cc (range 21-68 cc). Prostate cancer with a Gleason score of 6 (3 + 3) and 7 (3 + 4) was noted in seven and three patients, respectively. The median number of radiofrequency ablation cycles was 2.5 (range 2-5). All patients were catheter-free and able to void the day of surgery. Within 6 months after ablation, all adverse events were low grade, with the exception of one grade 3 hematuria that required cystoscopy without coagulation. Six months after ablation bowel, urinary and hormonal functions, and overall satisfaction remained stable. Erectile dysfunction occurred in two out of four patients who had normal sexual function before the procedure. Neither urinary incontinence nor urinary infection was noted. CONCLUSIONS: This first report on focal bipolar radiofrequency ablation documents a safe and feasible treatment option for selected patients with localized prostate cancer.

Overcome tumor heterogeneity-imposed therapeutic barriers through convergent genomic biomarker discovery: A braided cancer river model of kidney cancer.

Tumor heterogeneity, encompassing genetic, epigenetic, and microenvironmental variables, is extremely complex and presents challenges to cancer diagnosis and therapy. Genomic efforts on genetic intratumor heterogeneity (G-ITH) confirm branched evolution, support the trunk-branch cancer model, and present a seemingly insurmountable obstacle to conquering cancers. G-ITH is conspicuous in clear cell renal cell carcinoma (ccRCC), where its presence complicates identification and validation of biomarkers and thwarts efforts in advancing precision cancer therapeutics. However, long-term clinical benefits on targeted therapy are not uncommon in metastatic ccRCC patients, implicating that there are underlying constraints during ccRCC evolution, which in turn force a nonrandom sequence of parallel gene/pathway/function/phenotype convergence within individual tumors. Accordingly, we proposed a "braided cancer river model" depicting ccRCC evolution, which deduces cancer development based on multiregion tumor genomics of exceptional mTOR inhibitor (mTORi) responders. Furthermore, we employ an outlier case to explore the river model and highlight the importance of "Five NGS Matters: Number, Frequency, Position, Site and Time" in assessing cancer genomics for precision medicine. This mutable cancer river model may capture clinically significant phenotype-convergent events, predict vulnerability/resistance mechanisms, and guide effective therapeutic strategies. Our model originates from studying exceptional responders in ccRCC, which warrants further refinement and future validation concerning its applicability to other cancer types. The goal of this review is employing kidney cancer as an example to illustrate critical issues concerning tumor heterogeneity.

NCCN Guidelines Insights: Kidney Cancer, Version 2.2020.

The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for the clinical management of patients with clear cell and non-clear cell renal cell carcinoma, and are intended to assist with clinical decision-making. These NCCN Guidelines Insights summarize the NCCN Kidney Cancer Panel discussions for the 2020 update to the guidelines regarding initial management and first-line systemic therapy options for patients with advanced clear cell renal cell carcinoma.

Cystic Renal Cell Carcinoma: A Report on Outcomes of Surgery and Active Surveillance in Patients Retrospectively Identified on Pretreatment Imaging.

PURPOSE: We evaluated the outcomes of surgical intervention and active surveillance in patients diagnosed with cystic renal cell carcinoma at our hypothesized radiological cutoff of greater than 50% cystic. MATERIALS AND METHODS: We identified all 430 patients with a pathologically confirmed cystic renal mass that fit our criteria from 2000 to 2015. The 292 patients with a lack of computerized tomography, tumors less than 50% cystic on imaging, multifocal tumors and prior renal cell carcinoma were excluded from study. Patients were stratified into benign or malignant subgroups, and radiological, clinicopathological and oncologic features were determined. Univariate and multivariate associations between clinicoradiological parameters in each group were analyzed. We similarly reviewed the records of a separate cohort of patients treated with active surveillance for cystic renal cell carcinoma. RESULTS: Of the 138 identified cases of cystic renal cell carcinoma 102 (73.9%) were renal cell carcinoma and 36 (26.1%) were benign masses. Of the tumors 77.5% were Fuhrman grade 1-2, 83.4% were stage pT2 or less and 65.9% showed clear cell histology. On univariate analysis male gender, a solid component and increasing Bosniak classification were significant for malignancy. In a separate cohort we identified 38 patients on active surveillance. The growth rate was 1.0 mm per year overall and 2.3 mm per year for the solid component. At a median followup of more than 4 years in all cohorts there was no evidence of recurrence or metastasis of cystic renal cell carcinoma. CONCLUSIONS: Patients with unifocal cystic renal cell carcinoma evaluated using a standardized radiological threshold of greater than 50% cystic had an excellent prognosis on active surveillance and after surgical resection.

Validation of preoperative variables and stratification of patients to help predict benefit of cytoreductive nephrectomy in the targeted therapy ERA.

OBJECTIVES: To further elucidate which patients with metastatic renal cell carcinoma (mRCC) may benefit from cytoreductive nephrectomy (CN) before targeted therapy (TT), and to assess the overall survival of patients undergoing CN and TT versus TT alone. MATERIALS AND METHODS: We identified 88 patients who underwent CN at our institution prior to planned TT and 35 patients who received TT without undergoing CN. Preoperative risk factors described in the literature were assessed in our patient population (serum albumin, liver metastasis, symptomatic metastasis, clinical ≥T3 disease, retroperitoneal and supradiaphragmatic lymphadenopathy). Patients were stratified by number of pretreatment risk factors and overall survival (OS) was compared. RESULTS: TT patients had significantly more risk factors compared to CN patients (3.06 vs. 2.11, p<0.01). Patients who received TT alone had median OS of 5.8 months. All but one patient receiving TT alone had two or more risk factors. A comparison of the CN and TT groups was performed by constructing Kaplan-Meier curves. There was no significant difference in median OS for those patients with exactly two risk factors (447 vs. 389 days, p=0.24), and those with three or more risk factors (184 vs. 155 days, p=0.87). CONCLUSIONS: Using previously described pretreatment risk factors we found that patients with two or more risk factors derived no significant survival advantage from CN in the TT era. These risk factors should be incorporated in the assessment of patients for CN.

Molecular profiling of renal cell carcinoma: building a bridge toward clinical impact.

PURPOSE OF REVIEW: The daunting task of identifying key molecular drivers of renal cell carcinoma (RCC) has begun to reveal significant insights into tumor biology. This review provides an update on recent discoveries in this field and their possible clinical implications. RECENT FINDINGS: Molecular profiles within the classic RCC histologic subtypes present distinctive appreciation of tumor biology and also allow for exploitation of targeted treatment regimens for patients with metastatic disease. Prognostic signatures have demonstrated the ability to accurately predict many clinical outcomes. SUMMARY: The molecular and genomic profiling of RCC subtypes has identified a unique and diverse spectrum of alterations. Utilization of these characteristics to improve our prognostic and therapeutic outcomes in the clinical realm remains in its infancy but is rapidly advancing.

Prostate MRI: a national survey of Urologist's attitudes and perceptions.

INTRODUCTION: The use of multi-parametric (MP) MRI to diagnose prostate cancer has been the subject of intense research, with many studies showing positive results. The purpose of our study is to better understand the accessibility, role, and perceived accuracy of MP-MRI in practice by surveying practicing urologists. MATERIALS AND METHODS: Surveys were sent to 7,400 practicing American Urological Association member physicians with a current email address. The survey asked demographic information and addressed access, accuracy, cost, and role of prostate MRI in clinical practice. RESULTS: Our survey elicited 276 responses. Respondents felt that limited access and prohibitive cost of MP-MRI limits its use, 72% and 59% respectively. Academic urologists ordered more MP-MRI studies per year than those in private practice (43.3% vs. 21.1%; p<0.001). Urologists who performed more than 30 prostatectomies a year were more likely to feel that an MP-MRI would change their surgical approach (37.5% vs. 19.6%, p-value=0.002). Only 25% of respondents agreed or strongly agreed that MP-MRI should be used in active surveillance. For patients with negative biopsies and elevated PSA, 39% reported MP-MRI to be very useful. CONCLUSIONS: Our study found that MP-MRI use is most prominent among practitioners who are oncology fellowship-trained, practice at academic centers, and perform more than 30 prostatectomies per year. Limited access and prohibitive cost of MP-MRI may limit its utility in practice. Additionally, study participants perceive a lack of accuracy of MP-MRI, which is contrary to the recent literature.