From Detection to Cure - Emerging Roles for Urinary Tumor DNA (utDNA) in Bladder Cancer.

PURPOSE OF REVIEW: This review sought to define the emerging roles of urinary tumor DNA (utDNA) for diagnosis, monitoring, and treatment of bladder cancer. Building from early landmark studies the focus is on recent studies, highlighting how utDNA could aid personalized care. RECENT FINDINGS: Recent research underscores the potential for utDNA to be the premiere biomarker in bladder cancer due to the constant interface between urine and tumor. Many studies find utDNA to be more informative than other biomarkers in bladder cancer, especially in early stages of disease. Points of emphasis include superior sensitivity over traditional urine cytology, broad genomic and epigenetic insights, and the potential for non-invasive, real-time analysis of tumor biology. utDNA shows promise for improving all phases of bladder cancer care, paving the way for personalized treatment strategies. Building from current research, future comprehensive clinical trials will validate utDNA's clinical utility, potentially revolutionizing bladder cancer management.

Wound related complications and the anterior rectus sheath versus Gibson approach to kidney transplantation: A single center randomized controlled trial.

INTRODUCTION: Wound related complications (WRC) are a significant source of morbidity in kidney transplant recipients, and may be mitigated by surgical approach. We hypothesize that the anterior rectus sheath approach (ARS) may decrease WRC and inpatient opiate use compared to the Gibson Approach (GA). METHODS: This double-blinded randomized controlled trial allocated kidney transplant recipients aged 18 or older, exclusive of other procedures, 1:1 to ARS or GA at a single hospital. The ARS involves a muscle-splitting paramedian approach to the iliopsoas fossa, compared to the muscle-cutting GA. Patients and data analysts were blinded to randomization. RESULTS: Seventy five patients were randomized to each group between August 27, 2019 and September 18, 2020 with a minimum 12 month follow-up. There was no difference in WRC between groups (p = .23). Nine (12%) and three patients (4%) experienced any WRC in the ARS and GA groups, respectively. Three and one Clavien IIIb complications occurred in the ARS and GA groups, respectively. In a multiple linear regression model, ARS was associated with decreased inpatient opioid use (ß = -58, 95% CI: -105 to -12, p = .016). CONCLUSIONS: The ARS did not provide a WRC benefit in kidney transplant recipients, but may be associated with decreased inpatient opioid use.

Role of Lymphadenectomy during Radical Cystectomy for Nonmuscle-Invasive Bladder Cancer: Results from a Multi-Institutional Experience.

PURPOSE: While lymph node dissection (LND) at radical cystectomy (RC) for muscle-invasive bladder cancer has been studied extensively, the role of LND for nonmuscle-invasive bladder cancer (NMIBC) remains incompletely defined. Herein, we aim to assess the association between extent of LND during RC for NMIBC and local pelvic recurrence-free survival (LPRS), cancer-specific survival (CSS) and overall survival (OS). MATERIALS AND METHODS: A multi-institutional retrospective review was performed of patients with NMIBC undergoing RC at 3 large tertiary referral centers. To identify a threshold for lymph node yield (LNY) to optimize LPRS, CSS and OS, separate Cox regression models were developed for each possible LNY threshold. Model performance including Q-statistics and hazard ratios (HRs) were used to identify optimal LNY thresholds. RESULTS: A total of 1,647 patients underwent RC for NMIBC, with a median LNY of 15 (quartiles 9,23). Model performance curves suggested LNY of 10 and 20 to optimize LPRS and CSS/OS, respectively. On multivariable regression, LNY >10 was associated with lower risk of LPR compared to LNY ≤10 (HR 0.63, 95% CI 0.42-0.93, p=0.02). Similarly, LNY >20 was associated with improved CSS (HR 0.67, 95% CI 0.52-0.87, p=0.002) and OS (HR 0.75, 95% CI 0.64-0.88, p <0.001) compared to LNY ≤20. Similar results were observed in the cT1 and cTis subgroups. CONCLUSIONS: Greater extent of LND during RC for NMIBC is associated with improved LPRS, CSS and OS, supporting the inclusion of LND during RC for NMIBC, particularly among patients with cTis or cT1 disease. Future prospective studies are warranted to assess the ideal anatomical template of LND in NMIBC.

Contemporary management of advanced prostate cancer: an evolving landscape.

Recent population-based studies suggest that the incidence of advanced and metastatic prostate cancer may be increasing. Concurrently with this apparent stage migration toward advanced disease, several major developments have occurred in the treatment paradigm for men with advanced prostate cancer. These include the US Food and Drug Administration approval of 8 novel agents over the last decade. In addition to novel pharmaceuticals, rapidly evolving diagnostic tools have emerged. This review provides a primer for clinicians who treat men with advanced prostate cancer, including medical oncologists, radiation oncologists, and urologists.

Large Single Institution Comparison of Perioperative Outcomes and Complications of Open Radical Cystectomy, Intracorporeal Robot-Assisted Radical Cystectomy and Robotic Extracorporeal Approach.

PURPOSE: Bladder cancer management options include open radical cystectomy and robot-assisted radical cystectomy with intracorporeal or extracorporeal urinary diversion. The existing literature shows no difference in the major complication rate between open radical cystectomy and extracorporeal urinary diversion. However, the emerging popularity of intracorporeal urinary diversion has exposed the need to compare a completely intracorporeal method to alternative approaches. To our knowledge the robotic intracorporeal advantage regarding major complications has not yet been established in an evaluation of all 3 modalities. We compared outcomes and complications of open, intracorporeal and extracorporeal cystectomy techniques at a high volume institution. MATERIALS AND METHODS: We queried a prospectively maintained database for patients who underwent radical cystectomy from 2011 to 2018 for an oncologic indication. Perioperative and pathological outcomes, and 30 and 90-day major complications were assessed. Statistical analyses were done using the Pearson chi-square, Kruskal-Wallis and Kaplan-Meier tests, and multivariable regression. RESULTS: A total of 948 patients met the study criteria, including 272, 301 and 375 treated with open radical cystectomy, intracorporeal urinary diversion and extracorporeal urinary diversion, respectively. Median followup was 26 months. Intracorporeal urinary diversion cases had lower estimated blood loss (p <0.001), shorter hospitalization (p <0.001) and a lower ileus rate (p=0.023) than extracorporeal urinary diversion and open radical cystectomy cases. Importantly, intracorporeal urinary diversion was associated with lower 30 and 90-day major complication rates vs extracorporeal urinary diversion and open radical cystectomy (90-day Clavien-Dindo III-V 16.9% vs 24.8% and 26.1%, respectively, p=0.015). There was no significant difference in the readmission rate according to the surgical approach. Multivariable predictors of increased 90-day major complications were patient age, the Charlson Comorbidity Index and operative time. On multivariable analysis intracorporeal urinary diversion was associated with reduced 90-day major complications (OR 0.58, p=0.037). CONCLUSIONS: In a 3-way comparison intracorporeal urinary diversion demonstrated a lower major complication rate and perioperative benefits compared to extracorporeal urinary diversion and open radical cystectomy.

Bladder-sparing treatment of nonmetastatic muscle-invasive bladder cancer.

Bladder-sparing therapies for the treatment of nonmetastatic muscle-invasive bladder cancers are included in both American and European guidelines. Numerous treatment approaches have been described, including partial cystectomy, radiation monotherapy, and radical transurethral resection. However, the most oncologically favorable and well-studied regimen employs a multimodal approach that consists of maximal transurethral resection of the bladder tumor followed by concurrent radiosensitizing chemotherapy and radiotherapy. This sequence, referred to as trimodal therapy (TMT), has been evaluated with robust retrospective comparative studies and prospective series, although a randomized trial comparing TMT with radical cystectomy has not been performed. Despite promising reports of 5-year overall survival rates of 50% to 70% in well-selected patients, relatively few patients qualify as ideal candidates for TMT. Specifically, contemporary series exclude patients who have clinical stage T3 disease, multifocal tumors, coexisting carcinoma in situ, or hydronephrosis. Herein, we review all forms of bladder-preserving therapies with an emphasis on TMT, highlighting the rationale of each component, survival outcomes, and future directions.

Setting up a pediatric robotic urology program: A USA institution experience.

Implementing a robotic urological surgery program requires institutional support, and necessitates a comprehensive, detail-oriented plan that accounts for training, oversight, cost and case volume. Given the prevalence of robotic surgery in adult urology, in many instances it might be feasible to implement a pediatric robotic urology program within the greater context of adult urology. This involves, from an institutional standpoint, proportional distribution of equipment cost and operating room time. However, the pediatric urology team primarily determines goals for volume expansion, operative case selection, resident training and surgical innovation within the specialty. In addition to the clinical model, a robust economic model that includes marketing must be present. This review specifically highlights these factors in relationship to establishing and maintaining a pediatric robotic urology program. In addition, we share our data involving robot use over the program's first nine years (December 2007-December 2016).

Surgical Management and Oncologic Outcomes of Renal Cell Carcinoma and Inferior Vena Caval Thrombi With Aggressive Histologic Variants.

OBJECTIVE: To characterize the surgical management, perioperative, and cancer-specific outcomes, and the influence of aggressive histologic variants (AHV) on operative management among patients with renal cell carcinoma (RCC) and inferior vena cava (IVC) thrombus. RCC with rhabdoid and/or sarcomatoid differentiation, which we defined as AHV, portends a worse prognosis. AHV can be associated with a desmoplastic reaction which may complicate resection. METHODS: We reviewed patients undergoing radical nephrectomy and IVC thrombectomy between 1990 and 2020. Comparative statistics were employed as appropriate. Survival analysis was performed according to the Kaplan-Meier method, and intergroup analysis performed with log-rank statistics. Multivariable cox proportional hazards regression was used to assess the effect of AHV, age, thrombus level, vena cavectomy, metastases, and medical comorbidities on recurrence and overall survival (OS). RESULTS: Ninety-four of 403 (23.3%) patients had AHV, including 43 (46%) rhabdoid, 39 (41%) sarcomatoid, and 12 (13%) with both. AHV were more likely to present with advanced disease; however, increased perioperative complications or decreased OS were not observed. Median (IQR) survival was 16.7 (4.8-47) months without AHV and 12.6 (4-29) months with AHV (P = .157). Sarcomatoid differentiation was independently associated with worse OS (HR = 2.016, CI 1.38-2.95, P <.001), whereas rhabdoid alone or with sarcomatoid demonstrated similar OS (P = 0.063). CONCLUSION: RCC and IVC thrombus with AHV are more likely to present with metastatic disease, and sarcomatoid differentiation is associated with a worse OS. Resection of tumors with and without AHV have similar perioperative complications, suggesting that surgery can be safely accomplished in patients with RCC and IVC thrombus with AHV.

Impact of Neoadjuvant Chemotherapy on Pathologic Downstaging in Patients With Variant Histology Undergoing Radical Cystectomy.

INTRODUCTION: Variant histology (VH) bladder cancer is often associated with poor outcomes and the role of neoadjuvant chemotherapy (NAC) remains incompletely defined. Our objective was to determine comparative pathologic downstaging at radical cystectomy (RC) following NAC for patients with and without VH. PATIENTS AND METHODS: Patients who underwent RC at 2 tertiary referral centers (1996-2018) were included. Patients with VH (sarcomatoid, nested, micropapillary, plasmacytoid) were matched 1:2 to patients with pure urothelial carcinoma by age, sex, clinical T (cT)stage, clinical N (cN)stage, cystectomy year and receipt of NAC. The primary outcome was pathologic downstaging (pT-stage < cT-stage). The differential impact of NAC on pathologic downstaging between VH and non-VH was assessed using multivariable logistic regression with interaction analysis. RESULTS: 225 VH and 437 non-VH patients were included. One hundred twenty-eight of six hundred sixty-two (19.3%) patients experienced downstaging, including 54/121 (44.6%) patients who received NAC and 74/542 (13.2%) patients who did not (P < .01). Rates of downstaging after NAC for subgroups were: 45/78 (57.7%) urothelial, 3/8 (37.5%) sarcomatoid, 2/12 (16.7%) nested, 3/14 (21.4%) micropapillary, and 1/8 (12.5%) plasmacytoid. Collectively, 9/42 (21.4%) of VH patients who received NAC were downstaged. On multivariable analyses, NAC was associated with increased likelihood of downstaging in the overall cohort (OR 5.25, 95% CI, 3.29-8.36, P < .0001) and this effect was not modified by VH versus non-VH histology (P = .13 for interaction). VH patients had worse survival outcomes compared to non-VH (P < 0.01 for all). CONCLUSION: When comparing patients with VH to matched pure urothelial carcinoma controls, VH did not have an adverse effect on downstaging following NAC. VH patients should not be excluded from NAC if otherwise eligible.

Radial wave therapy does not improve early recovery of erectile function after nerve-sparing radical prostatectomy: a prospective trial.

Background: Low intensity shockwave therapy is an emerging treatment option for men with vasculogenic erectile dysfunction. Radial wave therapy (rWT), which differs from focused shockwave (fSWT) as it produces lower pressure waves with lower peak energy, is used to treat soft tissue and skin conditions and has some data to support its use in vasculogenic erectile dysfunction. There is limited data for the use of rWT for the treatment of erectile dysfunction after nerve-sparing (NS) radical prostatectomy. We report the first trial of rWT for penile rehabilitation after NS radical prostatectomy. Methods: We performed a prospective, non-randomized, open-label trial. Men with good pre-operative erectile function who underwent a NS radical prostatectomy at our institution from 2018-2020 were considered for inclusion. We compared post-operative erectile function outcomes between the rWT (6 weekly treatments initiated approximately 2 weeks post-operatively) plus standard of care (phosphodiesterase type 5 inhibitor) arm and the non-sham controlled standard of care arm. The primary end point for our study was the proportion of men who returned to "near normal" erectile function, defined as IIEF-5 score ≥17 and erectile hardness score (EHS) ≥3, by 3 months post-operatively between the intervention and control arm. We also compared mean IIEF-5 scores and median EHSs between the arms. Results: One hundred and six patients were enrolled, of whom 73 patients had at least one reported survey response between 6 and 12 weeks post-operatively. Five (17%) and 11 (26%) patients recovered erectile function in the control and intervention arms, respectively, which was not a statistically significant difference (P=0.37). However, the intervention arm did have a significantly higher median EHS compared to the control arm (1 vs. 2, P=0.03). There were 4 adverse events related to pain during treatment and required only treatment intensity de-escalation. Conclusions: rWT is safe but did not substantially improve the recovery of early erectile function after NS radical prostatectomy.

Survival Benefits of Adjuvant Chemotherapy for Positive Soft Tissue Surgical Margins Following Radical Cystectomy in Bladder Cancer with Extravesical Extension.

INTRODUCTION AND OBJECTIVE: Muscle invasive bladder cancer with extravesical extension is an aggressive disease entity that requires multimodal therapy. The benefits of adjuvant chemotherapy (AC) in patients with a positive soft-tissue surgical margin (STSM), however, are relatively unknown due to exclusion of this population in randomized controlled trials of AC. We sought to define survival benefits in this patient population through our institutional bladder cancer database. METHODS: Retrospective review of all patients undergoing radical cystectomy for urothelial carcinoma of the bladder from 2004-2020 with ≥pT3b disease irrespective of neoadjuvant chemotherapy (NAC) use was conducted. Progression-free survival (PFS) and overall survival (OS) estimates were obtained using the Kaplan-Meier method with log-rank test, and the Cox-proportional hazards model was used to identify predictors of improved PFS and OS. AC was defined by any chemotherapy use within 90 days of cystectomy, regardless of STSM status. RESULTS: 476 patients with pT3b disease or worse were identified. Median follow-up was 12.3 months. An amount of 21% of patients were treated with AC. An amount of 24% of patients had positive STSM. Median OS for patients with positive STSM was 8.4 months [95% CI 7-11.5] and 18.3 months [95% CI 15.6-20.8] (p < 0.001) for patients with negative STSM. In the overall cohort, positive STSM (HR 1.93, 95% CI 1.45-2.57, p < 0.001), AC use (HR 0.68, 95% CI 0.51-0.90, p = 0.007), and pN1-3 disease (HR 1.47, 95% CI 1.16-1.87, p = 0.002) were independent predictors of OS when adjusted for performance status, pT-stage, and neoadjuvant chemotherapy use. In patients with positive STSM, median survival was seven months [95% CI 5.2-8.4] without AC, compared to 16.2 months [95% CI 11.5-52.5] with AC (p = 0.0038). For patients with negative STSM, median survival was 17.4 months [95% CI 14-20.1] without AC compared to 22.3 months [95% CI 17.2-36.9] with AC (p = 0.23). In patients with positive STSM, AC use was the only factor associated with an OS benefit with a HR of 0.41 (95% CI 0.21-0.78, p = 0.007). In patients with negative STSM, pT4 and pN1-3 disease were the only factors associated with worse overall survival with a HR of 1.32 (95% CI 1.00-1.74, p = 0.050) and 1.97 (95% CI 1.49-2.60, p < 0.001), respectively. CONCLUSIONS: Administration of adjuvant chemotherapy is of particular benefit in patients with positive STSM following radical cystectomy for gross extravesical disease. Positive STSM may be a representative of "early metastatic" or micrometastatic disease.

Neighborhood Socioeconomic Disadvantage Associated With Increased 90-Day Mortality Following Radical Cystectomy.

OBJECTIVE: To examine relationships between neighborhood socioeconomic disadvantage and outcomes following radical cystectomy (RC). MATERIALS AND METHODS: A retrospective single institution study of consecutive RCs performed for bladder cancer between 2011 and 2019. Major complications, mortality and survival outcomes were compared using Cochran-Armitage or Kruskal-Wallis tests. Cox proportional hazards models were used for time-to-event analyses. RESULTS: A total of 906 patients were included in analysis. Overall 90-day mortality was 2.98% (27/906). Ninety-day mortality rates observed in the least (first) and most (fourth) disadvantaged ADI quartiles were 0% (0/115) and 6.5% (12/185), respectively. Patients from the fourth quartile demonstrated worse overall survival and recurrence free survival than those in the first quartile. ADI quartile was positively associated with muscle invasive (P = .0006) and node positive (P = .042) disease. ADI percentile was an independent predictor for 90-day mortality (adjusted OR: 1.022, CI: 1.004-1.04, P = .015). CONCLUSION: Higher rates of mortality and worse oncologic outcomes were observed for patients residing in the most disadvantaged quartile. ADI was associated with higher likelihood of 90-day mortality and may therefore be useful in patient counseling, risk stratification, and post-discharge management.

Survival outcomes following radical cystectomy in patients with prior pelvic radiation for prostate cancer: A matched cohort analysis.

OBJECTIVES: To determine the impact of prior pelvic radiation therapy (XRT) on outcomes following radical cystectomy (RC) for bladder cancer. MATERIALS AND METHODS: We performed a retrospective review comparing patients with bladder cancer requiring RC and prior history of XRT for prostate cancer to those undergoing RC without XRT history at our institution from 2011-2018. Propensity score matching was performed with the following variables: age, chronic kidney disease, nutritional deficiency, neoadjuvant chemotherapy use, Charlson comorbidity index, surgical approach, urinary diversion type, and pathologic T-stage. Perioperative, pathologic and oncologic outcomes were analyzed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Categorical variables were assessed utilizing the Pearson Chi Square Test, and continuous variables with the Wilcoxon rank-sum test. The Kaplan-Meier method with stratified-log rank was used to compare survival outcomes. Multivariable Cox proportional hazards models were utilized to identify predictors of overall and recurrence free survival. RESULTS: 227 patients were included, of which 47 had radiotherapy for prostate cancer. 47% of patients in the radiation cohort received external beam radiation therapy, 47% received brachytherapy and 7% received both. There were no differences in recurrence-free survival (P = 0.82) or overall survival (P = 0.25). Statistically significant differences in perioperative or postoperative outcomes such as 90-day complication, readmission, mortality rates, or ureteroenteric anastomotic stricture rates were not found. Rates of node-positive disease, median lymph node yield, positive surgical margin rates, lymphovascular invasion, or variant histology were not significantly different between cohorts. CONCLUSIONS: After matching for T-stage and other clinical variables, history of pelvic XRT for prostate cancer in patients who later required RC for bladder cancer, was not associated with an increased rate of perioperative complications or an independent predictor of RFS or OS.

Ability of the surgical Apgar score to predict acute kidney injury following radical cystectomy.

PURPOSE: Acute kidney injury (AKI) is a common complication after radical cystectomy (RC). Previous literature has shown that intraoperative hemodynamic instability measured via the surgical Apgar score is an independent predictor of major complications following RC. We sought to determine whether the surgical Apgar score is predictive of postoperative AKI. METHODS: We performed a retrospective review of RC patients at our institution from 2010 to 2017. Intraoperative hemodynamic instability was captured via the Apgar score based on the lowest intraoperative mean arterial blood pressure, lowest heart rate, and estimated blood loss. Patients were divided into 3 groups: high-risk (HR; Apgar ≤4), intermediate-risk (IR; Apgar score 5-6), and low-risk (LR; Apgar score ≥7). AKIs were graded according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. High grade AKIs were defined as KDIGO grade 2 or 3. Categorical variables were assessed using the Pearson Chi-Square test, quantitative with the Kruskal-Wallis test, and multivariable logistic regression to identify predictors of AKI and high grade AKIs within 30 days of RC. RESULTS: Eight hundred and seventy-three patients were included with a median follow-up of 35 months. AKI within 30 days was observed in 28% of patients. Predictors of AKI within 30 days on adjusted analysis included IR (OR: 1.83, P = 0.002) and HR (OR: 3.53, P < 0.001) Apgar scores. IR (OR: 2.23, P = 0.007) and HR (OR: 4.87, P < 0.001) Apgar scores were also predictors of high-grade AKIs. CONCLUSION: Intraoperative hemodynamic instability measured via the Apgar score can be predictive of AKI, which can guide individualized fluid management in the postoperative period.

The role of enhanced recovery after surgery protocols in the development of acute kidney injury following radical cystectomy.

PURPOSE: Recent reports have suggested that fluid restriction as part of Enhanced Recovery after Surgery (ERAS) pathways may increase the risk of AKI in radical cystectomy (RC) patients. We sought to evaluate the impact of ERAS initiation on AKI incidence at a high-volume tertiary care center. MATERIALS AND METHODS: We performed a retrospective review of our IRB approved database to identify patients receiving RC from 2010 to 2019. ERAS was initiated at our institution in October 2016. Acute kidney injuries were graded according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria and must have occurred within 7 days of indexed RC. Estimated glomerular filtration rate (eGFR) was captured at baseline, 1, 3, 6, and 12 months respectively. Categorical variables were compared with the Pearson-Chi square test. Quantitative variables were analyzed with the Wilcoxon-Rank sum test. Multivariable binary logistic regression and interaction analysis was used to identify predictors of AKI. RESULTS: Twelve hundred patients were included. Twenty-two percent of patients experienced an AKI within 7 days. Patients in the ERAS cohort experienced less AKIs after RC (18% vs. 25%, P = 0.003). When adjusting for year of surgery, ERAS was not a significant predictor for AKI on multivariable analysis (OR: 0.87, P = 0.73). On interaction analysis, during the ERAS era, intracorporeal robot-assisted radical cystectomy (iRARC) was associated with decreased odds of AKI (OR: 0.39, P = 0.034). There were no significant differences in eGFR at 12 months postoperatively (P = 0.16). CONCLUSION: Unlike previous reports, ERAS initiation was not associated with increased risk of AKI at a tertiary care high-volume center.

Intracorporeal Urinary Diversion in Robotic Radical Cystectomy.

Robotic-assisted radical cystectomy has gained increasing popularity over the past decade. Initially, the procedure was performed with extracorporeal urinary diversion given the technical challenges of the intracorporeal approach. Since then, innovative techniques have been described to facilitate bowel manipulation, assess ureteral and mesenteric vasculature, and perform ureteroenteric and urethro-ileal anastomosis. Overcoming the learning curve associated with intracorporeal urinary diversion can lead to decreased blood loss, shorter operative times, and faster convalescence, particularly with enhanced recovery protocols. Herein we review technical points, complications, outcomes, and future innovations in intracorporeal urinary diversion."

Comparison of renal function after open radical cystectomy, extracorporeal robot assisted radical cystectomy, and intracorporeal robot assisted radical cystectomy.

PURPOSE: Renal function outcomes following robot-assisted radical cystectomy (RARC) have not been well established. We sought to compare long-term renal function outcomes between open radical cystectomy, RARC with extracorporeal urinary diversion and intracorporeal urinary diversion at a high volume institution. MATERIALS AND METHODS: We retrospectively reviewed our institutional bladder cancer database for patients who underwent RC from 2010 to 2019 with pre-operative estimated glomerular filtration rate (eGFR) > 45 ml/min/1.73m2. Changes in renal function were assessed through locally weighted scatter plot smoothing and comparison of median eGFR between surgical groups. Chronic Kidney Disease Stage 3B was defined as eGFR < 45 ml/min/1.73m2. Renal function decline was defined as a ≥10 ml/min/1.73m2 drop in eGFR. Kaplan Meier method with log-rank was used to compare CKD 3B-free survival and renal function decline. Cox Proportional Hazards model was used to identify predictors of CKD 3B. RESULTS: Six hundred and forty four patients were included with median follow-up of 32 months (IQR 12-56). Preoperative characteristics were similar among the groups with no differences in median pre-operative eGFR (ORC: 74.6, extracorporeal urinary diversion: 74.3, intracorporeal urinary diversion: 71.6 ml/min/1.73m2, P=0.15). Median postoperative eGFR on follow up was not different between groups (P=0.56). 33% of patients developed CKD 3B. There were no differences in CKD 3B-free survival by surgical approach (P = 0.23) or urinary diversion (P = 0.09). 64% of patients experienced renal function decline with a median time of 2.4 years (P 0.23). Predictors of CKD were pathologic T3 disease or greater (HR: 1.77, P = 0.01), ureteroenteric anastomotic stricture (HR: 2.80, P < 0.001), preoperative CKD Stage 2 (HR: 1.81, P =0.02), and preoperative CKD Stage 3A (HR: 5.56, P < 0.001). CONCLUSION: Renal function decline is common after RC. Tumor stage, pre-operative eGFR, and ureteral stricture development, not surgical approach, influence renal function decline.

PTEN Hamartoma Tumor Syndrome: A Case of Renal Cell Carcinoma in a Young Female.

PTEN Hamartoma-Tumor-Syndrome (PHTS) describes a series of conditions characterized by germline-mutation of the PTEN tumor-suppressor gene. PHTS patients have an increased lifetime risk of multiple malignancies, including thyroid, breast, and endometrial cancers. PHTS patients also have 20-30 fold increased risk of renal cell carcinoma (RCC) compared to age-matched controls. As with many hereditary RCC syndromes, tumors present early and multifocally. We present a case of one of the youngest patients diagnosed with RCC in PHTS and review the urologic implications of this syndrome.