Intravenous Mannitol Versus Placebo During Partial Nephrectomy in Patients with Normal Kidney Function: A Double-blind, Clinically-integrated, Randomized Trial.

BACKGROUND: Mannitol is currently used as a renal protective agent to mitigate the effects of renal ischemia during nephron-sparing surgery (NSS). This routine practice lacks rigorous methodological study. OBJECTIVE: To assess the effect on renal function outcomes after surgery of mannitol infusion prior to renal ischemia during NSS. DESIGN, SETTING, PARTICIPANTS: This prospective, randomized, placebo-controlled, double-blind trial included 199 patients with a preoperative estimated glomerular filtration rate (eGFR) >45ml/min/1.73m2 scheduled for NSS; the trial was conducted between July 2012 and July 2015. INTERVENTION: Patients undergoing NSS were randomized to receive mannitol (12.5g) or placebo intravenously within 30min prior to renal vascular clamping. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the difference in eGFR (renal function) between the two groups at 6 mo following surgery assessed with an analysis of covariance model using preoperative eGFR, treatment group, and surgical approach as covariates. RESULTS AND LIMITATIONS: At baseline, the median age of the patients was 58 yr, and the median eGFR was 88ml/min/1.73m2. Comparing placebo with mannitol infusion, the adjusted difference of 0.2 eGFR units at 6 mo was not significant (p=0.9), with the upper bound of the 95% confidence interval (-3.1 to 3.5) excluding a clinically relevant effect of mannitol. Limitations include evaluation of a single mannitol dose and patients all had excellent preoperative renal function. CONCLUSIONS: Intraoperative 12.5g mannitol infusion during NSS has no demonstrable clinical benefit when compared with standardized fluid hydration in patients with normal preoperative renal function, and its use in this setting is not warranted. PATIENT SUMMARY: In this randomized trial, patients with normal kidney function who received mannitol during surgery to remove part of their kidney had no better kidney function 6 mo after surgery than those who did not receive mannitol. We conclude that this routine practice should be discontinued.

Alkaline phosphatase velocity predicts overall survival and bone metastasis in patients with castration-resistant prostate cancer.

INTRODUCTION AND OBJECTIVES: Identifying patients with prostate cancer (CaP) who will ultimately develop bone metastasis (BM) or die of disease is essential. Alkaline phosphatase velocity (APV) has been shown to predict overall survival (OS) and bone metastasis-free survival (BMFS) in an earlier study of an equal access military patient cohort of patients with castrate-resistant prostate cancer (CRPC). To confirm these findings, we examined a cohort of patients from a high-volume cancer center to validate a previous observation that faster alkaline phosphatase (AP) kinetics are predictive of OS and BMFS in this second cohort of patients. MATERIALS AND METHODS: A retrospective cohort study was conducted of patients with CRPC treated at Memorial Sloan Kettering Cancer Center between 1989 and 2010. All patients who received androgen deprivation therapy (ADT) as primary treatment in response to a rising PSA after definitive surgery for CaP were eligible. For those who received primary ADT or surgery followed by ADT, CRPC was defined as one rising PSA value after a PSA nadir ≤4ng/ml, and confirmed by a second rising PSA value, with concurrently documented testosterone levels <50ng/dl. APV was computed as the slope of the linear regression line of all AP values (>2 values per patient) plotted against time. Study outcome included BMFS and OS. Univariable Kaplan-Meier analysis was used to examine time-to-event outcomes. Multivariable Cox proportional hazards regression analysis was used to model time to BMFS and OS. RESULTS: Of 89 patients with CRPC with evaluable data and CRPC, 17 (19%) experienced BM and 26 (29%) died. APV was dichotomized at the uppermost quartile split of all observed APV values:≥5.42U/l/y vs. the lower 3 quartiles combined,<5.42U/l/y. Patients with faster APV had significantly worse outcomes, including faster progression to BM and poorer OS when compared with those with slower APV (P = 0.0451 and P = 0.0109, respectively). There was strong correlation between PSA doubling time (PSADT) (<10,≥10mo) and APV (≥5.42U/l/y vs.<5.42U/l/y) (P = 0.0289), preventing simultaneous evaluation of both factors in multivariable analysis. Kaplan-Meier analysis showed that PSADT was also predictive of BM and OS (log-rank P<0.0001). Separate multivariable Cox proportional hazards regression models were used to examine PSADT and APV, as predictors of each study outcome (BMFS and OS). Both PSADT and APV were strongly predictive of BMFS and OS (respectively). CONCLUSIONS: APV and PSADT were predictors of BM and OS in patients with CRPC, respectively. These data are additional evidence of the potential value of AP kinetics in patients with advanced CaP. Prospective studies will be required to clarify these associations. However, given the restrictions on the current patient population in excluding metastatic disease within 12 months of ADT and a PSA nadir >4ng/ml, the findings are not inappropriately generalized to other men.

Bilateral Testicular Germ Cell Tumors in the Era of Multimodal Therapy.

OBJECTIVE: To characterize the incidence, presentation, management, and relapse of a large population of bilateral testicular germ cell tumors (TGCT) from a single institution. PATIENTS AND METHODS: We identified bilateral TGCT diagnosed between January 1989 and February 2014. We categorized synchronous and metachronous TGCT, noting time between first and second TGCT, histology (seminoma vs nonseminoma [NSGCT]), stage, and treatments. Kaplan-Meier survival estimates characterized relapse. RESULTS: Of 5132 patients with TGCT, 128 (2.5%) had bilateral TGCT. Bilateral TGCT increased over time-1.7% in 1989-1994 up to 3.8% in 2010 to February 2014. The 35 (27%) synchronous cases of TGCT had 20 (57%) concordant seminoma, 5 (14%) concordant NSGCT, and 10 (29%) discordant NSGCT. The 93 (73%) metachronous cases had median time interval to second TGCT of 73 months (range: 5 months-28.6 years). Compared with first TGCT, 39 (42%) had discordant histology, 29 (31%) had concordant seminoma, and 25 (27%) had concordant NSGCT. Stage at first tumor was statistically similar to second TGCT (second stage I, II, II in 69%, 22%, 10%). Increasing duration between first and second TGCT was not associated with higher stage (II or III) at second TGCT (P = .09). Treatment at first tumor was not associated with stage at second tumor. Relapse following bilateral diagnosis was 16.8% (95% confidence interval 10.5%-26.2%) at 5 years. CONCLUSION: Incidence of bilateral TGCT increased with >25% of metachronous TGCT presenting ≥10 years after first TGCT; possible causes include increased survivorship and referral bias. Stage was statistically similar at first and second tumor; stage at second tumor was not associated with time interval between tumors or prior treatment modality at first tumor.

Second primary malignancies in renal cortical neoplasms: an updated evaluation from a single institution.

PURPOSE: To examine the incidence of secondary primary malignancies in patients with renal cortical neoplasms. METHODS: Between January 1989 and July 2010, 3647 patients underwent surgery at our institution for a renal cortical neoplasm and were followed through 2012. Occurrence of other malignancies was classified as antecedent, synchronous, or subsequent. All patients with antecedent malignancies (n = 498) and a randomly selected half of those with synchronous malignancies (n = 83) were excluded. The expected number of second primaries was calculated by multiplying Surveillance, Epidemiology, and End Results Program incidence rates of renal cortical neoplasms by person-years at risk within categories of age, sex, and year of diagnosis. The standardized incidence ratio (SIR) was calculated as observed cancers divided by expected incidence of the cancer, with approximation to the exact Poisson test used to obtain confidence intervals (CI) and p values. RESULTS: Of 3066 patients with renal cortical neoplasms, 267 had a second primary cancer; the five most common in men were prostate, colorectal, bladder, lung, and non-Hodgkin's lymphoma; the five most common in women were breast, colorectal, lung, endometrium, and thyroid. Men demonstrated higher than expected thyroid cancer rate (SIR 5.0; 95 % CI 1.83-10.88, p = 0.002), and women had higher than expected rates of stomach cancer (SIR 5.0; 95 % CI 1.61-11.67, p = 0.004) and thyroid cancer (SIR 4.62; 95 % CI 1.69-10.05, p = 0.003). CONCLUSIONS: The incidence of certain types of second malignancies may be higher in patients after diagnosis of renal cortical neoplasms compared to the general population. These observations can inform clinical follow-up in kidney cancer survivorship and future research studies.

The prognostic utility of preoperative neutrophil-to-lymphocyte ratio in localized clear cell renal cell carcinoma.

INTRODUCTION: To explore whether the association between preoperative neutrophil-to-lymphocyte ratio (NLR) elevation and worse survival is of use prognostically or merely a reflection of medical comorbidities in clear cell renal cell carcinoma (CC RCC). MATERIALS AND METHODS: We identified 1970 patients treated at Memorial Sloan Kettering Cancer Center from 1998-2012 by partial or radical nephrectomy for non-metastatic CC RCC. NLR was calculated by dividing absolute neutrophil count by absolute lymphocyte count; both were obtained from preoperative complete blood count. Uni- and multivariable Cox proportional hazards regression, which included established prognostic variables, were used to test for association between NLR and recurrence-free (RFS), cancer-specific (CSS), and overall survival (OS). RESULTS: Univariate analysis identified elevated NLR as significantly associated with worse RFS, CSS, and OS (all p < 0.0001). However, upon multivariable analysis, elevated NLR was significantly associated with only worse OS (p < 0.0001). After adding markers of comorbidity that were significantly correlated with NLR elevation-higher American Society of Anesthesiologists class (p = 0.013), older age, and higher estimated glomerular filtration rate (both p < 0.0001)--into the multivariable model, NLR remained significantly associated with OS (p = 0.001). The addition of NLR into the prognostic model for OS did not increase Harrell's concordance index from 0.776. CONCLUSIONS: In our cohort, preoperative NLR elevation is associated with worse OS, but there was no significant association with RFS or CSS on multivariable analysis. Preoperative NLR does not add unique prognostic information for patients undergoing surgical resection of renal tumors.

The effect of delaying nephrectomy on oncologic outcomes in patients with renal tumors greater than 4cm.

OBJECTIVES: Delaying nephrectomy<3 months does not adversely affect treatment outcome of renal tumors. Whether surgical waiting time (SWT; time from diagnosis to surgery)>3 months affects treatment outcome for large renal masses has not been well studied. We aimed to evaluate if SWT is associated with treatment outcome of renal masses >4cm and identify patients who are more likely to experience prolonged SWT. MATERIALS AND METHODS: Data from 1,484 patients undergoing radical or partial nephrectomy at a single institution for a nonmetastatic renal mass>4cm between 1995 and 2013 were reviewed. Patients with benign tumors and incomplete preoperative data were excluded. The association between SWT and disease upstaging at the time of surgery and recurrence at 2 and 5 years was assessed using logistic regression. Cancer-specific survival (CSS) and overall survival were assessed with landmark survival analyses and multivariable Cox proportional hazards models. All analyses were adjusted for patient and tumor characteristics. RESULTS: Of the final cohort of 1,278 patients, 267 (21%) had SWT>3 months. Patients with larger, symptomatic tumors had shorter SWT. Median follow-up for survivors was 3.8 years (interquartile range: 1.5-7.4). On multivariable analysis, SWT was not associated with disease upstaging, recurrence, or CSS. Longer SWT was associated with decreased overall survival (hazard ratio = 1.17; 95% CI: 1.08-1.27; P = 0.0002). Sex and tumor size, histology, and presentation were associated with disease upstaging, recurrence, and CSS. The most common cause for surgical delay>3 months was evaluation and treatment of comorbidities. CONCLUSION: Patient and tumor characteristics, rather than SWT, were associated with disease upstaging, recurrence, and CSS, and should guide the decision to delay surgery when treating nonmetastatic renal tumors>4cm.

New Chronic Kidney Disease and Overall Survival After Nephrectomy for Small Renal Cortical Tumors.

OBJECTIVE: To evaluate kidney functional and overall survival (OS) outcomes in a cohort of patients who underwent partial nephrectomy (PN) or radical nephrectomy (RN) for tumors ≤4 cm. MATERIALS AND METHODS: We performed a retrospective study on 2110 patients who underwent PN or RN with normal contralateral kidneys and normal serum creatinine from 1989 through 2012. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Primary end points were baseline incidence of CKD, OS, and new onset of eGFR ≤60 and ≤45 mL/min/1.73 m(2). RESULTS: Preoperatively, 30% and 8% of the cohort had eGFR ≤60 and ≤45 mL/min/1.73 m(2), respectively. Five-year freedom from eGFR ≤60 mL/min/1.73 m(2) was 24% (95% confidence interval [CI], 19%-30%) and 76% (95% CI, 72%-78%) for RN and PN, respectively, and 5-year freedom from eGFR ≤45 mL/min/1.73 m(2) was 51% (95% CI, 45%-56%) and 91% (95% CI, 89%-93%) for RN and PN, respectively. On multivariable analysis, hazard ratio for RN vs PN was 4.98 (95% CI, 4.11-6.04, P <.0001) for new onset of eGFR ≤60 mL/min/1.73 m(2) and 9.28 (95% CI, 7.26-11.86, P <.0001) for new onset of eGFR ≤45 mL/min/1.73 m(2). The RN group had a higher rate of death per year than the partial group (hazard ratio = 1.61, 95% CI, 1.24-2.08, P = .0003). CONCLUSION: The present study confirms published works demonstrating that a significant proportion of patients have pre-existing CKD. In patients with normal kidney function, RN is associated with a significantly higher risk for developing CKD and worse OS than PN.

Non-neoplastic parenchymal changes in kidney cancer and post-partial nephrectomy recovery of renal function.

OBJECTIVE: To explore the association of non-neoplastic parenchymal changes (nNPC) with patients' health and renal function recovery after partial nephrectomy (PN). MATERIALS AND METHODS: This retrospective review identified 800 pT1a patients who underwent PN at Memorial Sloan Kettering Cancer Center from 2007 to 2012. Pathology reports were reviewed for nNPC graded as mild or severe: vascular sclerosis (VS), glomerulosclerosis (GS), and fibrosis/scarring. Correlations between nNPC and known preoperative predictors of renal function [age, sex, African-American race, estimated glomerular filtration rate (eGFR), American Society of Anesthesiologists (ASA) score, body mass index, coronary artery disease, and hypertension (HTN)] were assessed using Spearman's rank correlation (ρ). Multivariable linear regression, adjusted for the described known preoperative risk predictors, was performed to evaluate whether the parenchymal features were able to predict 6-month postoperative eGFR. RESULTS: In this study, 46 % of tumors had benign surrounding parenchyma. We noted statistically significant yet weak associations of VS with age (ρ = 0.19; p < 0.001), ASA (ρ = 0.09; p < 0.001), preoperative eGFR (ρ = -0.14; p < 0.001), and HTN (ρ = 0.14; p < 0.001). GS also significantly correlated with HTN, but the correlation was again small (ρ = 0.12; p < 0.001). After adjusting for known risk predictors, only GS was a significant predictor of 6-month postoperative eGFR. When compared with no GS, mild and severe GS were negatively associated with a decrease of 4.9 and 10.8 mL/min/1.73 m(2) in 6-month postoperative eGFR, respectively. CONCLUSIONS: Presence of VS and GS correlated with patients' baseline health, and presence of GS predicted postoperative renal function recovery.

Predicting length of stay after robotic partial nephrectomy.

INTRODUCTION: To investigate factors predictive of length of stay (LOS) after robotic partial nephrectomy (RPN) in an effort to identify patients suitable for RPN with overnight stay at outpatient surgical facilities. MATERIALS AND METHODS: Retrospective chart review of patients who underwent RPN at Memorial Sloan Kettering Cancer Center from January 2007 to July 2012 was conducted. Univariate and multivariate analyses were performed to identify the main predictors of LOS. The discrimination of the multivariate model was measured using the area under the curve (AUC); tenfold cross-validation was performed to correct for over-fit. RESULTS: One hundred and eighty-six patients were included in the analysis; 84 (45 %) had LOS of ≤1 day (median LOS 2 day; interquartile range 1-2). On univariate analysis, preoperative variables associated with LOS > 1 included larger tumors (P < 0.0001), lower estimated glomerular filtration rate (P = 0.003), older age (P = 0.006), female gender (P = 0.035), and higher comorbidity score (P = 0.015); operative variables associated with LOS > 1 day included greater estimated blood loss (P < 0.0001) and longer operative (P < 0.0001) and ischemia (P < 0.0001) times. The AUC of the preoperative model was 0.61 (95 % CI 0.52-0.69) after tenfold cross-validation. CONCLUSIONS: LOS after RPN is influenced by age, gender, medical comorbidities, and tumor size. However, when analyzed retrospectively, these factors had limited ability to predict LOS after RPN with sufficient accuracy to develop a prediction tool.

Can renal hemangiomas be diagnosed preoperatively?

BACKGROUND: Renal hemangiomas are rare benign tumors seldom distinguished from malignant tumors preoperatively. OBJECTIVES: To describe the Memorial Sloan-Kettering Cancer Center (MSKCC) experience with diagnosing and treating renal hemangiomas, and to explore possible clinical and radiologic features that can aid in diagnosing renal hemangiomas preoperatively. METHODS: Patients with renal hemangiomas treated at MSKCC were identified in our prospectively collected renal tumor database. Descriptive statistics were used to describe the patient characteristics and the tumor characteristics. All available preoperative imaging studies were reviewed to assess common findings and explore possible characteristics distinguishing benign hemangiomas from malignant renal tumors preoperatively. RESULTS: Of 6341 patients in our database 15 were identified. Eleven (73%) were males, median age at diagnosis was 53.3 years, and the affected side was evenly distributed. All but two patients were treated surgically. The mean decrease in estimated glomerular filtration rate (eGFR) after surgery was 36.3%; one patient had an abnormal presurgical eGFR and only two patients had a normal eGFR after surgery. We could not identify radiographic features that would make preoperative diagnosis certain, but we did identify features characteristic of hepatic hemangiomas that were also present in some of the renal hemangiomas. CONCLUSIONS: Most renal hemangiomas cannot be distinguished from other common renal cortical tumors preoperatively. In select cases a renal biopsy can identify this benign lesion and the deleterious effects of extirpative surgery can be avoided.

Partial nephrectomy for renal tumors in solitary kidneys: postoperative renal function dynamics.

OBJECTIVE: To describe renal functional outcomes after partial nephrectomy (PN) for a tumor in a solitary kidney using the estimated glomerular filtration rate eGFR (MDRD equation). PATIENTS AND METHODS: A retrospective review of 103 cases of PN in a solitary kidney at Memorial Sloan-Kettering Cancer Center from December 1989 to July 2010 was conducted. The postoperative eGFR measurements were broken into three timeframes: 1-10 days after PN, 10 days-8 weeks after PN, and 4-12 months after PN. Several factors were analyzed for their impact on postoperative eGFR on univariate and multivariable analyses. To illustrate the change in eGFR after surgery over time, a univariate generalized estimating equation (GEE) model was constructed. RESULTS: Median preoperative eGFR was 47 ml/min/1.72 m(2) (IQR 39, 58). Higher preoperative eGFR, younger age at the time of PN, less estimated blood loss during PN, increased time between PN and previous radical nephrectomy, and decreased arterial clamp (ischemia) time were all significantly associated with increased postoperative eGFR in the early postoperative period on multivariable analysis. Younger age and higher preoperative eGFR were the only variables significantly associated with increased postoperative eGFR at all three time points. From the GEE model, postoperative eGFR continues to rise after PN until it reaches a plateau approximately 1 month after PN without attaining preoperative levels. CONCLUSION: PN for tumors in a solitary kidney is feasible and safe. In our model, non-modifiable factors predict the long-term postoperative eGFR: Young patients with healthy kidneys have superior renal functional results.

Preoperative predictive model of recovery of urinary continence after radical prostatectomy.

OBJECTIVE: To build a predictive model of urinary continence recovery after radical prostatectomy (RP) that incorporates magnetic resonance imaging (MRI) parameters and clinical data. PATIENTS AND METHODS: We conducted a retrospective review of data from 2,849 patients who underwent pelvic staging MRI before RP from November 2001 to June 2010. We used logistic regression to evaluate the association between each MRI variable and continence at 6 or 12 months, adjusting for age, body mass index (BMI) and American Society of Anesthesiologists (ASA) score, and then used multivariable logistic regression to create our model. A nomogram was constructed using the multivariable logistic regression models. RESULTS: In all, 68% (1,742/2,559) and 82% (2,205/2,689) regained function at 6 and 12 months, respectively. In the base model, age, BMI and ASA score were significant predictors of continence at 6 or 12 months on univariate analysis (P < 0.005). Among the preoperative MRI measurements, membranous urethral length, which showed great significance, was incorporated into the base model to create the full model. For continence recovery at 6 months, the addition of membranous urethral length increased the area under the curve (AUC) to 0.664 for the validation set, an increase of 0.064 over the base model. For continence recovery at 12 months, the AUC was 0.674, an increase of 0.085 over the base model. CONCLUSION: Using our model, the likelihood of continence recovery increases with membranous urethral length and decreases with age, BMI and ASA score. This model could be used for patient counselling and for the identification of patients at high risk for urinary incontinence in whom to study changes in operative technique that improve urinary function after RP.

Cost comparison of open and robotic partial nephrectomy using a short postoperative pathway.

OBJECTIVE: To compare immediate perioperative direct costs of open partial nephrectomy (OPN) and robotic partial nephrectomy (RPN), managed under a common care pathway. METHODS: Retrospective review of detailed institutional cost data for patients treated with OPN and RPN during 2011 was conducted. Cost and clinical data of OPN and RPN were compared for all patients and for patients stratified by length of stay (LOS), American Society of Anesthesiologists (ASA), and RENAL nephrometry scores. RESULTS: The study cohort included 190 OPN and 63 RPN cases. OPN was associated with higher ASA scores (P <.001), shorter operative times (P = .014), and higher estimated blood loss (P <.001). Median (interquartile range) LOS was 2 days (2-3 days) for OPN compared with 1 day (1-2 days) for RPN (P <.001). Median perioperative cost of OPN was lower than that of RPN with a difference of $3091 (P <.001). Although hospitalization costs were higher in OPN, surgical costs were higher in RPN ($854 and $3695 difference in median costs, respectively; P <.001 for both). The total cost of OPN for patients with an above-average LOS remained lower than that of RPN ($2680 difference in median costs; P = .001). RPN costs remained significantly higher when stratifying patients by their ASA and RENAL nephrometry scores. CONCLUSION: Despite the shorter hospital LOS associated with RPN, the immediate perioperative cost of OPN was lower than that of RPN for patients managed under a common care pathway, mainly due to high robotic purchase and maintenance costs. In light of the current health care debate, such financial disincentives may compromise the sustainability of advances in medical technology.

Interobserver variability of R.E.N.A.L., PADUA, and centrality index nephrometry score systems.

PURPOSE: To assess interobserver variability of R.E.N.A.L., preoperative aspects and dimensions used for an anatomical classification system (PADUA), and centrality index (C-Index) systems among observers with varying degrees of clinical experience and each system's subscale correlation with surgical outcome metrics. METHODS: Computed tomography images of 90 patients who underwent open, laparoscopic, or robot-assisted laparoscopic partial nephrectomy were scored by one radiology fellow, two urology fellows, one radiology resident, and one secondary school student. Agreement among readers was determined calculating intraclass correlation coefficients. Associations between radiology fellow scores (reference standard as reader with greatest clinical experience), ischemia time, and percent change in postoperative estimated glomerular filtration rate (eGFR) were evaluated using Spearman's correlation. RESULTS: Agreement using C-Index method (ICC = 0.773) was higher than with PADUA (ICC = 0.677) or R.E.N.A.L (ICC = 0.660). Agreement between reference and secondary school student was lower than with other physicians, although the differences were not statistically significant. The reference's scores were significantly (p < 0.05) associated with ischemia time on all three scoring systems and with percent change in eGFR at 6 weeks using C-Index (p = 0.016). Tumor size, nearness to sinus, and location relative to polar lines (R.E.N.A.L.) and tumor size, renal sinus involvement, and collecting system involvement (PADUA) correlated with ischemia time (all p ≤ 0.001). No R.E.N.A.L. or PADUA subscales significantly correlated with percent change in postoperative eGFR. CONCLUSIONS: Clinical experience reduces interobserver variability of existing nephrometry systems though not significantly and less so when using directly measureable anatomic variables. Consistently, only measures of tumor size and distance to intrarenal structures were useful in predicting clinically relevant outcomes.

Long-term survival rates after resection for locally advanced kidney cancer: Memorial Sloan Kettering Cancer Center 1989 to 2012 experience.

PURPOSE: We analyzed the 23-year Memorial Sloan Kettering Cancer Center experience with surgical resection, and concurrent adrenalectomy and lymphadenectomy for locally advanced nonmetastatic renal cell carcinoma. MATERIALS AND METHODS: We retrospectively reviewed the records of 802 patients who underwent nephrectomy with or without concurrent adrenalectomy or lymphadenectomy for locally advanced renal cell carcinoma, defined as stage T3 or greater and M0. Patients who received adjuvant treatment within 3 months of surgery or had fewer than 3 months of followup or bilateral renal masses at presentation were excluded from analysis. Five and 10-year progression-free and overall survival was estimated by the Kaplan-Meier method. Differences between groups were analyzed by the log rank test. RESULTS: A total of 596 (74%) and 206 patients (26%) underwent radical and partial nephrectomy, respectively. Renal cell carcinoma progressed in 189 patients and 104 died of the disease. Median followup in patients without progression was 4.6 years. Symptoms at presentation, ASA(®) classification, tumor stage, histological subtype, grade and lymph node status were significantly associated with progression-free and overall survival. On multivariate analysis adrenalectomy use decreased with time but lymphadenectomy use increased (OR 0.82 vs 1.16 per year). Larger tumors were associated with a higher likelihood of concurrent adrenalectomy and lymphadenectomy. CONCLUSIONS: In our series of patients with locally advanced nonmetastatic renal cell carcinoma survival was favorable in those in good health who were asymptomatic at presentation with T3 tumors and negative lymph nodes. Further, there has been a trend toward more selective use of adrenalectomy and increased use of lymphadenectomy.

Clinical role of pathological downgrading after radical prostatectomy in patients with biopsy confirmed Gleason score 3 + 4 prostate cancer.

OBJECTIVE: To identify preoperative factors predicting Gleason score downgrading after radical prostatectomy (RP) in patients with biopsy Gleason score 3+4 prostate cancer and to determine if prediction of downgrading can identify potential candidates for active surveillance (AS). PATIENTS AND METHODS: We identified 1317 patients with biopsy Gleason score 3+4 prostate cancers who underwent RP at the Memorial Sloan-Kettering Cancer Center between 2005 and 2013. Several preoperative and biopsy characteristics were evaluated by forward selection regression, and selected predictors of downgrading were analysed by multivariable logistic regression. Decision curve analysis was used to evaluate the clinical utility of the multivariate model. RESULTS: Gleason score was downgraded after RP in 115 patients (9%). We developed a multivariable model using age, prostate-specific antigen density, percentage of positive cores with Gleason pattern 4 cancer out of all cores taken, and maximum percentage of cancer involvement within a positive core with Gleason pattern 4 cancer. The area under the curve for this model was 0.75 after 10-fold cross validation. However, decision curve analysis revealed that the model was not clinically helpful in identifying patients who will downgrade at RP for the purpose of reassigning them to AS. CONCLUSION: While patients with pathological Gleason score 3 + 3 with tertiary Gleason pattern ≤4 at RP in patients with biopsy Gleason score 3 + 4 prostate cancer may be potential candidates for AS, decision curve analysis showed limited utility of our model to identify such men. Future study is needed to identify new predictors to help identify potential candidates for AS among patients with biopsy confirmed Gleason score 3 + 4 prostate cancer.

Black and White men younger than 50 years of age demonstrate similar outcomes after radical prostatectomy.

BACKGROUND: Black men with prostate cancer are diagnosed at a younger age, present with more aggressive disease, and experience higher mortality. We sought to assess pathological features and biochemical recurrence (BCR) in young men undergoing radical prostatectomy (RP) to determine if there is a difference between black and white men closer to the time of disease initiation. METHODS: We identified 551 white and 99 black men at a tertiary cancer center who underwent RP at ≤50 years of age. Baseline and pathological features were compared between the two groups. Cox proportional hazards models were utilized to examine the association of race and BCR, and Kaplan-Meier curves were generated to determine biochemical recurrence-free survival (bRFS). RESULTS: There were no differences in median age at surgery, biopsy Gleason score, or comorbidity. Black men had higher preoperative PSA (6.1 ng/ml vs 4.7 ng/ml, p = 0.004), but a greater percentage were cT1c (78% vs 63%), compared to white men. On multivariate analysis, black men demonstrated significantly lower odds of non-organ confined disease (OR 0.39; 95% CI: 0.18, 0.81; p = 0.01) and extracapsular extension (ECE) (OR 0.38; 95% CI: 0.18, 0.81, p = 0.01), and had no difference in Gleason score upgrading and seminal vesicle invasion compared to white men. There was no significant difference in bRFS in men with organ-confined disease; however, among men with locally advanced disease black men trended towards greater BCR (p = 0.052). Black men had 2-year bRFS of 56% vs 75% in white men. CONCLUSIONS: In this single institution study, there does not appear to be a racial disparity in outcomes among younger men who receive RP for prostate cancer. Black and white men in our cohort demonstrate similar bRFS with pathologically confirmed organ-confined disease. There may be greater risk of BCR among black men locally advanced disease compared to white men, suggesting that locally advanced disease is biologically more aggressive in black men.

Development of a nomogram model predicting current bone scan positivity in patients treated with androgen-deprivation therapy for prostate cancer.

PURPOSE: To develop a nomogram predictive of current bone scan positivity in patients receiving androgen-deprivation therapy (ADT) for advanced prostate cancer; to augment clinical judgment and highlight patients in need of additional imaging investigations. MATERIALS AND METHODS: A retrospective chart review of bone scan records (conventional (99m)Tc-scintigraphy) of 1,293 patients who received ADT at the Memorial Sloan-Kettering Cancer Center from 2000 to 2011. Multivariable logistic regression analysis was used to identify variables suitable for inclusion in the nomogram. The probability of current bone scan positivity was determined using these variables and the predictive accuracy of the nomogram was quantified by concordance index. RESULTS: In total, 2,681 bone scan records were analyzed and 636 patients had a positive result. Overall, the median pre-scan prostate-specific antigen (PSA) level was 2.4 ng/ml; median PSA doubling time (PSADT) was 5.8 months. At the time of a positive scan, median PSA level was 8.2 ng/ml; 53% of patients had PSA <10 ng/ml; median PSADT was 4.0 months. Five variables were included in the nomogram: number of previous negative bone scans after initiating ADT, PSA level, Gleason grade sum, and history of radical prostatectomy and radiotherapy. A concordance index value of 0.721 was calculated for the nomogram. This was a retrospective study based on limited data in patients treated in a large cancer center who underwent conventional (99m)Tc bone scans, which themselves have inherent limitations. CONCLUSION: This is the first nomogram to predict current bone scan positivity in ADT-treated prostate cancer patients, providing high predictive accuracy.

Comparison of perioperative outcomes of retroperitoneal and transperitoneal minimally invasive partial nephrectomy after adjusting for tumor complexity.

OBJECTIVE: To evaluate and compare perioperative outcomes of transperitoneal and retroperitoneal (RP) laparoscopic and robotic partial nephrectomies (LPNs) while adjusting for tumor complexity. MATERIALS AND METHODS: Retrospective review was conducted of 191 patients who underwent transperitoneal (n = 116) or RP (n = 75) LPN. To adjust for tumor complexity, individual components of the radius, exophytic or endophytic properties, nearness to the collecting system or sinus, anterior or posterior location, and location in reference to polar lines (R.E.N.A.L.) nephrometry score were used in multivariate linear and logistic regression models to compare perioperative outcomes between the 2 groups. A propensity approach was also used to adjust for multiple covariates. Investigated outcomes included estimated blood loss (EBL), ischemia and operative times, length of hospital stay, margin status, opioid use, postoperative estimated glomerular filtration rate, complications within 30 days, and readmission rates. RESULTS: Tumors resected by RPLPN were more likely to have lower complexity score by nephrometry (P = .04). Four of the 5 components of the R.E.N.A.L. nephrometry score were significantly different between the groups. After adjustment for these factors, a lower EBL was noted in the RP group (ß, -97; 95% confidence interval, -156 to -39; P = .001). Risk of readmission for the RP group was significantly lower (odds ratio, 0.15; P = .024) using propensity analysis. CONCLUSION: Using adjustment for tumor complexity, RPLPN was associated with lower EBL and readmission rates supporting the potential clinical advantage for this approach when feasible.

Multiparametric 3T MRI for the prediction of pathological downgrading after radical prostatectomy in patients with biopsy-proven Gleason score 3 + 4 prostate cancer.

OBJECTIVES: The aim of this study was to assess the diagnostic performance of pre-treatment 3-Tesla (3T) multiparametric magnetic resonance imaging (mpMRI) for predicting Gleason score (GS) downgrading after radical prostatectomy (RP) in patients with GS 3 + 4 prostate cancer (PCa) on biopsy. METHODS: We retrospectively reviewed 304 patients with biopsy-proven GS 3 + 4 PCa who underwent mpMRI before RP. On T2-weighted imaging and three mpMRI combinations (T2-weighted imaging + diffusion-weighted imaging [DWI], T2-weighted imaging + dynamic contrast-enhanced-MRI [DCE-MRI], and T2-weighted imaging + DWI + DCE-MRI), two radiologists (R1/R2) scored the presence of a dominant tumour using a 5-point Likert scale (1 = definitely absent to 5 = definitely present). Diagnostic performance in identifying downgrading was evaluated via areas under the curves (AUCs). Predictive accuracies of multivariate models were calculated. RESULTS: In predicting downgrading, T2-weighted imaging + DWI (AUC = 0.89/0.85 for R1/R2) performed significantly better than T2-weighted imaging alone (AUC = 0.72/0.73; p < 0.001/p = 0.02 for R1/R2), while T2-weighted imaging + DWI + DCE-MRI (AUC = 0.89/0.84 for R1/R2) performed no better than T2-weighted imaging + DWI (p = 0.48/p > 0.99 for R1/R2). On multivariate analysis, the clinical + mpMRI model incorporating T2-weighted imaging + DWI (AUC = 0.92/0.88 for R1/R2) predicted downgrading significantly better than the clinical model (AUC = 0.73; p < 0.001 for R1/R2). CONCLUSION: mpMRI improves the ability to identify a subgroup of patients with Gleason 3 + 4 PCa on biopsy who are candidates for active surveillance. DCE-MRI (compared to T2 + DWI) offered no additional benefit to the prediction of downgrading. KEY POINTS: Diagnostic performance of T2-weighted-imaging + DWI was better than T2-weighted-imaging alone. Diagnostic performance of T2-weighted-imaging + DWI was similar to T2-weighted-imaging + DWI + DCE-MRI. Combining clinical and T2-weighted-imaging + DWI features best predicted GS downgrading. mpMRI might prevent overtreatment by increasing eligibility for PCa active surveillance.