Limitations of Parenchymal Volume Analysis for Estimating Split Renal Function and New Baseline Glomerular Filtration Rate After Radical Nephrectomy.

PURPOSE: Accurately predicting new baseline glomerular filtration rate (NBGFR) after radical nephrectomy (RN) can improve counseling about RN vs partial nephrectomy. Split renal function (SRF)-based models are optimal, and differential parenchymal volume analysis (PVA) is more accurate than nuclear renal scans (NRS) for this purpose. However, there are minimal data regarding the limitations of PVA. Our objective was to identify patient-/tumor-related factors associated with PVA inaccuracy. MATERIALS AND METHODS: Five hundred and ninety-eight RN patients (2006-2021) with preoperative CT/MRI were retrospectively analyzed, with 235 also having NRS. Our SRF-based model to predict NBGFR was: 1.25 × (GlobalGFRPre-RN × SRFContralateral), where GFR indicates glomerular filtration rate, with SRF determined by PVA or NRS, and with 1.25 representing the median renal functional compensation in adults. Accuracy of predicted NBGFR within 15% of observed was evaluated in various patient/tumor cohorts using multivariable logistic regression analysis. RESULTS: PVA and NRS accuracy were 73%/52% overall, and 71%/52% in patients with both studies (n = 235, P < .001), respectively. PVA inaccuracy independently associated with pyelonephritis, hydronephrosis, renal vein thrombosis, and infiltrative features (all P < .03). Ipsilateral hydronephrosis and renal vein thrombosis associated with PVA underprediction, while contralateral hydronephrosis and increased age associated with PVA overprediction (all P < .01). NRS inaccuracy was more common and did not associate with any of these conditions. Even among cohorts where PVA inaccuracy was observed (22% of our patients), there was no significant difference in the accuracies of NRS- and PVA-based predictions. CONCLUSIONS: PVA was more accurate for predicting NBGFR after RN than NRS. Inaccuracy of PVA correlated with factors that distort the parenchymal volume/function relationship or alter renal functional compensation. NRS inaccuracy was more common and unpredictable, likely reflecting the inherent inaccuracy of NRS. Awareness of cohorts where PVA is less accurate can help guide clinical decision-making.

Practical Prediction of New Baseline Renal Function After Partial Nephrectomy.

BACKGROUND: Partial nephrectomy (PN) is generally preferred for localized renal masses due to strong functional outcomes. Accurate prediction of new baseline glomerular filtration rate (NBGFR) after PN may facilitate preoperative counseling because NBGFR may affect long-term survival, particularly for patients with preoperative chronic kidney disease. Methods for predicting parenchymal volume preservation, and by extension NBGFR, have been proposed, including those based on contact surface area (CSA) or direct measurement of tissue likely to be excised/devascularized during PN. We previously reported that presuming 89% of global GFR preservation (the median value saved from previous, independent analyses) is as accurate as the more subjective/labor-intensive CSA and direct measurement approaches. More recently, several promising complex/multivariable predictive algorithms have been published, which typically include tumor, patient, and surgical factors. In this study, we compare our conceptually simple approach (NBGFRPost-PN = 0.90 × GFRPre-PN) with these sophisticated algorithms, presuming that an even 90% of the global GFR is saved with each PN. PATIENTS AND METHODS: A total of 631 patients with bilateral kidneys who underwent PN at Cleveland Clinic (2012-2014) for localized renal masses with available preoperative/postoperative GFR were analyzed. NBGFR was defined as the final GFR 3-12 months post-PN. Predictive accuracies were assessed from correlation coefficients (r) and mean squared errors (MSE). RESULTS: Our conceptually simple approach based on uniform 90% functional preservation had equivalent r values when compared with complex, multivariable models, and had the lowest degree of error when predicting NBGFR post-PN. CONCLUSIONS: Our simple formula performs equally well as complex algorithms when predicting NBGFR after PN. Strong anchoring by preoperative GFR and minimal functional loss (≈ 10%) with the typical PN likely account for these observations. This formula is practical and can facilitate counseling about expected postoperative functional outcomes after PN.

Parenchymal volume analysis to assess longitudinal functional decline following partial nephrectomy.

OBJECTIVE: To identify factors associated with longitudinal ipsilateral functional decline after partial nephrectomy (PN). PATIENTS AND METHODS: Of 1140 patients managed with PN (2012-2014), 349 (31%) had imaging/serum creatinine levels pre-PN, 1-12 months post-PN (new baseline), and >3 years later necessary for inclusion. Parenchymal-volume analysis was used to determine split renal function. Patients were grouped as having significant renal comorbidity (CohortSRC : diabetes mellitus with insulin-dependence or end-organ damage, refractory hypertension, or severe pre-existing chronic kidney disease) vs not having significant renal comorbidity (CohortNoSRC ) preoperatively. Multivariable regression was used to identify predictors of annual ipsilateral parenchymal atrophy and functional decline relative to new baseline values post-PN, after the kidney had healed. RESULTS: The median follow-up was 6.3 years with 87/226/36 patients having cold/warm/zero ischaemia. The median cold/warm ischaemia times were 32/22 min. Overall, the median tumour size was 3.0 cm. The preoperative glomerular filtration rate (GFR) and new baseline GFR (NBGFR) were 81 and 71 mL/min/1.73 m2 , respectively. After establishment of the NBGFR, the median loss of global and ipsilateral function was 0.7 and 0.4 mL/min/1.73 m2 /year, respectively, consistent with the natural ageing process. Overall, the median ipsilateral parenchymal atrophy was 1.2 cm3 /year and accounted for a median of 53% of the annual functional decline. Significant renal comorbidity, age, and warm ischaemia were independently associated with ipsilateral parenchymal atrophy (all P < 0.01). Significant renal comorbidity and ipsilateral parenchymal atrophy were independently associated with annual ipsilateral functional decline (both P < 0.01). Annual median ipsilateral parenchymal atrophy and functional decline were both significantly increased for CohortSRC compared to CohortNoSRC (2.8 vs 0.9 cm3 , P < 0.01 and 0.90 vs 0.30 mL/min/1.73 m2 /year, P < 0.01, respectively). CONCLUSIONS: Longitudinal renal function following PN generally follows the normal ageing process. Significant renal comorbidities, age, warm ischaemia, and ipsilateral parenchymal atrophy were the most important predictors of ipsilateral functional decline following establishment of NBGFR.

Functional recovery after partial nephrectomy: next generation analysis.

OBJECTIVES: To provide a more rigorous assessment of factors affecting functional recovery after partial nephrectomy (PN) using novel tools that allow for analysis of more patients and improved accuracy for assessment of parenchymal volume loss, thereby revealing the potential impact of secondary factors such as ischaemia. PATIENTS AND METHODS: Of 1140 patients managed with PN (2012-2014), 670 (59%) had imaging and serum creatinine levels measured before and after PN necessary for inclusion. Recovery from ischaemia was defined as the ipsilateral glomerular filtration rate (GFR) saved normalised by parenchymal volume saved. Acute kidney injury was assessed through Spectrum Score, which quantifies the degree of acute ipsilateral renal dysfunction due to exposure to ischaemia that would otherwise be masked by the contralateral kidney. Multivariable regression was used to identify predictors of Spectrum Score and Recovery from Ischaemia. RESULTS: In all, 409/189/72 patients had warm/cold/zero ischaemia, respectively, with median (interquartile range [IQR]) ischaemia times for cold and warm ischaemia of 30 (25-42) and 22 (18-28) min, respectively. The median (IQR) global preoperative GFR and new baseline GFR (NBGFR) were 78 (63-92) and 69 (54-81) mL/min/1.73 m2 , respectively. The median (IQR) ipsilateral preoperative GFR and NBGFR were 40 (33-47) and 31 (24-38) mL/min/1.73 m2 , respectively. Functional recovery correlated strongly with parenchymal volume preserved (r = 0.83, P < 0.01). The median (IQR) decline in ipsilateral GFR associated with PN was 7.8 (4.5-12) mL/min/1.73 m2 with loss of parenchyma accounting for 81% of this loss. The median (IQR) recovery from ischaemia was similar across the cold/warm/zero ischaemia groups at 96% (90%-102%), 95% (89%-101%), and 97% (91%-102%), respectively. Independent predictors of Spectrum Score were ischaemia time, tumour complexity, and preoperative global GFR. Independent predictors of recovery from ischaemia were insulin-dependent diabetes mellitus, refractory hypertension, warm ischaemia, and Spectrum Score. CONCLUSIONS: The main determinant of functional recovery after PN is parenchymal volume preservation. A more robust and rigorous evaluation allowed us to identify secondary factors including comorbidities, increased tumour complexity, and ischaemia-related factors that are also independently associated with impaired recovery, although altogether these were much less impactful.

Assessing cancer risk in the anterior part of the prostate using micro-ultrasound: validation of a novel distinct protocol.

PURPOSE: To develop and validate a micro-ultrasound risk score that predicts the likelihood of significant prostate cancer in the anterior zone. METHODS: Patients were enrolled from three expert institutions familiar with micro-ultrasound. The study was conducted in two phases. First, the PRI-MUS anterior score was developed by assessing selected prostate videos from patients who subsequently underwent radical prostatectomy. Second, seven urology readers with varying levels of experience in micro-ultrasound examination evaluated prostate loops according to the PRI-MUS anterior score. Each reader watched the videos and recorded the likelihood of the presence of significant cancer in the anterior part of the prostate in a three-point scale. The coherence among the readers was calculated using the Fleiss kappa and the Cronbach alpha. RESULTS: A total of 102 selected prostate scans were used to develop the risk assessment for anterior zone cancer in the prostate. The score comprised three categories: likely, equivocal, and unlikely. The median (IQR) sensitivity, specificity, positive predictive value, and negative predictive value for the seven readers were 72% (68-84), 68% (64-84), 75% (72-81), and 73% (71-80), respectively. The mean SD ROC AUC was 0.75 ± 2%, while the Fleiss kappa and the Cronbach alpha were 0.179 and 0.56, respectively. CONCLUSION: Micro-ultrasound can detect cancerous lesions in the anterior part of the prostate. When combined with the PRI-MUS protocol to assess the peripheral part, it enables an assessment of the entire prostate gland. Pending external validation, the PRI-MUS anterior score developed in this study might be implemented in clinical practice.

Predicting GFR after radical nephrectomy: the importance of split renal function.

PURPOSE: To evaluate a conceptually simple model to predict new-baseline-glomerular-filtration-rate (NBGFR) after radical nephrectomy (RN) based on split-renal-function (SRF) and renal-functional-compensation (RFC), and to compare its predictive accuracy against a validated non-SRF-based model. RN should only be considered when the tumor has increased oncologic potential and/or when there is concern about perioperative morbidity with PN due to increased tumor complexity. In these circumstances, accurate prediction of NBGFR after RN can be important, with a threshold NBGFR > 45 ml/min/1.73m2 correlating with improved overall survival. METHODS: 236 RCC patients who underwent RN (2010-2012) with preoperative imaging (CT/MRI) and relevant functional data were included. NBGFR was defined as GFR 3-12 months post-RN. SRF was determined using semi-automated software that provides differential parenchymal-volume-analysis (PVA) from preoperative imaging. Our SRF-based model was: Predicted NBGFR = 1.24 (× Global GFRPre-RN) (× SRFContralateral), with 1.24 representing the mean RFC estimate from independent analyses. A non-SRF-based model was also assessed: Predicted NBGFR = 17 + preoperative GFR (× 0.65)-age (× 0.25) + 3 (if tumor > 7 cm)-2 (if diabetes). Alignment between predicted/observed NBGFR was assessed by comparing correlation coefficients and area-under-the-curve (AUC) analyses. RESULTS: The correlation-coefficients (r) were 0.87/0.72 for SRF-based/non-SRF-based models, respectively (p = 0.005). For prediction of NBGFR > 45 ml/min/1.73m2, the SRF-based/non-SRF-based models provided AUC of 0.94/0.87, respectively (p = 0.044). CONCLUSION: Previous non-SRF-based models to predict NBGFR post-RN are complex and omit two important parameters: SRF and RFC. Our proposed model prioritizes these parameters and provides a conceptually simple, accurate, and clinically implementable approach to predict NBGFR post-RN. SRF can be easily obtained using PVA software that is affordable, readily available (FUJIFILM-Medical-Systems), and more accurate than nuclear-renal-scans. The SRF-based model demonstrates greater predictive-accuracy than a non-SRF-based model, including the clinically-important predictive-threshold of NBGFR > 45 ml/min/1.73m2.

Race, Decisional Regret and Prostate Cancer Beliefs: Identifying Targets to Reduce Racial Disparities in Prostate Cancer.

PURPOSE: African American men are more likely to be diagnosed with, die of and experience decisional regret about their prostate cancer than nonAfrican American men. Although some clinical discrepancies may be attributed to genetic risk and/or access to care, explanations for racial discrepancies in decisional regret remain largely speculative. We aim to identify sources of prostate cancer decisional regret with a focus on racial disparities. MATERIALS AND METHODS: A cohort of 1,112 patients with localized prostate cancer treated at the Cleveland Clinic between 2010 and 2016 were matched by race, Gleason score, treatment (external beam radiation, brachytherapy, prostatectomy, active surveillance), prostate specific antigen at diagnosis, age at treatment and time since treatment. All patients received 4 surveys, including the Expanded Prostate Cancer Index Composite (EPIC) 26, the Decisional Regret Scale, our novel Prostate Cancer Beliefs Questionnaire and a modified EPIC demographics form. Descriptive and comparative statistics and multivariable logistic regression were used to compare survey outcomes by race and treatment method. RESULTS: Of 1,048 deliverable surveys 378 (36.07%) were returned. African American men had worse decisional regret than nonAfrican American men even after adjusting for relevant covariates (OR 2.46, p <0.0001). African American men also had higher Prostate Cancer Beliefs Questionnaire medical mistrust and masculinity scores, both of which predicted worse decisional regret independent of race (1.415 and 1.350, p=0.0001, respectively). CONCLUSIONS: African American men suffer worse decisional regret than nonAfrican American men, which may be partially explained by higher medical mistrust and concerns about masculinity as captured by the Prostate Cancer Beliefs Questionnaire. This novel survey may facilitate identifying targets to reduce racial disparities in prostate cancer.

New Baseline Renal Function after Radical or Partial Nephrectomy: A Simple and Accurate Predictive Model.

PURPOSE: Preoperative estimation of new baseline glomerular filtration rate after partial nephrectomy or radical nephrectomy for renal cell carcinoma has important clinical implications. However, current predictive models are either complex or lack external validity. We aimed to develop and validate a simple equation to estimate postoperative new baseline glomerular filtration rate. MATERIALS AND METHODS: For development and internal validation of the equation, a cohort of 7,860 patients with renal cell carcinoma undergoing partial nephrectomy/radical nephrectomy (2005-2015) at the Veterans Affairs National Health System was analyzed. Based on preliminary analysis of 94,327 first-year postoperative glomerular filtration rate measurements, new baseline glomerular filtration rate was defined as the final glomerular filtration rate within 3 to 12 months after surgery. Multivariable linear regression analyses were applied to develop the equation using two-thirds of the renal cell carcinoma Veterans Administration cohort. The simplest model with the highest coefficient of determination (R2) was selected and tested. This model was then internally validated in the remaining third of the renal cell carcinoma Veterans Administration cohort. Correlation/bias/accuracy/precision of equation were examined. For external validation, a similar cohort of 3,012 patients with renal cell carcinoma from an outside tertiary care center (renal cell carcinoma-Cleveland Clinic) was independently analyzed. RESULTS: New baseline glomerular filtration rate (in ml/minute/1.73 m2) can be estimated with the following simplified equation: new baseline glomerular filtration rate = 35 + preoperative glomerular filtration rate (× 0.65) - 18 (if radical nephrectomy) - age (× 0.25) + 3 (if tumor size >7 cm) - 2 (if diabetes). Correlation/bias/accuracy/precision were 0.82/0.00/83/-7.5-8.4 and 0.82/-0.52/82/-8.6-8.0 in the internal/external validation cohorts, respectively. Additionally, the area under the curve (95% confidence interval) to discriminate postoperative new baseline glomerular filtration rate ≥45 ml/minute/1.73 m2 from receiver operating characteristic analyses were 0.90 (0.88, 0.91) and 0.90 (0.89, 0.91) in the internal/external validation cohorts, respectively. CONCLUSIONS: Our study provides a validated equation to accurately predict postoperative new baseline glomerular filtration rate in patients being considered for radical nephrectomy or partial nephrectomy that can be easily implemented in daily clinical practice.

Role of Imaging in Renal Cell Carcinoma: A Multidisciplinary Perspective.

With the expansion in cross-sectional imaging over the past few decades, there has been an increase in the number of incidentally detected renal masses and an increase in the incidence of renal cell carcinomas (RCCs). The complete characterization of an indeterminate renal mass on CT or MR images is challenging, and the authors provide a critical review of the best imaging methods and essential, important, and optional reporting elements used to describe the indeterminate renal mass. While surgical staging remains the standard of care for RCC, the role of renal mass CT or MRI in staging RCC is reviewed, specifically with reference to areas that may be overlooked at imaging such as detection of invasion through the renal capsule or perirenal (Gerota) fascia. Treatment options for localized RCC are expanding, and a multidisciplinary group of experts presents an overview of the role of advanced medical imaging in surgery, percutaneous ablation, transarterial embolization, active surveillance, and stereotactic body radiation therapy. Finally, the arsenal of treatments for advanced renal cancer continues to grow to improve response to therapy while limiting treatment side effects. Imaging findings are important in deciding the best treatment options and to monitor response to therapy. However, evaluating response has increased in complexity. The unique imaging findings associated with antiangiogenic targeted therapy and immunotherapy are discussed. An invited commentary by Remer is available online. Online supplemental material is available for this article. ©RSNA, 2021.

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.

Partial Nephrectomy for Patients with Severe Chronic Kidney Disease-Is It Worthwhile?

PURPOSE: Partial nephrectomy is prioritized over radical nephrectomy in patients with chronic kidney disease whenever feasible. However, we hypothesized that some patients with severe chronic kidney disease might rapidly progress to end stage renal disease, in which case the morbidity that can be associated with partial nephrectomy would not be justified. MATERIALS AND METHODS: A retrospective review of all 62 patients with stage IV chronic kidney disease undergoing partial nephrectomy at our institution (1999-2015) was performed. We analyzed preoperative/intraoperative factors and postoperative outcomes. Survival-analyses evaluated factors associated with time-to-progression to end stage renal disease the primary end point. RESULTS: Median age was 67 years, 71% of patients were male, and 84% Caucasian. Comorbidities included hypertension (94%), cardiovascular disease (53%) and diabetes (32%). Median preoperative estimated glomerular filtration rate was 23 ml/minute/1.73 m2 and 73% had an open approach. Benign pathology was found in 10 (16%) patients; only 23 (37%) and 7 (11%) patients had tumor grade 3/4 or pT3a disease, respectively. Unfavorable outcomes occurred in 15 patients (24%) defined as either 90-day mortality (3%), postoperative complication Clavien IIIb or greater (14%), or positive surgical margin (12%). Median time to progression to end stage renal disease was only 27 months (58 months for preoperative glomerular filtration rate greater than 25 ml/minute/1.73 m2 versus only 14 months when preoperative glomerular filtration rate was less than 20 ml/minute/1.73 m2). On multivariable analysis African American race (HR 2.55 [1.10-5.95]), preoperative estimated glomerular filtration rate 20 to 25 ml/minute/1.73 m2 or less than 20 ml/minute/1.73 m2 (HR 2.59 [1.16-5.84] and 5.03 [2.03-12.4], respectively) and minimally invasive approach (HR 2.05 [1.01-4.19]) were independently associated with progression to end stage renal disease. CONCLUSIONS: Our data suggest that some patients with stage IV chronic kidney disease undergoing partial nephrectomy have substantial comorbidities and nonaggressive pathology, and are at risk for unfavorable perioperative outcomes and rapid-progression to end stage renal disease. Renal mass biopsy should be strongly considered to improve patient-selection. Alternate strategies (active surveillance or radical nephrectomy) may be more appropriate, particularly when partial nephrectomy is high complexity or when the patient is African American, or preoperative glomerular filtration rate is less than 25 ml/minute/1.73 m2.

Compensatory Changes in Parenchymal Mass and Function after Radical Nephrectomy.

PURPOSE: Loss of renal function remains a major limitation of radical nephrectomy. The extent of renal functional compensation by the preserved kidney after radical nephrectomy has not been adequately studied in this elderly population with comorbidities. MATERIALS AND METHODS: A total of 273 patients treated with radical nephrectomy without end stage renal disease with available preoperative nuclear renal scans were included in the analysis. Renal functional compensation was defined as percent change in estimated glomerular filtration rate of the preserved kidney after radical nephrectomy. Estimated glomerular filtration rate was calculated by the Chronic Kidney Disease-Epidemiology Collaboration formula up to 5 years postoperatively. Preoperative/postoperative parenchymal volumes of the preserved kidney were measured from cross-sectional imaging. Multiple regression was used to identify predictive factors for renal functional compensation. RESULTS: Median age was 67 years and 67% of the patients were male. Overall 70% had hypertension, 26% diabetes and 37% preexisting chronic kidney disease. Locally advanced (T3a or greater) tumors were found in 53% of cases. Renal functional compensation was observed at 2 weeks (median 10%) and increased during the first 3 months (median 26%) after radical nephrectomy. Functional stability was then observed to 5 years. Renal parenchymal volume increased a median of 10% at 3 to 12 months but in addition, the functional efficiency per unit of parenchymal volume also increased 8% (estimated glomerular filtration rate units/cm3 of parenchyma was 0.236 postoperatively vs 0.208 preoperatively, p=0.004). Age (-0.85, p <0.01), global preoperative estimated glomerular filtration rate (-0.28, p <0.01) and split renal function of the removed kidney (0.61, p <0.01) were independent predictors of renal functional compensation. CONCLUSIONS: Percent renal functional compensation after radical nephrectomy is greater in younger patients, when preoperative estimated glomerular filtration rate is lower and when the removed kidney has more robust function. Increases in measurable parenchymal mass and functional efficiency contribute substantially to renal functional compensation.

Impact of using 29 MHz high-resolution micro-ultrasound in real-time targeting of transrectal prostate biopsies: initial experience.

PURPOSE: This report presents our early experience at Cleveland Clinic replacing conventional ultrasound with a novel 29 MHz high-resolution micro-ultrasound system for both systematic sampling and real-time targeting of suspicious regions during prostate biopsy. The added value of micro-ultrasound and MRI over systematic biopsy is presented. METHODS: Sixty-seven consecutive subjects (January-August 2018) from our prospective database who underwent prostate biopsy using the micro-ultrasound system were included. 19/67 had prostate MRI imaging available. MRI targets were sampled using the UroNav fusion system. Patients had a median PSA of 5.37 ng/mL (IQR 4.13-8.74). RESULTS: 38/67 (56.7%) subjects were positive for prostate cancer. In six of these cases, systematic biopsy was negative with only micro-ultrasound targeted samples detecting cancer. In two other cases, patients were upgraded from Grade Group 1 to Grade Groups 4 and 2 based on micro-ultrasound targets. Micro-ultrasound targets detected cancer in two subjects where MRI was negative (Grade Groups 3 and 2). MRI targets alone did not change the overall diagnosis of any subjects. Switching biopsy guidance to real-time micro-ultrasound increased detection rate on prostate biopsy from 44.8% (30/67) to 56.7% (38/67), a relative increase of 26.7%. CONCLUSION: High-resolution micro-ultrasound identified clinically significant cancer that would have, otherwise, been missed by both MRI fusion and systematic biopsy and was useful in both biopsy naïve and repeat negative patients. Early results from this small, single-center cohort are promising, particularly given the ease with which micro-ultrasound can replace the conventional ultrasound in standard prostate biopsy procedures.

Hospital Quality Metrics for Radical Cystectomy: Disease Specific and Correlated to Mortality Outcomes.

PURPOSE: Measuring quality is a high priority for health care systems globally. Despite the high perioperative morbidity, mortality, expenditures and performance variation of radical cystectomy there is a paucity of validated bladder cancer quality metrics. We aimed to create a hospital quality scoring system for radical cystectomy which is disease specific and associated with patient centered outcomes. MATERIALS AND METHODS: We used the National Cancer Database to identify hospitals where radical cystectomy was performed from 2004 to 2014. Mixed effects models were constructed to assess variation in hospital performance across 7 quality indicators. Indirect standardization was used to case mix adjust hospital performance. We assessed associations between quality indicators as well as the novel BC-QS (Bladder Cancer Quality Score) composite hospital quality metric with 30-day, 90-day and overall mortality using logistic and Cox regression, respectively. RESULTS: At 1,200 facilities radical cystectomy was performed in a total of 48,341 patients from 2004 to 2014. Mixed effects models demonstrated significant between hospital variation across all quality indicators after case mix adjustment. The composite BC-QS metric was composed of the hospital positive margin rate, the lymph node dissection rate and the neoadjuvant chemotherapy rate. Better BC-QS performance was associated with lower 30-day and 90-day mortality (adjusted OR 0.78, 95% CI 0.64-0.96, and OR 0.84, 95% CI 0.72-0.97, respectively) and overall mortality (HR 0.86, 95% CI 0.81-0.92). Hospitals with a higher BC-QS had higher volume and more were affiliated with an academic institution than hospitals with a lower BC-QS (p <0.0001). CONCLUSIONS: The BC-QS captures variations in the hospital performance of radical cystectomy and it shows an association of higher quality with lower patient mortality. Our validation of this quality metric provides support for its potential use by policy makers and payers in efforts to measure hospital quality for high cost surgeries.

Can We Predict Functional Outcomes after Partial Nephrectomy?

PURPOSE: The percent of preserved parenchymal mass is the primary determinant of functional outcomes after partial nephrectomy. Accurate methods to predict the percent of preserved parenchymal mass based on preoperative imaging could facilitate patient counseling. MATERIALS AND METHODS: We evaluated the records of 428 patients who had undergone partial nephrectomy and the studies necessary to assess preserved ipsilateral parenchymal mass and function. Preoperative and postoperative ipsilateral parenchymal volumes were measured from contrast enhanced computerized tomography less than 2 months before and 3 to 12 months after partial nephrectomy and the actual percent of preserved parenchymal mass was determined. The ipsilateral percent of preserved parenchymal mass and the final global glomerular filtration rate were estimated based on preoperative imaging using subjective estimation, quantitative estimation, or estimation derived from the contact surface area or the R.E.N.A.L. (radius, exophytic/endophytic, nearness of tumor to collecting system or sinus, anterior/posterior and location relative to polar lines) score. RESULTS: Median tumor diameter was 3.5 cm, median contact surface area was 24 cm2 and the median R.E.N.A.L. score was 8. The median actual ipsilateral percent of preserved parenchymal mass was 84% and the preserved percent of the global glomerular filtration rate was 89%. The median estimated ipsilateral percent of preserved parenchymal mass was 85%, 87%, 88% and 83% based on subjective estimation, quantitative estimation, contact surface area and the R.E.N.A.L. score, respectively. Correlations between the actual and the estimated percent of preserved parenchymal mass were relatively weak in all instances (all r ≤0.46). Prediction of the final global glomerular filtration rate was strong for all 4 methods (all r = 0.91). However, a similarly strong correlation was obtained when presuming that 89% of the preoperative global glomerular filtration rate would be saved in each case (r = 0.91). On multivariable analyses a solitary kidney, the preoperative glomerular filtration rate and various estimates of the percent of preserved parenchymal mass were significantly associated with the final global glomerular filtration rate. However, the preoperative glomerular filtration rate proved to be the strongest predictor. It had more than a tenfold impact compared to the estimated percent of preserved parenchymal mass or a solitary kidney. CONCLUSIONS: Currently available methods to estimate the percent of preserved parenchymal mass have important limitations. The final global glomerular filtration rate, which is the most important functional outcome, could be predicted fairly accurately by all tested methods. However, none of them were better than simply presuming that 89% of function would be saved due to strong anchoring to the preoperative glomerular filtration rate.

Ser-486/491 phosphorylation and inhibition of AMPKα activity is positively associated with Gleason score, metastasis, and castration-resistance in prostate cancer: A retrospective clinical study.

BACKGROUND: We previously demonstrated that adenosine monophosphate-activated protein kinase (AMPKα) activity is significantly inhibited by Ser-486/491 phosphorylation in cell culture and in vivo models of metastatic and castration-resistant prostate cancer, and hypothesized these findings may translate to clinical specimens. METHODS: In this retrospective, single-institution pilot study, 45 metastatic prostate cancer cases were identified within the University Hospitals Cleveland Medical Center Pathology Archive with both metastasis and matched primary prostate tumor specimens in formalin-fixed, paraffin-embedded blocks, and complete electronic medical records. Thirty non-metastatic, hormone-dependent prostate cancer controls, who were progression-free as defined by undetectable prostate specific antigen for at least 79.6 months (range 79.6-136.0 months), and matched metastatic cases based on age, race, and year of diagnosis. All specimens were collected from 1991 to 2014; primary tumor specimens were obtained via diagnostic biopsy or prostatectomy, and metastasis specimens obtained via surgery or perimortem. 5-µ sequential slides were processed for phospho-Ser-486/491 AMPKα1 /α2 , phospho-Thr-172 AMPKα, AMPKα1 /α2 , phospho-Ser-792 Raptor, phospho-Ser-79 acetyl-CoA carboxylase, and phospho-Ser-872, 3-hydroxy-3-methylglutaryl-CoA reductase immunohistochemistry to determine expression, phosphorylation pattern, and activity of AMPKα. RESULTS: Increased inhibitory Ser-486/491 AMPKα1 /α2 phosphorylation, increased AMPKα protein expression, decreased AMPKα activity, and loss of nuclear AMPKα and p-AMPKα are associated with prostate cancer progression to metastasis. Increased p-Ser-486/491 AMPKα1 /α2 was also positively correlated with higher Gleason grade and progression to castration-resistance. CONCLUSIONS: p-Ser-486/491 AMPKα1 /α2 is a novel marker of prostate cancer metastasis and castration-resistance. Ser-486/491 phosphokinases should be pursued as targets for metastatic and castration-resistant prostate cancer chemotherapy.

Contemporary management of advanced renal cell carcinoma.

Kidney cancer is the eighth most commonly diagnosed cancer in the United States, and nearly one-third of patients have locally advanced or metastatic disease at presentation. Historically, survival outcomes for patients with advanced disease have been poor. In recent years, several novel targeted agents have emerged for the management of advanced renal cell carcinoma that have changed treatment paradigms. At the same time, surgical therapy continues to have a critical role in the management of selected patients. Recent medical and surgical advances have improved the prognosis for patients with a diagnosis of advanced disease. This review provides an overview of the current treatment landscape for patients with advanced renal cell carcinoma.

Development of a Combined MR Fingerprinting and Diffusion Examination for Prostate Cancer.

Purpose To develop and evaluate an examination consisting of magnetic resonance (MR) fingerprinting-based T1, T2, and standard apparent diffusion coefficient (ADC) mapping for multiparametric characterization of prostate disease. Materials and Methods This institutional review board-approved, HIPAA-compliant retrospective study of prospectively collected data included 140 patients suspected of having prostate cancer. T1 and T2 mapping was performed with fast imaging with steady-state precession-based MR fingerprinting with ADC mapping. Regions of interest were drawn by two independent readers in peripheral zone lesions and normal-appearing peripheral zone (NPZ) tissue identified on clinical images. T1, T2, and ADC were recorded for each region. Histopathologic correlation was based on systematic transrectal biopsy or cognitively targeted biopsy results, if available. Generalized estimating equations logistic regression was used to assess T1, T2, and ADC in the differentiation of (a) cancer versus NPZ, (b) cancer versus prostatitis, (c) prostatitis versus NPZ, and (d) high- or intermediate-grade tumors versus low-grade tumors. Analysis was performed for all lesions and repeated in a targeted biopsy subset. Discriminating ability was evaluated by using the area under the receiver operating characteristic curve (AUC). Results In this study, 109 lesions were analyzed, including 39 with cognitively targeted sampling. T1, T2, and ADC from cancer (mean, 1628 msec ± 344, 73 msec ± 27, and 0.773 × 10-3 mm2/sec ± 0.331, respectively) were significantly lower than those from NPZ (mean, 2247 msec ± 450, 169 msec ± 61, and 1.711 × 10-3 mm2/sec ± 0.269) (P < .0001 for each) and together produced the best separation between these groups (AUC = 0.99). ADC and T2 together produced the highest AUC of 0.83 for separating high- or intermediate-grade tumors from low-grade cancers. T1, T2, and ADC in prostatitis (mean, 1707 msec ± 377, 79 msec ± 37, and 0.911 × 10-3 mm2/sec ± 0.239) were significantly lower than those in NPZ (P < .0005 for each). Interreader agreement was excellent, with an intraclass correlation coefficient greater than 0.75 for both T1 and T2 measurements. Conclusion This study describes the development of a rapid MR fingerprinting- and diffusion-based examination for quantitative characterization of prostatic tissue. © RSNA, 2017 Online supplemental material is available for this article.

Risk of Pathological Upgrading and Up Staging among Men with Low Risk Prostate Cancer Varies by Race: Results from the National Cancer Database.

PURPOSE: The impact of African-American race on oncologic outcomes for low risk prostate cancer is unclear due to conflicting data. We investigated the effect of African-American race on pathological upgrading and/or up staging at prostatectomy in men with clinically low risk prostate cancer. MATERIALS AND METHODS: We queried the National Cancer Database for men with low risk prostate cancer (clinical stage T2a or less, Gleason score 6 or less, prostate specific antigen less than 10 ng/ml) treated with radical prostatectomy between 2010 and 2013. The outcomes were pathological upgrading to Gleason score greater than 6 (primary) or Gleason score greater than 3+4=7 (secondary) and/or up staging (pathological T3-4 or N1 disease). The association between race and the end points was assessed using multivariable logistic regression. To further adjust for potential confounders, stratification by urban residence and comorbidity score, and subgroup analyses were performed. RESULTS: With adjustment for age, comorbidity, income, urban residence, T stage, prostate specific antigen and percentage of positive biopsy cores, African-American race conferred 1.2-fold higher odds of pathological upgrading to Gleason score greater than 6 and/or up staging (OR 1.2, 95% CI 1.1-1.3, p <0.01). African-American race also was an independent predictor of pathological upgrading to Gleason score greater than 3+4=7 and/or up staging (p=0.03). CONCLUSIONS: African-American men with low risk prostate cancer are more likely to harbor higher risk disease, which may lead to adverse outcomes. This finding alone does not preclude active surveillance. However, race should be considered as men weigh the risks and benefits of active surveillance vs treatment.