Identifying and overcoming barriers to participation of minority populations in clinical trials: Lessons learned from the VanDAAM study.

Participation in cancer research trials by minority populations is imperative in reducing disparities in clinical outcomes. Even with increased awareness of the importance of minority patient inclusion in clinical research to improve cancer care and survival, significant barriers persist in accruing and retaining minority patients into clinical trials. This study sought to identify and address barriers to minority accrual to a minimal risk clinical research study in real-time.

Genomic Testing in Localized Prostate Cancer Can Identify Subsets of African Americans With Aggressive Disease.

BACKGROUND: Personalized genomic classifiers have transformed the management of prostate cancer (PCa) by identifying the most aggressive subsets of PCa. Nevertheless, the performance of genomic classifiers to risk classify African American men is thus far lacking in a prospective setting. METHODS: This is a prospective study of the Decipher genomic classifier for National Comprehensive Cancer Network low- and intermediate-risk PCa. Study-eligible non-African American men were matched to African American men. Diagnostic biopsy specimens were processed to estimate Decipher scores. Samples accrued in NCT02723734, a prospective study, were interrogated to determine the genomic risk of reclassification (GrR) between conventional clinical risk classifiers and the Decipher score. RESULTS: The final analysis included a clinically balanced cohort of 226 patients with complete genomic information (113 African American men and 113 non-African American men). A higher proportion of African American men with National Comprehensive Cancer Network-classified low-risk (18.2%) and favorable intermediate-risk (37.8%) PCa had a higher Decipher score than non-African American men. Self-identified African American men were twice more likely than non-African American men to experience GrR (relative risk [RR] = 2.23, 95% confidence interval [CI] = 1.02 to 4.90; P = .04). In an ancestry-determined race model, we consistently validated a higher risk of reclassification in African American men (RR = 5.26, 95% CI = 1.66 to 16.63; P = .004). Race-stratified analysis of GrR vs non-GrR tumors also revealed molecular differences in these tumor subtypes. CONCLUSIONS: Integration of genomic classifiers with clinically based risk classification can help identify the subset of African American men with localized PCa who harbor high genomic risk of early metastatic disease. It is vital to identify and appropriately risk stratify the subset of African American men with aggressive disease who may benefit from more targeted interventions.

Association of age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer.

PURPOSE: To assess the association of patient age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: We analyzed data from 1105 patients with MIBC. Patients age was evaluated as continuous variable and stratified in quartiles. Pathologic objective response (pOR; ypT0-Ta-Tis-T1N0) and pathologic complete response (pCR; ypT0N0), as well survival outcomes were assessed. We used data of 395 patients from The Cancer Genome Atlas (TCGA) to investigate the prevalence of TCGA molecular subtypes and DNA damage repair (DDR) gene alterations according to patient age. RESULTS: pOR was achieved in 40% of patients. There was no difference in distribution of pOR or pCR between age quartiles. On univariable logistic regression analysis, patient age was not associated with pOR or pCR when evaluated as continuous variables or stratified in quartiles (all p > 0.3). Median follow-up was 18 months (IQR 6-37). On Cox regression and competing risk regression analyses, age was not associated with survival outcomes (all p > 0.05). In the TCGA cohort, patient with age ≤ 60 years has 7% less DDR gene mutations (p = 0.59). We found higher age distribution in patients with luminal (p < 0.001) and luminal infiltrated (p = 0.002) compared to those with luminal papillary subtype. CONCLUSIONS: While younger patients may have less mutational tumor burden, our analysis failed to show an association of age with response to preoperative chemotherapy or survival outcomes. Therefore, the use of preoperative chemotherapy should be considered regardless of patient age.

Impact of sex on response to neoadjuvant chemotherapy in patients with bladder cancer.

OBJECTIVE: To assess the effect of patient's sex on response to neoadjuvant chemotherapy (NAC) in patients with clinically nonmetastatic muscle-invasive bladder cancer (MIBC). METHODS: Complete pathologic response, defined as ypT0N0 at radical cystectomy, and downstaging were evaluated using sex-adjusted univariable and multivariable logistic regression modeling. We used interaction terms to account for age of menopause and smoking status. The association of sex with overall survival and cancer-specific survival was evaluated using Cox regression analyses. RESULTS: A total of 1,031 patients were included in the analysis, 227 (22%) of whom were female. Female patients had a higher rate of extravesical disease extension (P = 0.01). After the administration of NAC, ypT stage was equally distributed between sexes (P = 0.39). On multivariable logistic regression analyses, there was no difference between the sexes or age of menopause with regards to ypT0N0 rates or downstaging (all P > 0.5). On Cox regression analyses, sex was associated with neither overall survival (hazard ratio 1.04, 95% confidence interval 0.75-1.45, P = 0.81) nor cancer-specific survival (hazard ratio 1.06, 95% confidence interval 0.71-1.58, P = 0.77). CONCLUSION: Our study generates the hypothesis that NAC equalizes the preoperative disparity in pathologic stage between males and females suggesting a possible differential response between sexes. This might be the explanation underlying the comparable survival outcomes between sexes despite females presenting with more advanced tumor stage.

The prognostic value of the neutrophil-to-lymphocyte ratio in patients with muscle-invasive bladder cancer treated with neoadjuvant chemotherapy and radical cystectomy.

INTRODUCTION: The neutrophil-to-lymphocyte ratio (NLR) is an attractive marker because it is derived from routine bloodwork. NLR has shown promise as a prognostic factor in muscle invasive bladder cancer (MIBC) but its value in patients receiving neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) is not yet established. Since NLR is related to an oncogenic environment and poor antitumor host response, we hypothesized that a high NLR would be associated with a poor response to NAC and would remain a poor prognostic indicator in patients receiving NAC. METHODS: A retrospective analysis was performed on patients with nonmetastatic MIBC (cT2-4aN0M0) who received NAC prior to RC between 2000 and 2013 at 1 of 19 centers across Europe and North America. The pre-NAC NLR was used to split patients into a low (NLR ≤ 3) and high (NLR > 3) group. Demographic and clinical parameters were compared between the groups using Student's t test, chi-squared, or Fisher's exact test. Putative risk factors for disease-specific and overall survival were analyzed using Cox regression, while predictors of response to NAC (defined as absence of MIBC in RC specimen) were investigated using logistic regression. RESULTS: Data were available for 340 patients (199 NLR ≤ 3, 141 NLR > 3). Other than age and rate of lymphovascular invasion, demographic and pretreatment characteristics did not differ significantly. More patients in the NLR > 3 group had residual MIBC after NAC than the NLR ≤ 3 group (70.8% vs. 58.3%, P = 0.049). NLR was the only significant predictor of response (odds ratio: 0.36, P = 0.003) in logistic regression. NLR was a significant risk factor for both disease-specific (hazard ratio (HR): 2.4, P = 0.006) and overall survival (HR:1.8, P = 0.02). CONCLUSION: NLR > 3 was associated with a decreased response to NAC and shorter disease-specific and overall survival. This suggests that NLR is a simple tool that can aid in MIBC risk stratification in clinical practice.

The History of Urology at the Minneapolis Veterans Affairs Health Care System.

OBJECTIVE: The Section of Urology at the Minneapolis Veteran's Affairs (VA) Medical Center has a long history of contributions to Urology including the Gleason Score, Fuhrman Grading system, testicular tumor marker development and the birth of Endourology. The objective of this manuscript is to compile and present the Urologic history of the Minneapolis VA. METHODS: The Urologic literature and institutional records originating from the Minneapolis VA Medical Center from 1946-2017 were reviewed and presented herein. RESULTS: The Minneapolis VA Health Care System originated in 1921 and currently employs 5 Urologist who serve over 16,000 veterans per year. Historic achievements from the Minneapolis VA Section of Urology include the development of the Veteran's Affairs Cooperative Research Group (VACURG) which was instrumental to development of the Gleason grading system for prostate cancer in 1965. Additional urologic oncology achievements originating from the Minneapolis VA Section of Urology included the development of the diagnostic utility of tumor markers in testis cancer in 1976 and The Fuhrman Grading System in 1982. Perhaps the greatest contribution to the field of Urology was the birth of Endourology at the Minneapolis VA in the late 1970s under the direction of Dr. Paul Lange. Currently the Minneapolis VA is a premier center for Evidence Based Urology by housing Cochrane Urology and the U.S. Grading of Recommendations Assessment, Development and Evaluation network (US GRADE). CONCLUSION: Since 1946, the section of Urology at the Minneapolis VA has contributed basic science, clinical technique and evidence based medicine to the field of Urology while providing care to the nation's veterans.

Survival Outcomes Associated With Female Primary Urethral Carcinoma: Review of a Single Institutional Experience.

BACKGROUND: Primary urethral carcinoma (PUC) is rare, and standard treatment recommendations are lacking. We examined the variation in treatments and survival outcomes of female PUC at a single, tertiary referral cancer center. METHODS: Records of women with PUC referred to our multidisciplinary genitourinary oncology service between 2003 and 2017 were reviewed. Clinical, demographic, pathologic, primary and salvage therapy details, and overall (OS) and recurrence-free survival (RFS) were recorded. Survival outcomes were analyzed for the entire cohort, and cases of locally-advanced (≥ T2 tumor), non-metastatic PUC were evaluated according to treatment intensity. Multimodal treatment (cystourethrectomy + concomitant therapy) was compared with non-multimodal therapy. Contingency analyses and Kaplan-Meier estimates were performed. RESULTS: Thirty-nine women with PUC were identified. In total, median OS was 36 months (95% confidence interval, 10.6-61.4 months). Twenty-four had T3 to T4 disease, 12 were node-positive, and 3 had distant metastases. Histology included 22 adenocarcinomas, 11 urothelial, 5 squamous, and 1 neuroendocrine. Patients with locally advanced, non-metastatic disease (n = 25) had significantly reduced OS (36 vs. 99 months; P = .016) and RFS (46 months vs. unmet; P = .011) compared with patients with locally confined tumors. Approximately one-half of locally advanced cases were managed with multimodal therapy (4 with neoadjuvant therapy + cystourethrectomy, 8 with cystourethrectomy + adjuvant therapy, and 1 with chemoradiation + consolidative cystourethrectomy). Multimodal therapy had nonsignificant longer OS (36 vs. 16 months) and RFS (58 vs. 16 months), P > .05. CONCLUSIONS: Locally advanced female PUC has relatively poor survival outcomes. Although we observed a nonsignificant interval improvement in survival with multimodality therapy, the treatment paradigm is inconsistent. Because it is a rare disease, collaborative multi-institutional studies are needed.

Improving risk stratification among veterans diagnosed with prostate cancer: impact of the 17-gene prostate score assay.

BACKGROUND: Active surveillance (AS) has been widely implemented within Veterans Affairs' medical centers (VAMCs) as a standard of care for low-risk prostate cancer (PCa). Patient characteristics such as age, race, and Agent Orange (AO) exposure may influence advisability of AS in veterans. The 17-gene assay may improve risk stratification and management selection. OBJECTIVES: To compare management strategies for PCa at 6 VAMCs before and after introduction of the Oncotype DX Genomic Prostate Score (GPS) assay. STUDY DESIGN: We reviewed records of patients diagnosed with PCa between 2013 and 2014 to identify management patterns in an untested cohort. From 2015 to 2016, these patients received GPS testing in a prospective study. Charts from 6 months post biopsy were reviewed for both cohorts to compare management received in the untested and tested cohorts. SUBJECTS: Men who just received their diagnosis and have National Comprehensive Cancer Network (NCCN) very low-, low-, and select cases of intermediate-risk PCa. RESULTS: Patient characteristics were generally similar in the untested and tested cohorts. AS utilization was 12% higher in the tested cohort compared with the untested cohort. In men younger than 60 years, utilization of AS in tested men was 33% higher than in untested men. AS in tested men was higher across all NCCN risk groups and races, particular in low-risk men (72% vs 90% for untested vs tested, respectively). Tested veterans exposed to AO received less AS than untested veterans. Tested nonexposed veterans received 19% more AS than untested veterans. Median GPS results did not significantly differ as a factor of race or AO exposure. CONCLUSIONS: Men who receive GPS testing are more likely to utilize AS within the year post diagnosis, regardless of age, race, and NCCN risk group. Median GPS was similar across racial groups and AO exposure groups, suggesting similar biology across these groups. The GPS assay may be a useful tool to refine risk assessment of PCa and increase rates of AS among clinically and biologically low-risk patients, which is in line with guideline-based care.

Change in Psoas Muscle Volume as a Predictor of Outcomes in Patients Treated with Chemotherapy and Radical Cystectomy for Muscle-Invasive Bladder Cancer.

Objective: Sarcopenia, or the age-related loss of skeletal muscle mass and function, has been investigated as a potential marker of adverse outcomes among surgical patients. Our aim was to assess for changes in psoas muscle volume (PMV) following administration of neoadjuvant chemotherapy (NAC) in patients with bladder cancer and to examine whether changes in PMV following NAC are predictive of perioperative complications, pathologic response or survival. Methods: During the period of 2009-2013, patients undergoing NAC and radical cystectomy (RC) at our institution with pre and post NAC cross sectional images available were included. Bilateral total psoas muscle volume (PMV) was obtained from pre- and post- NAC images and the proportion of PMV change was calculated by dividing the change PMV by pre-NAC PMV. Analyses for the assessment of factors predicting PMV loss, partial/complete pathologic response (pPR/pCR), complications, readmission, cancer specific (CSS), recurrence-free (RFS) and overall survival (OS) were performed. Results: Total of 60 patients had complete radiological data available. Post-NAC PMV and BMI declines were statistically significant, 4.9% and 0.05%, respectively. NAC dose reduction/delay was a significant predictor of PMV loss (coefficient B 4.6; 95% CI 0.05-9.2; p = 0.047). The proportion of PMV decline during NAC was not a predictor of pPR, pCR, complications, readmission, CSS, RFS, or OS. Conclusions: We observed an interval decline in PMV during the period of NAC administration and this decline was more than it could be appreciated with changes in BMI during the same period. PMV decline was associated with the need for dose reduction/dose delay during NAC. In our series, PMV changes occurring during NAC administration were not predictive of pathologic response to chemotherapy, postoperative complications or survival.

Functional Recovery From Extended Warm Ischemia Associated With Partial Nephrectomy.

OBJECTIVE: To evaluate the impact of extended warm ischemia on incidence of acute kidney injury (AKI) and ultimate functional recovery after partial nephrectomy (PN), incorporating rigorous control for loss of parenchymal mass, and embedded within comparison to cohorts of patients managed with hypothermia or limited warm ischemia. MATERIALS AND METHODS: From 2007 to 2014, 277 patients managed with PN had appropriate studies to evaluate changes in function/mass specifically within the operated kidney. Recovery from ischemia was defined as %function saved/%parenchymal mass saved. AKI was based on global renal function and defined as a ≥1.5-fold increase in serum creatinine above the preoperative level. RESULTS: Hypothermia was utilized in 112 patients (median = 27 minutes) and warm ischemia in 165 (median = 21 minutes). AKI strongly correlated with solitary kidney (P < .001) and duration (P < .001) but not type (P = .49) of ischemia. Median recovery from ischemia in the operated kidney was 100% (interquartile range [IQR] = 88%-109%) for cold ischemia, with 6 (5%) noted to have <80% recovery from ischemia. For the warm ischemia group, median recovery from ischemia was 91% (IQR = 82%-101%, P < .001 compared with hypothermia), and 34 (21%) had recovery from ischemia <80% (P < .001). For warm ischemia subgrouped by duration <25 minutes (n = 114), 25-35 minutes (n = 35), and >35 minutes (n = 16), median recovery from ischemia was 92% (IQR = 86%-100%), 90% (IQR = 78%-104%), and 91% (IQR = 80%-96%), respectively (P = .77). CONCLUSION: Our results suggest that AKI after PN correlates with duration but not with type of ischemia. However, subsequent recovery, which ultimately defines the new baseline glomerular filtration rate, is most reliable with hypothermia. However, most patients undergoing PN with warm ischemia still recover relatively strongly from ischemia, even if extended to 35-45 minutes.

Clinical and therapeutic factors associated with adverse pathological outcomes in clinically node-negative patients treated with neoadjuvant cisplatin-based chemotherapy and radical cystectomy.

PURPOSE: Several disease characteristics have been identified as potential predictors for pathological node involvement (pN+) following radical cystectomy (RC). However, these have not been assessed in patients treated with neoadjuvant chemotherapy (NAC). We endeavored to assess factors predicting adverse pathology in clinically node-negative patients treated with NAC and RC. METHODS: Patients from four North American institutions with cT2-4aN0M0 UC who received three or four cycles of NAC followed by RC were selected. Logistic regression was used to predict pN+,

A Novel Approach for the Treatment of Radiation-Induced Hemorrhagic Cystitis with the GreenLightTM XPS Laser.

INTRODUCTION: The treatment of pelvic malignancies with radiotherapy can develop severe sequelae, especially radiation-induced hemorrhagic cystitis. It is a progressive disease that can lead to the need for blood transfusion, hospitalizations, and surgical interventions. This tends to affect the quality of life of these patients, and management can at times be difficult. We have evaluated the GreenLight Xcelerated Performance System (XPS) with TruCoag, although primarily used for management of benign prostatic hypertrophy (BPH), for the treatment of radiation-induced hemorrhagic cystitis. MATERIALS AND METHODS: After International Review Board (IRB) approval, a retrospectivechart review was performed in addition to a literature search. A series of four male patients, mean age of 81 years, with radiation-induced hemorrhagic cystitis secondary to radiotherapy for pelvic malignancies (3 prostate cancer, 1 rectal cancer) were successfully treated with the GreenLight laser after unsuccessful treatment with current therapies described in the literature. RESULTS: All four patients treated with the GreenLight laser had resolution of their hematuria after one treatment and were discharge from the hospital with clear urine. CONCLUSION: The GreenLight XPS laser shows promising results for the treatment of patients with radiation-induced hemorrhagic cystitis, and deserves further evaluation and validation, especially since there is limited data available in the literature regarding the use of this technology for the treatment of this devastating condition.

A Novel Approach for the Treatment of Radiation-Induced Hemorrhagic Cystitis with the GreenLight™ XPS Laser

The treatment of pelvic malignancies with radiotherapy can develop severe sequelae, especially radiation-induced hemorrhagic cystitis. It is a progressive disease that can lead to the need for blood transfusion, hospitalizations, and surgical interventions. This tends to affect the quality of life of these patients, and management can at times be difficult. We have evaluated the GreenLight Xcelerated Performance System (XPS) with TruCoag, although primarily used for management of benign prostatic hypertrophy (BPH), for the treatment of radiation-induced hemorrhagic cystitis.

Survival and Functional Stability in Chronic Kidney Disease Due to Surgical Removal of Nephrons: Importance of the New Baseline Glomerular Filtration Rate.

BACKGROUND: Chronic kidney disease (CKD) can be associated with a higher risk of progression to end-stage renal disease and mortality, but the etiology of nephron loss may modify this. Previous studies suggested that CKD primarily due to surgical removal of nephrons (CKD-S) may be more stable and associated with better survival than CKD due to medical causes (CKD-M). OBJECTIVE: We addressed limitations of our previous work with comprehensive control for confounding factors, differentiation of non-renal cancer-related mortality, and longer follow-up for more discriminatory assessment of the impact of CKD-S. DESIGN, SETTING, AND PARTICIPANTS: From 1999 to 2008, 4299 patients underwent surgery for renal cancer at a single institution. The median follow-up was 9.4 yr (7.3-11.0). The new baseline glomerular filtration rate (GFR) was defined as the highest GFR between the nadir and 42 d after surgery. Three cohorts were retrospectively evaluated: no CKD (new baseline GFR >60 ml/min/1.73 m(2)); CKD-S (new baseline GFR<60 but preoperative >60 ml/min/1.73 m(2)); and CKD-M/S (new baseline and preoperative GFR both <60 ml/min/1.73 m(2)). Cohort status was permanently set at 42 d after surgery. INTERVENTION: Renal surgery. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Decline in renal function (50% reduction in GFR or dialysis), all-cause mortality, and non-renal cancer mortality were examined using a multivariable Cox proportional hazards model. RESULTS AND LIMITATIONS: CKD-M/S had a higher incidence of relevant comorbidities and the new baseline GFR was lower. On multivariable analysis (controlling for age, gender, race, diabetes, hypertension, and cardiac disease), CKD-M/S had higher rates of progressive decline in renal function, all-cause mortality, and non-renal cancer mortality when compared to CKD-S and no CKD (hazard ratio [HR] 1.69-2.33, all p<0.05). All-cause mortality was modestly higher for CKD-S than for no CKD (HR 1.19, p=0.030), but renal stability and non-renal cancer mortality were similar for these groups. New baseline GFR of <45 ml/min/1.73 m(2) significantly predicted adverse outcomes. The main limitation is the retrospective design. CONCLUSIONS: CKD-S is more stable than CKD-M/S and has better survival, approximating that for no CKD. However, if the new baseline GFR is <45 ml/min/1.73 m(2), the risks of functional decline and mortality increase. These findings may influence counseling for patients with localized renal cell carcinoma and higher oncologic potential when a normal contralateral kidney is present. PATIENT SUMMARY: Survival is better for surgically induced chronic kidney disease (CKD) than for medically induced CKD, particularly if the postoperative glomerular filtration rate is ≥45 ml/min/1.73 m(2). Patients with preexisting CKD are at risk of a significant decline in kidney function after surgery, and kidney-preserving treatment should be strongly considered in such cases.

Analysis of Atrophy After Clamped Partial Nephrectomy and Potential Impact of Ischemia.

OBJECTIVE: Ischemia is a potential contributor to decline of function after partial nephrectomy (PN), although loss of parenchymal mass related to excision and reconstruction appears to be a more significant factor. However, loss of parenchymal mass could also be due to global effects of ischemia leading to parenchymal atrophy. In this study, we evaluated parenchymal volumes in regions away from the operated site to assess for atrophy. MATERIALS AND METHODS: A total of 164 patients undergoing PN for whom detailed analysis of function and parenchymal mass within the operated kidney could be performed were assessed for opposite pole volume (OPV) before and 4-12 months after surgery. Tumor location was required to be ≥2 cm away from the opposite polar line to exclude local effects related to excision or reconstruction. OPV was estimated by software analysis, and the ratio of the estimates (OPV ratio = postoperative OPV to preoperative OPV) was used to assess for atrophy. RESULTS: Patient demographics and tumor characteristics were representative of conventional PN populations, and warm ischemia (n = 101; median, 21 minutes) and cold ischemia (n = 63; median, 26 minutes) were applied by surgeon discretion. OPVs before and after PN were 63.2 and 62.5 cm(3), respectively (P = .76). The median OPV ratio was 0.99 suggesting that significant atrophy did not occur. OPV ratio was 0.99 for warm ischemia cases and 0.99 for cold ischemia cases (P = .95). CONCLUSION: Limited warm ischemia or hypothermia was not associated with significant parenchymal atrophy after PN, which suggests that parenchymal volume loss in this setting is primarily due to excision or reconstruction.

Decline in renal function after partial nephrectomy: etiology and prevention.

PURPOSE: Partial nephrectomy is the reference standard for the management of small renal tumors and is commonly used for localized kidney cancer. A primary goal of partial nephrectomy is to preserve as much renal function as possible. New baseline glomerular filtration rate after partial nephrectomy can have prognostic significance with respect to long-term outcomes. Recent studies provide an increased understanding of the factors that determine functional outcomes after partial nephrectomy as well as preventive measures to minimize functional decline. We review these advances, highlight ongoing controversies and stimulate further research. MATERIALS AND METHODS: A comprehensive literature review consistent with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria was performed from January 2006 to April 2014 using PubMed®, Cochrane and Ovid Medline. Key words included partial nephrectomy, renal function, warm ischemia, hypothermia, nephron mass, parenchymal volume, surgical approaches to partial nephrectomy, preoperative and intraoperative imaging, enucleation, hemostatic agents and energy based resection. Relevant reviews were also examined as well as their cited references. An additional Google Scholar search was conducted to broaden the scope of the review. Only English language articles were included in the analysis. The primary outcomes of interest were the new baseline level of function after early postoperative recovery, percent decline in function, potential etiologies and preventive measures. RESULTS: Decline in function after partial nephrectomy averages approximately 20% in the operated kidney, and can be due to incomplete recovery from the ischemic insult or loss of nephron mass related to parenchymal excision or collateral damage during reconstruction. Compensatory hypertrophy in the contralateral kidney after partial nephrectomy in adults is marginal and decline in global renal function for patients with 2 kidneys averages about 10%, although there is some variance based on tumor size and location. Irreversible ischemic injury can be minimized by pharmacological intervention or surgical approaches such as hypothermia, limited warm ischemia, or zero or segmental ischemia. Excessive loss of nephron mass can be minimized by improved preoperative or intraoperative imaging, use of a bloodless field, enucleation and vascular microdissection. Hemostatic agents or energy based resection that minimizes the need for parenchymal and capsular suturing can also optimize preservation of the vascularized nephron mass. CONCLUSIONS: Our understanding of the decline in renal function after partial nephrectomy has advanced considerably, including better appreciation of its magnitude and impact in various settings, possible etiologies and potential preventive measures. Many controversies persist and this remains an important area of investigation.

Multicenter assessment of neoadjuvant chemotherapy for muscle-invasive bladder cancer.

BACKGROUND: The efficacy of neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (BCa) was established primarily with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), with complete response rates (pT0) as high as 38%. However, because of the comparable efficacy with better tolerability of gemcitabine and cisplatin (GC) in patients with metastatic disease, GC has become the most commonly used regimen in the neoadjuvant setting. OBJECTIVE: We aimed to assess real-world pathologic response rates to NAC with different regimens in a large, multicenter cohort. DESIGN, SETTING, AND PARTICIPANTS: Data were collected retrospectively at 19 centers on patients with clinical cT2-4aN0M0 urothelial carcinoma of the bladder who received at least three cycles of NAC, followed by radical cystectomy (RC), between 2000 and 2013. INTERVENTION: NAC and RC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was pathologic stage at cystectomy. Univariable and multivariable analyses were used to determine factors predictive of pT0N0 and ≤pT1N0 stages. RESULTS AND LIMITATIONS: Data were collected on 935 patients who met inclusion criteria. GC was used in the majority of the patients (n=602; 64.4%), followed by MVAC (n=183; 19.6%) and other regimens (n=144; 15.4%). The rates of pT0N0 and ≤pT1N0 pathologic response were 22.7% and 40.8%, respectively. The rate of pT0N0 disease for patients receiving GC was 23.9%, compared with 24.5% for MVAC (p=0.2). There was no difference between MVAC and GC in pT0N0 on multivariable analysis (odds ratio: 0.89 [95% confidence interval, 0.61-1.34]; p=0.6). CONCLUSIONS: Response rates to NAC were lower than those reported in prospective randomized trials, and we did not discern a difference between MVAC and GC. Without any evidence from randomized prospective trials, the best NAC regimen for invasive BCa remains to be determined. PATIENT SUMMARY: There was no apparent difference in the response rates to the two most common presurgical chemotherapy regimens for patients with bladder cancer.

Presurgical sunitinib reduces tumor size and may facilitate partial nephrectomy in patients with renal cell carcinoma.

OBJECTIVE: To determine whether presurgical sunitinib reduces primary renal cell carcinoma (RCC) size and facilitates partial nephrectomy (PN). METHODS: Data from potential candidates for PN treated with sunitinib with primary RCC in situ were reviewed retrospectively. Primary outcome was reduction in tumor bidirectional area. RESULTS: Included were 72 potential candidates for PN who received sunitinib before definitive renal surgery on 78 kidneys. Median primary tumor size was 7.2 cm (interquartile range [IQR]: 5.3-8.7 cm) before and 5.3 cm (IQR: 4.1-7.5 cm) after sunitinib treatment (P<0.0001), resulting in 32% reduction in tumor bidirectional area (IQR: 14%-46%). Downsizing occurred in 65 tumors (83%), with 15 partial responses (19%). Tumor complexity per R.E.N.A.L. score was reduced in 59%, with median posttreatment score of 9 (IQR: 8-10). Predictors of lesser tumor downsizing included clinical evidence of lymph node metastases (P<0.0001), non-clear cell histology (P = 0.0017), and higher nuclear grade (P = 0.023). Surgery was performed for 68 tumors (87%) and was not delayed in any patient owing to sunitinib toxicity. Grade ≥ 3 surgical complications occurred in 5 patients (7%). PN was performed for 49 kidneys (63%) after sunitinib, including 76% of patients without and 41% with metastatic disease (P = 0.0026). PN was completed in 100%, 86%, 65%, and 60% of localized cT1a, cT1b, cT2, and cT3 tumors, respectively. CONCLUSION: Presurgical sunitinib leads to modest tumor reduction in most primary RCC, and many patients can be subsequently treated with PN with acceptable morbidity and preserved renal function. A randomized trial is required to definitively determine whether presurgical therapy enhances feasibility of PN.