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This AUA Guideline focuses on evaluation/counseling/management of adult patients with clinically-localized renal masses suspicious for cancer, including solid-enhancing tumors and Bosniak 3/4 complex-cystic lesions.The Renal Mass and Localized Renal Cancer guideline underwent an update literature review which resulted in the 2021 amendment. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text]).Great progress has been made regarding the evaluation/management of clinically-localized renal masses. These guidelines provide updated, evidence-based recommendations regarding evaluation/counseling including the evolving role of renal-mass-biopsy (RMB). Given great variability of clinical/oncologic/functional characteristics, index patients are not utilized and the panel advocates individualized counseling/management. Options for intervention (partial-nephrectomy (PN), radical-nephrectomy (RN), and thermal-ablation (TA)) are reviewed including recent data about comparative-effectiveness/potential morbidities. Oncologic issues are prioritized while recognizing the importance of functional-outcomes for survivorship. Granular criteria for RN are provided to help reduce overutilization of RN while also avoiding imprudent PN. Priority for PN is recommended for clinical T1a lesions, along with selective utilization of TA, which has good efficacy for tumors≤3.0 cm. Recommendations for genetic-counseling have been revised and considerations for adjuvant-therapies are addressed. Active-surveillance and follow-up after intervention are discussed in an adjunctive article.Several factors require consideration during counseling/management of patients with clinically-localized renal masses including general health/comorbidities, oncologic-considerations, functional-consequences, and relative efficacy/potential morbidities of various management-strategies.

Neoadjuvant chemotherapy (NAC) prior to surgery and immune checkpoint therapy (ICT) have revolutionized bladder cancer management. However, stratification of patients that would benefit most from these modalities remains a major clinical challenge. Here, we combine single nuclei RNA sequencing with spatial transcriptomics and single-cell resolution spatial proteomic analysis of human bladder cancer to identify an epithelial subpopulation with therapeutic response prediction ability. These cells express Cadherin 12 (CDH12, N-Cadherin 2), catenins, and other epithelial markers. CDH12-enriched tumors define patients with poor outcome following surgery with or without NAC. In contrast, CDH12-enriched tumors exhibit superior response to ICT. In all settings, patient stratification by tumor CDH12 enrichment offers better prediction of outcome than currently established bladder cancer subtypes. Molecularly, the CDH12 population resembles an undifferentiated state with inherently aggressive biology including chemoresistance, likely mediated through progenitor-like gene expression and fibroblast activation. CDH12-enriched cells express PD-L1 and PD-L2 and co-localize with exhausted T-cells, possibly mediated through CD49a (ITGA1), providing one explanation for ICT efficacy in these tumors. Altogether, this study describes a cancer cell population with an intriguing diametric response to major bladder cancer therapeutics. Importantly, it also provides a compelling framework for designing biomarker-guided clinical trials., The identification of response biomarkers for surgery, chemotherapy and immune checkpoint therapy in bladder cancer is crucial. Here, single nuclei RNA sequencing and spatial profiling identify a cancer cell population expressing Neural Type Cadherin 2 that associates with distinct treatment outcomes.

Nonmuscle-invasive bladder cancer is treated by resection within the bladder and bladder instillment with bacillus Calmette-Guérin or chemotherapy. For bacillus Calmette-Guérin-refractory disease, systemic anti-PD-1 (programmed cell death protein 1) immune checkpoint inhibition is a treatment. Our aim is to test whether intravesical instillment with anti-PD-1 inhibitor treats localized bladder cancer as effectively as systemic administration.We investigated an orthotopic mouse model of urothelial bladder cancer using MBT2 cells instilled into the bladders of syngeneic, wild-type C3H mice. Groups of 10 mice received each treatment for comparison of intravesical anti-PD-1, intraperitoneal anti-PD1, and intravesical chemotherapy. The primary outcome was overall survival and secondary outcomes included long-term immunity and toxicity.Anti-PD-1 administered by bladder instillment (intravesical route) successfully treats localized bladder cancer and has similar overall survival to anti-PD-1 by systemic route. Anti-PD-1 by either route provides a significant survival advantage over control antibody. Anti-PD-1 increases CD8+ cell infiltration in tumors, particularly when administered intravesically. Antibody treatment avoids toxicity observed for intravesical chemotherapy. Mice who cleared their tumors after initial treatment were rechallenged with tumor engraftment 3-9 months later without any additional treatment. Initial anti-PD-1-treated mice did not grow tumors when rechallenged, which suggests long-term immunity exists, but initial mitomycin-treated mice readily grew tumors indicating no immunity occurred by chemotherapy treatment.Intravesical administration of anti-PD-1 is a promising treatment route for localized bladder cancer, with comparable overall survival to systemic anti-PD-1 in this mouse model. Intravesical anti-PD-1 increases CD8+ T cells in treated tumors and long-term immunity was seen to tumor rechallenge.

Intravesical therapy for nonmuscle invasive bladder cancer decreases recurrence and progression but carries a high risk of side effects, which limit patient adherence. Appropriate management of the toxicities from intravesical therapy requires consideration of the agent used, the side effects experienced, and the timing of those side effects. Management strategies for intravesical toxicities ideally improve patient tolerance without sacrificing oncologic outcomes. This review aims to provide a comprehensive overview of the available evidence regarding the side effects of intravesical therapies for nonmuscle invasive bladder cancer and to propose practical strategies for toxicity management.

OBJECTIVES To examine the effect of hospital volume on short and long-term outcomes for radical nephroureterectomy (RNUx). Upper tract urothelial carcinoma is a rare malignancy that few surgeons have experience with. The hospital volume-outcome relationship has been well established for other cancers but not RNUx. METHODS The National Cancer Database was queried for all cases of upper tract urothelial carcinoma that underwent RNUx from 2004 to 2016. Average annual hospital volume for radical nephroureterectomy was stratified into tertiles. The upper tertile, defined as 6 or more RNUx per year, was considered high volume while low volume was less than 6 RNUx per year. Kaplan-Meier and Cox proportional hazards regression were used to identify independent predictors of overall survival, and logistic regression was used to identify predictors of perioperative outcomes. RESULTS We identified 37,479 RNUx performed across 1290 hospitals. There were no differences in baseline health or cancer staging between patients who presented at low- versus high-volume centers. Both peri-operative survival (30- and 90-day mortality) and long-term overall survival were improved in patients treated at high-volume centers. On multivariable survival analysis, treatment at a high-volume center was associated with improved hazards of survival. This relationship for long-term survival remained consistent on landmark analysis where patients who died within 90 days of surgery were removed. CONCLUSIONS Treatment at a high-volume hospital was associated not only with improved short-term perioperative outcomes but also with improved overall long-term survival. The mechanism behind this is likely multifactorial with surgeon volume, and ancillary support services all playing critical roles.

Non-muscle invasive bladder cancer is a heterogeneous disease with widely varying risks of recurrence and progression to muscle invasion. Risk stratification within current treatment guidelines are an attempt to address this heterogeneity. This heterogeneity stems from a number of pathologic characteristics as well as recurrence status. Radical cystectomy, while the definitive, curative therapy for muscle invasive disease, is not often utilized for non-muscle invasive disease, even when it may be a superior option to bladder-sparing therapy. A majority of American Urologists have been reported to defer cystectomy for less invasive therapies when it is a guideline driven option. Both cystectomy and bladder-sparing therapy have excellent oncologic outcomes, but very different morbidity and mortality profiles. Timely, initial cystectomy provides improved oncologic outcomes for patients with high-risk non-muscle invasive bladder cancer, as opposed to delayed cystectomy following prolonged, failed bladder-sparing therapy. Patient selection is paramount when considering timely, initial cystectomy, given the increased rates of morbidity and mortality. The heterogeneity of non-muscle invasive pathologic characteristics includes a number of factors that may help differentiate patients who would benefit from a timely, initial cystectomy as opposed to bladder-sparing therapy. A rapidly evolving understanding of bladder cancer biology may help improve risk stratification and further aid in the selection of patients for timely, initial cystectomy.

Extraction site incisional hernia (IH) has been recognized as an important complication in minimally invasive procedures but has not been as well characterized following robotic-assisted laparoscopic prostatectomy (RALP). Approximately 29% of IH required surgical repair. A number of techniques have been utilized to reduce the rates of IH following minimally invasive procedures. First, off-midline extraction was investigated, this did not demonstrate a reduction in incisional hernia rates. Recently, supra-umbilical transverse incisions have been utilized to extract prostate specimen and this method decreased the extraction site IH rate compared to the vertical midline incision. In addition, the choice of fascial closure technique and choice of the suture may influence the incidence of extraction site IH. For example, studies showed that abdominal fascial closure using a nonabsorbable suture and a continuous running suture technique decreased IH rate from 32 to 17%. Finally, “the small bites technique” has been recommended to reduce hernia incidence after midline fascial closure following a randomized controlled trial (RCT) which demonstrated the superiority of the small-bite technique. In summary, a supra-umbilical transverse incision to extract the specimen was shown to decrease the rate of extraction site IH. In vertical midline incisional closure, the small bites technique with slowly- or non-absorbable suture, such as #0 or 2–0 PDS II with SH or CT-2 needle (26 mm arch length), reduces the IH rate. Urologists should consider this data to reduce the risk of IH following RALP.

INTRODUCTION AND OBJECTIVE:Patients with NMIBC CIS unresponsive to BCG have limited treatment options. N-803 (Anktiva) is an mutant IL-15-based immunostimulatory fusion protein complex (IL-15RαFc) ...

Purpose:We designed a prospective randomized, controlled pilot trial to investigate the effects of an enriched oral nutrition supplement on body composition and clinical outcomes following radical cystectomy.Materials and Methods:A total of 61 patients were randomized to an oral nutrition supplement or a multivitamin multimineral supplement twice daily during an 8-week perioperative period. Body composition was determined by analyzing abdominal computerized tomography images at the L3 vertebra. Sarcopenia was defined as a skeletal muscle index of less than 55 cm2/m2 in males and less than 39 cm2/m2 in females. The primary outcome was the difference in 30-day hospital free days. Secondary outcomes included hospital length of stay, complications, readmissions and mortality.Results:The oral nutrition supplement group lost less weight (–5 vs –6.5 kg, p = 0.04) compared to the multivitamin multimineral supplement group. The proportion of patients with sarcopenia did not change in the oral nutrition supplement ...

Objectives To investigate the relationship between gender, body mass index (BMI), and prognosis in renal cell carcinoma (RCC) patients. Materials and Methods We retrospectively reviewed 1353 patients with RCC who underwent a partial or radical nephrectomy between 1988 and 2015. The association among sex, BMI, stage, grade, overall survival (OS), and recurrence-free survival (RFS) was analyzed. Results The median age of the patients was 59.4 ± 11.9 years. Female patients had proportionally lower grade tumors than male patients (Grade I-II in 75.5% vs. 69.3% in women and men, respectively, P = 0.022). There was no relationship between Fuhrman grade and BMI when substratified by gender (p > 0.05). There was a nonsignificant trend toward more localized disease in female patients (p = 0.058). There was no relationship between T stage and BMI when stratified by gender (p > 0.05). Patients with higher BMI had significantly better OS (p = 0.0004 and P = 0.0003) and RFS (P = 0.0209 and P =0.0082) whether broken out by lower 33rd or 25th percentile. Male patients with higher BMI had significantly better OS and RFS rates. However, there was no relationship between BMI and OS or RFS for female patients (P > 0.05). Multivariate analysis of the entire cohort demonstrated that a BMI in the lower quartile independently predicts OS (hazard ratio 1.604 [95% confidence interval: 1.07-2.408], P = 0.022) but not RFS (P > 0.05). When stratified by gender, there was no relationship between BMI and either OS or RFS (P > 0.05). Conclusions Increasing BMI was associated with RCC prognosis. However, the clinical association between BMI and oncologic outcomes may be different between men and women.

Objective To examine the relationship between hospital volume and the management of bladder cancer variant histology. Variant histologies of bladder cancer are rare which limits the ability for providers to develop expertise however there is a clear hospital and/or surgeon-volume relationship for management of rare or complex surgical and/or medical diseases. Methods We queried the National Cancer Database from 2004-2016 for all cases of bladder cancer, identifying cases of variant histology. Our primary outcome was overall survival while secondary outcomes included identifying treatment patterns. Hospitals were stratified into those that managed ≤2, >2-4, >4-6, and ≥6 cases per year of variant histology. Results We identified 23,284 patients with bladder cancer of variant histology who were treated at 1301 hospitals. Few institutions had high volume experience with this disease: 18.5% (n = 241) treated >2 patients annually and 5.7% (n = 76) treated >4 cases annually. Hospital volume positively correlated with utilization of early radical cystectomy (RC) in non–muscle invasive disease and neoadjuvant chemotherapy in muscle-invasive disease. On multivariable analysis, increased hospital volume was associated with improved survival. After stratifying by sub-type, hospital volume continued to be associated with improved survival for squamous, small cell, and sarcomatoid cancers. Conclusion Management of variant histology urothelial carcinoma at high-volume centers is associated with improved overall survival. The mechanisms of this are multifactorial, and future research should focus on improvement opportunities for low-volume hospitals, centralization of care, and/or increased access to care at high-volume centers.

INTRODUCTION AND OBJECTIVE: Readmission rates after radical cystectomy are among the highest of any surgery. The Hospital Readmissions Reduction Program (HRRP) penalizes hospitals with excess readmissions for certain targeted conditions, including total hip and knee arthroplasty. We examined whether changes made by hospitals in response to the HRRP had spillover effects on radical cystectomy readmissions. METHODS: We used a 20% sample of Medicare data to identify patients undergoing cystectomy from 2010 to 2014 and measured 30-day adjusted cystectomy readmission rates. To determine the effect of the HRRP, we calculated adjusted readmission rates following total hip or knee arthroplasty and stratified hospitals into quartiles (most improved, middle quartiles, least improved) based on their improvement in reducing those targeted readmissions. Multivariable logistic regression was used to identify factors associated with spillover effects from the targeted joint surgery to cystectomy. RESULTS: We identified 2,394 patients undergoing radical cystectomy. Of these, 606 were treated at hospitals in the “most improved” quartile and 522 in the “least improved.” Patients undergoing cystectomy were similar in age, comorbidity, and SEC independent of hospital performance quartile. The readmission rate following cystectomy was 26% in the most improved quartile and 24% in the least improved. No spillover effect was identified between readmission reduction after major joint surgery and radical cystectomy (adjusted OR 0.90, p=0.42). CONCLUSIONS: Hospitals that succeeded in reducing readmissions following major joint surgery targeted by the HRRP did not have similar reductions in readmissions following radical cystectomy. This lack of spillover effect suggests that each surgical condition may require tailored interventions to prevent readmissions.

INTRODUCTION AND OBJECTIVE:Upper tract urothelial carcinoma (UTUC) is a rare genitourinary malignancy that represents only 5-10% of all urothelial carcinoma (UC). While the majority of these cancer...

The heterogenous nature of high-risk nonmuscle invasive bladder cancer encompasses a wide range of tumor biologies with varying recurrence and progression risks. Radical cystectomy provides excellent oncologic outcomes but is often underutilized. Timing for these patients is critical, however, to its effectiveness. Certain unfavorable tumor characteristics predict worse outcomes and may help select the most appropriate patients for more aggressive initial therapy. This manuscript aims to outline factors that predict worse outcomes in high-risk nonmuscle invasive bladder cancer and proposes which patients may benefit most from a timely radical cystectomy.

PURPOSE: The RAZOR (Randomized Open versus Robotic Cystectomy) trial revealed noninferior 2-year progression-free survival for robotic radical cystectomy. This update was performed with extended followup for 3 years to determine potential differences between the approaches. We also report 3-year overall survival and sought to identify factors predicting recurrence, and progression-free and overall survival. MATERIALS AND METHODS: We analyzed the per protocol population of 302 patients from the RAZOR study. Cumulative recurrence was estimated using nonbladder cancer death as the competing risk event and the Gray test was applied to assess significance in differences. Progression-free survival and overall survival were estimated by the Kaplan-Meier method and compared with the log rank test. Predictors of outcomes were determined by Cox proportional hazard analysis. RESULTS: Estimated progression-free survival at 36 months was 68.4% (95% CI 60.1–75.3) and 65.4% (95% CI 56.8–72.7) in the robotic and open groups, respectively (p=0.600). At 36 months overall survival was 73.9% (95% CI 65.5–80.5) and 68.5% (95% CI 59.8–75.7) in the robotic and open groups, respectively (p=0.334). There was no significant difference in the cumulative incidence rates of recurrence (p=0.802). Patient age greater than 70 years, poor performance status and major complications were significant predictors of 36-month progression-free survival. Stage and positive margins were significant predictors of recurrence, and progression-free and overall survival. Surgical approach was not a significant predictor of any outcome. CONCLUSIONS: This analysis showed no difference in recurrence, 3-year progression-free survival or 3-year overall survival for robotic vs open radical cystectomy. It provides important prospective data on the oncologic efficacy of robotic radical cystectomy and high level data for patient counseling.

Item does not contain fulltext PURPOSE: To provide a summary of the Third International Consultation on Bladder Cancer recommendations for the management of non-muscle invasive bladder cancer (NMIBC). METHODS: A detailed review of the literature was performed focusing on original articles for the management of NMIBC. An international committee assessed and graded the articles based on the Oxford Centre for Evidence-based Medicine system. The entire spectrum of NMIBC was covered such as prognostic factors of recurrence and progression, risk stratification, staging, management of positive urine cytology with negative white light cystoscopy, indications of bladder and prostatic urethral biopsies, management of Ta low grade (LG) and high risk tumors (Ta high grade [HG], T1, carcinoma in situ [CIS]), impact of BCG strain and host on outcomes, management of complications of intravesical therapy, role of alternative therapies, indications for early cystectomy, surveillance strategies, and new treatments. The working group provides several recommendations on the management of NMIBC. RESULTS: Recommendations were summarized with regard to staging; management of primary and recurrent LG Ta and high risk disease, positive urine cytology with negative white light cystoscopy and prostatic urethral involvement; indications for timely cystectomy; and surveillance strategies. CONCLUSION: NMIBC remains a common and challenging malignancy to manage. Accurate staging, grading, and risk stratification are critical determinants of the management and outcomes of these patients. Current tools for risk stratification are limited but informative, and should be used in clinical practice when determining diagnosis, surveillance, and treatment of NMIBC.

Summary Background Radical cystectomy is the surgical standard for invasive bladder cancer. Robot-assisted cystectomy has been proposed to provide similar oncological outcomes with lower morbidity. We aimed to compare progression-free survival in patients with bladder cancer treated with open cystectomy and robot-assisted cystectomy. Methods The RAZOR study is a randomised, open-label, non-inferiority, phase 3 trial done in 15 medical centres in the USA. Eligible participants (aged ≥18 years) had biopsy-proven clinical stage T1–T4, N0–N1, M0 bladder cancer or refractory carcinoma in situ. Individuals who had previously had open abdominal or pelvic surgery, or who had any pre-existing health conditions that would preclude safe initiation or maintenance of pneumoperitoneum were excluded. Patients were centrally assigned (1:1) via a web-based system, with block randomisation by institution, stratified by type of urinary diversion, clinical T stage, and Eastern Cooperative Oncology Group performance status, to receive robot-assisted radical cystectomy or open radical cystectomy with extracorporeal urinary diversion. Treatment allocation was only masked from pathologists. The primary endpoint was 2-year progression-free survival, with non-inferiority established if the lower bound of the one-sided 97·5% CI for the treatment difference (robotic cystectomy minus open cystectomy) was greater than −15 percentage points. The primary analysis was done in the per-protocol population. Safety was assessed in the same population. This trial is registered with ClinicalTrials.gov, number NCT01157676. Findings Between July 1, 2011, and Nov 18, 2014, 350 participants were randomly assigned to treatment. The intended treatment was robotic cystectomy in 176 patients and open cystectomy in 174 patients. 17 (10%) of 176 patients in the robotic cystectomy group did not have surgery and nine (5%) patients had a different surgery to that they were assigned. 21 (12%) of 174 patients in the open cystectomy group did not have surgery and one (1%) patient had robotic cystectomy instead of open cystectomy. Thus, 302 patients (150 in the robotic cystectomy group and 152 in the open cystectomy group) were included in the per-protocol analysis set. 2-year progression-free survival was 72·3% (95% CI 64·3 to 78·8) in the robotic cystectomy group and 71·6% (95% CI 63·6 to 78·2) in the open cystectomy group (difference 0·7%, 95% CI −9·6% to 10·9%; p non-inferiority =0·001), indicating non-inferiority of robotic cystectomy. Adverse events occurred in 101 (67%) of 150 patients in the robotic cystectomy group and 105 (69%) of 152 patients in the open cystectomy group. The most common adverse events were urinary tract infection (53 [35%] in the robotic cystectomy group vs 39 [26%] in the open cystectomy group) and postoperative ileus (33 [22%] in the robotic cystectomy group vs 31 [20%] in the open cystectomy group). Interpretation In patients with bladder cancer, robotic cystectomy was non-inferior to open cystectomy for 2-year progression-free survival. Increased adoption of robotic surgery in clinical practice should lead to future randomised trials to assess the true value of this surgical approach in patients with other cancer types. Funding National Institutes of Health National Cancer Institute.

Organ-sparing cystectomy remains an operation for a highly selected patient population that can offer similar oncologic outcomes but improved sexual function in men and women. Occult prostate cancer in men may occur even with screening but the majority is of clinical insignificance. Paramount to patient selection are oncologic concerns, but preoperative sexual function, age, performance status, and postoperative expectations must also be evaluated during patient selection. Improved diagnostic and surveillance tools may facilitate and improve patient selection in the future.

Prostate specific antigen based screening for prostate cancer has had a significant impact on the epidemiology of the disease. Its use has been associated with a significant decrease in prostate cancer mortality but has also resulted in the over diagnosis and overtreatment of indolent prostate cancer, exposing many men to the harms of treatment without benefit. The USPSTF (U.S. Preventive Services Task Force) in 2008 issued a recommendation against screening men older than 75 years, and in 2012 against routine screening for all men, indicating that in its interpretation the harms of screening outweigh the benefits. We review changes in the use of prostate specific antigen testing, performance of prostate biopsy, incidence of prostate cancer and stage of disease at presentation since 2012.An English language literature search was performed for terms that included "prostate specific antigen," "screening" and "United States Preventive Services Task Force" in various combinations. A total of 26 original studies had been published on the effects of the USPSTF recommendations on prostate specific antigen based screening or prostate cancer incidence in the United States as of December 1, 2016.Review of the literature from 2012 through the end of 2016 indicates that there has been a decrease in prostate specific antigen testing and prostate biopsy. As a result, there has been a decline in the incidence of localized prostate cancer, including low, intermediate and high risk disease. The data regarding stage at presentation have yet to mature but there are some early signs of a shift toward higher burden of disease at presentation.These findings raise concern about a reversal of the observed improvement in prostate cancer specific mortality during preceding decades. Alternative screening strategies would 1) incorporate patient preferences by allowing shared decision-making, 2) preserve the survival benefits associated with screening, 3) improve the specificity of screening to reduce unnecessary biopsies and detection of low risk disease, and 4) promote the use of active surveillance for low risk cancers if they are detected.

Using contemporary population based epidemiological data we measured the relationship between the preoperative serum albumin level and hospital length of stay after cystectomy and urinary diversion.Data were acquired from the 2014 to 2015 NSQIPPreoperative serum albumin was independently associated with hospital length of stay after cystectomy. Increasing preoperative serum albumin below a threshold of 4 gm/dl was associated with decreased length of stay (HR 1.05, 95% CI 1.01-1.09, p0.004). Other significant predictors associated with longer length of stay included patient age (HR 0.84, 95% CI 0.77-0.91, p0.001), nonCaucasian race (HR 0.81, 95% CI 0.70-0.93, p = 0.003) and American College of Surgeons classification 4 (class 4 vs 3 HR 0.78, 95% CI 0.62-0.97, p = 0.008). Minimally invasive cystectomy was associated with a shorter length of stay (HR 1.23, 95% CI 1.07-1.42, p = 0.004).This study provides evidence that nutritional optimization prior to cystectomy shortens the length of stay after surgery but there are diminishing returns above a threshold of 4 gm/dl.

One in 5 patients who undergo surgical resection for clinically localized renal cell carcinoma (RCC) develop local and/or distant recurrences which, when detected early, may be amenable to salvage local and systemic therapies. When considering that approximately half of these recurrences will occur during the first 2 years, a clear rationale exists for optimizing surveillance strategies after surgery. Although there is a notable dearth of high-quality data on this subject, clinical principles can guide clinicians as they attempt to balance the burden of surveillance strategies with potential clinical benefit. The objective of this review is to summarize the evidence regarding optimal surveillance protocols after surgery for RCC. We provide an overview of the rationale supporting surveillance after surgery, a summary of the American Urological Association and NCCN guidelines, reasons against routine long-term surveillance, surveillance costs, and ancillary issues, such as the utility of bone scan, PET/CT scan, and surveillance after thermoablation.

The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for the clinical management of patients with clear cell and non-clear cell renal carcinoma. These guidelines are developed by a multidisciplinary panel of leading experts from NCCN Member Institutions consisting of medical oncologists, hematologists and hematologic oncologists, radiation oncologists, urologists, and pathologists. The NCCN Guidelines are in continuous evolution and are updated annually or sometimes more often, if new high-quality clinical data become available in the interim.

Our aims were to determine if targeting protein for Xklp2 (TPX2) is correlated with clear cell renal cell carcinoma (ccRCC) histology and oncologic outcomes using The Cancer Genome Atlas (TCGA) and an institutional tissue microarray (TMA).Clinicopathological data obtained from the TCGA consisted of 415 samples diagnosed with ccRCC. A TMA was constructed from tumors of 207 patients who underwent radical nephrectomy for ccRCC. TPX2 expression by immunohistochemistry on TMA was assessed by a genitourinary pathologist. Clinical data were extracted and linked to TMA cores. TPX2 and Aurora-A mRNA coexpression were evaluated in the TCGA cohort. Overall survival (OS), cancer-specific survival, and recurrence-free survival (RFS) were analyzed using the Kaplan-Meier method and log-rank statistics. Univariate and multivariate analyses were conducted using Cox proportional hazard models.Median follow-up time for the TCGA cohort was 3.07 years. Aurora-A and TPX2 mRNA coexpression were significantly correlated (Pearson correlation = 0.918). High TPX2 mRNA expression was associated with advanced stage, metastasis, poor OS, and RFS. Median follow-up time for the TMA cohort was 5.3 years. Elevated TPX2 protein expression, defined as greater than 75th percentile staining intensity, was identified in 47/207 (22.7%) patients. Increased TPX2 immunostaining was associated with poor OS (P = 0.0327, 53% 5-year mortality), cancer-specific survival (P0.01, 47.8% 5-year cancer-specific mortality), RFS (P = 0.0313, 73.6%, 5-year recurrence rate), grade, T stage, and metastasis. Multivariate analysis demonstrated elevated expression served as an independent predictor of RFS (hazard ratio = 3.62 (1.13-11.55), P = 0.029).We show TPX2, a regulator of Aurora-A, is associated with high grade and stage of ccRCC, and is an independent predictor of recurrence. Future studies are warranted testing its role in ccRCC biology, and its potential as a therapeutic target.

Item does not contain fulltext CONTEXT: Currently, there is no standard of care for patients with non-muscle-invasive bladder cancer (NMIBC) who recur despite bacillus Calmette-Guerin (BCG) therapy. Although radical cystectomy is recommended, many patients decline to undergo or are ineligible to receive it. Multiple agents are being investigated for use in this patient population. OBJECTIVE: To systematically synthesize and describe the efficacy and safety of current and emerging treatments for NMIBC patients after treatment with BCG. EVIDENCE ACQUISITION: A systematic literature search of MEDLINE, Embase, and the Cochrane Controlled Register of Trials (period limited to January 2007-June 2019) was performed. Abstracts and presentations from major conference proceedings were also reviewed. Randomized controlled trials were assessed using the Cochrane risk of bias tool. Data for single-arm trials were pooled using a random-effect meta-analysis with the proportions approach. Trials were grouped based on the minimum number of prior BCG courses required before enrollment and further stratified based on the proportion of patients with carcinoma in situ (CIS). EVIDENCE SYNTHESIS: Thirty publications were identified with data from 23 trials for meta-analysis, of which 17 were single arm. Efficacy and safety outcomes varied widely across studies. Heterogeneity across trials was reduced in subgroup analyses. The pooled 12-mo response rates were 24% (95% confidence interval [CI]: 16-32%) for trials with two or more prior BCG courses and 36% (95% CI: 25-47%) for those with one or more prior BCG courses. In a subgroup analysis, inclusion of >/=50% of patients with CIS was associated with a lower response. CONCLUSIONS: The variability in efficacy and safety outcomes highlights the need for consistent endpoint reporting and patient population definitions. With promising emerging treatments currently in development, efficacious and safe therapeutic options are urgently needed for this difficult-to-treat patient population. PATIENT SUMMARY: We examined the efficacy and safety outcomes of treatments for non-muscle-invasive bladder cancer after bacillus Calmette-Guerin therapy. Outcomes varied across studies and patient populations, but emerging treatments currently in development show promising efficacy.

High rates of APOBEC-signature mutations are found in many tumors, but factors affecting this mutation pattern are not well understood. Here, we explored the contribution of two common germline variants in the APOBEC3 region. A single nucleotide polymorphism, rs1014971, was associated with bladder cancer risk, increased APOBEC3B expression, and enrichment with APOBEC-signature mutations in bladder tumors. In contrast, a 30 Kb deletion that eliminates APOBEC3B and creates APOBEC3AB chimera, was not important in bladder cancer, while being associated with breast cancer risk and enrichment with APOBEC-signature mutations in breast tumors. In vitro, APOBEC3B was predominantly induced by treatment with a DNA-damaging drug in bladder cancer cell lines and APOBEC3A was induced as part of antiviral interferon-stimulated response in breast cancer cell lines. These findings suggest a tissue-specific role of environmental oncogenic triggers, particularly in individuals with germline APOBEC3 risk variants.

INTRODUCTION AND OBJECTIVES:Patients with non-muscle-invasive bladder cancer (NMIBC) who do not respond to Bacillus Calmette-Guerin (BCG) therapy have limited treatment options: the standard of car...

INTRODUCTION AND OBJECTIVES:The advantage of health-related quality of life (HRQoL) in continent (C) urinary diversions (UD) over non-continent (NC) UD remains controversial. We compared outcomes b...