A Randomized Feasibility Trial Comparing Surveillance Regimens for Patients with Low and Low-Intermediate Risk Non-Muscle Invasive Bladder Cancer.

BACKGROUND: Surveillance regimens for non-muscle invasive bladder cancer (NMIBC) are disparate and controlled trials could inform guidelines. The feasibility of randomizing patients to variable frequency surveillance is unknown. OBJECTIVES: To determine patient willingness to randomization to high frequency (HF) versus low frequency (LF) surveillance regimen for NMIBC and compare patient comfort and healthcare costs across regimens. METHODS: A non-blinded, two-arm, randomized-controlled study of patients with low or low-intermediate risk NMIBC was conducted at two institutions where patients were offered randomization to HF vs. LF surveillance following initial tumor resection. The HF group underwent cystoscopy every three months for 2 years, then every 6 months for 2 years, then annually. The LF group underwent cystoscopy at 9 months following the 3-month cystoscopy, then annually. Assuming 75% of patients approached would agree to enrollment, a sample size of n = 35 patients per arm provided a one-sided 95% exact Clopper-Pearson confidence lower-limit of 60%. RESULTS: Of 70 patients approached, 45 (64.3%) agreed to participate and 25 (35.7%) declined enrollment due to preference for HF. Twelve biopsies were performed, including 4 (19%) of 21 patients in the HF group and 8 (33.3%) of 24 patients in the LF group. Disease recurrence (low grade Ta) was observed in 3 (14.3%) and 5 (20.8%) patients in the HF and LF groups, respectively. No patients experienced high grade recurrence or progression. Both groups had similar patient-reported procedure-related discomfort and quality of life measures over time. Patient out-of-pocket cost and healthcare systems costs were $383.80 more per patient annually in the HF group. CONCLUSIONS: Randomization to variable frequency surveillance is challenging as over a third of patients declined participation. However, these data provide important preliminary insights into the potential effects of surveillance frequency on oncologic and economic outcomes in patients with low and low-intermediate risk bladder cancer.

Long term oncologic outcome in patients with bladder cancer after radical cystectomy: Impact of carcinoma in situ in the era of neoadjuvant chemotherapy.

PURPOSE: To assess the impact of carcinoma in situ (CIS) on oncologic outcomes in patients who underwent radical cystectomy, with a focus on those who received neoadjuvant chemotherapy (NAC) including patients with down-staging to ≤ pT1cancer after chemotherapy. MATERIALS AND METHODS: All patients who underwent radical cystectomy for urothelial cancer with curative intent from 1985 to 2011 were included. The impact of CIS on recurrence free and overall survival (OS) was assessed in the whole cohort and a subgroup who received NAC as well as those with response to chemotherapy and down-staging to ≤ pT1. RESULTS: A total of 2518 patients with a median follow-up period of 9 years were included. Among all, 1397 (55.5%) had concomitant CIS on final pathology. CIS was associated with high risk pathologic features including high-grade disease, multifocality, and nodal involvement as well as worse recurrence free survival (RFS) with no impact on OS. We did not find a significant association between CIS and oncologic outcomes in a subset of patients who received NAC including those with down-staging to ≤ pT1 disease. In multivariate analysis, CIS had no association with either recurrence free or OS. CONCLUSIONS: Concomitant CIS in radical cystectomy specimens is associated with decreased RFS; however, in multivariate analysis, it was not an independent predicting factor of oncologic outcomes. Moreover, the impact of CIS on oncologic outcomes in a subset of patients who received NAC was insignificant.

Optimizing Diagnosis of Urothelial Bladder Cancer with Blue Light Cystoscopy via Recognition of False-Positive Lesions.

Introduction: Blue light cystoscopy (BLC) using hexaminolevulinate (Cysview®) improves the detection of nonmuscle invasive bladder cancer (NMIBC).1-3 BLC results in lower recurrence rate and a better recurrence-free survival, as well as a progression benefit.4 However, false-positive (FP) fluorescence can occur for various reasons and can vary among different series. Studies have shown that FP rates are not significantly different from white light (WL) cystoscopy. We evaluated different scenarios producing FP in BLC. Methods: Under institutional review board approval, we prospectively enrolled consecutive patients undergoing transurethral resection of bladder lesions into a BLC registry between April 2014 and December 2016. Several cases are highlighted in the video demonstrating cystoscopic view under WL and blue light in specific circumstances increasing the chance of detecting an FP lesion. Results: BLC with Cysview is demonstrated in several challenging cases for the detection of NMIBC. Possible FP scenarios include tangential views of the bladder neck or side walls (1) trigone, trabeculations, or diverticula; (2) in setting of inflammation like cystitis; (3) postintravesical therapy, that is, <6 weeks interval from prior bacillus Calmette-Guérin (BCG); (4) prior resection within 6 weeks; (5) bright tiny spots; and (6) site of ureterectomy/bladder cuff resection, early fading lesions (after irrigation). Unnecessary biopsy of these lesions can be avoided through simple techniques such as changing the angle of the cystoscopic view, several rounds of irrigation, and avoiding BLC too early after BCG instillation or prior resection. Conclusions: Use of BLC with Cysview can help with the detection of NMIBC as well as carcinoma in situ in patients undergoing transurethral resection of bladder tumor for bladder cancer. The reported FP rates of BLC will decrease with experience and recognition of the mentioned scenarios. Prior presentation: None. No competing financial interests exist. Runtime of video: 7 mins 16 secs.

Satisfaction With Testicular Prosthesis After Radical Orchiectomy.

OBJECTIVES: To determine patient satisfaction with testicular prostheses (TP) for testicular cancer. Reconstruction represents an important part of surgical oncology, yet placement of TP following orchiectomy is infrequently performed. Improved data on patient satisfaction with TP would help in counseling patients with testicular cancer. MATERIALS AND METHODS: Forty patients who underwent orchiectomy and TP placement for testicular cancer participated in a survey that was blinded to the providers in an outpatient clinic (2012-2014) to evaluate TP satisfaction. Categorical variables associated with satisfaction were compared using the Fisher's exact test. RESULTS: Median age at TP placement was 31 years (17-59). Most patients had their prosthesis in place for >1 year (81%) at the time of the survey. No patient reported complications from the TP and none underwent explantation. All patients felt that being offered an implant before orchiectomy was important. Overall, 33 patients (82.5%) rated the TP as good or excellent, and 35 men (87.5%) would have the prosthesis implanted again. Thirty-seven patients (92.5%) found the TP to be comfortable or very comfortable. However, 44% considered the TP too firm and 20% felt the position was not appropriate. Appropriate size, appropriate position, and TP comfort were significantly associated with good or excellent overall TP satisfaction (P < .05). CONCLUSION: Overall satisfaction with testicular implants after orchiectomy for testicular cancer is high. Patients should be offered a testicular prosthesis, especially at the time of orchiectomy. Efforts should be made to optimize implant firmness, and care should be given to proper size selection and positioning.

Circulating Tumor Cells in Genitourinary Malignancies: An Evolving Path to Precision Medicine.

Precision medicine with molecularly directed therapeutics is rapidly expanding in all subspecialties of oncology. Molecular analysis and treatment monitoring require tumor tissue, but resections or biopsies are not always feasible due to tumor location, patient safety, and cost. Circulating tumor cells (CTCs) offer a safe, low-cost, and repeatable tissue source as an alternative to invasive biopsies. "Liquid biopsies" can be collected from a peripheral blood draw and analyzed to isolate, enumerate, and molecularly characterize CTCs. While there is deserved excitement surrounding new CTC technologies, studies are ongoing to determine whether these cells can provide reliable and accurate information about molecular drivers of cancer progression and inform treatment decisions. This review focuses on the current status of CTCs in genitourinary (GU) cancer. We will review currently used methodologies to isolate and detect CTCs, their use as predictive biomarkers, and highlight emerging research and applications of CTC analysis in GU malignancies.

Lymph node dissection in bladder cancer: Where do we stand?

Radical cystectomy with lymphadenectomy remains the standard-of-care treatment for muscle-invasive bladder cancer. Lymphadenectomy is a central component of the operation because it continues to play both diagnostic and therapeutic roles. Routinely available preoperative imaging has limited diagnostic accuracy as it relies mostly on size to identify nodal metastasis increasing the value of lymphadenectomy. While the merits of lymphadenectomy are not in question, the extent of lymphadenectomy required to provide maximum benefit while limiting morbidity remains controversial. Furthermore, although robotic-assisted surgery has gained popularity in many centers, concern remains regarding the learning curve required and skill needed to replicate the quality of an open lymphadenectomy. Research efforts have been focused on these unresolved issues, and several trials are currently ongoing to help address these knowledge deficit areas. In this update, we will focus on the current state of lymphadenectomy for bladder cancer and highlight recent advances.

Preoperative Imaging for Clinical Staging Prior to Radical Cystectomy.

The importance of patient selection for quality outcomes following radical cystectomy is critical. Clinical staging is one of the key elements necessary for patient selection, and staging relies on accurate preoperative imaging. Many imaging modalities are available and have been utilized for preoperative staging with published operating characteristics. In this update, we review recently published literature for advances in preoperative imaging prior to radical cystectomy.

Utilization of retroperitoneal lymph node dissection for testicular cancer in the United States: Results from the National Cancer Database (1998-2011).

INTRODUCTION: Retroperitoneal lymph node dissection (RPLND) for the treatment of testicular cancer is a relatively rare and complex operation that may contribute to differences in utilization. We sought to characterize the use of RPLND between different categories of cancer center facilities in the United States. MATERIALS AND METHODS: The National Cancer Database was queried for patients with germ cell tumors treated at different types of cancer centers between 1998 and 2011. The proportion of patients who underwent RPLND was stratified by stage and histology and then compared between treatment facilities. RPLND utilization was then compared between facility types as a function of time. RESULTS: A total of 59,652 patients met inclusion criteria and 5,475 (9.2%) underwent RPLND. The proportion of patients treated with RPLND for non-seminomatous germ cell tumor (NSGCT) was significantly different between cancer center types for all stages (P<0.001) and used most often in academic comprehensive cancer centers. There was no difference in the proportion of RPLND utilization for stage II and III seminoma stratified by treatment facility. There was a significantly decreased trend in the utilization of RPLND for stage I (P = 0.032) NSGCT whereas utilization was increased for stage III NSGCT (P≤0.001) over the study period. CONCLUSIONS: The proportion of patients undergoing RPLND for NSGCT varies significantly by the type of cancer center and is used most often in academic cancer centers. Utilization of RPLND decreased for stage I NSGCT and increased for stage III NSGCTs during the study period.

Orthotopic urinary diversion in the elderly.

INTRODUCTION: Age is an established risk factor for developing bladder cancer and is associated with increased stage and worse treatment outcomes. Furthermore, elderly patients who require radical cystectomy are more likely to undergo an incontinent urinary diversion compared with younger patients. METHODS: To evaluate whether evidence exists to support performing an orthotopic neobladder in the elderly, we reviewed the literature to identify studies reporting outcomes, complications, patient-selection criteria, and quality-of-life data on elderly patients who underwent orthotopic neobladder following radical cystectomy. RESULTS: While age was shown to be a risk factor for complications following orthotopic neobladder, similar complication rates were reported between those who received either an orthotopic neobladder or ileal conduit when compared within age groups. Additionally, in properly selected elderly patients, similar outcomes and quality of life can be expected when compared with younger patients. CONCLUSIONS: It is appropriate to offer an orthotopic neobladder to well-selected elderly patients following radical cystectomy.

Sequential intravesical mitomycin plus Bacillus Calmette-Guérin for non-muscle-invasive urothelial bladder carcinoma: translational and phase I clinical trial.

PURPOSE: To determine the safety and toxicities of sequential MMC (mitomycin C) + BCG (bacillus Calmette-Guérin) in patients with non-muscle-invasive bladder cancer (NMIBC) and explore evidence for potentiation of BCG activity by MMC. EXPERIMENTAL DESIGN: A 3 + 3 phase I dose-escalation trial of six weekly treatments was conducted in patients with NMIBC. MMC (10, 20, or 40 mg) was instilled intravesically for 30 minutes, followed by a 10-minute washout with gentle saline irrigation and then instillation of BCG (half or full strength) for 2 hours. Urine cytokines were monitored and compared with levels in a control cohort receiving BCG only. Murine experiments were carried out as described previously. RESULTS: Twelve patients completed therapy, including 3 patients receiving full doses. The regimen was well tolerated with no treatment-related dose-limiting toxicities. Urinary frequency and urgency, and fatigue were common. Eleven (91.7%) patients were free of disease at a mean (range) follow-up of 21.4 (8.4-27.0) months. Median posttreatment urine concentrations of IL2, IL8, IL10, and TNFα increased over the 6-week treatment period. A greater increase in posttreatment urinary IL8 during the 6-week period was observed in patients receiving MMC + BCG compared with patients receiving BCG monotherapy. In mice, intravesical MMC + BCG skewed tumor-associated macrophages (TAM) toward a beneficial M1 phenotype. CONCLUSIONS: Instillation of sequential MMC + BCG is safe tolerable up to 40-mg MMC plus full-strength BCG. This approach could provide improved antitumor activity over BCG monotherapy by augmenting beneficial M1 TAMs.

Radical Cystectomy after BCG Immunotherapy for High-Risk Nonmuscle-Invasive Bladder Cancer in Patients with Previous Prostate Radiotherapy.

Purpose. Intravesical Bacillus Calmette-Guerin (BCG) immunotherapy is indicated for high-grade nonmuscle-invasive bladder cancer (NMIBC). The efficacy of BCG in patients with a history of previous pelvic radiotherapy (RT) may be diminished. We evaluated the outcomes of radical cystectomy for BCG-treated recurrent bladder cancer in patients with a history of RT for prostate cancer (PC). Methods. A retrospective chart review was performed to identify patients with primary NMIBC. We compared the outcomes of three groups of patients who underwent radical cystectomy for BCG-refractory NMIBC: those with a history of RT for PC, those who previously underwent radical prostatectomy (RP), and a cohort without PC or RT exposure. Results. From 1996 to 2008, 53 patients underwent radical cystectomy for recurrent NMIBC despite BCG. Those with previous pelvic RT were more likely to have a higher pathologic stage and decreased recurrence-free survival compared to the groups without prior RT exposure. Conclusion. Response rates for intravesical BCG therapy may be impaired in those with prior prostate radiotherapy. Patients with a history of RT who undergo radical cystectomy after failed BCG are more likely to be pathologically upstaged and have decreased recurrence-free survival. Earlier consideration of radical cystectomy may be warranted for those with NMIBC who previously received RT for PC.

Illinois statewide dual kidney transplantation experience--are we appropriately selecting kidneys?

PURPOSE: Dual kidney transplantation is a technique that some transplant centers have adopted to increase organ use. We investigated whether kidneys that were recovered and discarded were similar to those kidneys used for dual kidney transplantation. MATERIALS AND METHODS: We reviewed all kidneys recovered, biopsied and placed on machine perfusion in the state of Illinois from January 2002 to October 2009. We selected those kidneys used in dual kidney transplant, and compared their characteristics to those of kidneys that were recovered and biopsied but ultimately discarded. The immediate and 1-year outcomes of the dual kidney transplant recipients were analyzed. RESULTS: During the study period 60 dual transplants were performed while 94 kidney pairs were discarded. Overall donors from the used group had a lower mean creatinine clearance, older mean patient age, lower percentage of glomerulosclerosis, higher final flow rate and lower resistance. However, the comparison between those kidneys used successfully with 1-year graft survival and those discarded demonstrated only 3 less favorable parameters among the discarded group, namely a higher percentage of glomerulosclerosis (18.5% vs 13.9%, p=0.024), a higher degree of interstitial fibrosis and a higher final resistance (0.39 vs 0.31, p<0.001). CONCLUSIONS: The considerable overlap in demographics, histology and perfusion parameters between used and discarded kidneys suggests that many kidneys that were recovered and discarded could have been used in dual kidney transplantation with acceptable outcomes. This highlights the need for further study of how kidneys are selected and used.

Prognostic variables and nomograms for renal cell carcinoma.

The term renal cell carcinoma (RCC) is used to describe a heterogeneous group of tumors that vary histologically, genetically and molecularly. Extensive research has been conducted to identify characteristics that predict outcomes among patients with RCC. In addition to histological subtype these include tumor size, patient age, mode of presentation and various hematological indices, among others. Several groups have incorporated these clinical and pathological features into nomograms which help the clinician better define individual patient prognosis and direct the optimum therapeutic approach. In the present article we review these prognostic variables and nomograms for RCC.

Size does matter: donor renal volume predicts recipient function following live donor renal transplantation.

PURPOSE: With the now routine use of computerized tomography angiography with 3-dimensional reconstruction in the donor evaluation, renal volume can be easily determined using volume calculating software. We evaluated whether donor renal volume could predict recipient renal function. MATERIALS AND METHODS: Clinical data of all donor and recipient pairs undergoing live donor kidney transplantation at our institution between January 2006 and October 2009 were reviewed. The volume of the kidney selected for transplant was determined using volume calculating software, and correlated to transplant recipient nadir and 1-year serum creatinine. Multivariate regression analysis was performed to adjust for demographic and clinical variables. RESULTS: During the study period 114 patients underwent live donor renal transplantation. Recipient nadir and 1-year serum creatinine levels were significantly correlated with the volume of donated kidney even after adjusting for age, body mass index, body surface area and donor creatinine clearance. Kidney volume also retained significance after excluding recipients from analysis who experienced acute rejection episodes. CONCLUSIONS: Larger kidney volumes calculated using 3-dimensional computerized tomography with volume calculating software are correlated with lower recipient nadir and 1-year serum creatinine levels.

Transplant tourism--a dangerous journey?

INTRODUCTION: While the ethical aspects of transplant tourism have received much attention recently, less has been written about the medical safety of this practice. We retrospectively evaluated the outcomes of patients who purchased organs internationally and presented to our center for follow-up care. METHODS: Baseline demographic characteristics were recorded. Post-operative outcomes including patient survival, graft survival, five-yr graft function, and complications were assessed. RESULTS: Eight patients who purchased international organs for transplant were identified. The country of transplant was China (n = 3), Pakistan (n = 3), India (n = 1), and the Philippines (n = 1). All patients were born in either Asia or the Middle East and traveled to the region of their ethnicity for transplantation. The mean time to presentation was 49 d post-operatively. The overall one- and two-yr patient survival rates were 87% and 75%, respectively. One patient died of miliary tuberculosis and another of Acinetobacter baumanii sepsis. There was one case of newly acquired hepatitis B infection. At last follow-up, all six surviving patients had functioning grafts with a mean creatinine level of 1.26 mg/dL at five yr. CONCLUSION: Although intermediate-term graft function is acceptable, the early morbidity and mortality among transplant tourists is high. These results suggest that the associated risks may not justify the trip.

Risk factors for recurrence following radical cystectomy for pathologic node negative bladder cancer.

BACKGROUND AND OBJECTIVES: To evaluate for risk factors associated with bladder cancer recurrence in patients with pathologically negative lymph nodes. METHODS: A retrospective review of 405 patients undergoing radical cystectomy for bladder cancer between 1996 and 2008 was performed. Patients with node-positive disease and <6 months of follow up were excluded. Clinical and pathological characteristics including stage, lymphadenectomy type (standard vs. extended), number of nodes removed, margin status, lymphovascular invasion (LVI), perineural invasion (PNI), presence of carcinoma in situ, and site of recurrence were evaluated. Kaplan-Meier analysis was used to calculate 5-year recurrence-free survival stratified by lymph node yield. RESULTS: Two hundred sixty patients met the inclusion criteria. Overall, 80 (30.8%) patients recurred within 5 years. Univariate analysis identified LVI, PNI, extravesical disease, positive margins, and lymph node yield <14 to be significant predictors of disease recurrence. On multivariate analysis LVI, PNI, and node yield <14 retained significance (P = 0.01, 0.037, 0.038, respectively). There was no difference in 5-year recurrence free survival when stratified by node yield using the Kaplan-Meier method (P = 0.138). CONCLUSIONS: We identified LVI, PNI, and lymph node yield <14 as three independent risk factors for bladder cancer recurrence in patients with node-negative bladder cancer.

Long-term outcomes of salvage radiotherapy for PSA-recurrent prostate cancer: validation of the Stephenson nomogram.

PURPOSE: Approximately one-third of patients who undergo radical prostatectomy for clinically localized prostate cancer will ultimately develop a biochemical recurrence. We report our long-term outcomes of salvage radiotherapy (SRT), and in so doing, validate a recently published prognostic nomogram. METHODS: A retrospective chart review was performed of all patients treated with SRT following radical prostatectomy for biochemical PSA recurrence at our institution between 1992 and 2003. We calculated the probability of 6-year biochemical progression-free survival following SRT and performed a goodness-of-fit test to ascertain whether the previously published nomogram correctly predicted our observations. RESULTS: During the study period, 96 patients were treated with SRT. At a median follow-up of 71 months, 44 (46%) had a durable PSA-free response. There was no significant difference between the observed progression-free survival and that predicted by the Stephenson nomogram (P = 0.7). Multivariate logistic regression analysis determined that PSA value at the initiation of SRT (P = 0.02) and pathologic Gleason Score (P = 0.04) were significantly associated with the probability of recurrence. CONCLUSIONS: During the study period, nearly half of patients treated with SRT for PSA recurrence following radical prostatectomy had a durable treatment response. We found the predictive nomogram developed by Stephenson, et al. to be valid when tested on our independent cohort of patients.

Cost analysis and clinical applicability of the Resonance metallic ureteral stent.

The Resonance metallic stent is a new wire-based ureteral stent that was initially developed for patients with malignant ureteral obstruction. Potential advantages over traditional stents include resistance to encrustation and to external compression, allowing for increased dwell times and the maintenance of upper tract drainage when traditional polymer stents have failed. We present a comparative cost analysis of Resonance metallic and standard polymer stent use in patients with benign urinary obstruction and review the literature regarding the Resonance stent.

A novel technique for the removal of minimally encrusted ureteral stents.

The removal of encrusted ureteral stents typically necessitates secondary treatment modalities, such as ureteroscopy, extracorporeal shock wave lithotripsy, or antegrade nephroscopy. We present a novel technique for the removal of minimally encrusted stents using a suture and a ureteral access sheath.

Endoscopic management of upper tract urothelial carcinoma.

While radical nephroureterectomy remains the gold standard of treatment for patients with upper tract urothelial tumors, technological advances have made endoscopic management possible. The careful selection of patients for such an approach is dependent upon an accurate diagnosis and an understanding of the natural history of the disease. High grade tumors behave aggressively and warrant radical extirpation unless an absolute contraindication exists. Motivated patients with low grade tumors and relative contraindications to nephroureterectomy can be managed with percutaneous or retrograde ureteroscopic techniques. High recurrence rates in the ipsilateral upper tract and bladder mandate close surveillance of patients treated conservatively. We review the important diagnostic, staging, technical, and surveillance issues in the endoscopic treatment of upper tract urothelial carcinoma.