The association of salvage intravesical therapy following BCG with pathologic outcomes and survival after radical cystectomy for patients with high-grade non-muscle invasive bladder cancer: A multi-institution analysis.

INTRODUCTION: While numerous current clinical trials are testing novel salvage therapies (ST) for patients with recurrent nonmuscle invasive bladder cancer (NMIBC) after bacillus Calmette-Guérin (BCG), the natural history of this disease state has been poorly defined to date. Herein, we evaluated oncologic outcomes in patients previously treated with BCG and ST who subsequently underwent radical cystectomy (RC). METHODS: We identified 378 patients with high-grade NMIBC who received at least one complete induction course of BCG (n = 378) with (n = 62) or without (n = 316) additional ST and who then underwent RC between 2000 and 2018. Oncologic outcomes were compared using the Kaplan-Meier method and Cox proportional hazards models. Sensitivity analyses were conducted stratifying by presenting tumor stage, matched 1:3 for receipt vs. no receipt of ST. RESULTS: Patients receiving ST were more likely to initially present with CIS (26% vs. 17%) and less likely with T1 disease (34% vs. 50%, P = 0.06) compared to patients not treated with ST. Receipt of ST was not associated with increased risk of adverse pathology (≥pT2 or pN+) at RC (31% vs. 41%, P = 0.14). Likewise, 5-year cancer-specific survival did not significantly differ between groups on univariable Kaplan-Meier analysis (73% for ST and 74% for no ST, P = 0.7). Moreover, on multivariable analysis, receipt of ST was not significantly associated the risk of death from bladder cancer (HR 1.12; 95% CI 0.60-2.09, P = 0.7). Results were unchanged on sensitivity analysis. CONCLUSIONS: These data suggest that, in carefully selected patients, ST following BCG for high grade NMIBC does not compromise oncologic outcomes for patients who ultimately undergo RC.

A rare case of pancreatic adenocarcinoma metastasized to the bladder.

Pancreatic cancer is usually detected in late stages due to lack of identifiable symptoms and rapid progression. It commonly metastasizes to the liver, lung, and peritoneum, but only rarely to the bladder. We present a 41-year-old female with a history of pancreatic adenocarcinoma, asthma, gastroesophageal reflux disease, uterine fibroids, and tobacco use who presented with hematuria, polyuria, and abdominal pain. The CT showed bilateral hydroureteronephrosis with a hyperdense region in the posterior wall of the bladder. Pathology revealed metastatic pancreatic adenocarcinoma to the bladder. This is the fourth reported case of pancreatic adenocarcinoma metastasizing to the bladder since 1953.

Transurethral resection and surveillance of a well-differentiated neuroendocrine tumor in a ileal neobladder.

Our patient presented with a small, well-differentiated neuroendocrine tumor (NET) of the ileal neobladder 21-years after radical cystectomy for urothelial cell carcinoma. Given the rarity of NETs in urinary diversions, there are no established guidelines regarding management in this unique population. We propose that transurethral resection and close cystoscopic surveillance of the neobladder is a feasible, low morbidity approach to management of a well-differentiated, solitary ileal NET tumor.

National management trends in clinical stage IIA nonseminomatous germ cell tumor (NSGCT) and opportunities to avoid dual therapy.

INTRODUCTION: For marker-negative clinical stage (CS) IIA nonseminomatous germ cell tumor (NSGCT), National Comprehensive Cancer Network and American Urological Association guidelines recommend either retroperitoneal lymph node dissection (RPLND) or induction chemotherapy. The goal is cure with one form of therapy. We evaluated national practice patterns in the management of CSIIA NSGCT and utilization of secondary therapies. METHODS: The National Cancer Data Base was used to identify 400 men diagnosed with marker negative CSIIA NSGCT between 2004 and 2014 treated with RPLND or chemotherapy. Trends in the utilization of initial and adjuvant treatment (chemotherapy only, RPLND only, RPLND with adjuvant chemotherapy, and postchemotherapy RPLND) were analyzed. RESULTS: Of the 400 cases, 233 (58%) underwent induction chemotherapy with surveillance, 51 (20%) underwent RPLND with surveillance, 89 (22%) underwent RPLND followed by adjuvant chemotherapy, and 14 (4%) underwent induction chemotherapy followed by RPLND. Thirty percent of patients received dual therapy. After RPLND with pN1 staging, 43 (61%) underwent adjuvant chemotherapy. The pN0 rate after primary RPLND was 22%. Five year overall survival ranged from 95% to 100% based on initial treatment choice. CONCLUSIONS: For marker negative CS IIA nonseminoma, dual, therapy, and treatment with chemotherapy is common. With low volume retroperitoneal disease resected at RPLND, adjuvant chemotherapy was frequently administered but has debatable therapeutic value. These data highlight opportunities to decrease treatment burden in patients with CS IIA nonseminoma.

Defining risk of micrometastatic disease and tumor recurrence in patients with stage I testicular germ cell tumors.

There is controversy in the management of patients with clinical stage I non-seminomatous germ cell tumor (NSGCT). Some experts recommend surveillance for all patients regardless of risk factors while others suggest a more risk-adapted approach by using lymphovascular invasion (LVI) and the embryonal component in the primary tumor to select patients most likely to benefit from primary treatment [retroperitoneal lymph node dissection (RPLND) or chemotherapy]. With the surveillance for all strategy, only patients who relapse are treated. While this minimizes the over treatment, problem associated with the risk adapted approach, this exposes young men to the effects of full induction cisplatin-based chemotherapy when these men could have received fewer cycles of bleomycin, etoposide, and cisplatin (BEP) or a curative primary RPLND. The challenge is identifying these men who are most likely to benefit from upfront treatment more precisely. This paper explores the currently risk adapted approaches as well as promising emerging biomarkers (microRNA) that, in early data, appear to more accurately predict the presence of microscopic disease in the retroperitoneum over conventional markers.

The Impact of Lymphovascular Invasion on Risk of Upstaging and Lymph Node Metastasis at the Time of Radical Cystectomy.

BACKGROUND: Lymphovascular invasion (LVI) in muscle-invasive bladder cancer is associated with a poor prognosis when identified from radical cystectomy (RC) specimens. However, LVI is not clearly emphasized in any risk models to guide clinical decision-making. The impact of LVI on the risk of lymph node (LN) metastasis after a transurethral resection of bladder tumor (TURBT) specimen is less understood. OBJECTIVE: The goal was to describe the impact of LVI and the risk of LN metastasis at each clinical stage of urothelial carcinoma of the bladder (UC). DESIGN, SETTING, AND PARTICIPANTS: The National Cancer Database was queried for patients with bladder cancer who underwent RC with LN dissection from 2004 to 2014. Patients with non-bladder primary, non-UC histology, clinical metastatic disease, and having received chemotherapy/radiation were excluded. Pathologic LN positive rates at RC were determined. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was pathologic upstaging at RC and pathologic node positivity. Secondary outcomes included determining overall survival (OS). All hypotheses testing were two-sided and a p value of <0.05 was considered statistically significant. All statistical analyses were performed using Stata version 13.1. RESULTS AND LIMITATIONS: A total of 3007 patients with UC underwent RC with pelvic LN dissection. In patients with LVI, the risk of LN metastasis was significantly higher at each clinical stage as was the rate of pathologic upstaging. Patients with LVI on TURBT had worse OS stage for stage in pure UC (p<0.001). Limitations include that there was no central pathologic review and the number of TURBTs per patient was not known. CONCLUSIONS: Patients with UC with LVI had worse OS and are at higher risk for LN-positive disease and pathologic upstaging at surgery than patients without LVI. PATIENT SUMMARY: In this report we examined the impact of lymphovascular invasion (LVI) at transurethral resection of bladder tumor on pathologic upstaging and lymph node metastasis at radical cystectomy using the National Cancer Database. We identified LVI as being prognostic at each stage of urothelial carcinoma.

Current Clinical Trials in Non-muscle-Invasive Bladder Cancer: Heightened Need in an Era of Chronic BCG Shortage.

PURPOSE OF REVIEW: BCG is the gold standard agent used in high-risk non-muscle-invasive bladder cancer (NMIBC) that is amenable to bladder sparing management. However, recent BCG shortages appear to be a chronic problem. There are limited effective intravesical options in lieu of BCG or in patients in whom BCG is not effective. This review aims to highlight emerging bladder sparing therapies and trials for NMIBC. RECENT FINDINGS: Patients with high-risk NMIBC who do not respond to BCG are at increased risk for progression and death from bladder cancer. There are a variety of clinical trials exploring different therapeutic approaches including checkpoint inhibition, novel chemotherapy and drug delivery, viral and gene therapy, vaccines, and targeted therapy. In the era of limited supply of BCG, there is a need for both effective first-line alternatives as and options for patients who do not respond to BCG. Fortunately, there are a variety of active trials and mechanisms exploring these areas aggressively.

The Impact of Omission of Intraoperative Frozen Section Prior to Orthotopic Neobladder Reconstruction.

PURPOSE: Current guidelines recommend confirming a negative urethral margin prior to orthotopic neobladder reconstruction. We investigated our rate of urethral positive margins and recurrence in the absence of intraoperative frozen section. MATERIALS AND METHODS: We retrospectively reviewed clinical and pathological data on 357 patients who underwent radical cystectomy and orthotopic urinary diversion without intraoperative frozen section. At a median followup of 27 months the rates of positive urethral margins and urethral recurrence were tabulated. Differences in overall and recurrence-free survival in patients with a positive urethral margin were analyzed by Cox regression to generate the HR with the 95% CI. RESULTS: We identified 6 urethral recurrences (1.6%) during followup. The urethral recurrence rate was not higher in patients with a positive urethral margin (p=0.22). In the 15 patients with positive urethral margins overall survival was unchanged (HR 0.98, 95% CI 0.24-4.04). When accounting for lymph node staging, recurrence-free survival was not significantly worse in patients with positive urethral margins (HR 2.33, 95% CI 0.95-5.73). CONCLUSIONS: Omitting intraoperative frozen section prior to orthotopic neobladder reconstruction appears safe with a rate of urethral recurrence similar to that in historical series. It may allow for increased performance of orthotopic urinary diversions.

The impact of surgical duration on complications after transurethral resection of the prostate: an analysis of NSQIP data.

BACKGROUND: Transurethral resection of the prostate is the most commonly performed procedure for the management of benign prostatic obstruction. However, little is known about the effect surgical duration has on complications. We assess the relationship between operative time and TURP complications using a modern national surgical registry. METHODS: We queried the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) from 2006 to 2016 for patients undergoing TURP. Patients were separated into five groups based on operative time: 0-30 min, 30.1-60 min, 60.1-90 min, 90.1-120 min, and greater than 120 min. Standard statistical analysis, including multivariate regression, was performed to determine factors associated with complications. RESULTS: 31,813 patients who underwent TURP were included. The overall complication rate was 9.0% and increased significantly with longer surgical duration (p < 0.001). Longer operative time was associated with a greater risk of postoperative sepsis or shock, transfusion, reoperation, and deep vein thrombus or pulmonary embolism. Longer surgical duration was associated with increased odds of any complication and, specifically, blood transfusion after controlling for age, race, comorbidities, American Society of Anesthesia (ASA) class, type of anesthesia administered, and trainee involvement. The adjusted risk of each of the above complications remained significantly increased for surgeries lasting longer than 120 min. CONCLUSIONS: As surgical duration increases, there is a significant increase in the rate of complications after TURP. These data demonstrate that this procedure is safest when performed in under 90 min.

Emerging therapies in the management of high-risk non-muscle invasive bladder cancer (HRNMIBC).

PURPOSE: BCG is the gold standard in management of high-risk non-muscle invasive bladder cancer (HRNMIBC). However, in patients who fail BCG, there are few effective intrasvesical options. This review aims to explore standard and emerging therapies in HRNMIBC. METHODS: A non-systematic literature review was performed using Medline and PubMed. Literature focused on HRNMIBC and BCG failure studies, with particular attention to Phase II and III clinical trials. RESULTS: The only FDA approved therapy for BCG failure patients in Valrubicin. Patients with HRNMIBC and BCG failure patients are at increased risk for progression and death from bladder cancer. There are a variety of clinical trials exploring different therapeutic approaches such as immunotherapy, vaccines, radiotherapy, and gene therapy. These trials are showing some promise in the early reporting phase. CONCLUSION: Despite limited intravesical treatment options in BCG failure patients, there are several promising therapies currently being developed and several with promising early results.

The role of inguinal lymph node dissection in men with urethral squamous cell carcinoma.

INTRODUCTION: Urethral squamous cell cancer is a rare disease with limited clinical recommendations regarding management of the inguinal lymph nodes. Despite the similarities to penile cancer in terms of squamous cell carcinoma (SCC) histology and lymphatic drainage, there is not enough evidence to recommend for or against a prophylactic inguinal lymph node dissection (ILND) in patients with clinically negative groins and a primary tumor stage of T1b or higher. The objective of the study was to identify the rate of prophylactic inguinal lymph node dissection, node positive rate, and overall survival in patients with clinical T1 to T4 stage. The patients were separated into clinical N stage and the rates of node positivity were compared. We hypothesize that the node positivity rate would be similar to that observed in penile cancer of similar clinical T and N stage and provide evidence for prophylactic inguinal lymph node dissection in urethral squamous cancer. We also sought to determine the value of ILND in clinically node positive (cN+) and clinically node negative (cN-) patients. METHODS: The National Cancer Database was queried for all cases of primary urethral cancer in men from 2004 to 2014. Patients with other cancer diagnoses, metastasis, nonsquamous histology, female patients, and patients with a history of radiation therapy were excluded. Male patients with urethral squamous cell cancer of the anterior urethra with T1 or higher T stage were included in this study. All-cause mortality was compared using multivariable Cox regression controlling for covariates. RESULTS: The study included 725 men with urethral SCC with T1 or higher clinical T stage. The median age was 63 years (33-83 interquartile range). Of the 725 men, 536 men did not receive an ILND and 189 (26%) underwent ILND. Patients who received LND had significantly higher clinical T and clinical N stage. There was no difference in age, sex, or histology between those with ILND versus no ILND. In patients with T1 to T4 and clinical N0, the ILND rate was 21.8% (89/396). The lymph node positive rate in patients with N0 and T1 to T4 primary tumor was 9%. In patients with clinically node positive disease (N1/N2), the overall ILND rate was 76%. The lymph node positive rate for patients with clinical nodal disease was 84%. On multivariable analysis cox regression, lymph node positivity was associated with worse overall survival when controlling for T stage, clinical N stage, and age (HR 1.56, 95% 1.3-1.9, P = 0.000). On multivariable analysis after controlling for T stage, sex, and age, having an ILND was associated with improved OS in patients with clinical N1 or N2 disease (HR 0.46, 95% 0.28-0.78 P = 0.002). CONCLUSION: The node positivity rate in patients with T1 to T4 and N0 is 9%, much lower than reported in penile cancer with a high-risk primary tumor but clinically negative groins. This argues against routine prophylactic inguinal ILND in patients with urethral SCC who are clinically N0, perhaps suggesting different biological behavior of urethral SCC compared to penile SCC. Performing a lymph node dissection in patients with clinically N1 or N2 disease is associated with improved OS.

Multidisciplinary Management of Muscle-Invasive Bladder Cancer: Current Challenges and Future Directions.

The treatment of muscle-invasive bladder cancer (MIBC) is complex and requires a multidisciplinary collaboration among surgery, radiation, and medical oncology. Although neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) and lymph node dissection has been considered the standard treatment for MIBC, many patients are unfit for surgery or cisplatin-ineligible, and considerations for bladder-preservation strategies not only are increasingly recognized as optimal treatment alternatives, but also should feature in the range of management options presented to patients at the time of diagnosis. Apart from chemotherapy, immunotherapy has also been used with success in locally advanced and metastatic bladder cancer and is moving into the MIBC space. Prospective studies addressing trends in management that span systemic, surgical, and radiation options for patients are discussed in this article.

Indications, evolving technique, and early outcomes with robotic retroperitoneal lymph node dissection.

PURPOSE OF REVIEW: Examine and discuss indications, technique, and outcomes for robotic retroperitoneal lymph node dissection (RPLND) for testicular cancer. RECENT FINDINGS: Open RPLND has been the longstanding standard of care for both primary and post chemotherapy RPLND. Recently, robotic RPLND has been an attractive option with the intent of reducing the morbidity associated with open surgery while providing identical oncologic efficacy. Naysayers of robotic RPLND suggest it is often inappropriately used as a staging procedure and consequently can compromise oncologic efficacy. SUMMARY: Robotic RPLND is being evaluated as a therapeutic equivalent to open RPLND. On the basis of limited published data with modest follow-up from experienced centers, robotic RPLND appears to provide effective staging and therapeutic data mirroring that of open surgery.

Testicular Cancer: Epidemiology, Diagnosis, and Management.

There were an estimated 8720 new cases of testicular cancer (TC) in the United States in 2016. The cause of the disease is complex, with several environmental and genetic risk factors. Although rare, the incidence has been steadily increasing. Fortunately, substantial advances in treatment have occurred over the last few decades, making TC one of the most curable malignancies. However, because TC typically occurs in younger men, considerations of the treatment impact on fertility, quality of life, and long-term toxicity are paramount; an individualized approach must be taken with patients based on their clinical and pathologic findings.

Prophylactic antibiotics following radical cystectomy reduces urinary tract infections and readmission for sepsis from a urinary source.

INTRODUCTION: Urinary tract infections (UTI) and sepsis contribute significantly to the morbidity associated with cystectomy and urinary diversion in the first 30 days. We hypothesized that continuous antibiotic prophylaxis decreased UTIs in the first 30 days following radical cystectomy. METHODS: Patients with urothelial carcinoma of the bladder who underwent a radical cystectomy with urinary diversion for bladder cancer at Oregon Health and Science University from January 2014 to May 2015 were included in the study. The ureteral stents were kept for 3 weeks in both groups. In October 2014, we enacted a Department Quality Initiative to reduce UTIs. Following the initiative, all radical cystectomy patients were discharged home on antibiotic prophylaxis following a postoperative urine culture obtained during hospitalization. To evaluate the effectiveness of the initiative, the last 42 patients before the initiative were compared to the first 42 patients after the initiative with regard to the rate of UTI in the first 30 days following surgery. We used a combination of comprehensive chart review and the American College of Surgeons' National Surgical Quality Improvement Program (NSQIP) to determine UTI and readmission for urosepsis in the first 30 days following surgery. This ensured accurate capture of all patients developing a UTI. RESULTS: A total of 12% in the prophylactic antibiotic group had a documented UTI, whereas 36% in the no antibiotic group had a urinary tract infection (P<0.004). A total of 1 (2%) patient in the antibiotic group was readmitted for urosepsis whereas 7 (17%) patients in the no antibiotic group were admitted for urosepsis (P = 0.02). There was no association noted between urine culture at discharge and the development of UTI in the 30-day postdischarge period (P = 0.75). The median time to UTI was 19 days and the most common organism was Enterococcus (32%). Thirty-percent of patients not receiving prophylaxis developed a UTI 1 day after ureteral stent removal. No patients had a UTI following stent removal in the prophylaxis group. No adverse antibiotic related events were noted. CONCLUSION: Prophylactic antibiotics in the 30 days following radical cystectomy is associated with a significant decrease in urinary tract infections and readmission from urosepsis after surgery.