Multiparametric Magnetic Resonance Imaging-Ultrasound Fusion Biopsy Improves but Does Not Replace Standard Template Biopsy for the Detection of Prostate Cancer.

PURPOSE: There exists a growing debate as to whether multiparametric magnetic resonance imaging with fusion transrectal ultrasound guided prostate biopsy alone without a standard template biopsy is sufficient to evaluate patients with suspected prostate cancer. Our objective was to describe our experience with fusion targeted prostate biopsy and assess whether it could obviate the need for concomitant standard 12-core template prostate biopsy. MATERIALS AND METHODS: We retrospectively reviewed our prospectively collected database of patients who underwent fusion transrectal ultrasound guided prostate biopsy. All images and lesions were graded according to the Prostate Imaging Reporting and Data System, version 2. All patients underwent targeted biopsy followed by standard 12-core double sextant biopsy within the same session. Clinically significant prostate cancer was defined as Grade Group 2 or greater prostate cancer. RESULTS: A total of 506 patients were included in analysis. Indications were elevated prostate specific antigen with a previous negative prostate biopsy in 46% of cases, prostate cancer on active surveillance in 35%, elevated prostate specific antigen without a prior prostate biopsy in 15% and an isolated abnormal digital rectal examination in 3%. For standard vs fusion prostate biopsy the overall cancer detection rate was 57.7% vs 54.0% (p=0.12) and the clinically significant prostate cancer detection rate was 24.7% vs 30.8% (p=0.001). Of the 185 patients diagnosed with clinically significant prostate cancer 29 (16%) would have been missed if only targeted fusion prostate biopsy had been performed. CONCLUSIONS: Fusion targeted prostate biopsy is associated with a higher detection rate of clinically significant prostate cancer compared to standard double sextant biopsy. However, standard double sextant biopsy should still be performed as part of the routine fusion targeted prostate biopsy procedure to avoid missing a significant proportion of clinically significant prostate cancer.

Efficacy of High-Intensity Local Treatment for Metastatic Urothelial Carcinoma of the Bladder: A Propensity Score-Weighted Analysis From the National Cancer Data Base.

Purpose Evidence from studies of other malignancies has indicated that aggressive local treatment (LT), even in the presence of metastatic disease, is beneficial. Against a backdrop of stagnant mortality rates for metastatic urothelial carcinoma of the bladder (mUCB) at presentation, we hypothesized that high-intensity LT of primary tumor burden, defined as the receipt of radical cystectomy or ≥ 50 Gy of radiation therapy delivered to the bladder, affects overall survival (OS). Patients and Methods We identified 3,753 patients within the National Cancer Data Base who received multiagent systemic chemotherapy combined with high-intensity versus conservative LT for primary mUCB. Patients who received no LT, transurethral resection of the bladder tumor alone, or < 50 Gy of radiation therapy delivered to the bladder were included in the conservative LT group. Inverse probability of treatment weighting (IPTW) -adjusted Kaplan-Meier curves and Cox regression analyses were used to compare OS of patients who received high-intensity versus conservative LT. Results Overall, 297 (7.91%) and 3,456 (92.09%) patients with mUCB received high-intensity and conservative LT, respectively. IPTW-adjusted Kaplan-Meier curves showed that median OS was significantly longer in the high-intensity LT group than in the conservative LT group (14.92 [interquartile range, 9.82 to 30.72] v 9.95 [interquartile range, 5.29 to 17.08] months, respectively; P < .001). Furthermore, in IPTW-adjusted Cox regression analysis, high-intensity LT was associated with a significant OS benefit (hazard ratio, 0.56; 95% CI, 0.48 to 0.65; P < .001). Conclusion We report an OS benefit for individuals with mUCB treated with high-intensity versus conservative LT. Although the findings are subject to the usual biases related to the observational study design, these preliminary data warrant further consideration in randomized controlled trials, particularly given the poor prognosis associated with mUCB.

The Contemporary Incidence and Sequelae of Rhabdomyolysis Following Extirpative Renal Surgery: A Population Based Analysis.

PURPOSE: We evaluate the contemporary incidence and consequences of postoperative rhabdomyolysis after extirpative renal surgery. MATERIALS AND METHODS: We conducted a population based, retrospective cohort study of patients who underwent extirpative renal surgery with a diagnosis of a renal mass or renal cell carcinoma in the United States between 2004 and 2013. Regression analysis was performed to evaluate 90-day mortality (Clavien grade V), nonfatal major complications (Clavien grade III-IV), hospital readmission rates, direct costs and length of stay. RESULTS: The final weighted cohort included 310,880 open, 174,283 laparoscopic and 69,880 robotic extirpative renal surgery cases during the 10-year study period, with 745 (0.001%) experiencing postoperative rhabdomyolysis. The presence of postoperative rhabdomyolysis led to a significantly higher incidence of 90-day nonfatal major complications (34.7% vs 7.3%, p <0.05) and higher 90-day mortality (4.4% vs 1.02%, p <0.05). Length of stay was twice as long for patients with postoperative rhabdomyolysis (incidence risk ratio 1.83, 95% CI 1.56-2.15, p <0.001). The robotic approach was associated with a higher likelihood of postoperative rhabdomyolysis (vs laparoscopic approach, OR 2.43, p <0.05). Adjusted 90-day median direct hospital costs were USD 7,515 higher for patients with postoperative rhabdomyolysis (p <0.001). Our model revealed that the combination of obesity and prolonged surgery (more than 5 hours) was associated with a higher likelihood of postoperative rhabdomyolysis developing. CONCLUSIONS: Our study confirms that postoperative rhabdomyolysis is an uncommon complication among patients undergoing extirpative renal surgery, but has a potentially detrimental impact on surgical morbidity, mortality and costs. Male gender, comorbidities, obesity, prolonged surgery (more than 5 hours) and a robotic approach appear to place patients at higher risk for postoperative rhabdomyolysis.

Trends in utilisation, perioperative outcomes, and costs of nephroureterectomies in the management of upper tract urothelial carcinoma: a 10-year population-based analysis.

OBJECTIVE: To perform a population-based study to evaluate contemporary utilisation trends, morbidity, and costs associated with nephroureterectomies (NUs), as contemporary data for NUs are largely derived from single academic institution series describing the experience of high-volume surgeons and it is unclear if the same favourable results occur at a national level. PATIENTS AND METHODS: Using the Premier Hospital Database, we captured patients undergoing a NU with diagnoses of renal pelvis or ureteric neoplasms from 2004 to 2013. We fitted regression models, adjusting for clustering by hospitals and survey weighting to evaluate 90-day postoperative complications, operating-room time (OT), prolonged length of stay (pLOS), and direct hospital costs among open (ONU), laparoscopic (LNU) and robotic (RNU) approaches. RESULTS: After applying sampling and propensity weights, we derived a final study cohort of 17 254 ONUs, 13 317 LNUs and 3774 RNUs for upper tract urothelial carcinoma (UTUC) in the USA between 2004 and 2013. During that period, minimally invasive NU (miNU) increased from 36% to 54%, while the total number of NUs decreased by nearly 20%. No differences were noted in perioperative outcomes between the three surgical approaches, including when the analysis was restricted to the highest-volume hospitals and highest-volume surgeons. The OT was longer for LNU and RNU (P < 0.001), while the pLOS rates were decreased (P < 0.001). Adjusted 90-day median direct hospital costs were higher for LNU and RNU (P < 0.001), which disappeared when adjusting for the highest-volume groups, except for RNUs performed by high-volume surgeons. CONCLUSIONS: During this contemporary 10-year study, miNU has been replacing ONU for UTUC with a recent surge in RNU, along with a concurrent reduction in total NUs performed. Despite not being associated with a clinically significant improvement in perioperative outcomes, the costs for miNUs were consistently higher. However, higher hospital volumes suggest a potential cost containment strategy when performing miNUs.

Contemporary trends in high-dose interleukin-2 use for metastatic renal cell carcinoma in the United States.

BACKGROUND: Targeted therapies (TTs) have revolutionized metastatic renal cell carcinoma (mRCC) treatment in the past decade, largely replacing immunotherapy including high-dose interleukin-2 (HD IL-2) therapy. We evaluated trends in HD IL-2 use for mRCC in the TT era. METHODS: Our cohort comprised a weighted estimate of all patients undergoing HD IL-2 treatment for mRCC from 2004 to 2012 using the Premier Hospital Database. We assessed temporal trends in HD IL-2 use including patient, disease, and hospital characteristics stratified by era (pre-TT uptake: 2004-2006, uptake: 2007-2009, and post-TT uptake: 2010-2012) and fitted multivariable regression models to identify predictors of treatment toxicity and tolerability. RESULTS: An estimated 2,351 patients received HD IL-2 therapy for mRCC in the United States from 2004 to 2012. The use decreased from 2004 to 2008. HD IL-2 therapy became increasingly centralized in teaching hospitals (24% of treatments in 2004 and 89.5% in 2012). Most patients who received HD IL-2 therapy were men, white, younger than 60 years, had lung metastases, and were otherwise healthy. Vasopressors, intensive care unit admission, and hemodialysis were necessary in 53.4%, 33.0%, and 7.1%, respectively. Factors associated with toxicities in multivariable analyses included being unmarried, male sex, and multiple metastatic sites. African Americans and patients with single-site metastases were less likely to receive multiple treatment cycles. CONCLUSIONS: HD IL-2 therapy is used infrequently for mRCC in the United States, and its application has diminished with the uptake of TT. Patients are being increasingly treated in teaching hospitals, suggesting a centralization of care and possible barriers to access. A recent slight increase in HD IL-2 therapy use likely reflects recognition of the inability of TT to effect a complete response.

The Effect of Resident Involvement on Perioperative Outcomes in Transurethral Urologic Surgeries.

OBJECTIVE: To conduct the first study of intra- and postoperative outcomes related to intraoperative resident involvement in transurethral resection procedures for benign prostatic hyperplasia and bladder cancer in a large, multi-institutional database. DESIGN: Relying on the American College of Surgeons National Surgical Quality Improvement Program Participant User Files (2005-2012), we abstracted all cases of endoscopic prostate surgery (EPS) for benign prostatic hyperplasia and transurethral resection of bladder tumors (TURBTs). Multivariable logistic regression models were constructed to assess the effect of trainee involvement (postgraduate year [PGY] 1-2: junior, PGY 3-4: senior, PGY ≥ 5: chief or fellow) vs attending only on operative time and length of hospital stay, as well as 30-day complication, reoperation, and readmission rates. RESULTS: In all, 5093 EPS and 3059 TURBTs for a total of 8152 transurethral resection procedures were performed during the study period for which data on resident involvement were available. In multivariable analyses, resident involvement in EPS or TURBT was associated with increased odds of prolonged operative times and hospital readmissions in 30 days independent of resident level of training. Resident involvement was not associated with overall complications or reoperation rates. CONCLUSIONS: Resident involvement in lower urinary tract surgeries is associated with increased readmissions. Strategies to optimize resident teaching of these common urologic procedures in order to minimize possible risks to patients should be explored.

Racial Disparities in Postoperative Complications After Radical Nephrectomy: A Population-based Analysis.

OBJECTIVE: To perform a population-based study that evaluates contemporary racial disparities in the morbidity profile of patients undergoing radical nephrectomy in the United States. METHODS: Using the Premier hospital database (Premier Inc, Charlotte, NC), which collects data from over 600 nonfederal hospitals throughout the United States, we identified patients undergoing a total nephrectomy as their primary procedure and also had a concurrent diagnosis of a kidney mass or cancer from 2003 to 2010. The primary outcome was 90-day major complication rates, based on the Clavien classification system. Multivariate logistic regression models were performed, adjusting for clustering by hospitals and survey weighting to ensure nationally representative estimates. RESULTS: The study population included 25,517 patients translating into a weighted sample of 185,135 radical nephrectomies. In a multivariate model including patient, hospital, and surgical characteristics, blacks were more commonly associated with a major complication (odds ratio, 2.1; P <.0001). When we incorporated Charlson comorbidity score into the model, the racial disparity in major complications was attenuated by 36% (odds ratio, 1.7; P <.0001). Adjusting for annual surgical volume in the multivariate model did not alter results. CONCLUSION: Our contemporary evaluation of patients undergoing radical nephrectomy in the United States demonstrates that blacks are associated with a markedly elevated rate of major complications as compared to whites. This disparity is possibly a result of unequal access to routine health care.

Predictors of positive surgical margins after radical prostatectomy at a single institution: preoperative and pathologic factors, and the impact of surgeon variability and technique on incidence and location.

INTRODUCTION: To identify and assess predictive factors for positive surgical margins (PSM) in patients undergoing radical prostatectomy (RP). MATERIALS AND METHODS: An Institution Review Board (IRB) approved retrospective review of 1751 patients that underwent RP from March 2000 to June 2013 was performed. Identified were 1740 patients whom had not received neoadjuvant therapy; these were used for the purpose of this analysis. Univariate and multivariate analysis were performed to determine factors associated with and predictive of PSMs, divided into preoperative and pathological. Variables analyzed include age, body mass index (BMI), race, surgeon, surgical modality, pathologic T-stage and Gleason sum, extracapsular extension (ECE), seminal vesicle involvement (SVI), perineural invasion (PNI) and prostate weight. Finally, each surgical technique was analyzed to determine the most common site of PSM. RESULTS: Rate of PSM was 23.6%. Our analysis showed that preoperative prostate-specific antigen (PSA) level ≥ 10ng/mL, and pathologic T3/T4-stage and PNI significantly predicted PSM. Age > 60 years and prostate weight > 60 g were predictive against PSM. Gleason score ≥ 7 and PSM were significant risk factors for biochemical recurrence (BCR). Surgical approach did not affect the rate of PSM. Open RP was associated with a higher apical PSM rate (38.5%) and robotic RP with a higher posterolateral PSM rate (52.3%). CONCLUSIONS: High preoperative PSA levels, and advanced TNM-staging predicted positive surgical margins in our cohort. Patients with PSM were subsequently found to have higher risk of BCR.

Practical guide to immunotherapy in castration resistant prostate cancer: the use of sipuleucel-T immunotherapy.

INTRODUCTION: New treatment options for metastatic castration resistant prostate cancer (mCRPC) have become available over the last few years should primary treatments and androgen deprivation therapies fail. While historically not considered to be amenable to immunotherapy, the treatment of advanced prostate cancer using this approach is an area of intense interest and now clinical application. MATERIALS AND METHODS: Recent literature on castration resistant prostate cancer management with a focus on immunotherapeutic strategies was reviewed. Mechanisms of action involving the immunologic treatment of cancer were identified. Agents in clinical trials with near term application in prostate cancer were also identified. RESULTS: Numerous immunotherapeutic agents for mCRPC are in current clinical trials. The autologous, active cellular immunotherapy, sipuleucel-T, which utilizes a patient's own antigen-presenting cells, is the only Food and Drug Administration (FDA) approved agent. It provides a 4.1 month survival advantage. Other investigational agents in this area include GVAX, a whole cell irradiated vaccine, and a vaccinia-PSA-TRICOM pox virus based approach, all in phase III trials. Immune-checkpoint inhibitors that enhance T-cell activity and potentiate antitumor effects are also promising. CONCLUSIONS: A first in class novel treatment modality, sipuleucel-T, is available in the United States for mCRPC. Other immunotherapies are in development and may be available in the near future. Understanding the detailed patient evaluation, initiation and administration of sipuleucel-T as described in this paper, will allow this novel cancer immunotherapy to be better understood and potentially benefit a larger group of appropriately selected patients.

Blue light cystoscopy for detection and treatment of non-muscle invasive bladder cancer.

In patients with non-muscle invasive bladder cancer, fluorescence cystoscopy can improve the detection and ablation of bladder tumors. In this paper we describe the technique and practical aspects of hexaminolevulinate (HAL) fluorescence cystoscopy, also known as "blue light cystoscopy".