Treatment of Low-grade Intermediate-risk Nonmuscle-invasive Bladder Cancer With UGN-102 ± Transurethral Resection of Bladder Tumor Compared to Transurethral Resection of Bladder Tumor Monotherapy: A Randomized, Controlled, Phase 3 Trial (ATLAS).

PURPOSE: Low-grade intermediate-risk nonmuscle-invasive bladder cancer is a chronic illness commonly treated by repetitive transurethral resection of bladder tumor. We compared the efficacy and safety of intravesical chemoablation with UGN-102 (a reverse thermal gel containing mitomycin), with or without subsequent transurethral resection of bladder tumor, to transurethral resection of bladder tumor alone in patients with low-grade intermediate-risk nonmuscle-invasive bladder cancer. MATERIALS AND METHODS: This prospective, randomized, phase 3 trial recruited patients with new or recurrent low-grade intermediate-risk nonmuscle-invasive bladder cancer to receive initial treatment with either UGN-102 once weekly for 6 weeks or transurethral resection of bladder tumor. Patients were followed quarterly by endoscopy, cytology, and for-cause biopsy. The primary end point was disease-free survival. All patients were followed for adverse events. RESULTS: Trial enrollment was halted by the sponsor to pursue an alternative development strategy after 282 of a planned 632 patients were randomized to UGN-102 ± subsequent transurethral resection of bladder tumor (n=142) or transurethral resection of bladder tumor monotherapy (n=140), rendering the trial underpowered to perform hypothesis testing. Patients were predominantly male and ≥65 years of age. Tumor-free complete response 3 months after initial treatment was achieved by 92 patients (65%) who received UGN-102 and 89 patients (64%) treated by transurethral resection of bladder tumor. The estimated probability of disease-free survival 15 months after randomization was 72% for UGN-102 ± transurethral resection of bladder tumor and 50% for transurethral resection of bladder tumor (hazard ratio 0.45). The most common adverse events (incidence ≥10%) in the UGN-102 group were dysuria, micturition urgency, nocturia, and pollakiuria. CONCLUSIONS: Primary, nonsurgical chemoablation with UGN-102 for the management of low-grade intermediate-risk nonmuscle-invasive bladder cancer offers a potential therapeutic alternative to immediate transurethral resection of bladder tumor monotherapy and warrants further investigation.

Association of Human Development Index with global bladder, kidney, prostate and testis cancer incidence and mortality.

OBJECTIVES: To describe contemporary worldwide age-standardized incidence and mortality rates for bladder, kidney, prostate and testis cancer and their association with development. MATERIALS AND METHODS: We obtained gender-specific, age-standardized incidence and mortality rates for 184 countries and 16 major world regions from the GLOBOCAN 2012 database. We compared the mortality-to-incidence ratios (MIRs) at national and regional levels in males and females, and assessed the association with socio-economic development using the 2014 United Nations Human Development Index (HDI). RESULTS: Age-standardized incidence rates were 2.9 (bladder) to 7.4 (testis) times higher for genitourinary malignancies in more developed countries compared with less developed countries. Age-standardized mortality rates were 1.5-2.2 times higher in more vs less developed countries for prostate, bladder and kidney cancer, with no variation in mortality rates observed in testis cancer. There was a strong inverse relationship between HDI and MIR in testis (regression coefficient 1.65, R2 = 0.78), prostate (regression coefficient -1.56, R2 = 0.85), kidney (regression coefficient -1.34, R2 = 0.74), and bladder cancer (regression coefficient -1.01, R2 = 0.80). CONCLUSION: While incidence and mortality rates for genitourinary cancers vary widely throughout the world, the MIR is highest in less developed countries for all four major genitourinary malignancies. Further research is needed to understand whether differences in comorbidities, exposures, time to diagnosis, access to healthcare, diagnostic techniques or treatment options explain the observed inequalities in genitourinary cancer outcomes.

Bladder Cancer Mortality in the United States: A Geographic and Temporal Analysis of Socioeconomic and Environmental Factors.

PURPOSE: We assessed the association of temporal, socioeconomic and environmental factors with bladder cancer mortality in the United States. Our hypothesis was that bladder cancer mortality is associated with distinct environmental and socioeconomic factors with effects varying by region, race and gender. MATERIALS AND METHODS: NCI (National Cancer Institute) age adjusted, county level bladder cancer mortality data from 1950 to 2007 were analyzed to identify clusters of increased bladder cancer death using the Getis-Ord Gi* statistic. Socioeconomic, clinical and environmental data were assessed using geographically weighted spatial regression analysis adjusting for spatial autocorrelation. County level socioeconomic, clinical and environmental data were obtained from national databases, including the United States Census, CDC (Centers for Disease Control and Prevention), NCHS (National Center for Health Statistics) and County Health Rankings. RESULTS: Bladder cancer mortality hot spots and risk factors for bladder cancer death differed significantly by gender, race and geographic region. From 1996 to 2007 smoking, unemployment, physically unhealthy days, air pollution ozone days, percent of houses with well water, employment in the mining industry and urban residences were associated with increased rates of bladder cancer mortality (p <0.05). Model fit was significantly improved in hot spots compared to all American counties (R(2) = 0.20 vs 0.05). CONCLUSIONS: Environmental and socioeconomic factors affect bladder cancer mortality and effects appear to vary by gender and race. Additionally there were temporal trends of bladder cancer hot spots which, when persistent, should be the focus of individual level studies of occupational and environmental factors.

National trends in prostate cancer screening among older American men with limited 9-year life expectancies: evidence of an increased need for shared decision making.

BACKGROUND: Prostate-specific antigen (PSA) screening for prostate cancer remains controversial. Most groups recommend informed decision making for men with 10 years of remaining life expectancy. The primary objective of this observational cohort study was to investigate the association between predicted 9-year mortality and prostate cancer screening among American men aged ≥65 years in 2005 and 2010. The second objective was to analyze the proportions of men who discussed screening with their physicians. METHODS: Data were extracted from the 2005 and 2010 National Health Interview Surveys. Men aged ≥65 years without prostate cancer were divided into predicted 9-year mortality quartiles. The proportions of men confirming a screening PSA within the prior year were determined. Logistic regression was used to compare screening rates. RESULTS: Screening rates for men aged ≥65 years were 48% in 2005 and 48% in 2010 (P = .9). Men ages 65 to 74 years who had <27% predicted 9-year mortality were most commonly screened, with 56% screened in 2010, compared with 34% of men aged ≥75 years with >75% predicted 9-year mortality. Approximately 55% of screened men aged ≥75 years who had ≥53% predicted 9-year mortality recalled discussing the advantages of screening, whereas 25% recalled discussing the disadvantages. CONCLUSIONS: Prostate cancer screening with PSA did not differ significantly between 2005 and 2010 for men aged ≥65 years based on predicted 9-year mortality. Approximately 33% of older men with a high likelihood of 9-year mortality were screened despite minimal clinical benefit. Twice as many men recalled discussing the potential advantages of screening compared with the disadvantages. Cancer 2014;120:1491-1498. © 2014 American Cancer Society.

Early removal of urethral catheter with suprapubic tube drainage versus urethral catheter drainage alone after robot-assisted laparoscopic radical prostatectomy.

PURPOSE: Retrospective single institution data suggest that postoperative pain after robot-assisted laparoscopic radical prostatectomy is decreased by early removal of the urethral catheter with suprapubic tube drainage. In a randomized patient population we determined whether suprapubic tube drainage with early urethral catheter removal would improve postoperative pain compared with urethral catheter drainage alone. MATERIALS AND METHODS: Men with a body mass index of less than 40 kg/m(2) who had newly diagnosed prostate cancer and elected robot-assisted laparoscopic radical prostatectomy were included in analysis. Block randomization by surgeon was used and randomization assignment was done after completing the urethrovesical anastomosis. In patients assigned to suprapubic tube drainage the urethral catheter was removed on postoperative day 1 and all catheters were removed on postoperative day 7. Visual analog pain scale and satisfaction questionnaires were administered on postoperative days 0, 1 and 7. RESULTS: A total of 29 patients were randomized to the urethral catheter vs 29 to the suprapubic tube plus early urethral catheter removal at the time of interim futility analysis. Mean visual analog pain scale scores did not differ between the groups at any time point and a similar percent of patients cited the catheter as the greatest bother with nonsignificant differences in treatment related satisfaction. Complications during postoperative week 1 did not vary between the groups. Based on interim results the trial was terminated due to lack of effect. CONCLUSIONS: Patients randomized to suprapubic tube vs urethral catheter drainage for the week after prostatectomy had similar pain, catheter related bother and treatment related satisfaction in the perioperative period. We no longer routinely offer suprapubic tube drainage with early urethral catheter removal at our institution.

Does robot-assisted laparoscopic ileocystoplasty (RALI) reduce peritoneal adhesions compared with open surgery?

OBJECTIVES: To compare perioperative outcomes between open ileocystoplasty and robot-assisted laparoscopic ileocystoplasty (RALI) in a porcine model, as objective data comparing outcomes between these two approaches in children with neurogenic bladder are lacking. We specifically examined differences in postoperative peritoneal adhesion formation between the groups. MATERIALS AND METHODS: In all, 20 pigs were assigned to an open ileocystoplasty or RALI study arm. All the pigs underwent an initial urodynamic study (UDS). In the RALI arm, reconstructive steps were performed intracorporeally using a standard da Vinci(®) system. Postoperatively, variables including first stool, weight gain, and complications were recorded. After 42 days, the pigs underwent a final UDS followed by adhesion assessment. Intraperitoneal adhesions were quantified by a third-party 'blinded' surgeon according to previously described objective scoring systems. RESULTS: Preoperative variables including UDS were similar in both groups. Overall operating time was significantly shorter for open ileocystoplasty than for RALI (149 vs 287 min, P < 0.001, respectively). Postoperatively, all variables including time to first stool, weight gain, and urodynamic parameters were similar amongst the groups. Pigs in the open arm developed significantly more adhesions (P = 0.02) and adhesions with a higher complexity (P = 0.04). CONCLUSIONS: In this porcine model, RALI achieved similar functional outcomes as the open approach, but required longer procedural times. The number and complexity of surgical adhesions among the groups favoured the RALI cohort. This may be of clinical significance in the paediatric spina bifida population, who generally undergo multiple surgical procedures in their lifetime, with increased risk for development of adhesions and subsequent intestinal obstruction.

Salvage radical prostatectomy as management of locally recurrent prostate cancer: outcomes and complications.

PURPOSE: Management of prostate cancer following radiation therapy remains challenging, especially for younger men or those with life expectancy greater than 10 years. We outline the efficacy, safety and adequacy of radical prostatectomy for the treatment of radiorecurrent localized prostate cancer. METHODS: A systematic review was performed in September 2012 searching MEDLINE articles from 1980 to 2012 on salvage radical prostatectomy. We excluded unpublished data and non-English-language articles. RESULTS: The ideal candidate for salvage radical prostatectomy (SRP) has a life expectancy greater than 10 years, a PSA < 10 ng/ml and whose initial clinical staging was T1 or T2. A prostate biopsy and imaging studies to rule out metastatic disease should be performed prior to SRP. Salvage RP has a high complication rate, but this appears to be decreasing over time. Urinary continence rates range from 36 to 81%, whereas erectile function following SRP was generally poor with less than 30% of men regaining adequate erectile function. Men with good erectile function prior to SRP fared better than those with pre-operative erectile dysfunction. Biochemical recurrence-free probability at 5 years ranged from 37 to 55% and the estimated cancer-specific survival at 10 years ranged from 70 to 83%. Minimally invasive SRP is feasible and early outcomes suggest that this approach is not inferior to open surgery. CONCLUSION: SRP offers a potentially curative option with proven long-term disease-free survival in appropriately selected patients. Given the morbidity of this procedure, judicious patient selection and referral to providers experienced with salvage surgery may optimize patient outcomes.

Ultrasonography in prostate cancer: current roles and potential applications in radiorecurrent disease.

The use of ultrasound technology for prostate cancer imaging has evolved over many years. In order to fully appreciate today's application of prostate ultrasound in the primary diagnostic setting as well as for radiorecurrent prostate cancer, it is helpful to understand the progression of this technology from its inception. This review begins with a brief history of the development of ultrasonography for the prostate. This is followed by a summary of the data evaluating ultrasound in the primary diagnosis of prostate cancer. Its application in the post-treatment setting is then addressed. Finally, several emerging technologies are discussed, including contrast-enhanced ultrasound, elastography and HistoScanning. These new modalities may hold promise for identifying incompletely ablated prostate tissue following radiation therapy or other ablative techniques.

Comparative effectiveness of minimally invasive versus open lymphadenectomy in urological cancers.

PURPOSE OF REVIEW: With increasing adoption of minimally invasive surgical techniques in urologic oncology, the efficacy, safety, and adequacy of lymphadenectomy were reviewed for studies about prostate, bladder, kidney, upper tract urothelial, testicular, and penile cancer published in the past 18 months. RECENT FINDINGS: In prostate cancer, in which robotic prostatectomy has become the predominant approach, use of extended lymphadenectomy has increased with lymph node yield nearing 20. Minimally invasive lymphadenectomy in bladder cancer does not yet approach the yield seen at high-volume open cystectomy centers, but a larger proportion of robotic lymph node dissections surpass the oncologic threshold of 10-14 lymph nodes compared with open surgery. Comparative lymphadenectomy data for kidney and upper tract urothelial cancers remain muddled as routine lymphadenectomy is not performed and both open and laparoscopic/robotic nephroureterectomy carry no consensus on templates. Minimally invasive retroperitoneal lymph node dissection carries safety and oncologic equivalence to the open technique only in limited centers, whereas minimally invasive ilioinguinal lymphadenectomy for penile cancer remains exploratory at this time. SUMMARY: Findings from the prior year suggest that - in high-volume centers - lymph node dissection for urologic cancers is equivalent between open and minimally invasive techniques in lymph node yield and short-term to medium-term oncologic results.

Targeting P21-Activated Kinase-1 for Metastatic Prostate Cancer.

Metastatic prostate cancer (mPCa) has limited therapeutic options and a high mortality rate. The p21-activated kinase (PAK) family of proteins is important in cell survival, proliferation, and motility in physiology, and pathologies such as infectious, inflammatory, vascular, and neurological diseases as well as cancers. Group-I PAKs (PAK1, PAK2, and PAK3) are involved in the regulation of actin dynamics and thus are integral for cell morphology, adhesion to the extracellular matrix, and cell motility. They also play prominent roles in cell survival and proliferation. These properties make group-I PAKs a potentially important target for cancer therapy. In contrast to normal prostate and prostatic epithelial cells, group-I PAKs are highly expressed in mPCA and PCa tissue. Importantly, the expression of group-I PAKs is proportional to the Gleason score of the patients. While several compounds have been identified that target group-I PAKs and these are active in cells and mice, and while some inhibitors have entered human trials, as of yet, none have been FDA-approved. Probable reasons for this lack of translation include issues related to selectivity, specificity, stability, and efficacy resulting in side effects and/or lack of efficacy. In the current review, we describe the pathophysiology and current treatment guidelines of PCa, present group-I PAKs as a potential druggable target to treat mPCa patients, and discuss the various ATP-competitive and allosteric inhibitors of PAKs. We also discuss the development and testing of a nanotechnology-based therapeutic formulation of group-I PAK inhibitors and its significant potential advantages as a novel, selective, stable, and efficacious mPCa therapeutic over other PCa therapeutics in the pipeline.

First-in-human, phase 1 study of PF-06753512, a vaccine-based immunotherapy regimen (VBIR), in non-metastatic hormone-sensitive biochemical recurrence and metastatic castration-resistant prostate cancer (mCRPC).

BACKGROUND: This phase 1 study evaluated PF-06753512, a vaccine-based immunotherapy regimen (PrCa VBIR), in two clinical states of prostate cancer (PC), metastatic castration-resistant PC (mCRPC) and biochemical recurrence (BCR). METHODS: For dose escalation, patients with mCRPC received intramuscular PrCa VBIR (adenovirus vector and plasmid DNA expressing prostate-specific membrane antigen (PSMA), prostate-specific antigen (PSA), and prostate stem cell antigen (PSCA)) with or without immune checkpoint inhibitors (ICIs, tremelimumab 40 or 80 mg with or without sasanlimab 130 or 300 mg, both subcutaneous). For dose expansion, patients with mCRPC received recommended phase 2 dose (RP2D) of PrCa VBIR plus tremelimumab 80 mg and sasanlimab 300 mg; patients with BCR received PrCa VBIR plus tremelimumab 80 mg (Cohort 1B-BCR) or tremelimumab 80 mg plus sasanlimab 130 mg (Cohort 5B-BCR) without androgen deprivation therapy (ADT). The primary endpoint was safety. RESULTS: Ninety-one patients were treated in dose escalation (mCRPC=38) and expansion (BCR=35, mCRPC=18). Overall, treatment-related and immune-related adverse events occurred in 64 (70.3%) and 39 (42.9%) patients, with fatigue (40.7%), influenza-like illness (30.8%), diarrhea (23.1%), and immune-related thyroid dysfunction (19.8%) and rash (15.4%), as the most common. In patients with mCRPC, the objective response rate (ORR, 95% CI) was 5.6% (1.2% to 15.4%) and the median radiographic progression-free survival (rPFS) was 5.6 (3.5 to not estimable) months for all; the ORR was 16.7% (3.6% to 41.4%) and 6-month rPFS rate was 45.5% (24.9% to 64.1%) for those who received RP2D with measurable disease (n=18). 7.4% of patients with mCRPC achieved a ≥50% decline in baseline PSA (PSA-50), with a median duration of 4.6 (1.2-45.2) months. In patients with BCR, 9 (25.7%) achieved PSA-50; the median duration of PSA response was 3.9 (1.9-4.2) and 10.1 (6.9-28.8) months for Cohorts 5B-BCR and 1B-BCR. Overall, antigen specific T-cell response was 88.0% to PSMA, 84.0% to PSA, and 80.0% to PSCA. CONCLUSIONS: PrCa VBIR overall demonstrated safety signals similar to other ICI combination trials; significant side effects were seen in some patients with BCR. It stimulated antigen-specific immunity across all cohorts and resulted in modest antitumor activity in patients with BCR without using ADT. TRIAL REGISTRATION NUMBER: NCT02616185.

Inappropriate utilization of radiographic imaging in men with newly diagnosed prostate cancer in the United States.

BACKGROUND: The use of radiographic imaging (bone scan and computerized tomography) is only recommended for men diagnosed with high-risk prostate cancer characteristics. The authors sought to characterize utilization patterns of imaging in men with newly diagnosed prostate cancer. METHODS: The authors performed a population-based observational cohort study using the US Surveillance, Epidemiology, and End Results-Medicare linked data to identify 30,183 men diagnosed with prostate cancer during 2004 to 2005. RESULTS: Thirty-four percent of men with low-risk and 48% with intermediate-risk prostate cancer underwent imaging, whereas only 60% of men with high-risk disease received imaging before treatment. Radiographic imaging utilization was greater for men who were older than 75 years (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.20-1.37; P < .001), were black (OR, 1.11; 95% CI, 1.01-1.21; P = .030), resided in wealthier areas (OR, 1.19; 95% CI, 1.08-1.32 for median income >$60,000 vs <$35,000; P < .001), lived in rural regions (OR, 1.23; 95% CI, 1.12-1.36; P < .001), or underwent standard radiation therapies (OR, 1.71; 95% CI, 1.60-1.84; P < .001). Imaging utilization was less for men living in areas with greater high school education (OR, 0.83; 95% CI, 0.75-0.91 between highest and lowest graduation rates; P < .001) or opting for active surveillance (OR, 0.17; 95% CI, 0.15-0.19 vs radical prostatectomy; P < .001). The estimated cost of unnecessary imaging over this 2-year period exceeded $3.6 million. CONCLUSIONS: In the United States, there is widespread overutilization of imaging for low-risk and intermediate-risk prostate cancer, whereas a worrisome number of men with high-risk disease did not receive appropriate imaging studies to exclude metastases before therapy.

The association of the human development index with global kidney cancer incidence and mortality.

PURPOSE: We describe contemporary worldwide age standardized incidence and mortality rates for kidney cancer, and their association with social and economic development metrics. MATERIALS AND METHODS: We obtained gender specific, age standardized incidence and mortality rates for 184 countries and 16 major world regions from the GLOBOCAN 2008 database. We compared the mortality-to-incidence ratio on the national and regional levels in males and females, and assessed the association with the development level of each country using the United Nations Human Development Index. RESULTS: The age standardized incidence rate varied twentyfold worldwide with the highest rate in North America, and the lowest in Africa and South Central Asia (11.8 vs 1.2 and 1.0/100,000 individuals, respectively). The geographic distribution of the age standardized mortality rate was similar to that of the age standardized incidence rate with the highest rates in Europe and North America (3.1 and 2.6/100,000 individuals, respectively) and the lowest rates in Asian and African regions (0.6 to 1.5). Age standardized incidence and mortality rates were 4.5 and 2.8 times higher, respectively, in more developed countries than in developing countries. However, the mortality-to-incidence ratio was highest in Africa and Asia, and lowest in North America (0.6 to 0.8 vs 0.2/100,000 individuals). There was a strong inverse relationship between the Human Development Index and the mortality-to-incidence ratio (regression coefficient -0.79, p<0.0001). CONCLUSIONS: Kidney cancer incidence and mortality rates vary widely throughout the world while the mortality-to-incidence ratio is highest in less developed nations. These observations suggest significant health care disparities and may reflect differences in risk factors, health care access, quality of care, diagnostic modalities and treatment options available. Future research should assess whether the mortality-to-incidence ratio decreases with increasing development.

Factors associated with the adoption of minimally invasive radical prostatectomy in the United States.

PURPOSE: Minimally invasive radical prostatectomy has supplanted radical retropubic prostatectomy in popularity despite the absence of strong comparative effectiveness data demonstrating its superiority. We examined the influence of patient, surgeon and hospital characteristics on the use of minimally invasive radical prostatectomy vs radical retropubic prostatectomy. MATERIALS AND METHODS: Using SEER (Surveillance, Epidemiology and End Results)-Medicare linked data we identified 11,732 men who underwent radical prostatectomy from 2003 to 2007. We assessed the contribution of patient, surgeon and hospital characteristics to the likelihood of undergoing minimally invasive radical prostatectomy vs radical retropubic prostatectomy using multilevel logistic regression mixed models. RESULTS: Patient factors (36.7%) contributed most to the use of minimally invasive radical prostatectomy vs radical retropubic prostatectomy, followed by surgeon (19.1%) and hospital (11.8%) factors. Among patient specific factors Asian race (OR 1.86, 95% CI 1.27-2.72, p = 0.001), clinically organ confined tumors (OR 2.71, 95% CI 1.60-4.57, p <0.001) and obtaining a second opinion from a urologist (OR 3.41, 95% CI 2.67-4.37, p <0.001) were associated with the highest use of minimally invasive radical prostatectomy while lower income was associated with decreased use of minimally invasive radical prostatectomy. Among surgeon and hospital specific factors, higher surgeon volume (OR 1.022, 95% CI 1.015-1.028, p <0.001), surgeon age younger than 50 years (OR 2.68, 95% CI 1.69-4.24, p <0.001) and greater hospital bed size (OR 1.001, 95% CI 1.001-1.002, p <0.001) were associated with increased use of minimally invasive radical prostatectomy, while solo or 2 urologist practices were associated with decreased use of minimally invasive radical prostatectomy (OR 0.48, 95% CI 0.27-0.86, p = 0.013). CONCLUSIONS: The adoption of minimally invasive radical prostatectomy vs radical retropubic prostatectomy is multifactorial, and associated with specific patient, surgeon and hospital related factors. Obtaining a second opinion from another urologist was the strongest factor associated with opting for minimally invasive radical prostatectomy.

Comparative effectiveness of perineal versus retropubic and minimally invasive radical prostatectomy.

PURPOSE: While perineal radical prostatectomy has been largely supplanted by retropubic and minimally invasive radical prostatectomy, it was the predominant surgical approach for prostate cancer for many years. In our population based study we compared the use and outcomes of perineal radical prostatectomy vs retropubic and minimally invasive radical prostatectomy. MATERIALS AND METHODS: We identified men diagnosed with prostate cancer from 2003 to 2005 who underwent perineal (452), minimally invasive (1,938) and retropubic (6,899) radical prostatectomy using Surveillance, Epidemiology and End Results-Medicare linked data through 2007. We compared postoperative 30-day and anastomotic stricture complications, incontinence and erectile dysfunction, and cancer therapy (hormonal therapy and/or radiotherapy). RESULTS: Perineal radical prostatectomy comprised 4.9% of radical prostatectomies during our study period and use decreased with time. On propensity score adjusted analysis men who underwent perineal vs retropubic radical prostatectomy had shorter hospitalization (median 2 vs 3 days, p < 0.001), received fewer heterologous transfusions (7.2% vs 20.8%, p < 0.001) and required less additional cancer therapy (4.9% vs 6.9%, p = 0.020). When comparing perineal vs minimally invasive radical prostatectomy men who underwent the former required more heterologous transfusions (7.2% vs 2.7%, p = 0.018) but experienced fewer miscellaneous medical complications (5.3% vs 10.0%, p = 0.045) and erectile dysfunction procedures (1.4 vs 2.3/100 person-years, p = 0.008). The mean and median expenditure for perineal radical prostatectomy in the first 6 months postoperatively was $1,500 less than for retropubic or minimally invasive radical prostatectomy (p < 0.001). CONCLUSIONS: Men who undergo perineal vs retropubic and minimally invasive radical prostatectomy experienced favorable outcomes associated with lower expenditure. Urologists may be abandoning an underused but cost-effective surgical approach that compares favorably with its successors.

Trends in the care of radical prostatectomy in the United States from 2003 to 2006.

OBJECTIVE: • o determine differences in surgical outcomes by surgical approach during a period of rapid adoption of minimally invasive surgical approaches in radical prostatectomy. PATIENTS AND METHODS: • We identified 19 542 men undergoing minimally invasive (MIRP), perineal (PRP), and retropubic (RRP) radical prostatectomy from 2003 to 2006 from the MarketScan® Medstat database, a national employer-based administrative database. • We assessed for temporal trends in perioperative complications, use of postoperative cystography and anastomotic strictures by surgical approach. RESULTS: • Between 2003 and 2006, MIRP use increased 33.6% vs 31.8% and 1.7% decreases in RRP and PRP, respectively. During the 4-year study, median length of stay for MIRP decreased from 2.0 to 1.0 day (P = 0.004) and overall perioperative complications decreased from 13.8 to 10.7%, (P = 0.023). • These findings were driven by reductions in genitourinary complications (3.3 to 2.5%, P = 0.049), miscellaneous surgical complications (3.6 to 2.3%, P = 0.006) and intestinal injury (1.5 to 0.1%, P= 0.009). • Median length of stay for RRP decreased from 3.2 to 2.9 days, (P < 0.001), overall perioperative complications decreased from 18.1 to 14.6%, (P = 0.007), because of reductions in both wound/bleeding complications (2.0 to 1.1%, P = 0.002) and heterologous blood transfusions. • Men undergoing MIRP vs RRP were less likely to have perioperative complications (12.5 vs 17.1%, P < 0.001), blood transfusions (1.5 vs 8.9%, P < 0.001) and anastomotic strictures (6.3 vs 12.8%, P < 0.001), and they had shorter mean lengths of stay (1.8 vs 3.1 days, P < 0.001) during the study period. CONCLUSION: • The increased use of MIRP corresponds with a decreasing trend for complications, blood transfusions, lengths of stay and need for reoperation. Additionally, MIRP was found to have fewer associated complications compared with men undergoing open procedures. Further study is needed to assess the impact of tumour characteristics and surgeon volume on these perioperative outcomes as well as effects on long-term cancer control.

Utilization of pharmacotherapy for erectile dysfunction following treatment for prostate cancer.

INTRODUCTION: Pharmacotherapies improve sexual function following treatments for localized prostate cancer; however, patterns of care remain unknown. Aim. To ascertain post-treatment utilization of pharmacotherapies for erectile dysfunction (ED) using a population-based approach. METHODS: We identified 38,958 men who underwent definitive treatment for localized prostate cancer during 2003-2006 from the MarketScan Medstat data. MAIN OUTCOME MEASURES: We compared the use of ED pharmacotherapy at baseline (up to 3 months prior) and up to 30 months following radical prostatectomy (RP) or radiotherapy (RT) for localized prostate cancer by utilizing National Drug Classification codes for phosphodiesterase-5 inhibitors (PDE5I), intracavernosal injectable therapies (IT), urethral suppositories and vacuum erection devices (VED). In adjusted analyses, we controlled for the effect of age, comorbidity, type of treatment, health plan and use of adjuvant hormone therapy on the use of pharmacotherapies. Results. Men undergoing RP vs. RT were younger with less co-morbid conditions. Utilization of PDE5I was up to three times greater for men undergoing RP vs. RT, 25.6% vs. 8.8%, (P < 0.0001) in the first post-treatment year, and usage of these agents was greatest for men undergoing minimally-invasive RP procedures. A higher percentage of men also used IT, suppositories and VED after RP vs. RT (P < 0.001). However, more men in the RT group received adjuvant hormonal therapy (39.53% vs. 5.25% for RP, P < 0.01). In adjusted analyses, men undergoing RP vs. RT were more than two times likely (OR 2.1, 95% CI 1.98, 2.26) to use PDE5I post-treatment while men on adjuvant hormonal therapy were less likely to use PDE5I (OR 0.74, 95% CI 0.70-0.79, P < 0.0001). CONCLUSION: Men undergoing RP vs. RT, particularly minimally-invasive RP, are more likely to employ IT, suppositories, VED, and PDE5I pharmacotherapy post-treatment.

Surgical apgar outcome score: perioperative risk assessment for radical cystectomy.

PURPOSE: Currently objective perioperative risk assessment metrics are lacking for radical cystectomy. Using a simple 10-point scale similar to neonatal Apgar assessment we evaluated whether a surgical outcome score calculated immediately after radical cystectomy would predict major complications and mortality. MATERIALS AND METHODS: We identified 155 consecutive radical cystectomies performed between 2005 and 2007 at our institution. Data were collected on 45 preoperative and intraoperative variables. We used a framework established by the National Surgical Quality Improvement Program to evaluate major complications within 30 days of surgery. We used a 10-point scoring system that had been previously validated in general and vascular surgery populations, comprising estimated blood loss, lowest heart rate and lowest mean arterial pressure. RESULTS: A total of 40 (26%) patients undergoing radical cystectomy experienced a major complication within 30 days of the operation. There was a progressive decrease in complications with increasing surgical Apgar score, in that patients with a low vs a high Apgar score were more likely to experience complications (OR 6.9, 95% CI 1.9-24.2). Coronary artery disease, American Society of Anesthesiologists class, intraoperative blood transfusion, volume of intravenous fluid administered and female gender were also associated with major complications (p <0.05). CONCLUSIONS: In patients undergoing radical cystectomy the surgical Apgar score predicts major postoperative complications and death. This simple and objective postoperative metric may be used to dictate the intensity of care. Prospective studies are needed to determine whether treatment decisions based on this scoring system improve radical cystectomy outcomes.