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Studies indicate that molecular subtypes in muscle invasive bladder cancer predict the clinical outcome. We evaluated whether subtyping by a simplified method and established classifications could predict the clinical outcome.We subtyped institutional cohort 1 of 52 patients, including 39 with muscle invasive bladder cancer, an Oncomine™ data set of 151 with muscle invasive bladder cancer and TCGA (The Cancer Genome Atlas) data set of 402 with muscle invasive bladder cancer. Subtyping was done using simplified panels (MCG-1 and MCG-Ext) which included only transcripts common in published studies and were analyzed for predicting metastasis, and cancer specific, overall and recurrence-free survival. TCGA data set was further analyzed using the Lund taxonomy, the Bladder Cancer Molecular Taxonomy Group Consensus and TCGA 2017 mRNA subtype classifications.Muscle invasive bladder cancer specimens from cohort 1 and the Oncomine data set showed intratumor heterogeneity for transcript and protein expression. MCG-1 subtypes did not predict the outcome on univariate or Kaplan-Meier analysis. On multivariate analysis N stage (p ≤0.007), T stage (p ≤0.04), M stage (p=0.007) and/or patient age (p=0.01) predicted metastasis, cancer specific and overall survival, and/or the cisplatin based adjuvant chemotherapy response. In TCGA data set publications showed that subtypes risk stratified patients for overall survival. Consistently the MCG-1 and MCG-Ext subtypes were associated with overall but not recurrence-free survival on univariate and Kaplan-Meier analyses. TCGA data set included 21 low grade specimens of the total of 402 and subtypes associated with tumor grade (p=0.005). However, less than 1% of muscle invasive bladder cancer cases are low grade. In only high grade specimens the MCG-1 and MCG-Ext subtypes could not predict overall survival. On univariate analysis subtypes according to the Bladder Cancer Molecular Taxonomy Group Consensus, TCGA 2017 and the Lund taxonomy were associated with tumor grade (p0.0001) and overall survival (p=0.01 to0.0001). Regardless of classification, subtypes had about 50% to 60% sensitivity and specificity to predict overall and recurrence-free survival. On multivariate analyses N stage and lymphovascular invasion consistently predicted recurrence-free and overall survival (p=0.039 and 0.003, respectively).Molecular subtypes reflect bladder tumor heterogeneity and are associated with tumor grade. In multiple cohorts and subtyping classifications the clinical parameters outperformed subtypes for predicting the outcome.

Given the lack of urology specific directives for the periprocedural management of anticoagulant and antiplatelet medications, the AUA (American Urological Association) and ICUD (International Consultation on Urological Disease) named an international multidisciplinary panel to develop consensus based recommendations.A systematic literature review was queried by a methodologist for 3 questions. 1) When and in whom can anticoagulant/antiplatelet prophylaxis be stopped in preparation for surgery? 2) What procedures can be safely performed without discontinuing anticoagulant/antiplatelet prophylaxis? 3) What periprocedural strategies can adequately balance the risk of major surgical bleeding vs the risk of major thrombotic event? Hematology and cardiology guidelines, and 79 articles were selected for full review.Multidisciplinary management of anticoagulant/antiplatelet medications for patients with recent thromboembolic events, mechanical cardiac valves, atrial fibrillation and cardiac stents would reduce the high morbidity and mortality of inexpertly discontinuing or modifying these lifesaving therapies. No elective procedures requiring interruption of dual antiplatelet therapies should be performed with a recent bare metal or drug eluting stent. The risk of significant bleeding complications is low for patients who require continuation of aspirin for ureteroscopy, transrectal prostate biopsies, laser prostate outlet procedures and percutaneous renal biopsy. Open extirpative prostate and renal procedures can be performed with a low risk of significant hemorrhage for patients on aspirin and those requiring heparin based bridging strategies. The current literature does not give direction on the timing of the resumption of anticoagulant/antiplatelet prophylaxis other than that it be resumed as soon as the risk of bleeding has decreased.A total of 2,674 nonredundant article abstracts were obtained and assessed for relevance to key questions outlined by the panel. Overall 106 articles were selected for full text review and accepted or rejected based on the relation to the topic, quality of information and key questions. A total of 79 articles were accepted. Reasons for rejection (27 articles) included abstract only (12), insufficient information or unrelated to topic (13) and redundancy (2). We extracted study design, patient population, followup period and results from accepted articles, which serve as the evidence base.

We examined the expression of 2 bladder tumor markers, hyaluronic acid (HA) and hyaluronidase (HAase), in bladder tissues and correlated tissue staining with the inferences of the HA-HAase urine test, which detects bladder cancer.A biotinylated HA binding protein and an antiHYAL1 antibody were used to localize HA and HYAL1 type HAase, respectively, in 83 bladder tissues. Immunoblot analysis was performed using an antiHYAL1 antibody to detect HYAL1.A total of 12 normal bladder tissues showed no (66%) to 1+ (34%) HA staining and 0 (83%) to 1+ (17%) HYAL1 staining. The staining intensity of HA and HYAL1 increased in 71 bladder tumor specimens on chi-square analysis (p0.001). Grade 1 tumors demonstrated 1+ (50%) to 2+ (50%) staining for HA and 1+ to 3+ staining for HYAL1 (37%, 37% and 26%, respectively). Grades 2 and 3 tumors showed 2+ to 3+ HA (94%) and HYAL1 (79%) staining. HA was expressed in tumor associated stroma and in tumor cells, whereas only tumor cells expressed HYAL1. In bladder tumor tissues HYAL1 expression was confirmed by immunoblot analysis. In 33 of the 34 patients (97%) with bladder cancer from whom urine and tumor tissue specimens were obtained at the same time 2+ to 3+ staining of HA and/or HYAL1 in 12 and 21, respectively, constituted a positive HA-HAase urine test (kappa = 0.945).To our knowledge this is the first report of HA localization in bladder tissues and of HYAL1 in any normal or tumor tissue. A close correlation of elevated HA and HYAL1 levels in tumor tissues with a positive HA-HAase urine test indicates that in patients with bladder cancer tumor associated HA and HYAL1 are secreted in urine, causing the HA-HAase test to be positive.

Inferior vena cava tumor thrombus complicates radical nephrectomy. Various approaches have been used to deal with this problem, including venovenous and cardiopulmonary bypass. Applying organ transplant techniques enhances the exposure of urological tumors and may avoid bypass.A total of 26 patients underwent surgery by techniques developed to facilitate orthotopic liver transplantation. Of the patients 15 with renal cell carcinoma and an intracaval tumor thrombus underwent piggyback style mobilization of the liver off of the retrohepatic inferior vena cava to allow enhanced access and vascular control, while 11 underwent conventional mobilization of the liver and retrohepatic inferior vena cava en bloc to allow enhanced access to various renal, adrenal and retroperitoneal tumors.In the 11 patients surgery was successful with a median blood loss of 200 ml. Postoperative ileus in 1 case was the only complication. We resected 5 infrahepatic thrombi without complications and with a median blood loss of 500 ml. In 7 patients with a retrohepatic inferior vena caval thrombus median blood loss was 1,500 ml., including 1 who died postoperatively, presumably due to a massive pulmonary embolus. Caval atrial tumor thrombus in 3 cases was successfully removed via a completely abdominal approach and sternotomy in 2. Cardiopulmonary bypass with hypothermic circulatory arrest was required in 1 of these cases.Liver mobilization was helpful for managing difficult urological tumors. Patients with a retrohepatic or even suprahepatic inferior vena caval thrombus may be treated without sternotomy or thoracotomy and cardiopulmonary bypass.

Purpose: The purpose of this trial was to evaluate an immunoassay for urinary nuclear matrix protein, NMP22,* *Matritech, Inc., Newton, Massachusetts. as an indicator for transitional cell carcinoma of the urinary tract.Materials and Methods: Three groups of subjects participated in this trial of NMP22: 1--175 with transitional cell carcinoma, 2--117 with benign urinary tract conditions and 3--375 healthy volunteers. Each subject provided a single (3 voids) urine sample for analysis at the time of study entry. Each sample was assayed for the level of NMP22.Results: In normal healthy volunteers and in subjects with benign conditions median NMP22 levels were 2.9 and 3.3 units per ml., respectively. Median urinary NMP22 levels in patients with transitional cell carcinoma were significantly greater than in comparison subjects. Patients with active transitional cell carcinoma had significantly greater median urinary NMP22 levels than those with no evidence of disease (6.04 versus 4.11 units per ml., p ...

PURPOSE Nonrandomized clinical trials have suggested that preoperative androgen deprivation can decrease the likelihood of positive surgical margins in patients with clinically localized prostate cancer. A multicenter prospective randomized trial compared radical prostatectomy alone to radical prostatectomy after 3 months of leuprolide acetate depot and flutamide in patients with stage cT2bNxM0 prostate cancer and a serum prostate specific antigen level less than 50 ng./ml. MATERIALS AND METHODS We randomized 149 patients to undergo androgen deprivation and 138 to undergo lymphadenectomy with (137) or without (1) prostatectomy. Of the 154 patients randomized to the surgery alone group 144 underwent pelvic node dissection with (138) or without (6) prostatectomy. RESULTS There was no statistically significant difference between the 2 groups in operating time, blood loss, need for transfusion, postoperative morbidity or length of hospital stay. There were 4 rectal and 2 ureteral injuries in the surgery alone group and none in the pretreatment group (p < 0.05). Patients who received androgen deprivation preoperatively had a significantly lower rate of capsule penetration (47% versus 78%, p < 0.001), positive surgical margins (18% versus 48%, p < 0.001) and tumor at the urethral margin (6% versus 17%, p < 0.01). CONCLUSIONS Long-term followup data will be needed to determine whether there will be a lower incidence of biochemical relapse as determined by prostate specific antigen, local recurrence or metastasis, with an improvement in patient survival.

Molecular markers could aid prostate specific antigen, biopsy Gleason sum and clinical stage to provide accurate information on prostate cancer progression. HYAL-1 hyaluronidase and hyaluronic acid staining in prostatectomy specimens predicts biochemical recurrence. We examined whether hyaluronic acid and HYAL-1 staining in biopsy specimens predicts biochemical recurrence and correlates with staining in matched prostatectomy specimens.Biopsy and prostatectomy specimens were obtained from 61 patients with clinically localized prostate cancer from multiple centers, including 23 with (group 1) and 38 without (group 2) biochemical recurrence. Mean followup was 103.1 months. Biotinylated hyaluronic acid binding protein and anti-HYAL-1 antibody were used for hyaluronic acid and HYAL-1 staining, respectively. Staining was graded between 0 and 300 depending on staining intensity and area.HYAL-1 and hyaluronic acid were expressed in tumor cells and stroma, respectively. In biopsy specimens HYAL-1 and hyaluronic acid expression was higher in group 1 than in group 2 (203.9 and 182.1 vs 48.8 and 87.0, respectively, p0.0001). On univariate analysis hyaluronic acid, HYAL-1, biopsy Gleason and prostate specific antigen significantly predicted biochemical recurrence (p0.001). On multivariate analysis only HYAL-1 staining independently predicted recurrence with an accuracy of 81.8% (p0.001). In prostatectomy specimens only HYAL-1 staining correlated with staining in biopsy specimens (Spearman rho = 0.72, p = 0.0002) and predicted biochemical recurrence.To our knowledge this is the first report that HYAL-1 staining in biopsy specimens is an independent predictor of biochemical recurrence. This may be useful when selecting treatment.

For select men with low risk prostate cancer active surveillance is more often being considered a management strategy. In a multicenter retrospective study we evaluated the actuarial rates and predictors of remaining on active surveillance, the incidence of cancer progression and the pathological findings of delayed radical prostatectomy.A cohort of 262 men from 4 institutions met the inclusion criteria of age 75 years or younger, prostate specific antigen 10 ng/ml or less, clinical stage T1-T2a, biopsy Gleason sum 6 or less, 3 or less positive cores at diagnostic biopsy, repeat biopsy before active surveillance and no treatment for 6 months following the repeat biopsy. Active surveillance started on the date of the second biopsy. Actuarial rates of remaining on active surveillance were calculated and univariate Cox regression was used to assess predictors of discontinuing active surveillance.With a median followup of 29 months 43 patients ultimately received active treatment. The 2 and 5-year probabilities of remaining on active surveillance were 91% and 75%, respectively. Patients with cancer on the second biopsy (HR 2.23, 95% CI 1.23-4.06, p = 0.007) and a higher number of cancerous cores from the 2 biopsies combined (p = 0.002) were more likely to undergo treatment. Age, prostate specific antigen, clinical stage, prostate volume and number of total biopsy cores sampled were not predictive of outcome. Skeletal metastases developed in 1 patient 38 months after starting active surveillance. Of the 43 patients undergoing delayed treatment 41 (95%) are without disease progression at a median of 23 months following treatment.With a median followup of 29 months active surveillance for select patients appears to be safe and associated with a low risk of systemic progression. Cancer at restaging biopsy and a higher total number of cancerous cores are associated with a lower likelihood of remaining on active surveillance. A restaging biopsy should be strongly considered to finalize eligibility for active surveillance.

Pre-prostate specific antigen era series demonstrated an increased risk of bladder cancer and rectal cancer in men who received radiotherapy for prostate cancer. We estimated the risk of secondary bladder cancer and rectal cancer after prostate radiotherapy using a contemporary population based cohort.We identified 243,082 men in the Surveillance, Epidemiology and End Results database who underwent radical prostatectomy or radiotherapy for prostate cancer between 1988 and 2003. We estimated the incidence rate, standardized incidence ratio and age adjusted incidence rate ratio of subsequent bladder cancer and rectal cancer associated with radical prostatectomy, external beam radiotherapy, brachytherapy, and a combination of external beam radiotherapy and brachytherapy.The relative risk of bladder cancer developing after external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy compared to radical prostatectomy was 1.88, 1.52 and 1.85, respectively. Compared to the general United States population the standardized incidence ratio for bladder cancer developing after radical prostatectomy, external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy was 0.99, 1.42, 1.10 and 1.39, respectively. The relative risk of rectal cancer developing after external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy compared to radical prostatectomy was 1.26, 1.08 and 1.21, respectively. The standardized incidence ratio for rectal cancer developing after radical prostatectomy, external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy was 0.91, 0.99, 0.68 and 0.86, respectively.Men who receive radiotherapy for localized prostate cancer have an increased risk of bladder cancer compared to patients undergoing radical prostatectomy and compared to the general population. The risk of rectal cancer is increased in patients who receive external beam radiotherapy compared to radical prostatectomy. Patients should be counseled appropriately regarding these risks.

We reviewed outcomes and features in patients with bladder cancer who underwent cystectomy and had a history of radiation for prostate cancer.We performed a retrospective analysis of the University of Miami cystectomy database and identified 34 patients with a history of radiotherapy for prostate cancer. An age and stage matched control group was used to compare survival. Our entire male cystectomy population was used to compare clinicopathological features.Mean age in the 34 patients with cystectomy was 75 years with a mean latency of 5 years from prostate cancer radiation. Radiotherapy was the primary treatment modality for prostate cancer in 32 of 34 patients and 2 received adjuvant radiation. Of the patients 86% received external beam radiation. Hematuria was the initial symptom in 86% of the cases. In 53% of the patients the initial diagnosis was muscle invasive bladder cancer. An ileal conduit was the method of urinary diversion in 33 cases. Major perioperative complications developed in 9% of the patients. There was 1 perioperative death, resulting in a mortality rate of 2.9%. Of the patients 54% presented with a locally advanced (pT3-4) tumor. Patients with a history of radiation therapy for prostate cancer had significantly poorer overall and bladder cancer specific survival than the matched control group.Most bladder cancers in patients with a history of radiation for prostate cancer present as locally advanced tumors and patients have poorer survival than age and stage matched controls.

We established a database on the incidence of intraoperative and postoperative complications associated with transurethral bladder tumor resection (TURBT) in an academic teaching setting, and we prospectively recorded all TURBTs performed by residents and fellows in our urology department.: We prospectively evaluated all TURBTs performed between November 2003 and October 2004. All cases were performed at least in part by residents and fellows under direct attending supervision at a single academic medical center with 3 different teaching hospitals. Intraoperative complications were recorded by the resident and attending surgeon at the completion of the operative procedure. At patient discharge from the hospital the data sheet was reviewed, and length of stay, postoperative transfusions and any other complications were recorded.A total of 173 consecutive TURBTs were performed by residents and fellows at 3 different teaching hospitals. There were 10 (5.8%) complications, including 4 (2.3%) cases of hematuria that required blood transfusion and 6 (3.5%) cases of bladder perforation. Of these 6 perforations 4 were small extraperitoneal perforations requiring only prolonged catheter drainage. These perforations were caused by residents in their first or third year of urology training. Two perforations were intraperitoneal, caused by a senior resident or a fellow, 1 of which required abdominal exploration to control bleeding.TURBT is a reasonably safe procedure when performed by urologists in training under direct attending supervision. The complication rate was 5.8%, however only 1 case required surgical intervention. Contrary to expected findings, more senior residents were involved in the complications, likely secondary to their disproportionate roles in more difficult resections.

Tumor volume is an important prognosticator for predicting prostate cancer recurrence following radical prostatectomy (RP). We assessed the ability of the visual estimate of the percent of carcinoma (VEPC) to predict recurrence.As performed by 1 surgeon (MSS), 1,114 men underwent radical prostatectomy between 1992 and February 2002. Patients who had less than 12 months of followup, who underwent salvage RP or in whom VEPC was not assessed in the pathology specimen were excluded. VEPC and other clinical variables were analyzed. We performed univariate analysis using the Kaplan-Meier log rank test. Multivariate analysis using Cox proportional hazards regression was performed.A total of 692 patients with a mean age of 61 +/- 7 years met the criteria for this analysis. Mean followup was 52 +/- 30 months. Of the patients 17% had biochemical recurrence. Mean VEPC was 25% and 13% in those with and without recurrence, respectively. On univariate analysis all variables were significant predictors of recurrence. However, multivariate analysis showed that the only significant predictors of recurrence were patient age, initial prostate specific antigen 10 ng/ml or greater, RP Gleason 8 to 10, extraprostatic extension, seminal vesicle involvement and VEPC. Based on disease-free survival curves patients were stratified into 3 broad groups, namely low, intermediate and high volume. The HR for biochemical recurrence was 2.1 for the intermediate VEPC group (9.1% to 20%) and 2.7 for the high VEPC group (greater than 20%). In the reference group it was less than 9% (low volume).VEPC is a simple and inexpensive method that is an independent predictor of recurrence after RP.

The majority of patients with stage Ta or T1 bladder cancer will have a subsequent tumor. Many of these patients invariably undergo multiple transurethral resections to manage small subsequent tumors or recurrences. We report our experience monitoring patients whose subsequent tumors appear to be small, low grade and papillary.A total of 32 patients with small, papillary, low grade appearing tumors and a history of Ta or T1 transitional cell carcinoma were monitored. The decision to delay resection or fulguration and observe these tumors was based on bladder cancer history, endoscopic appearance of the tumor and presence or lack of symptoms. All patients had a previous Ta tumor, and the tumor being observed was always papillary and appeared to be low grade. The decision to resect the tumor(s) was based on change in appearance (size or configuration) at followup endoscopy or hematuria. Patient records were reviewed, and bladder cancer history and tumor observation periods were recorded. Several patients underwent a number of observation periods. Tumor grade and stage before the observation interval were compared to the pathology of the observed tumor(s) after eventual resection. Tumor growth rate was calculated based on estimated tumor size documented at each interval.Mean patient age was 72 years (range 39 to 88). Mean time since diagnosis of bladder cancer (initial urothelial tumor event) was 71 months (range 12 to 139). Mean number of subsequent tumor episodes or recurrences per patient was 3.8 (range 1 to 10). Mean number of transurethral resections was 3.8. Mean tumor-free interval before development of a subsequent tumor or mean time to recurrence was 13.4 months based on 104 tumor episodes. Not all tumor recurrences were observed. Mean number of tumor observation periods per patient was 1.8 (range 1 to 5) with a mean duration of 10.09 months per period based on 56 observation intervals. Mean time since the beginning of the initial observation period was 38 months (range 6 to 126). Mean tumor growth rate for 37 tumors was 1.77 mm per month (range 0 to 5.8). Only 3 of 45 (6.7%) patients had tumor progression from a pre-observation, low grade, noninvasive (TaG1 to 2) to a high grade Ta or T1 tumor. In the 3 observation periods in which the patient's most recent tumor was T1, 2 (67%) patients had TaG1 on resection after observation. Every patient with a T1 tumor before observation of a small new tumor had a history of a Ta tumor. No disease progressed to muscle invasion.Small, recurrent, low grade appearing bladder tumors are slow growing and pose minimal risk. Therefore, as an alternative to in office fulguration to minimize morbidity and cost associated with repeat transurethral resection it may not be necessary to remove these tumors promptly at new tumor occurrence or recurrence.

Historically inferior vena caval thrombus associated with renal cell carcinoma was a deterrent to surgery. During the last 3 decades there has been steady improvement in surgical techniques and perioperative care, which has dramatically improved the ability to resect safely these tumors. We acknowledge these improvements in chronological order.A comprehensive literature review of the different techniques used for resecting renal cell carcinoma with inferior vena caval involvement was performed using MEDLINE. Data focused on surgical techniques, including various incisions, exposures, adjuncts to surgery and outcomes.Tumor thrombus associated with renal cell carcinoma is no longer considered to have a detrimental impact on survival. Patients who are acceptable surgical candidates have survival rates as high as 68%. Although there is a great deal of emphasis on the importance of an aggressive surgical approach, a uniform operative strategy based on the level of the tumor thrombus has not been established. Surgical techniques derived from liver transplant surgery and cardiac arrest with cardiopulmonary bypass have drastically decreased operative complications associated with extensive involvement of the inferior vena cava with tumor thrombus.The only curative approach to renal cell carcinoma is surgery. An aggressive approach is warranted when tumor involves the renal vein and inferior vena cava. Surgical strategy depends on the level of the inferior vena caval thrombus. Patients with extension of the thrombus above the diaphragm are a greater technical challenge. Hypothermic circulatory arrest should be considered when treating vena caval-atrial tumor thrombus. Surgeons familiar with liver mobilization can greatly facilitate the exposure needed for safely operating in these cases.

We assessed biochemical and pathological factors as predictors of recurrence in men with seminal vesicle invasion.A consecutive series of 812 men who underwent radical retropubic prostatectomy between 1992 and 2000 included 106 (13%) with seminal vesicle invasion. Disease recurrence was defined as prostate specific antigen (PSA) 0.4 ng./ml. or greater. Patients with less than 12 months of followup, salvage radical retropubic prostatectomy, lymph node metastases and adjuvant therapy were excluded from study. Data on the remaining 66 cases were analyzed using the chi-square test, bivariate logistic regression, Kaplan-Meier analyses and Cox proportional regression. Variables included demographics, recurrence, time from surgery to recurrence, positive margins, capsular invasion, extracapsular extension, Gleason score (2 to 6, 7 and 8 to 10), and dichotomized values of preoperative PSA (10 or less versus 10 ng./ml.) and tumor volume (20% or less versus greater than 20%).Mean patient age was 62 years (range 48 to 74). At an average followup of 47.7 months (range 13 to 109) 53% of the patients were free of biochemical recurrence. Mean time to recurrence was 18.6 months (range 1.7 to 51.6). Univariate analyses revealed a statistical significant increased risk of recurrence in patients with PSA greater than 10 ng./ml. (p0.0001), capsular invasion (p = 0.01) and age (p = 0.036). When adjusting for potential covariates, Cox proportional regression analysis indicated that higher PSA (hazard ratio 7.33, 95% CI 2.57 to 20.95), larger tumor volume (hazard ratio 5.64, 95% CI 1.97 to 16.19) and higher age (hazard ratio 1.13, 95% CI 1.04 to 1.22) were significantly associated with shorter time to recurrence.PSA greater than 10 ng./ml., tumor volume greater than 20% and age are significant predictors of recurrence after radical retropubic prostatectomy in patients with prostate cancer and seminal vesicle invasion. Hopefully future randomized trials may show a survival benefit of adjuvant therapy in patients at high risk.

Level III thrombus in the inferior vena cava poses a challenge to the surgeon due to its relative inaccessibility. We introduce a new system to redefine level III thrombus in anatomical relation to the hepatic veins and describe a technique of safe resection of these tumors through a transabdominal approach without recourse to cardiopulmonary bypass.From August 1997 to July 2001, 23 patients underwent resection of renal cell carcinoma with a level III thrombus. Intraoperative as well as postoperative variables such as operative time, estimated blood loss, number of transfusions, cardiopulmonary bypass, postoperative complications, pathological findings and survival were recorded.A total of 15 male and 8 female patients with a mean age of 62 years (range 25 to 83) underwent resection of a level III thrombus emanating from renal cell carcinoma. Patients were divided into groups IIIa-9 with an infrahepatic thrombus, IIIb-6 with a hepatic thrombus, IIIc-5 with a suprahepatic, infradiaphragmatic thrombus and IIId-3 with a suprahepatic, supradiaphragmatic, infra-atrial thrombus. Mean operative time was 5 hours 42 minutes (range 4 to 7.5 hours). The number of transfusions was 0 to 4. Estimated blood loss was 100 to 5,000 cc (mean 500). Neither cardiopulmonary bypass nor veno-venous bypass was required. Median followup was 25 months. Two patients (9%) died, including 1 in the immediate postoperative period and the other from metastasis 15 months after surgery. At the last followup 3 patients (13%) had metastasis and 18 (78%) were disease-free for overall and disease-free survival rates of 91% and 78%, respectively.An aggressive surgical approach remains the mainstay of treatment to achieve cure. We believe that the extent of dissection is different in each subgroup and, therefore, the need exists to redefine level III thrombus of the inferior vena cava. The application of liver transplant techniques for mobilizing the liver off of the inferior vena cava as well as the inferior vena cava off of the posterior abdominal wall contributes to excellent exposure and enables adequate vascular control of the inferior vena cava.

We assessed the effect of location and number of positive margins on biochemical progression in patients after radical retropubic prostatectomy for prostate cancer.The incidence, location and number of positive surgical margins as well as recurrence and time to recurrence were evaluated in a consecutive series of 734 men who underwent radical retropubic prostatectomy for localized prostate cancer from 1992 through February 1999.Surgical margins were positive in 210 patients (29%), of whom 157 (75%) and 53 (25%) had 1 and more than 1 positive margin, respectively. Of the patients 53 (25%) with tumor at any inked margin had biochemical recurrence. We identified no significant association of a particular location with biochemical recurrence. Bladder neck location did not carry an increased risk of recurrence (hazard ratio 1.23, 95% confidence interval 0.54 to 2.80). However, these findings were made in a limited number of cases with positive bladder neck margins. Patients with more than 1 positive surgical margin were at increased risk for recurrence compared with those with a single positive surgical margin (hazard ratio 2.19, 95% confidence interval 1.11 to 4.32). In addition, prostate specific antigen greater than 20 ng./ml. and seminal vesicle invasion were significant predictors of progression.In patients with localized prostate cancer and positive surgical margins biochemical progression is not dictated by the specific location of a positive margin. However, multiple positive margins are associated with a significantly increased risk of biochemical recurrence. Longer followup and larger sample size are necessary to confirm these findings.

We surveyed urologists in community and academic practice regarding their standard approach to patient preparation and their technique of transrectal ultrasound guided prostate biopsy.We mailed 110 surveys to community urologists in Florida and urological oncologists at academic centers across the United States. Responses were calculated per group.Of the 88 respondents 34% were at academic centers and 66% were community urologists. Overall 79% of respondents prescribe an enema in preparation for biopsy, 81% administer an oral fluoroquinolone before biopsy, 50% give some type of analgesia, usually an oral agent, 63% obtain 8 or more cores per biopsy session, 36% biopsy the lateral and midline locations, and 83% do not use prostate specific antigen density to plan the biopsy strategy.The majority of urologists who responded to our survey ask their patients to use an enema in preparation for a transrectal biopsy procedure, prescribe an oral antibiotic and administer some type of analgesia. Few urologists administer a periprostatic nerve block. The majority obtain at least 8 biopsies and only 17% perform sextant biopsy. Some of these practices are not consistent with the literature. This survey provides insight into the practice patterns of urologists in regard to one of the most commonly performed office procedures.

In the initial report of the Lupron Depot Neoadjuvant Prostate Cancer Study Group patients who received 3 months of androgen deprivation had a significant decrease in the positive margin rate. We monitored these patients for 5 years and to our knowledge present the longest followup of any neoadjuvant trial.A multi-institutional prospective randomized trial was performed between February 1992 and April 1994 involving patients with stage cT2b prostate cancer, including 138 who received 3 months of leuprolide plus flutamide before radical prostatectomy and 144 who underwent radical prostatectomy only. Patients were followed every 6 months with serum prostate specific antigen (PSA) testing for 5 years. Biochemical recurrence was defined as PSA greater than 0.4 ng./ml.At 5 years there was no difference in the biochemical recurrence rate. PSA was less than 0.4 ng./ml. in 64.8% of the patients in the neoadjuvant androgen ablation plus prostatectomy and 67.6% in the prostatectomy only group (p = 0.663).Although 3 months of androgen deprivation before radical prostatectomy resulted in an apparently significant decrease in positive surgical margins, a 5-year followup does not indicate any difference in the recurrence rate. Until studies document improvement in biochemical or clinical recurrence with longer periods of treatment, induction androgen deprivation before radical prostatectomy is not indicated.

We evaluated the pharmacokinetics, safety and efficacy of the implantable Viadur++ leuprolide delivery system during 12 months in patients with advanced prostate cancer.Our open label, multicenter, dose ranging study was done in 2 phases. The treatment phase was a stratified, randomized, parallel evaluation of the safety and efficacy of 1 or 2 implants. The safety extension phase assessed the long-term safety and efficacy of 1 implant. Implant insertion and removal, pharmacokinetic profile and patient satisfaction were also evaluated. The primary efficacy parameter was testosterone suppression for 12 months but luteinizing hormone and prostate specific antigen were also evaluated.Of the 51 patients 27 received 1 and 24 received 2 implants, of whom 49 completed the 12-month treatment phase. Steady serum leuprolide concentration was maintained from day 3 through the remainder of the 12-month treatment phase and for 2 months after reimplantation. Implantation and reimplantation were well tolerated and acceptable to physicians and patients. Testosterone suppression to the castrate range was 100% in each group. At 12 months mean prostate specific antigen decreased from a baseline of approximately 84% and 91% in groups 1 and 2, respectively. Serious adverse events during the study period in 15 patients were not attributable to treatment.The implantable leuprolide delivery system provides effective suppression of testosterone in patients with advanced prostate cancer.

Patients with transitional cell carcinoma of the bladder are at risk for concurrent or subsequent cancer of the upper tract. Traditionally disease is monitored by radiography (excretory or retrograde urography). Some elect to sample the upper tract by obtaining urine for cytology. Are the results meaningful when performed in a patient with bladder cancer?We evaluated 27 consecutive patients with transitional cell cancer of the bladder (grade 1 to 3, Ta to T2) with bladder wash for cytology and cystoscopy as well as resection of visible tumor. A 5F ureteral catheter was positioned at each ureteral orifice, flushed with saline and passed into each renal pelvis. Urine was collected for cytology.Of 19 patients (68%) with high grade (grade 3) bladder cancer 13 had a positive bladder wash, including 6 (32%) with tumor cells detected in the urine from the upper tract. Of 8 patients (38%) with low grade (grade 1 to 2) transitional cell cancer 3 had a positive bladder wash and 2 (25%) had a positive upper tract cytology. All patients had a normal upper tract by excretory or retrograde urography. Ureteroscopy was not performed.Given the normal appearance of the upper urinary tract, it is highly unlikely that most, if any, of these patients with bladder cancer have tumor in the upper tract despite tumor cells in urine obtained by retrograde catheterization. Thus, upper tract sampling by a retrograde technique lacks specificity for localizing transitional cell cancer to the upper tract when performed in a patient with bladder cancer.

Digital rectal examination is integral to staging prostate cancer. Ultrasound guided biopsy establishes the diagnosis, and it may provide useful information regarding disease grade and extent. Treatment decisions are largely based on information gained from digital rectal examination and biopsy but this information is only useful if it correlates with the radical prostatectomy specimen and prognosis. We correlated digital rectal examination and transrectal ultrasound guided biopsy results with a detailed analysis of the radical prostatectomy specimen.The accuracy of an abnormal digital rectal examination for predicting the location and extent of cancer was assessed in 89 patients thought to have clinical stage T2 disease. We evaluated 155 patients with clinical stages T1c and T2 disease to correlate the location of positive biopsies with the tumor site in the prostate. Radical prostatectomy specimens were completely sectioned at 2 mm. intervals, and tumor extent and location were recorded.In 85 patients a unilateral lesion was suspicious on digital rectal examination, that is stage cT2. The final pathological review revealed cancer on the suspicious side in 82 cases (96%) with tumor confined to the same lobe in only 23 (27%), bilateral disease in 59 (69%) and tumor confined to the contralateral lobe in 3 (4%). In 4 patients with a palpable bilateral abnormality a bilateral lesion was confirmed on final pathological evaluation. Digital rectal examination demonstrated a 36 and 31% incidence of extracapsular tumor extension and positive surgical margins, respectively, on the clinically benign side. In 100 patients only unilateral biopsy was positive. The final pathological evaluation revealed cancer in the biopsy positive side in 95 cases (95%) with tumor confined to the ipsilateral lobe in only 26 (26%), bilateral disease in 69 (69%) and tumor confined to the contralateral lobe in 5 (5%). In 46 of the 55 patients (84%) with bilateral positive biopsies tumor involved both sides but the pathologist did not identify cancer in both lobes in 9 (16%). While 100 patients had a unilateral negative biopsy, analysis of the prostatectomy specimen revealed carcinoma in the benign lobe in 74 (74%). Moreover, extracapsular tumor extension and a positive surgical margin were observed on the biopsy negative side in 31% of the patients. The degree to which digital rectal examination and biopsy results confirmed the final pathological evaluation was assessed using the kappa statistic, which revealed only slight agreement with each factor. The correlation of digital rectal examination and biopsy results with the location of extracapsular extension and positive margins was evaluated by the Spearman coefficient of correlation, which indicated poor agreement. When patients with unilateral versus bilateral positive biopsy were compared with respect to prognostic parameters, the difference was statistically significant for initial serum prostate specific antigen, the percentage of surface involved by tumor, biopsy and final Gleason scores, and the incidence of extracapsular extension of tumor.Digital rectal examination and the interpretation of prostate biopsy are not accurate clinical tools for defining the location and extent of prostatic carcinoma. Bilateral positive biopsy may be useful as an adjunct to the current clinical staging system.

Purpose: The safety, efficacy and pharmacokinetics of bicalutamide were investigated in 150 patients with stage D2 prostate cancer.Materials and Methods: Patients received 50 mg. bicalutamide daily in an open label multicenter North American trial.Results: The objective response rate (modified European Organization for Research in Cancer Therapy criteria) was 70 percent. Of 150 patients 59 (39 percent) met prostate specific antigen criteria for partial response, and 88 (59 percent) reached treatment failure end points and withdrew. Extent of disease was a significant predictor of response but baseline testosterone was not. Breast pain and gynecomastia developed in 76 percent and 60 percent of patients, respectively. Mean drug plasma concentration was 8,528 plus/minus 2,928 ng./ml.Conclusions: Bicalutamide (50 mg.) daily was well tolerated and efficacious. However, suboptimal effects on prostate specific antigen have led to additional trials to evaluate monotherapy at higher doses.

Intravesical therapy with bacillus Calmette-Guerin (BCG) has proved to be more effective in the prophylaxis and treatment of superficial bladder tumors and carcinoma in situ than most chemotherapeutic agents. Compared to intravesical chemotherapy, instillations with BCG provoke more local and systemic reactions. In addition to the commonly induced granulomatous inflammatory changes in the bladder, which produce irritative symptoms, this therapy may cause systemic side effects varying from mild malaise and fever to, in rare instances, life-threatening or fatal sepsis. We report the incidence and varieties of toxicities in 2,602 patients treated with intravesical BCG. Side effects are classified according to local and systemic toxicity. Treatment options vary according to the severity of toxicity from delaying or withholding instillations to treatment with antituberculous drugs for up to 6 months. In general, 95% of the patients have no serious side effects. Recognition of risk factors, particularly traumatic catheterization or concurrent cystitis, that result in systemic BCG absorption, as well as the prompt and appropriate treatment of early side effects should significantly decrease the incidence of severe toxicity.

We reviewed the clinical courses of 86 men after radical cystoprostatectomy for transitional cell carcinoma of the bladder to determine who were at highest risk for urethral recurrence. We assessed patients for prostatic involvement as well as tumor extent in the bladder and distal ureters. Of the 30 patients with tumor in the prostate 11 (37%) suffered urethral recurrences. Of the 56 patients with all other types of tumor involvement patterns exclusive of disease in the prostate only 2 (4%) had recurrence. We recommend rigorous screening for transitional cell carcinoma of the prostate before cystectomy. Prophylactic urethrectomy is indicated for patients with prostatic involvement, while those without such involvement may be considered at low risk for urethral recurrence.

Treatment in patients with a positive surgical margin after radical retropubic prostatectomy is controversial. Options are observation, radiation therapy and early hormone therapy. Making the appropriate choice should be based on an understanding of the risk of recurrence without treatment.We reviewed the records of 1,383 patients after radical retropubic prostatectomy was performed by a single surgeon. All specimens were analyzed by a single pathologist. Of the patients 936 met criteria for analysis.Mean followup in these 936 patients was 45.8 months (minimum 12). The overall PSA biochemical recurrence rate was 11.5% (108 of 936 cases). Of the 936 patients 350 (37%) had tumor at an inked margin. These patients had a recurrence rate of 19% (67 of 350), while patients with negative margins had a recurrence rate of 7% (41 of 586). This difference was statistically significant (p0.01). Multivariate HR analysis revealed that significant risk factors for recurrence in the 936 patients were PSA greater than 20 ng/ml, clinical stage T2 or greater, Gleason 7 or greater, seminal vesicle involvement, extraprostatic extension, a visual estimate of prostate cancer volume of greater than 9.1% and positive surgical margins. Statistically significant risk factors for recurrence in patients with a positive margin on multivariate HR analysis were PSA greater than 20 ng/ml, Gleason score 7 or greater and seminal vesicle involvement.Although the positive margin rate in this series was 37%, the recurrence rate in these patients was only 19%. It is important to consider other factors, such as PSA, Gleason score, seminal vesicle involvement and extraprostatic extension, when making treatment decisions.

We studied 36 patients with stages O and A (Tis, Ta and T1) bladder cancer who had received 8 weekly doses of 30 or 40mg. mitomycin C as definitive therapy. Of this group 16 had failed thiotepa therapy and 13 had grade III tumors (6 multifocal carcinoma in situ). The complete response rate at 12 weeks was 45 per cent (negative biopsy and cytology), while an additional 33 per cent had a partial response. Response did not correlate with tumor grade or stage. Patients who had failed thiotepa therapy were less likely to have a complete response, although the over-all response rate was identical to patients who had either not received prior chemotherapy or were not clear thiotepa failures. Followup of these patients indicates that the complete responders were benefited by this regimen since the subsequent recurrence rate was reduced when compared prior to initiation of mitomycin C. Most of these patients received monthly maintenance therapy.

The circadian and day-to-day variation of serum levels of prostatic acid phosphatase determined by radioimmunoassay was investigated in 10 men with a normal prostate, 8 with benign prostatic hyperplasia and 10 with prostate cancer. Serum samples were obtained on 1 day at 8 a.m., 12:00 noon and 4:30 p.m. in 23 patients, and on 3 consecutive days at 8 a.m. in an additional 5 patients.There was a variability in enzyme level throughout the day but without any distinct pattern. Prostate cancer patients with elevated levels of prostatic acid phosphatase did demonstrate a greater variability throughout the day than patients with a normal prostate or with benign prostatic hyperplasia.The day-to-day serum prostatic acid phosphatase in patients with a normal prostate varied little and remained within the normal range.

Combination chemotherapy consisting of cyclophosphamide, doxorubicin hydrochloride and 5-fluorouracil was evaluated in 21 patients with metastatic adenocarcinoma of the prostate who were unresponsive to conventional therapy. All patients had extensive bone metastases. Of the 21 patients 5 (29 per cent) had a subjective response and an additional 12 (57 per cent) remained stable for 2 to 13 months after initiation of therapy. The median survival of patients with a subjective response was 60 weeks compared to 40 weeks for the stable patients. Patients who progressed on therapy had a median survival of 22 weeks. The significant response rate with a corresponding improvement in survival for patients on this 3-drug regimen suggests a need for additional trials to determine the response rate and survival compared to single agents.

We studied 454 patients with prostatic adenocarcinoma who were assigned a preliminary clinical stage on the basis of serum acid phosphatase, routine bone survey and physical examination. Subsequently, they were assigned a final clinical stage after radioisotopic bone scanning, lymphangiography and staging pelvic lymph node dissection. Only 53, 54, 57 and 26 per cent, respectively, of patients initially assigned the preliminary clinical stage of IB, II, III or IVA remained at that stage after the additional studies.

A total of 70 patients received intravesical mitomycin C for treatment of superficial bladder cancer. The drug was instilled weekly for 8 weeks. Thirty-nine patients (56 per cent) had failed thiotepa therapy and 25 had high grade tumors. Of the patients 27 (39 per cent) had complete eradication of tumor at the initial 3-month evaluation and an additional 27 had a partial response. The response did not vary with initial tumor grade or stage. Followup averaged 28 months for the 70 patients. A muscle invasive tumor developed during followup in 7 per cent of the patients with an initial complete response, 15 per cent with a partial response and 25 per cent of the initial failures. To date 5 patients (7 per cent) have died of bladder cancer. Intravesical mitomycin C is an effective modality for treatment of superficial bladder cancer. Patients achieving a complete response are at little risk for progressive disease.