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Introduction Active surveillance with delayed intervention aims to minimize the discomfort, potential complications and costs associated with immediate treatment of recurrent low grade Ta tumors of the bladder. We reviewed the data supporting this management strategy for low risk bladder cancer. Methods A PubMed® query was performed to identify relevant literature on the topic of active surveillance for low risk bladder cancer. English language publications were reviewed and select data presented. Results Available data suggest that only 5% to 10% of patients diagnosed with a low grade appearing papillary bladder tumor will have progression in stage or grade. Coupled with the discomfort and potential for complications associated with transurethral resection, this supports the role of active surveillance for patients with small, recurrent, low risk bladder cancer. In addition, this management strategy stands to benefit the health care system by reducing the costs associated with caring for patients with bladder cancer. Conclusions Active surveillance with delayed intervention represents a safe and cost-effective strategy for patients with recurrent low risk bladder cancer.

SDF-1 is a ligand of the chemokine receptors CXCR4 and 7. The 6 known SDF-1 isoforms are generated by alternative mRNA splicing. While SDF-1 expression has been detected in various malignancies, only few groups have reported differential expression of SDF-1 isoforms and its clinical significance. We evaluated the expression of 3 SDF-1 isoforms (α, β and γ) in bladder cancer.Using quantitative polymerase chain reaction we measured SDF-1α, β and γ mRNA levels in 25 normal and 44 bladder cancer tissues, and in 210 urine specimens (28 normal, 74 benign, 57 bladder cancer, 35 bladder cancer history, 8 other cancer history and 8 other cancer) from consecutive patients. Levels were correlated with clinical outcome.Of the SDF-1 isoforms only SDF-1β mRNA was significantly over expressed 2.5-fold to sixfold in bladder cancer compared to normal bladder tissues. SDF-1α was expressed in bladder tissues but SDF-1γ was undetectable. On multivariate analysis SDF-1β was an independent predictor of metastasis and disease specific mortality (p=0.017 and 0.043, respectively). In exfoliated urothelial cells only SDF-1β mRNA levels were differentially expressed with 91.2% sensitivity and 73.8% specificity for detecting bladder cancer. In patients with a bladder cancer history increased SDF-1β levels indicated a 4.3-fold increased risk of recurrence within 6 months (p=0.0001).SDF-1 isoforms are differentially expressed in bladder tissues and exfoliated urothelial cells. SDF-1β mRNA levels in bladder cancer tissues predict a poor prognosis. Furthermore, SDF-1β mRNA levels in exfoliated cells detect bladder cancer with high sensitivity and they are a potential predictor of future recurrence.

Item does not contain fulltext PURPOSE: Despite being one of the most important clinical outcomes in nonmuscle invasive bladder cancer, there is currently no standard definition of disease progression. Major clinical trials and meta-analyses have used varying definitions or have failed to define this end point altogether. A standard definition of nonmuscle invasive bladder cancer progression as determined by reproducible and reliable procedures is needed. We examine current definitions of nonmuscle invasive bladder cancer progression, and propose a new definition that will be more clinically useful in determining patient prognosis and comparing treatment options. MATERIALS AND METHODS: The IBCG (International Bladder Cancer Group) analyzed published clinical trials and meta-analyses that examined nonmuscle invasive bladder cancer progression as of December 2012. The limitations of the definitions of progression used in these trials were considered, as were additional parameters associated with the advancement of nonmuscle invasive bladder cancer. RESULTS: The most commonly used definition of nonmuscle invasive bladder cancer progression is an increase in stage from nonmuscle invasive to muscle invasive disease. Although this definition is clinically important, it fails to include other important parameters of advancing disease such as progression to lamina propria invasion and increase in grade. CONCLUSIONS: The IBCG proposes the definition of nonmuscle invasive bladder cancer progression as an increase in T stage from CIS or Ta to T1 (lamina propria invasion), development of T2 or greater or lymph node (N+) disease or distant metastasis (M1), or an increase in grade from low to high. Investigators should consider the use of this new definition to help standardize protocols and improve the reporting of progression.

We analyzed the prognostic implications of positive margins and extraprostatic extension missed by different methods of partially sampling prostatectomy specimens.The study group consisted of 1,499 patients treated with radical prostatectomy. All specimens were processed uniformly and submitted entirely. For each patient with a positive margin or extraprostatic extension we determined whether these pathological characteristics would have been diagnosed had the specimen been examined by 3 partial sampling techniques. The Harrell concordance index was used to quantify the predictive performance of the Cox models based on the potential findings of the different sampling methods.Partial sampling methods 1 and 2, which included the examination of alternate slides, missed 13% to 21% of positive margins and 27% to 46% of extraprostatic extensions. The effect on biochemical recurrence-free survival of these undetected pathological features was similar to that of positive margins and extraprostatic extension that would have been diagnosed by corresponding techniques. Method 3, which sampled the entire posterior region, the mid anterior prostate and the rest of the ipsilateral anterior gland (if sizeable tumor was seen), detected 95% of positive margins and 94% of extraprostatic extensions. The extraprostatic extension missed by this method was not associated with a significant increase in the risk of biochemical recurrence. The Harrell concordance index of the multivariate models was 0.806, 0.797, 0.795 and 0.804 based on the results of complete sampling, and methods 1, 2 and 3, respectively.Examining alternate sections of prostatectomy specimen results in missing clinically important positive margins and extraprostatic extension. It decreases our ability to predict biochemical recurrence-free survival.

Currently there is no global agreement as to how ex- tensively a radical prostatectomy specimen should be sectioned and histologically examined. We analyzed the ability of different methods of partial sampling in detecting positive margin (PM) and extraprostatic extension (EPE)—2 pathologic features of prostate cancer that are most easily missed by partial sampling of the prostate. Radical prostatectomy specimens from 617 pa- tients treated with open radical prostatectomy between 1992 and 2011 were analyzed. Examination of the entirely submitted prostate detected only PM in 370 (60%), only EPE in 100 (16%), and both in 147 (24%) specimens. We determined whether these pathologic features would have been diagnosed had the examination of the specimen been limited only to al- ternate sections (method 1), alternate sections representing the posterior aspect of the gland in addition to one of the mid- anterior aspects (method 2), and every section representing the posterior aspect of the gland in addition to one of the mid- anterior aspects, supplemented by the remaining ipsilateral an- terior sections if a sizeable tumor is seen (method 3). Methods 1 and 2 missed 13% and 21% of PMs and 28% and 47% of EPEs, respectively. Method 3 demonstrated better results missing only 5% of PMs and 7% of EPEs. Partial sampling techniques missed slightly more PMs and EPEs in patients with low-risk to intermediate-risk prostate cancer, although even in high-risk cases none of the methods detected all of the studied aggressive pathologic features.

Active surveillance is an established management option for patients with low risk prostate cancer. However, little is known about the characteristics associated with the increased probability of progression in patients on active surveillance. We analyzed our active surveillance cohort in search of such features.A total of 272 men with prostate cancer have enrolled in our active surveillance program since 1994, of whom 249 underwent at least 1 surveillance biopsy and were included in analysis. Our active surveillance inclusion criteria are biopsy Gleason grade less than 7, 2 or fewer positive biopsy cores, 20% or less tumor in any core and clinical stage T1-T2a. Changes in any of these parameters during followup that went beyond these limits were considered progression. Univariate and multivariate Cox regression analysis was done to determine patient characteristics associated with an increased risk of progression.A total of 64 patients (26%) showed progression at a median 2.9-year followup on a mean of 2.3 surveillance biopsies. The progression risk was significantly increased in black patients (adjusted HR 3.87-4.12), and in men with a smaller prostate and higher prostate specific antigen density. The latter 2 variables had no specific cutoff for an association with progression.Black men with low risk prostate cancer should be advised that the risk of progression on active surveillance may be higher than that in the available literature. Integral prognostic tools incorporating race and prostate specific antigen density may be useful to accurately assess the individual risk of progression in patients on active surveillance.

Molecular characterization of renal cell carcinoma may help differentiate benign oncocytoma from malignant renal cell carcinoma subtypes and predict metastasis. Chemokines, eg IL-8 and chemokine receptors such as CXCR4 and 7, promote inflammation and metastasis. SDF-1 is a CXCR4 and 7 ligand with 6 known isoforms. We evaluated the expression of these chemokines and chemokine receptors in kidney specimens.Using quantitative polymerase chain reaction we measured mRNA levels of IL-8, CXCR4 and 7, and SDF1 isoforms α, β and γ in a total of 166 specimens from 86 patients, including 86 tumor samples and 80 matched normal kidney samples. Mean ± SD followup was 18.9 ± 12 months (median 19.5). Renal cell carcinoma specimens included the clear cell, papillary and chromophobe subtype in 65, 10 and 5 cases, respectively, and oncocytoma in 6. A total of 17 cases were positive for metastasis.Median CXCR4 and 7, and SFD1-γ levels were increased twofold to tenfold. SDF1-α and β were unchanged or lower in clear cell renal cell carcinoma and papillary tumors than in normal tissue. Median SDF1-γ, IL-8, and CXCR4 and 7 were increased threefold to fortyfold in chromophobe tumors compared to oncocytoma. CXCR4 and 7 were increased in tumors less than 4 cm (mean 3,057 ± 2,230 and 806 ± 691) compared to oncocytoma (336 ± 325 and 201 ± 281, respectively, p ≤0.016). On multivariate analysis CXCR4 (p = 0.01), CXCR7 (p = 0.02) and SDF1-β (p = 0.005) were independently associated with metastasis. Combined CXCR7 plus SDF1-α and CXCR7 plus IL-8 markers showed the highest sensitivity (71% to 81%) and specificity (75% to 80%) of all individual or combined markers.Chemokines and chemokine receptors differentiate renal cell carcinoma and oncocytoma. Combined SDF1-α plus CXCR7 and IL-8 plus CXCR7 markers have about 80% accuracy for predicting renal cell carcinoma metastasis.

Prostate cancer is the most common cancer diagnosed in men and remains the second most lethal malignancy. Most patients undergoing treatment elect for radical prostatectomy or radiation. As the number of patients treated has increased and survival improved, delayed complications of these modalities has assumed increased importance. Recent studies report an increased risk of certain cancers after radiation for prostate cancer. This review aims to summarize recent data.Recent studies have confirmed the association of prostate radiation with secondary cancers. The most common secondary malignancy is bladder carcinoma. We have treated 44 patients with bladder cancer who had radiation therapy for prostate cancer. At diagnosis, 60% had tumor, which invaded the bladder muscle (T2 or greater disease). The mean latency from radiation to diagnosis of bladder cancer was 5.5 years.Radiation therapy for prostate cancer is associated with an increased risk of bladder cancer. In our series, patients presented at higher stage than expected from population-based studies of bladder cancer. Patients and their physicians should be aware of such risks when choosing therapy for prostate cancer. Hematuria following radiation therapy for prostate cancer should be investigated rather than being attributed to radiation-induced cystitis.

Intravesical therapy is an integral part of treatment in patients with superficial urothelial carcinoma of the bladder. The American Urological Association and European Association of Urology guidelines on bladder cancer incorporate it for the treatment of superficial bladder cancer. Given the extensive use of intravesical immunotherapy and chemotherapy, it is essential for the practicing urologist to be aware of the local and systemic side effects of these therapies.We reviewed the literature on intravesical immunotherapy and chemotherapy with particular emphasis on side effects, complications and their management. A Medline search of the English language literature for the last 25 years was done on Entrez PubMed and all relevant articles were studied in full. All side effects and complications were studied and their management was reviewed.Intravesical therapy for transitional cell carcinoma of the bladder is generally safe. There is a high incidence of local, usually self-limiting, relatively minor side effects and infrequent, potentially severe local and systemic side effects. Most side effects are avoidable.Although intravesical therapy is generally safe, local and systemic side effects occur and it is important to be aware of them. Identifying complications early, preventing them when possible and managing them efficiently are critical. Most complications are preventable. Knowing the risks and benefits of chemotherapeutic and immunotherapeutic agents may decrease the short-term and long-term toxicity of these agents. Adherence to guidelines may prevent inappropriate use, which can lead to unnecessary complications, resulting in bladder dysfunction and even cystectomy.

We examined the implications of underestimating Gleason score by prostate biopsy in patients with biopsy Gleason 6 prostate cancer with respect to adverse pathological findings and biochemical recurrence after radical prostatectomy.We retrospectively reviewed clinical and pathological data on a cohort of 531 patients with Gleason score 6 on prostate biopsy who underwent radical retropubic prostatectomy between June 1992 and January 2002. Patients were excluded if they received neoadjuvant androgen deprivation. Concordance between biopsy and radical prostatectomy Gleason score was examined. A comparison was made with respect to final radical prostatectomy specimen pathology and the risk of biochemical recurrence between cases that remained Gleason 6 and those with a final grade of 7 or greater.A total of 451 patients were included in the analysis. Mean followup was 55.1 months (range 12 to 123.4). Of the patients 184 (41%) had a Gleason score of 7 or greater after a review of the entire prostate, while 37 (8%) had a score of less than 6 and 230 remained with Gleason 6. Patients who were under graded were more likely to have extraprostatic extension (22% vs 4%, p0.01), seminal vesicle invasion (9% vs 2%, p0.01) and biochemical recurrence (10% vs 3%, p0.01) compared to those who remained with Gleason score 6.Gleason grade on needle biopsy is an inexact predictor of the final grade following radical prostatectomy. Patients with biopsy Gleason score 6 who are under graded are at significantly higher risk for adverse pathological features and biochemical recurrence than patients who remain with Gleason score 6 or less on final pathology findings.

Purpose: We assessed the effect of location and number of positive margins on biochemical progression in patients after radical retropubic prostatectomy for prostate cancer.Materials and Methods: 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.Results: 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. Pati...

Purpose Stroma-Derived Factor (SDF)-1 is a ligand for chemokine receptors CXCR4 and CXCR7. The six known SDF-1 isoforms are generated by alternative mRNA splicing. While SDF-1 expression has been detected in various malignancies, only a few studies have reported differential expression of SDF-1 isoforms and its clinical significance. In this study we evaluated the expression three SDF-1 isoforms (α,β,γ) in bladder cancer (BCa).

(G1, G2); sum of G1 and tertiary Gleason pattern (G3) if >G2. The Goodman-Kruskal gamma statistic (g) was used as a measure of agreement. RESULTS: Median age was 65 years (51-78) with median PSA 8.2 ng/ml (1.7-53). Final GS was 6 (14%), 7 (68%), and 8-9 (18%); a G3 was assigned in 18 (32%) men. In the 57 men, 107 MRI targets for biopsy were identified, 60/107 (56%) of which were CaP positive; Tbx yielded CaP in more men than MBx (84% versus 70%). Max GG was detected by Mbx in 52%, by Tbx in 60%, and by the combination in 82% of cases. The upgrading rate was 16% when both the Mbx and Tbx were combined. One case was downgraded on final pathology (2%). The combination of Tbx (g1⁄40.43-0.48) and Mbx (g1⁄40.56-0.68) were needed to obtain the best predictive accuracy (g1⁄40.89-0.97) (table). CONCLUSIONS: Use of MR-US fusion biopsy allows for prediction of final prostate pathology with greater accuracy than that reported using conventional methods. Accurate knowledge of wholeorgan pathology, provided by fusion biopsy, has important clinical implications.

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.

Purpose: We reviewed currently available bladder cancer tests in the context of the clinical expectations of a noninvasive bladder cancer test.Materials and Methods: We reviewed the literature on bladder cancer tests that are commercially available or have shown clinical usefulness and examined how each test compares with standard methods of bladder cancer diagnosis.Results: The clinical necessity for a noninvasive test for bladder cancer is 2-fold, including the early detection of high grade bladder tumors before muscle invasion and monitoring tumor recurrence or new onset. An ideal noninvasive test should be sensitive, specific, rapid, technically simple and have low intra-assay and interassay variability. Urine cytology has high specificity but limited applicability due to its relatively low sensitivity and subjective nature. Hematuria detection by Hemastix * *Bayer Corp., Elkhart, Indiana. dipstick is sensitive but not specific for detecting bladder cancer. Molecules associated with bladder tumor grow...

We reviewed our radical cystectomy series to determine whether the majority of patients present with muscle invasive bladder cancer.The records of 184 radical cystectomies performed by 1 surgeon from 1992 to 1999 were reviewed, and all slides of presenting pathology were reviewed by 1 pathologist. The pathological stage of the tumor at presentation was noted in each case, and the number of muscle invasive tumors at presentation was compared to 2 earlier series.Radical cystectomy was performed for muscle invasive transitional cell carcinoma of the bladder in 176 cases and for other histology in 8. There were 101 (57.3%) patients with muscle invasive cancer at presentation compared to 84% and 91% in the 2 earlier series, respectively, which was a statistically significant decrease (p0. 0001) in the number of de novo muscle invasive bladder cancers. Women were more likely to be diagnosed with muscle invasion primarily than men (85.2% and 50.7%, respectively), and younger patients (younger than 50 years) were more likely to present with superficial bladder cancer compared to those older than 50 years who were more likely to present with de novo muscle invasive bladder cancer.Analysis of our data supports the findings of the earlier series that the majority of patients present with muscle invasive bladder cancer. However, there is a significant decrease in the percentage of tumors invading the muscularis propria at presentation. Although this observation is encouraging, we emphasize that it is not as dramatic as the stage migration associated with prostate cancer, which may be largely attributed to the widespread use of prostate specific antigen for early detection. Therefore, we support the suggestion that therapeutic gains might follow from improved education regarding the signs and symptoms associated with bladder cancer, with enhanced focus on women and consideration of screening methods for those at high risk for bladder cancer.

Purpose: With the advent of prostate specific antigen (PSA) testing and transrectal ultrasound guided prostate biopsy there has been stage migration in the diagnosis of prostate cancer, so that more younger men are being diagnosed with organ confined prostate cancer. Many patients elect radiation therapy, while some have recurrent or new prostate cancer with absent systemic disease and life expectancy greater than 10 years. We present our experience with salvage radical prostatectomy in these cases.Materials and Methods: Between 1995 and 2000, 6 men treated with curative intent with radiotherapy for prostate cancer were subsequently treated with salvage surgery for clinically localized prostate cancer. All men had biopsy proved recurrent or persistent prostate cancer, increasing serum PSA, no evidence of systemic disease at surgery and life expectancy greater than 10 years. We assessed the morbidity associated with this procedure and compared results to those in the contemporary literature.Results: Six pa...

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.

Specific patterns of progression and frequent recurrence of bladder tumors determine the choice of treatment, frequency of surveillance, quality of life, and ultimately, patient prognosis. The prognosis would be improved if an accurate noninvasive test was available for diagnosis. Identification of markers that function in bladder cancer progression would be helpful in designing such diagnostic tests. The glycosaminoglycan, hyaluronic acid (HA), promotes tumor metastasis. Hyaluronidase (HAase), an endoglycosidase, degrades HA into small fragments that promote angiogenesis. We have previously shown that both HA and HAase are associated with bladder cancer and may function in bladder tumor angiogenesis. In this study we examined whether urinary HA and HAase levels serve as bladder cancer markers.Among the 513 urine specimens analyzed, 261 were from transitional cell carcinoma (TCC) patients, 9 from patients with non-TCC tumors, and 243 from controls (normals, patients with other genitourinary (GU) conditions or a history of bladder cancer (HxBCa)). The urinary HA and HAase levels were measured by two ELISA-like assays that utilize a biotinylated HA binding protein for detection. These levels were normalized to total urinary protein and were expressed as ng./mg. (HA test) and mU/mg. (HAase test), respectively.The urinary HA levels were elevated (2.5 to 6.5 fold) in bladder cancer patients (1173.7+/-173.4; n = 261) as compared with normals (246.1+/-38.5; n = 41); GU patients (306.6+/-32.2; n = 133), and patients with a HxBCa (351.1+/-49.1; n = 69) (p0.001). The urinary HAase levels were elevated (3 to 7 fold) in G2/G3 bladder cancer patients (26.2+/-3.2) as compared with normals (4.5+/-0.9) and patients with either GU conditions (5.8+/-1.3), HxBCa (8.2+/-2.6) or G1 tumors (9.7+/-2.5) (p0.001). The HA test showed 83.1% sensitivity, 90.1% specificity and 86.5% accuracy in detecting bladder cancer, regardless of the tumor grade. The HAase test showed 81.5% sensitivity, 83.8% specificity and 82.9% accuracy to detect G2/G3 patients. Combining the inferences of the HA and HAase tests (HA-HAase test) resulted in detection of bladder cancer, regardless of tumor grade and stage, with higher sensitivity (91.2%) and accuracy (88.3%), and comparable specificity (84.4%).Our results show that the HA-HAase urine test is a noninvasive, highly sensitive and specific method for detecting bladder cancer and evaluating its grade.

Purpose: During radical prostatectomy for prostate cancer tumor at the surgical margin is a relatively frequent finding. We summarize the literature on the incidence, etiology, location, prevention and treatment of positive surgical margins after radical prostatectomy.Materials and Methods: The literature was reviewed for data on positive margins during radical prostatectomy for prostate cancer.Results: Positive surgical margins may result from artifacts induced by tissue processing, incising inadvertently into the prostate or incising into extraprostatic tumor that has extended beyond the limits of resection. Patients with 10 ng./ml. or greater preoperative prostate specific antigen, biopsy Gleason score 7, multiple positive biopsies, or clinical stage T2b, T2c or T3 cancer have a higher risk of positive margins. Preoperative endorectal magnetic resonance imaging may be useful in staging a select group of patients. Neoadjuvant androgen deprivation reduces the incidence of positive margins but doe...

INTRODUCTION AND OBJECTIVES: Active surveillance (AS) for low-risk prostate cancer (LRPC) is becoming more accepted alternative to treatment. However, there is always a risk of Gleason score under-grading by trans-rectal ultrasound (TRUS) guided biopsy. Our aim is to assess the risk of having high grade PC in AS patients by describing the outcomes of patients who met our AS protocol and underwent radical prostatectomy (RP) immediately after diagnosis. METHODS: Between 1992 and 2012, 2354 men underwent RP at our institution. We identified men who met our AS criteria and elected to undergo RP immediately after diagnosis. Our AS protocol criteria are Gleason score of 6, PSA 15.0 ng/dl, 2 positive cores on TRUS biopsy, and tumor volume not to exceed 20% in any of the positive cores. We described the pathological and biochemical recurrence free survival outcomes of these patients. RESULTS: 624 (26.5%) patients met the AS criteria. The mean age was 59.5 years (36-79), mean PSA was 6.0 (0.5-15.0) and mean follow-up was 60 (1.0-219.0) months. The mean percentage of tumor involvement in the final pathology was 9% (1.0-50.0). Twenty one (3.4%) patients had high grade Gleason score (8-10), 173 (27.7%) had Gleason 7 on the final pathology. Thirty six (5.8) had extra-prostatic extension (EPE) and 19 (3.0%) had seminal vesicle invasion (SVI). Only one patient (0.2%) had one positive lymph node. Table1. The 2 and 5 years recurrence free survival was 94.4%, 83.4% respectively. CONCLUSIONS: Among AS candidates, the risk of harboring high grade PC is 3.4% and the risk of having intermediate grade is 27.7%. This is more or less equal to the risk of progression on surveillance TRUS biopsies. Patients electing AS need to be counseled about their risk of having extraprostatic disease and harboring a high or intermediate grade PC. Table1. Risk of upgrading and upstaging. Estimatedrisk Upgrading of Gleason score 31.1 % Upgrading to Gleason 7 27.7% Upgrading to Gleason 8-10 3.4% EPE 5.8% SVI 3.0% Lymph nodes involvement 0.2% EPE; extra prostatic extension, SVI; seminal vesicle invasion.

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 ...

We evaluated the ability of an immunoassay for nuclear matrix protein 22 (NMP22 test kit) to predict the subsequent disease status of patients with transitional cell carcinoma of the urinary tract at approximately 10 days after transurethral resection of bladder tumor.A total of 90 patients with transitional cell carcinoma provided voided urine samples at least 5 days postoperatively. NMP22 was determined using a commercial test kit. At initial cystoscopic examination 3 to 6 months later the disease status was recorded, and the NMP22 values before and after transurethral resection of bladder tumor were compared.Of 125 followup cystoscopic examinations (60 patients had 1, 26 had 2, 3 had 3 and 1 had 4 recurrences) transitional cell carcinoma was pathologically confirmed in 33. No malignancy was present at 79 examinations (if tumor was seen endoscopically, pathological evaluation indicated atypia, dysplasia or no abnormality). NMP22 values in these 2 populations were significantly different (malignancy median 20.81 units per ml. and no malignancy median 5.72 units per ml., Mann-Whitney U test for differences between 2 medians p = 0.00005). Of the 33 recurrences 23 (70%) had NMP22 values greater than the reference range (10 units per ml.). Additionally, NMP22 identified all 6 subjects (100%) who had invasive disease 3 to 6 months later. Of 72 patients with NMP22 less than 10 units per ml. 62 (86%) had no malignancy at subsequent cystoscopy.NMP22 was highly predictive of tumor status at followup cystoscopy. This quantitative, noninvasive assay, with high negative predictive value (86%) and sensitivity to detect malignancy (100% for invasive disease and 70% overall), may be a helpful adjunct to cytology and endoscopy for monitoring disease status after endoscopic tumor resection.

Purpose: The impact of radical prostatectomy and external beam radiotherapy on the quality of life of patients was compared.Materials and Methods: A total of 136 patients underwent radical prostatectomy and 60 underwent external beam radiotherapy for clinically localized prostate cancer. Patients were asked to complete a questionnaire containing The Functional Living Index: Cancer, the Profile of Moods States, and a series of questions evaluating bladder, bowel and sexual function.Results: The radical prostatectomy group had worse sexual function and urinary incontinence, while the external beam radiotherapy group had worse bowel function. Of the patients 90 percent from both groups stated that they would undergo the treatment again.Conclusions: Radical prostatectomy and external beam radiotherapy have comparable impact upon quality of life.

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 surg...

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.

We reassessed the role of routine pelvic cavity drainage to prevent complications after radical retropubic prostatectomy (RRP).RRP was performed in 116 consecutive patients with clinically localized adenocarcinoma of the prostate. Clinical and pathological information was recorded for each patient. After the prostate was removed and the anastomotic sutures were tied the bladder was filled with saline through the urethral catheter. If there was no significant leakage, a drain was not placed.We did not place a drain in 85 of the 116 patients (73%). There were 3 immediate postoperative complications. In a patient without a drain, a urinoma developed that required percutaneous placement of a drain on postoperative day 2. None of the 116 patients had clinical evidence of infection, lymphocele or hematoma. Two patients had hematuria 2 weeks after catheter removal and needed bladder irrigation. Neither patient had a drain. Three patients (drain and no drain in 1 each) were in urinary retention after catheter removal, which required catheter reinsertion for an additional week. None had an anastomotic stricture.The morbidity of RRP is low when performed by those who regularly perform this procedure. If the bladder neck is preserved or meticulously reconstructed, there may be little or no extravasation and, thus, routine drainage may be unnecessary. In properly selected cases morbidity is not increased by omitting a drain from the pelvic cavity after RRP.

Some patients report that the penis is smaller after radical retropubic prostatectomy for prostate cancer. We performed a prospective study which measured penile length before and after radical retropubic prostatectomy.A total of 124 men consented to penile measurements before radical prostatectomy performed by the same surgeon. Repeat measurements were performed at 3-month intervals following surgery. Penile measurements (cm.) consisted of flaccid length, stretched length, depth of prepubic fat pad and circumference. Statistical analysis of penile measurements was performed using the paired samples and independent Student's t test, Pearson's correlation and analysis of variance.Mean patient age was 59.1 (range 42 to 76). No patient had a penile abnormality, for example Peyronie's disease, or history of penile or urethral surgery. The size of the penis was significantly smaller after prostatectomy, and there was a significant difference for flaccid (p0.001), stretched (p0.001), prepubic fat pad (p = 0.02) and circumference measurements (p0.01). Twelve patients (19%) had a 15% or greater decrease in stretched penile length. When dichotomizing groups at the cut point of 15% decrease, the independent t test of prostate size was not significant (t[df 36.7] = -1.83, p = 0.076). Nerve sparing was not significant in relation to change in penile stretched length, (F[df 2, 62] = 0.501, p = 0.609).Our findings support observations of decreased penile length after radical prostatectomy. Men should be counseled before radical prostatectomy that penile shortening may occur.