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Patients with one or more low-grade bladder tumors of the urinary bladder will often develop a subsequent tumor but these so called "recurrences" are almost always of similar grade and rarely invade beyond the basement membrane. Therefore, the clinician should try to minimize the morbidity associated with treating these new tumors. Since many of these patients are elderly or have comorbidities, active surveillance is a very reasonable initial approach if these tumors are very small and appear low-grade. Another alternative is fulguration in the outpatient setting using a flexible cystoscope and electrode. The goal is to try to avoid the hospital and performing a formal transurethral resection. This adds potential morbidity, inconvenience, and cost.

Purpose: To determine whether implementation of the 2004 WHO/ISUP bladder cancer (BCa) grading system caused a grade migration, i.e., more tumors being graded as high grade (HG)., Methods: Data on 1040 BCa cases from 668 patients treated at our institution between 2000 and 2013 and reviewed by six pathologists were evaluated: low grade (LG): 249; HG: 791; Ta: 389; T1: 214; CIS: 95; ≥T2: 342. Differences in LG or HG cases (expressed as %BCa cases/year) were analyzed by Mann-Whitney test. Correlation between the year of diagnosis and clinical/pathological parameters was evaluated by logistic regression analyses., Results: During the study period, BCa cases diagnosed as LG significantly decreased with a corresponding increase in HG cases. Nonlinear regression analysis indicated that ~2008 was the crossover point for grade migration; %LG: 31.8 ± 4.8 (2000-2007); 14.1 ± 7.0 (2008-2013); %HG: 68.2 ± 4.8 (2000-2007); 85.9 ± 6.9 (2008-2013), P = 0.004. The grade migration was confined to Ta cases with %LG Ta cases diagnosed decreasing by 3.6-fold from 2000-2007 to 2008-2013 (P = 0.004). Univariate and multivariate analyses confirmed the grade migration following the adoption of the 2004 system (P < 0.0001). Kaplan-Meier curves showed no significant differences between the two time intervals in terms of disease progression (P > 0.05)., Conclusions: Implementation of the 2004 WHO/ISUP system caused a significant increase in pathologists grading Ta cases as HG; however, this increase did not seem to correlate with disease progression. Since LG and HG Ta tumors are treated differently, grade migration may impact the clinical management of BCa patients.

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.

Context: Cigarette smoking is an established risk factor for urothelial carcinoma., Objective: To elucidate the association between pretreatment smoking status, cumulative exposure, and time since smoking cessation and the development of and outcomes for urothelial carcinoma of the bladder (UCB) in patients treated with transurethral resection of the bladder (TURBT) or radical cystectomy (RC)., Evidence Acquisition: A literature search was performed in September 2014 using the PubMed and Scopus databases limited to articles published in English since 1990. Eight contemporary studies on smoking and UBC development and 26 studies on smoking and UBC prognosis met the inclusion criteria., Evidence Synthesis: Current cigarette smoking increases the risk of UCB incidence by two to fourfold, while smoking cessation attenuates this risk. Smoking status, exposure, and cessation have an evident impact on disease recurrence for patients who undergo TURBT, with weaker associations between smoking and other endpoints for TURBT and RC patients., Conclusion: Retrospective evidence suggests that smoking markedly increases UCB risk and may lead to unfavorable outcomes for patients who already have UCB; smoking cessation can attenuate these undesirable effects., Patient Summary: Current evidence proves that cigarette smoking is an established risk factor for the development of urothelial carcinoma of the bladder (UCB). There is a growing body of evidence that smoking negatively affects outcomes for UCB patients treated with transurethral resection and/or radical cystectomy, although not uniformly. Long-term smoking cessation seems to mitigate the detrimental effects of smoking in non-muscle-invasive and muscle-invasive bladder cancer., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

The International Consultations on Urological Diseases are international consensus meetings, supported by the World Health Organization and the Union Internationale Contre le Cancer, which have occurred since 1981. Each consultation has the goal of convening experts to review data and provide evidence-based recommendations to improve practice. In 2012, the selected subject was bladder cancer, a disease which remains a major public health problem with little improvement in many years. The proceedings of the 2nd International Consultation on Bladder Cancer, which included a 'Pathology of Bladder Cancer Work Group,' have recently been published; herein, we provide a summary of developments and consensus relevant to the practicing pathologist. Although the published proceedings have tackled a comprehensive set of issues regarding the pathology of bladder cancer, this update summarizes the recommendations regarding selected issues for the practicing pathologist. These include guidelines for classification and grading of urothelial neoplasia, with particular emphasis on the approach to inverted lesions, the handling of incipient papillary lesions frequently seen during surveillance of bladder cancer patients, descriptions of newer variants, and terminology for urine cytology reporting., Competing Interests: Disclosure/conflict of interest The authors declare no conflict of interest.

Introduction: To evaluate the potential significance of cystoscopy findings following neoadjuvant chemotherapy (NAC) as prognostic indicator in patients undergoing radical cystectomy for muscle-invasive bladder cancer (MIBC)., Materials and Methods: Patients who received NAC prior to radical cystectomy for MIBC were analyzed. Patients were divided into two groups according to cystoscopy performed after two cycles of NAC: responders and non-responders. Univariate analysis was performed to analyze associations between observed response to chemotherapy and pT stage, pN stage and tumor downstaging. Logistic regression modeling was fitted to evaluate predictors for extravesical disease and pathologic downstaging. Kaplan-Meier analysis was used to evaluate disease specific survival., Results: We identified 101 patients who received neoadjuvant chemotherapy prior to radical cystectomy. According to the cystoscopy findings, 60 patients (59%) were identified as responders to NAC. Stage pT0 at cystectomy was confirmed in 22 patients (36.5%) in the responder group versus only 1 patient (2.5%) in the non-responder group. Univariate analysis showed statistically significant association between response to chemotherapy observed on cystoscopy and pT stage as well as tumor downstaging. Multivariate regression modeling revealed that cystoscopy findings were an independent predictor of extravesical disease and pathologic downstaging. There was a distinct survival benefit in NAC responder group (p < 0.001). Cox proportional hazard model identified cystoscopy findings as an independent predictor of survival (OR 0.38, 95% CI 0.20-0.74, p = 0.004)., Conclusions: Observed response to NAC on follow up cystoscopy is associated with favorable pathological outcomes and is a significant predictor of survival in patients undergoing radical cystectomy for MIBC.

Purpose: 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., Materials and Methods: 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., Results: 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., Conclusions: 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., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: 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., Materials and Methods: 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., Results: 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)., Conclusions: 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., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

A complete transurethral resection of a bladder tumor (TURBT) is essential for adequately diagnosing, staging, and treating bladder cancer. A TURBT is deceptively difficult and is a highly underappreciated procedure. An incomplete resection is the major reason for the high incidence of recurrence following initial transurethral resection and thus to the suboptimal care of our patients. Our objective was to review the preoperative, intraoperative, and postoperative considerations for performing an optimal TURBT. The European Association of Urology, Society of International Urology, and The American Urological Association guidelines emphasize a complete resection of all visible tumor during a TURBT. This review will emphasize the various techniques and treatments, including photodynamic cystoscopy, intravesical chemotherapy, and a perioperative checklist, that can be used to help to enable a complete resection and reduce the recurrence rate. A Medline/PubMed search was completed for original and review articles related to transurethral resection and the treatment of non-muscle-invasive bladder cancer. The major findings were analyzed and are presented from large prospective, retrospective, and review studies.

Background: Most newly diagnosed bladder cancers present as non-muscle invasive bladder cancer (NMIBC). NMIBC is a heterogeneous disease with varying treatment options, follow-up schedules, and oncologic outcomes. We sought to review the role of active surveillance for low risk bladder cancer in the literature., Methods: A PubMed search was performed using the following keywords: active surveillance, low risk, bladder, transurethral resection of bladder tumor, cost, and quality of life. Relevant articles were reviewed and utilized., Results: Low-risk bladder cancer--defined as pTa low-grade papillary tumors--is the type of NMIBC with the most favorable oncologic outcome and which almost never progresses to muscle invasive disease or metastasizes. Bladder cancer has the highest per patient treatment costs of all cancers. One of the reasons is the high rate of recurrence. Patients with low-grade bladder tumors often experience a recurrence after primary transurethral resection. Many patients undergo multiple resections in the hospital., Conclusions: Appropriately selected patients with recurrent low-risk bladder cancer could be managed with either office fulguration or cystoscopic surveillance. Active surveillance for patients with low-risk bladder cancer avoids or delays the surgical and anesthetic risks of a TURBT, thus optimizing quality of life without compromising the patient's risk of cancer progression., (Published by Elsevier Inc.)

Background: Many patients with low-risk prostate cancer (PC) who are diagnosed with Gleason score 6 at biopsy are ultimately found to harbor higher grade PC (Gleason ≥ 7) at radical prostatectomy. This finding increases risk of recurrence and cancer-specific mortality. Validated clinical tools that are available preoperatively are needed to improve the ability to recognize likelihood of upgrading in patients with low-risk PC., Methods: More than 30 clinicopathologic parameters were assessed in consecutive patients with Gleason 6 PC upon biopsy who underwent radical prostatectomy. A nomogram for predicting upgrading (Gleason ≥ 7) on final pathology was generated using multivariable logistic regression in a development cohort of 431 patients. External validation was performed in 2 separate cohorts consisting of 1151 patients and 392 patients. Nomogram performance was assessed using receiver operating characteristic curves, calibration, and decision analysis., Results: On multivariable analysis, variables predicting upgrading were prostate-specific antigen density using ultrasound (odds ratio [OR] = 229, P = .003), obesity (OR = 1.90, P = .05), number of positive cores (OR = 1.23, P = .01), and maximum core involvement (OR = 0.02, P = .01). On internal validation, the bootstrap-corrected predictive accuracy was 0.753. External validation revealed a predictive accuracy of 0.677 and 0.672. The nomogram demonstrated excellent calibration in all 3 cohorts and decision curves demonstrated high net benefit across a wide range of threshold probabilities. The nomogram demonstrated areas under the curve of 0.597 to 0.672 for predicting upgrading in subsets of men with very low-risk PC who meet active surveillance criteria (all P < .001), allowing further risk stratification of these individuals., Conclusions: A nomogram was developed and externally validated that uses preoperative clinical parameters and biopsy findings to predict the risk of pathological upgrading in Gleason 6 patients. This can be used to further inform patients with lower risk PC who are considering treatment or active surveillance., (Copyright © 2013 American Cancer Society.)

Prostate cancer (PC) is the most often diagnosed non-skin cancer and the second leading cause of cancer-related death among men in the United States. As a result, for many years the American Urological Association (AUA) and the American Cancer Society have issued statements recommending screening for PC, resulting in its widespread implementation in the United States. Recently, the United States Preventative Services Task Force gave PC screening a recommendation of D, that is, against PC screening for all men. The AUA countered this recommendation, stating that since the development of PC screening using prostate-specific antigen, a reduction in PC-specific mortality has been seen, and that the risk reduction occurred in a setting in which many of the patients were not aggressively treated for prostate cancer. Active surveillance may be described as a method to potentially delay or obviate the need for treatment in men with clinically insignificant PC or PC thought to be at low risk for progression. Studies have shown no significant difference in outcome or pathology between men with low risk PC who receive treatment at the point of progression and those undergoing immediate treatment. Ongoing studies are evaluating the efficacy and utility of active surveillance for low-risk PC. Interim results of these studies have shown that approximately 30% of patients progress on active surveillance. However, "progression" does not necessarily mean treatment failure; rarely do patients develop locally advanced or metastatic disease. Active surveillance has also been shown to be cost-effective when compared with immediate treatment for PC. Longer follow-up may continue to show an increased benefit of active surveillance as a reasonable initial approach to the management of men with low-risk, clinically localized PC.

Purpose: This study aimed to identify non-neoplastic pathologic changes in partial nephrectomy specimens of patients without a known history of medical comorbidities. Routine analysis of this tissue may allow the clinician to identify subclinical renal disease., Methods: We retrospectively reviewed our database of patients who underwent open partial nephrectomy for a small renal mass. Non-neoplastic tissue of partial nephrectomy specimens of patients without a known history of chronic kidney disease, diabetes mellitus, hypertension, or coronary artery disease was evaluated for glomerular, interstitial, and vascular pathologic changes., Results: A rim of non-neoplastic tissue was adequate for pathologic evaluation in 91.8% of specimens. A total of 45 patients were studied with a median age of 52.0 years. Atherosclerosis was the most commonly identified pathologic finding in 9 (20%) patients, followed by mesangial expansion and interstitial fibrosis, each found in 8 (17.8%) patients. Linear regression found interstitial fibrosis to be the only pathologic lesion associated with preoperative serum creatinine (coefficient = 0.697, P = 0.001). Male gender was also associated with a higher preoperative creatinine (coefficient = 0.270, P = 0.034). Postoperative serum creatinine was not associated with any of the examined lesions., Conclusions: Current surgical techniques provide adequate non-neoplastic tissue for pathologic evaluation. We observed a striking degree of pathologic disease in patients without a known history of medical comorbidities. Routine inspection of the non-neoplastic parenchyma of partial nephrectomy specimens should be performed as it can alert the clinician to presence subclinical renal disease allowing for medical intervention.

Purpose: We analyzed the prognostic implications of positive margins and extraprostatic extension missed by different methods of partially sampling prostatectomy specimens., Materials and Methods: 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., Results: 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., Conclusions: 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., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: Radical prostatectomy (RP) and radiation therapy are standard curative approaches for low-risk prostate cancer (PC). Active surveillance (AS) is becoming an increasingly accepted management alternative for low-risk PC. Our aim is to compare the cumulative medical costs of treatment vs. AS., Methods and Materials: We collected data on the cumulative medical costs of open radical retropubic prostatectomy (RRP), robotic-assisted radical prostatectomy (RARP), external beam radiotherapy (EBRT), brachytherapy (BT), and AS at our institution. For physicians' reimbursements, Medicare values of our region were used to maintain uniformity. For inpatient costs other than reimbursements, we used the mean cost at our institution. The costs of RRP and RARP involve preoperative investigations, medical clearance, physicians' fees, inpatient costs, and pathologic examination of prostatectomy specimen and follow-up. The inpatient costs include the operating room, disposable equipment, anesthesia, post-anesthesia care, transfusion, and hospital stay. The cost of EBRT involves the cost of consultation, planning, simulation and treatment sessions, and follow-up. BT costs involved radiotherapy planning as well as inpatients costs. AS protocol involves regular visits, transrectal ultrasound guided biopsies, prostate specific antigen (PSA) testing. To evaluate the cost of treating complications, treatment after AS, and treatment for recurrence, we created a Markov model based on recent studies and our experience., Results: The cumulative costs of RRP are $9,732 (1 year), $10,360 (2 years), $12,209 (5 years), and $15,084 (10 years). While for RARP, the costs are $17,824 (1 year), $18,308 (2 years), $20,117 (5 years), and $22,762 (10 years). The costs of EBRT are $20,730 (1 year), $20,969 (2 years), $22,043 (5 years), and $23,953 (10 years). BT costs are $14,061 (1 year), $14,300 (2 years), $15,374 (5 years), and $17,284 (10 years). The costs of AS are $1,154 (1 year), $2,308 (2 years), $8,761 (5 years), and $13,116 (10 years)., Conclusions: The cumulative medical costs of RARP and EBRT are much higher than BT, RRP, and AS. AS is associated with a different cost distribution in which the initial cost is low and relatively higher cost of follow-up. Despite the higher follow-up cost, AS remains the most cost effective alternative for low-risk PC., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To develop a clinical tool that integrates different risk factors and provides individual predictions of the risk of biopsy progression in patients with prostate cancer managed by active surveillance., Materials and Methods: Our analysis included 205 patients on active surveillance, each of whom had had at least two surveillance biopsies. We used the Cox proportional hazard regression model to analyse the association between different risk factors and progression-free survival over successive biopsies. This multivariate model was then used to develop a nomogram. Discrimination and calibration of the nomogram were internally validated using 200 bootstrap resamplings., Results: The median follow-up of patients free of progression was 4.6 years. A total of 58 (28%) patients experienced progression. Factors significantly associated with progression were: overall number of positive cores in the diagnostic and first surveillance biopsies, race and prostate-specific antigen density. The bootstrapping concordance index of the nomogram including these variables was 81%. The nomogram tended to underestimate the probability of progression but it identified fairly accurately the distinct groups of patients at low, intermediate and high risk of progression., Conclusions: In the development cohort, the nomogram was able to separate patients with respect to their risk of biopsy progression. Since accurate risk stratification is essential to optimize patient care, this tool, if external validation confirms its performance, may prove useful for both the counselling and management of patients with low-volume, Gleason 6 prostate cancer., (© 2013 BJU International.)

Context: Bladder cancer (BCa) is the fourth most common cancer in men. Survival from the disease has not improved in the last 25 yr. Population-based screening theoretically provides the best opportunity to improve the outcomes of aggressive BCa., Objective: To review the current literature regarding the usefulness and feasibility of screening for bladder cancer., Evidence Acquisition: We conducted a nonsystematic review restricted to English using the keywords urinary bladder neoplasms, mass screening, mandatory testing, and early detection of cancer. We retrieved 184 articles and selected 22., Evidence Synthesis: There was no level 1 evidence (obtained from a randomised controlled trial [RCT]) addressing the impact of screening on BCa survival or tumour downstaging. No study assessed the diagnostic performance of urinary markers in the context of screening. Two case-control series suggested a benefit of screening on survival, and a third found a nonsignificant beneficial trend in favour of screening. Two studies suggested downstaging of BCa at diagnosis. Other reports concluded that most cancers detected with screening were of low grade and that current urinary testing cannot detect all tumours. Screening is likely to be of benefit in high-risk populations using cost-efficient high-performing urinary biomarkers. There was insufficient evidence to define an efficient screening protocol., Conclusions: Although BCa screening is theoretically feasible in a high-risk population, there is currently insufficient evidence to recommend it. This is due to insufficient data to define an efficient screening protocol with selection of an appropriate population and the lack of accurate and cost-effective urinary markers able to discriminate low-risk from high-risk cancers. Major improvements are needed in the evaluation of urinary biomarkers before evaluation in a RCT can be achieved., (Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To validate and compare the accuracy and performance of nomograms predicting insignificant prostate cancer and to analyze their performance in patients with different cancer locations., Methods: Our cohort consisted of 370 radical prostatectomy patients with Gleason ≤6 prostate cancer diagnosed on transrectal biopsy with at least 10 cores. We quantified the performance of each nomogram with respect to discrimination, calibration, predictive accuracy at different cut points, and the clinical net benefit. We also evaluated these parameters in subgroups of patients with predominantly anterior-apical (AA) and posterior-basal (PB) tumor location., Results: Insignificant prostate cancer was present in 141 patients (38%). The Kattan and Steyerberg nomograms outperformed other studied models and demonstrated fair discrimination (areas under the receiver operating characteristics curve 0.768 and 0.770, respectively), good calibration, balanced predictive accuracy, and the highest net benefit. All nomograms were less accurate at higher levels of predicted probability. The performance of the nomograms was better in patients with PB tumors than in those with AA tumors. The loss of correlation with the actual prevalence of insignificant prostate cancer at higher levels of predicted probability was not seen in the PB subgroup but was particularly noticeable in the AA subgroup., Conclusion: The Kattan and Steyerberg nomograms demonstrated the best performance in predicting the probability of insignificant prostate cancer in a contemporary cohort of patients with Gleason ≤6 cancer diagnosed on specimens from an extended transrectal biopsy. However, all studied nomograms were more accurate in identifying significant rather than insignificant disease, particularly for tumors located in the apical and anterior prostate., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Unlabelled: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Active surveillance is an established management option for patients with favourable-risk prostate cancer. However, about 25-30% of active surveillance patients demonstrate biopsy progression within the first 3-5 years of follow-up. Although several factors, such as the results of the diagnostic and surveillance biopsies, are known to be associated with the risk of progression, our ability to accurately predict this risk remains limited. Our analysis demonstrated that the overall number of positive cores in the diagnostic and first surveillance biopsies is strongly associated with the risk of progression in active surveillance patients. Furthermore, combined results of diagnostic and first surveillance biopsies provide more information about the probability of progression than they do separately. The most important variable affecting the progression-free survival was the overall number of cores positive for cancer. By 3 years of active surveillance, most of the patients who had four positive cores in the diagnostic and surveillance biopsies progressed, while those who had only one positive core had an excellent prognosis. These findings could be used to improve the accuracy of assessments of the prognosis of patients with low-risk prostate cancer and to help them make informed decisions about their treatment., Objective: To analyse the prognostic importance of information provided by the diagnostic biopsy, the first surveillance biopsy and a combination thereof to identify active surveillance patients with a particularly high risk of progression., Materials and Methods: The present study included 161 active surveillance patients who had at least two surveillance biopsies. The first surveillance biopsy was performed within 1 year of the diagnosis. Further surveillance biopsies usually took place every 1-2 years. Progression on the surveillance biopsy was defined as the presence of Gleason 4/5 cancer, > two positive cores or >20% involvement of any core. Cox proportional hazards regression analysis was used to examine the relationship between biopsy characteristics and progression. Three distinct statistical models were built using characteristics of diagnostic biopsies, surveillance biopsies, and a combination thereof. Harrell's c-index was used to quantify the predictive accuracy of each multivariate Cox model., Results: The median follow-up was 3.6 years; 46 (28.6%) patients progressed. In multivariate analysis the major factor associated with progression was the number of positive cores. The model based on the combined results of diagnostic and first surveillance biopsies was significantly more predictive than the models based on the individual results of each biopsy. Patients with four positive cores in the diagnostic and first surveillance biopsies had estimated 5-year progression rate of 100%., Conclusion: The total number of positive cores in the diagnostic and first surveillance biopsies provides important information about the risk of prostate cancer progression in active surveillance patients., (© 2012 The Authors. BJU International © 2012 BJU International.)

Unlabelled: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: A significant proportion of patients diagnosed with prostate cancer do not require immediate treatment and could be managed by active surveillance, which usually includes serial measurements of prostate-specific antigen (PSA) levels and regular biopsies. The rate of rise in PSA levels, which could be calculated as PSA velocity or PSA doubling time, was previously suggested to be associated with the biological aggressiveness of prostate cancer. Although these parameters are obvious candidates for predicting tumour progression in active surveillance patients, earlier studies that examined this topic provided conflicting results. Our analysis showed that PSA velocity and PSA doubling time calculated at different time-points, by different methods, over different intervals, and in different sub-groups of active surveillance patients provide little if any prognostic information. Although we found some significant associations between PSA velocity and the risk of progression as determined by biopsy, the actual clinical significance of this association was small. Furthermore, PSA velocity did not add to the predictive accuracy of total PSA., Objective: To study whether prostate-specific antigen (PSA) velocity (PSAV) and PSA doubling time (PSADT) are associated with biopsy progression in patients managed by active surveillance., Patients and Methods: Our inclusion criteria for active surveillance are biopsy Gleason sum <7, two or fewer positive biopsy cores, ≤20% tumour present in any core, and clinical stage T1-T2a. Changes in any of these parameters during the follow-up that went beyond these limits are considered to be progression. This study included 250 patients who had at least one surveillance biopsy, an available PSA measured no earlier than 3 months before diagnosis, and at least one PSA measurement before each surveillance biopsy. We evaluated the association between PSA kinetics and progression at successive surveillance biopsies in different sub-groups of patients by calculating the area under the curve (AUC) as well as sensitivity and specificity of different thresholds., Results: Over a median follow-up of 3.0 years, the disease of 64 (26%) patients progressed. PSADT was not associated with biopsy progression, whereas PSAV was only weakly associated with progression in certain sub-groups. However, incorporation of PSAV in models including total PSA resulted in a moderate increase in AUC only when the entire cohort was analysed. In other sub-groups the predictive accuracy of total PSA was not significantly improved by adding PSAV., Conclusions: Our findings confirm that PSA kinetics should not be used in decision-making in patients with low-risk prostate cancer managed by active surveillance. Regular surveillance biopsies should remain as the principal method of monitoring cancer progression in these men., (© 2012 The Authors. BJU International © 2012 BJU International.)

Context: Pathology standards for the diagnosis of bladder cancer (BCa) have recently evolved to better reflect patient diagnosis and clinical outcomes., Objective: To update pathology reporting standards for BCa., Evidence Acquisition: We searched the international medical literature and reviewed all articles that addressed BCa gross dissection, pathologic diagnosis, staging, and reporting as of June 6, 2012. We also reviewed the proceedings from the recent Second International Consultation on Bladder Cancer (Vienna, Austria). The literature selected for review focuses on evidence-based studies that address histopathologic factors in BCa, with emphasis placed on factors that influence patient diagnosis and clinical outcomes., Evidence Synthesis: We separated data into three main components for analysis based on the type of specimen obtained: (1) transurethral resection specimens, with an emphasis on pathologic staging, variants of urothelial carcinoma, angiolymphatic invasion, and relevant ancillary techniques such as immunohistochemistry in assessing these features; (2) cystectomy specimens, with an emphasis on pT0 disease, prostatic involvement by urothelial carcinoma and lymph node dissection and analysis; and (3) cytology correlates, with recommendations for the use of cytology paired with tissue-based sampling. Areas of controversy are described and recommendations based on existing guidelines are provided. The value of a multidisciplinary team is highlighted., Conclusions: Ongoing international collaborations amongst pathologists have led to emerging standards in the reporting and microscopic diagnosis of BCa specimens. Although some areas remain controversial, we present the most up-to-date data and guidelines relevant to neoplastic pathology of the urinary bladder., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Currently there is no global agreement as to how extensively 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 patients 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 alternate 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 anterior 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.

Context: The Second International Consultation on Bladder Cancer recommendations on urothelial carcinoma (UC) of the prostate were presented at the 2011 European Association of Urology Congress in Vienna, Austria, on March 18, 2011., Objective: Our aim is to summarize the Second International Consultation on Bladder Cancer recommendations on UC of the prostate to help clinicians assess the current evidence-based management., Evidence Acquisition: The committee performed a thorough review of new data and updated previous recommendations. Levels of evidence and grades of recommendation were assigned based on a systematic review of the literature that included a search of online databases and review articles., Evidence Synthesis: Once a non-muscle-invasive high-grade tumor or carcinoma in situ (CIS) of the bladder has been diagnosed, careful follow-up of the prostatic urethra is necessary. Noninvasive UC including CIS of the prostate should be treated with intravesical bacillus Calmette-Guérin (BCG) following endoscopic resection. A transurethral resection of the prostate may improve contact of BCG with the prostatic urethra, and it appears that response rates to BCG are increased (level of evidence: 3). Transurethral biopsy of the prostatic urethra is effective in identifying prostatic involvement but may not accurately reveal the extent of involvement, particularly with stromal invasion. Stromal invasion by UC of the prostate carries a poor prognosis. Radical cystoprostatectomy is the treatment of choice for locoregional control in patients with prostatic stromal invasion., Conclusions: These recommendations contain updated information on the diagnosis and treatment of UC of the prostate. However, prospective trials are needed to further elucidate the best management of these patients., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: 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., Materials and Methods: 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., Results: 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., Conclusions: 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., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Context: New guidelines of the International Consultation on Urological Diseases for the treatment of muscle-invasive bladder cancer (MIBC) have recently been published., Objective: To provide a comprehensive overview of the current role of radical cystectomy (RC) in MIBC., Evidence Acquisition: A detailed Medline analysis was performed for original articles addressing the role of RC with regard to indication, timing, surgical extent, perioperative morbidity, oncologic outcome, and follow-up. The analysis also included radiation-based bladder-preserving strategies., Evidence Synthesis: The major findings are presented in an evidence-based fashion and are based on large retrospective unicenter and multicenter series with some prospective data., Conclusions: Open RC is the standard treatment for locoregional control of MIBC. Delay of RC is associated with reduced cancer-specific survival. In males, standard RC includes the removal of the bladder, prostate, seminal vesicles, and distal ureters; in females, RC includes an anterior pelvic exenteration including the bladder, entire urethra and adjacent vagina, uterus, and distal ureters. A procedure sparing the urethra and the urethra-supplying autonomous nerves can be performed in case of a planned orthotopic neobladder. Further technical variations (ie, seminal-sparing or vaginal-sparing techniques) aimed at improving functional outcomes must be weighed against the risk of a positive margin. Laparoscopic surgery is promising, but long-term data are required prior to accepting it as an option equivalent to the open procedure. Lymphadenectomy should remove all lymphatic tissue around the common iliac, external iliac, internal iliac, and obturator region bilaterally. Complications after RC should be reported according to the modified Clavien grading system. In selected patients with MIBC, bladder-preserving therapy with cystectomy reserved for tumor recurrence represents a safe and effective alternative to immediate RC., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Context: We present a summary of the Second International Consultation on Bladder Cancer recommendations on chemotherapy for the treatment of bladder cancer using an evidence-based strategy., Objective: To review the data regarding chemotherapy in patients with clinically localized and metastatic bladder cancer with a focus on its use for patients in the neoadjuvant and adjuvant settings., Evidence Acquisition: Medline databases were searched for original articles published prior to April 1, 2012, using the following search terms: bladder cancer, urothelial cancer, metastatic, advanced, neoadjuvant, and adjuvant therapy. Proceedings of major conferences from the last 5 yr also were searched. Novel and promising drugs currently in clinical trials were included., Evidence Synthesis: The major findings are addressed in an evidence-based manner. Prospective trials and important cohort data were analyzed., Conclusions: Cisplatin-based combination chemotherapy for advanced and metastatic bladder cancer is an established standard, improving overall survival. In the advanced setting, cisplatin-ineligible patients may benefit from gemcitabine and carboplatin. Meta-analyses undertaken for neoadjuvant cisplatin-based combination chemotherapy show a 5% benefit in overall survival. Pathologic complete remission may be an intermediate surrogate for survival, but requires further validation. Use of neoadjuvant chemotherapy is low, and is attributable to patient and physician choice because of limited benefit, advanced age, and comorbidities including renal and/or cardiac dysfunction. Sufficient data to support adjuvant chemotherapy are lacking., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Primary lymphoma of the spermatic cord is rare. We report a case of primary lymphoma of the spermatic cord and review the literature. A 77-year-old man presented with a 5 month history of an enlarging right inguino-scrotal mass. On physical exam, the mass involved the spermatic cord. Computerized tomography and magnetic resonance imaging revealed a 10 cm x 4 cm inguinoscrotal mass related to the spermatic cord. A right inguinal orchidectomy with wide local excision was performed. Pathological and immunohistochemical evaluation identified the tumor as a diffuse large B cell lymphoma of the spermatic cord. Postoperatively, patient began a chemoradiotherapy regimen consistent with metastatic lymphoma.

Unlabelled: What's known on the subject? and What does the study add? The surgical implications of renal cell carcinoma with coexisting bland and tumour thrombi of the inferior vena cava is not well described. In this study we review our experience managing these tumours. On multivariate analysis, we found that the presence of bland thrombus was associated with an increased need for surgical interruption of the inferior vena cava., Objective: • To study the role of interruption of the inferior vena cava (IVC) in patients with renal cell carcinoma (RCC) and associated bland and tumour thrombi., Methods: • We reviewed 129 consecutive patients with the preoperative diagnosis of RCC with tumour thrombus who underwent radical nephrectomy and tumour thrombectomy in one academic institution between May 1997 and February 2011., Results: • Percentages of patients with levels I, II, III and IV tumour thrombus were 29%, 13%, 48% and 9%, respectively. • The perioperative mortality rate was 2.3%. There were 29 (22%) perioperative complications recorded. • In all, 19 patients underwent surgical interruption of the IVC by ligation or segmental resection, including one level II, 14 level III and four level IV thrombi. • A total of 15 patients (12%) had bland thrombus associated with the tumour thrombus; four of these underwent intraoperative IVC filter placement and eight underwent surgical IVC interruption. • Advanced level of tumour thrombus was the only significant factor predicting association of bland thrombus (odds ratio [OR]= 2.09, 95% confidence interval [CI]: 1.082-4.037, P= 0.028). • On multivariate analysis, level of thrombus (OR = 3.1, 95% CI: 1.30-7.74, P= 0.011) and association of bland thrombus (OR = 9.07, 95% CI: 2.42-34.01, P= 0.001) were significant factors for IVC interruption., Conclusions: • Surgical interruption of the IVC is a feasible option in selected patients with chronic IVC obstruction. Association of bland thrombus with tumour thrombus should alert the surgical team to the potential for a challenging surgery. • Precise preoperative imaging to assess the degree of venous obstruction and to help with differentiation between bland and tumour thrombus is key to achieving a surgical outcome with minimal morbidity., (© 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.)

Context: Prostate cancer (PCa) remains an increasingly common malignancy worldwide. The optimal management of clinically localized, early-stage disease remains unknown, and profound quality of life issues surround PCa interventions., Objective: To systematically summarize the current literature on the management of low-risk PCa with active surveillance (AS), with a focus on patient selection, outcomes, and future research needs., Evidence Acquisition: A comprehensive search of the PubMed and Embase databases from 1980 to 2011 was performed to identify studies pertaining to AS for PCa. The search terms used included prostate cancer and active surveillance or conservative management or watchful waiting or expectant management. Selected studies for outcomes analysis had to provide a comprehensive description of entry characteristics, criteria for surveillance, and indicators for further intervention., Evidence Synthesis: Data from seven large AS series were reviewed. Inclusion criteria for surveillance vary among studies, and eligibility therefore varies considerably (4-82%). PCa-specific mortality remains low (0-1%), with the longest published median follow-up being 6.8 yr. Up to one-third of patients receive secondary therapy after a median of about 2.5 yr of surveillance. Surveillance protocols and triggers for intervention vary among institutions. Most patients are treated for histologic reclassification (27-100%) or prostate-specific antigen doubling time <3 yr (13-48%), while 7-13% are treated with no evidence of progression. Repeat prostate biopsy with a minimum of 12 cores appears to be important for monitoring patients for changes in tumor histology over time., Conclusions: AS for PCa offers an opportunity to limit intervention to patients who will likely benefit the most from radical treatment. This approach confers a low risk of disease-specific mortality in the short to intermediate term. An early, confirmatory biopsy is essential for limiting the risk of underestimating tumor grade and amount., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate the effect of prostate cancer zonal origin on the biochemical outcome after radical prostatectomy, to analyze clinicopathological features of tumors arising in different zones and to test the ability of the nomogram to predict the probability of transition zone cancer at radical prostatectomy., Methods: Our cohort consisted of 1441 patients who underwent radical prostatectomy who did not receive neoadjuvant treatment. Clinicopathological characteristics and biochemical outcomes were compared between the groups of men with different zonal location of prostate cancer. Performance of the nomogram in predicting cancer location was evaluated with respect to discrimination and calibration., Results: The rates of positive margin were similar in men with transition zone and mixed tumors and were significantly higher than those with peripheral zone tumors. Most of the positive margins in patients with transition zone and mixed cancers were located at the apico-anterior part of the gland. On multivariate analysis, transition zone cancer location was associated with better biochemical recurrence-free survival (P = .043). The Harrel c-index of the models that did and did not include zonal origin of cancer was 0.810 and 0.807, respectively. Performance of the nomogram was poor., Conclusion: The association between transition zone tumor origin and the risk of biochemical recurrence does not add important predictive value to the standard prognostic factors. Although information about the risk of prostate cancer involvement of the transition zone may be important for surgical planning, our ability to predict this risk preoperatively is limited., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: The purpose of our analysis was to determine if delays in treatment caused by active surveillance result in significant pathological changes when patients no longer meet the criteria on repeat biopsy and to study whether or not these changes may affect treatment outcomes., Methods: Out of 207 men who were on active surveillance, 47 (23%) no longer met the criteria after one of the repeat biopsies. Twenty-two underwent radical prostatectomy at our institution and formed the main group (Group 1) of this study. One hundred sixty-four patients met the criteria for active surveillance but underwent immediate surgery. Of these patients, we selected 38 (23%) with the lowest predicted biochemical recurrence-free survival. These patients formed the comparison group (Group 2). Pathological features as well as postoperative biochemical outcomes were compared between the groups., Results: Seven patients (32%) in Group 1 and four (11%) in Group 2 have predominantly high-grade cancer (i.e., ≥4/5 + 3) at pathology. The visually estimated percent of carcinoma was also higher in patients initially managed by active surveillance (median 12.5 vs. 5.0 in Groups 1 and 2, respectively, P = 0.009). Other pathological characteristics were similar in both groups. With limited duration of follow-up, postoperative biochemical recurrence-free survival did not differ significantly between the groups., Conclusions: Our study has demonstrated that both tumor grade and volume may increase during active surveillance. However, the clinical significance of these changes with respect to the outcomes of delayed treatment remains to be established., (Copyright © 2012 Wiley Periodicals, Inc.)

Introduction: Chemotherapy was shown to improve survival in patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). The initiation and completion rates for perioperative chemotherapy are variable. Our aim is to compare the likelihood of initiating and completing neoadjuvant (NAC) and adjuvant chemotherapy (AC) in patients who underwent of RC for MIBC., Materials and Methods: We performed a retrospective analysis of patients who underwent RC between 1992 and 2011. NAC was advised for patients with clinical stage ≥T2, hydronephrosis, extensive lymphovascular invasion (LVI), or prostatic stromal invasion. Patients with ≥pT3 or lymph node metastases were considered for AC., Results: A total of 363 patients were considered for perioperative chemotherapy. Among the 141 patients who were offered NAC, 125 (88.6%) initiated NAC. A total of 222 were considered for AC, and 151 (68.0%) initiated AC (P < 0.001). In the NAC group, 118 (83.5%) completed planned number of cycles of chemotherapy and 7 (5.6%) did not complete the planned chemotherapy. In the AC group, 79 (35.5%) completed at least four cycles and 72 (47.3%) could not complete the planned cycles (P < 0.001)., Conclusions: Patients with MIBC are more likely to initiate and complete NAC than AC.

Purpose: Gender, smoking history, patient age, and tumor size have been found to impact the likelihood of benign histology at the time of nephron-sparing surgery (NSS). Providing external validation of these variables and evaluating the relationship between body mass index (BMI) and tumor location on the likelihood of benign histology during NSS for T1 tumors were the objectives of this study., Methods: Data were analyzed for consecutive patients undergoing NSS for T1 disease. Central tumors either were completely encircled by renal parenchyma, descended below the cortico-medullary junction, or were in direct opposition to the collecting system, renal sinus, or the hilar structures. Categorical variables were evaluated with chi-square test, and continuous variables were analyzed with independent sample t test. Logistic regression identified independent predictors of final pathology., Results: NSS was performed in 316 patients, of whom 79 (24 %) had benign tumors. Patients with benign tumors were more likely to be female, to have a lower BMI, and to have peripheral tumors. On multivariate analysis, female gender (hazard ratio, 3.97; 95 % CI, 2.92-4.53, p < 0.001), peripheral tumor location (hazard ratio, 2.27; 95 % CI, 1.73-3.21, p = 0.014), and lower BMI (hazard ratio, 1.5; 95 % CI, 1.12-1.94, p = 0.015) were independently associated with benign histopathology at the time of surgical resection., Conclusions: Prospectively identifying which T1 tumors are benign would have tremendous implications for the patient. Ours is the first study that has identified the impact of tumor location and BMI on the risk of benign histology. Additional studies are needed to corroborate these findings and incorporate these data into future nomograms.

Background: Although the rationale for active surveillance (AS) in patients with low-risk prostate cancer is well established, eligibility criteria vary significantly across different programs., Objective: To compare the ability of contemporary AS criteria to identify patients with certain pathologic tumor features based on the results of an extended transrectal prostate biopsy., Design, Settings, and Participants: The study cohort included 391 radical prostatectomy patients who had prostate cancer with Gleason scores ≤ 6 on transrectal biopsy with ≥ 10 cores., Intervention: Radical prostatectomy without neoadjuvant treatment., Outcome Measurements and Statistical Analysis: We identified patients who fulfilled the inclusion criteria of five AS protocols including those of Epstein, Memorial Sloan-Kettering Cancer Center, Prostate Cancer Research International: Active Surveillance (PRIAS), University of California, San Francisco, and University of Miami (UM). We evaluated the ability of these criteria to predict three pathologic end points: insignificant disease defined using a classical and updated formulation, and organ-confined Gleason ≤ 6 prostate cancer. Measures of diagnostic accuracy and areas under the receiver operating curve were calculated for each protocol and compared., Results and Limitations: A total of 75% of the patients met the inclusion criteria of at least one protocol; 23% were eligible for AS by all studied criteria. The PRIAS and UM criteria had the best balance between sensitivity and specificity for both definitions of insignificant prostate cancer and a higher discriminative ability for the end points than any criteria including patients with two or more positive cores. The Epstein criteria demonstrated high specificity but low sensitivity for all pathologic end points, and therefore the discriminative ability was not superior to those of other protocols., Conclusions: Significant variations exist in the ability of contemporary AS criteria to predict pathologically insignificant prostate cancer at radical prostatectomy. These differences should be taken into account when making treatment choices in patients with low-risk prostate cancer., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: We assessed the impact of hexaminolevulinate fluorescence cystoscopic detection of papillary, nonmuscle invasive bladder cancer on the long-term recurrence rate., Materials and Methods: Long-term followup was assessed in 551 participants enrolled in a prospective, randomized study of fluorescence cystoscopy for Ta or T1 urothelial bladder cancer. In the original study 280 patients in the white light cystoscopy group and 271 in the fluorescence cystoscopy group were followed with cystoscopy for 3, 6 and 9 months after initial resection or until recurrence. A study extension protocol was done for long-term followup of these patients., Results: Followup information was obtained for 261 of the 280 patients (93%) in the white light group and 255 of the 271 (94%) in the fluorescence group. Median followup in the white light and fluorescence groups was 53.0 and 55.1 months, and 83 (31.8%) and 97 patients (38%) remained tumor free, respectively. Median time to recurrence was 9.4 months in the white light group and 16.4 months in the fluorescence group (p = 0.04). The intravesical therapy rate was similar in the 2 groups (46% and 45%, respectively). Cystectomy was done in 22 of 280 cases (7.9%) in the white light group and in 13 of the 271 (4.8%) in the fluorescence group (p = 0.16)., Conclusions: Hexaminolevulinate fluorescence cystoscopy significantly improves long-term bladder cancer time to recurrence with a trend toward improved bladder preservation., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: The objective of this report is to describe the oncologic outcomes of men with margin-positive prostate cancer who were managed expectantly following radical prostatectomy., Materials and Methods: Between January 1992 and January 2011, 2166 men underwent an open radical prostatectomy by a single surgeon. Of these patients, 1592 (74%) had complete data and met the inclusion criteria of negative lymph nodes and no history of neoadjuvant or adjuvant therapy. This cohort was dichotomized by the presence or absence of at least one positive surgical margin. Groups were compared for differences in recurrence-free and overall survival., Results: In total, 507 (32%) of 1592 patients had at least one positive surgical margin. Clinical and pathological characteristics of these patients indicated more aggressive disease. The median follow up for biochemical recurrence and overall survival was 3.4 years and 7.7 years, respectively. Of those patients with a positive margin, 147 (29%) recurred, with estimated 5 and 10 year biochemical recurrence rates of 31% and 47%, respectively. Multivariate analysis demonstrated that the presence of a positive margin was associated with a 2.45-fold increased hazard of recurrence (p < 0.001). Despite initial observation, surgical margin status was not associated with a decrease in overall survival on both uni- (p = 0.684) and multivariate analyses (p = 0.177)., Conclusion: Although a positive surgical margin is associated with an increased risk of biochemical recurrence, patients in our series were not at an increased risk of all-cause mortality.

Purpose: To evaluate oncologic outcomes following the use of intraoperative cell salvage (IOCS) as a blood loss management strategy during open radical prostatectomy (RP)., Methods: We retrospectively reviewed all open retropubic RP cases performed by a single surgeon. Patients were identified who received IOCS blood and evaluated for an increased risk of biochemical recurrence (BCR) and overall mortality., Results: The study cohort consisted of 1,862 men, 395 (21.2%) of whom received IOCS blood. At a median follow-up of 47.0 months, men who received IOCS blood were not at an increased risk of BCR (P = 0.323) or all-cause mortality (P = 0.892). IOCS use did not confer an increased risk of BCR within any D'Amico preoperative risk category (low risk, P = 0.592; intermediate risk, P = 0.107; and high risk, P = 0.697)., Conclusions: IOCS is safe for the management of blood loss during RP. At long-term follow-up, IOCS use was not associated with an increased risk of BCR or death. While it remains preferable to avoid any form of blood transfusion, we advocate for the use of IOCS in place of allogeneic blood. These conclusions are drawn from our study of the largest and longest followed cohort patients who received IOCS blood during RP.

Background: This study aimed to survey urologists regarding their knowledge, acceptance and practice of active surveillance (AS) for low-risk prostate cancer., Methods: An email-based survey was distributed to 4987 urologists. Respondents were surveyed regarding their knowledge and acceptance of AS. Those who felt AS was a reasonable strategy were asked their opinions on the criteria for AS enrollment and the details of their practice of AS. Respondents who felt AS was not a reasonable alternative were queried as to the reasons why., Results: A total of 425 (9%) urologists successfully completed the survey and 387 (91%) were both familiar with AS and aware that AS differed from watchful waiting. Of this latter group, 370 (96%) respondents felt AS was a reasonable management strategy, 95% of whom manage patients with this approach. A minority of respondents (6%) felt that patients with a PSA>10 ng ml(-1) were eligible for AS. Further, most participants (74%) felt that patients required a Gleason score ≤6. There was little agreement on the timing of follow-up biopsies. Respondents who objected to AS were most commonly concerned with missing an opportunity for curative treatment (76%) and the risk of tumor undergrading (65%)., Conclusions: The majority of participants were knowledgeable and accepting of AS. Respondents were in relative agreement regarding the PSA and Gleason score criteria for AS enrollment. In contrast, there was a lack of agreement on the timing of follow-up biopsies. In the future, comparative studies are required to determine the optimal enrollment criteria and follow-up protocol for patients managed with AS.

Background: The clinical and prognostic significance of unifocal prostatic carcinoma is not clearly understood. In the current study, we sought to characterize the clinical and pathologic characteristics of unifocal and multifocal prostate cancers and to investigate the effects of tumor focality on biochemical outcome after radical prostatectomy., Methods: Our analysis included 1,444 radical prostatectomy patients with available information concerning the number and location of tumor foci in the specimen. Each patient was assigned to one of three groups depending on whether they had unifocal, multifocal, or extensive cancer. Clinical and pathological features as well as biochemical outcomes were compared between the groups., Results: Two hundred and seventy-two mens in the study cohort (18.8%) had unifocal cancer. The rates of unifocal cancer did not differ significantly between the three studied time intervals (17.3% in 1992-1998, 20.5% in 1999-2004, and 17.8% in 2005-2011). The number of positive biopsy cores was slightly lower in the unifocal group, while the overall amount of biopsy tissue containing cancer was similar in both groups. The patients in the multifocal group had higher pathologic Gleason scores, increased incidence of positive surgical margin, and larger tumors. The rate of clinically significant Gleason score upgrade was significantly higher in the multifocal group compared to the unifocal group (35.7% vs. 21.7%, respectively, P < 0.001). The biochemical outcome after radical prostatectomy did not differ between patients with unifocal and multifocal cancers both on univariate and multivariate analyses., Conclusions: Tumor focality is not an independent prognostic factor of biochemical outcome in radical prostatectomy patients., (Copyright © 2011 Wiley Periodicals, Inc.)